This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages, and presents a novel efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses: from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. Best practice and also rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls and 'forgotten' or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of the multivalent soft-matter nanorods.

As Li-ion batteries use is spreading, incidents in large energy storage systems (stationary storage containers, …) or in large-scale cell and battery storages (warehouse, recyclers, …), often leading to fire, are occurring on regular basis. Water remains one of the most efficient fire extinguishing agents for tackling those battery incidents and large quantities are usually necessary. Since bat-teries contains various potentially harmful components (metals and their oxides or salts, sol-vents…) and that thermal runway induced battery incidents are accompanied with complex and potentially multistage fume emissions (containing both gas and particles) the potential impact of fire run-off water on the environment should be considered and assessed carefully. The tests presented in this paper focus on the analysis of the composition of run-off waters used to spray NMC Li-ion modules under thermal runaway. It highlights that waters used for fire-fighting are susceptible to contain many metals, including Ni, Mn, Co, Li and Al mixed with other carbonaceous species (soot, tarballs) and sometimes undecomposed solvents used in the elec-trolyte. Extra-polation of pollutant concentrations compared with PNEC values showed that, for large scale incidents, run-off water could be potentially hazardous to the environment.

Background. Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. Case presentation. We identified across different Cancer Centers six cases of both BRCA wild-type and BRCA-mutated EOC spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as by clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Conclusion. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for optimal disease control of this unfortunate patient’s subset. Albeit not being directly investigated in BM patients, the PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited.

Cry toxins produced by the bacterium Bacillus thuringiensis are of significant agronomic value worldwide due to their potent and highly specific activity against various insect orders. However, some of these pore-forming toxins display specific activity against a range of human cancer cells whilst possessing no known insecticidal activity, Cry41Aa is one such toxin. Cry41Aa has similarities to its insecticidal counterparts in both its 3-domain toxic core structure and pore-forming abilities, but how it has evolved to target human cells is a mystery. This work shows that some insecticidal Cry toxins can enhance the toxicity of Cry41Aa against hepatocellular carcinoma cells, despite possessing no intrinsic toxicity themselves. This interesting crossover is not limited to human cancer cells, as Cry41Aa was found to inhibit some Aedes-active Cry toxins in mosquito larval assays. Here, we present findings that suggest that Cry41Aa shares a receptor with several insecticidal toxins indicating a stronger evolutionary relationship than their divergent activities might suggest.

The development of multiple drug resistant (MDR) cancer all too often signals the need for alternative toxic therapy or palliative care. Our recent in vivo and in vitro studies using canine MDR lymphoma cancer cells demonstrated that the Anaphase Promoting Complex (APC) is impaired in MDR cells compared to normal canine control and drug sensitive cancer cells. Here, we sought to establish whether this phenomena is a generalizable mechanism independent of species, malignancy type or chemotherapy regime. To test the association of blunted APC activity with MDR cancer behavior, we used matched parental and MDR MCF7 human breast cancer cells, and a patient derived xenograft (PDX) model of human breast cancer. We show that APC activating mechanisms, such as APC subunit 1 (APC1) phosphorylation and CDC27/CDC20 protein associations, are reduced in MCF7 MDR cells when compared to chemosensitive matched cell lines. Consistent with impaired APC function in MDR cells, APC substrate proteins failed to be effectively degraded. Similar to our previous observations in canine MDR lymphoma cells, chemical activation of the APC using Mad2 Inhibitor-1 (M2I-1) in MCF7 MDR cells enhanced APC substrate degradation and resensitized MDR cells in vitro to the cytotoxic effects of the alkylating chemotherapeutic agent, Doxorubicin (DOX). Using cell cycle arrest/release experiments we show that chemo-sensitive and -resistant MCF7 cells progress through the cell cycle at similar rates, but mitosis is delayed in MDR cells with elevated substrate levels. When treated with M2I-1, MDR cells progress through mitosis at a faster rate that coincides with reduced levels of APC substrates. In our PDX model, mice growing a clinically-MDR human breast cancer tumor show significantly reduced tumor growth when treated with M2I-1, with evidence of increased DNA damage and apoptosis. Thus, our results strongly support the hypothesis that APC impairment is a driver of aggressive tumor development and that targeting the APC for activation has the potential for meaningful clinical benefits in treating recurrent cases of MDR malignancy.

Background: We investigated the tumor immune response in gastric cancer patients receiving third line nivolumab monotherapy to identify immune-related biomarkers for better patient se-lection. Methods: Nineteen patients (10 males, median age 67 years) who received nivolumab as a third or later line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients. Pre-treatment and early-on-treatment tumor transcriptomes were examined, and gene expression profiles, immunograms, and T cell receptor (TCR) repertoire were analyzed. Results: DCB was observed in 15.8% of patients, with comparable secondary endpoints (ORR, OS, PFS) to previous trials. Individual immunograms showed no significant changes before and ear-ly-on-treatment, nor consistent alterations among DCB cases. The intratumoral immune response was suppressed by previous treatments in most third or later line nivolumab recipients. TCR repertoire analysis revealed newly emerged clonotypes in on-treatment tumors, but clonal re-placement did not impact efficacy. High T cells/Tregs ratios and a low UV radiation response gene signature were linked to DCB and treatment response. Conclusions: This study emphasizes the tumor immune response's importance in nivolumab ef-ficacy for gastric cancer. High T cells/Tregs ratios and specific gene expression signatures show promise as potential biomarkers for treatment response. Larger cohort validation is crucial to optimize immune checkpoint inhibitors in gastric cancer treatment.

The oncogenicity of the human cytomegalovirus (CMV) is debated to this day. In recent years, mounting evidence addresses an anti-cancer effect via T cell-mediated CMV-targeted tumor de-struction. However, the data mostly comes from single-center studies and in vitro experiments. Broad geographic coverage is required to offer a global perspective. This study examined the correlation between country-specific CMV seroprevalence (n=73) and age-standardized inci-dence rates for 34 tumors using data obtained from the International Agency for Research on Cancer of the World Health Organization. The association between CMV and cancer incidences in 10-year age increments was also analyzed. The study revealed a worldwide inverse correlation between CMV seroprevalence and incidences of 88.2% tumors. Notably, this inverse link persists for all cancers combined (Spearman’s ρ= -0.732, p= 0.001). An antithetical and significant correlation is also observed in particular age groups for the vast majority of tumors. Our results corroborate the conclusions of previous studies and indicate that this phenomenon holds true on a global scale. It applies to a wide spectrum of cancer histologies, suggesting a common under-lying mechanism – CMV-stimulated T cell tumor targeting. Although these results further advance the notion of CMV-based therapies, further in-depth investigation of host-virus interactions is warranted.

Abstract: (1) Background: Surgery is the best curative option for Gastric Cancer (GC). However, morbimortality associated with surgery still a significant problem. Thus, it is essential to determine the preoperative surgical risk, to optimize outcomes in higher risk patients. (2) Methods: Patients who underwent curative gastrectomy between January 2010 and December 2013 were included, obtaining a sample of 131 patients, and the acuity of the scales understudy was evaluated. The predictive power of the scales was evaluated through calibration and discrimination. (3) Results and Conclusions: Regarding mortality, the scales demonstrated good calibration, with POSSUM and P-POSSUM obtaining the best O:E ratio. The scales presented good discrimination, with POSSUM showing the best result. Considering morbidity, the scales showed good calibration and discrimination. POSSUM and P-POSSUM seem to have potential in predicting morbidity and mortality when applied to the studied population, but there is a need for further studies in this area.

: Aim: The aim in this study was to conduct a prospective survey regarding the sociodemographics and lifestyle risk factors for cancer of a population of Caribbean immigrants living in the U.S. Materials and Methods: The data were processed and analysed using SPSS software 27 and Excel. Crosstabulations were performed. The chi-square test was used to evaluate different hypotheses. Statistical significance was defined as p < 0.05. Results: Statistically significant differences in the country of birth of the Caribbean immigrants were found for sex (p = 0.038) and the cleanness of their neighbourhoods (p = 0.045). We found differences in occupations between men and women (p = 0.001). Men were less unemployed than women (p = 0.011). Sex also showed statistically significant differences in how easily the immigrants balanced their work and personal life (p = 0.044). Age groups depicted differences in the physical health of the immigrants (p = 0.001). The use of alcohol and tobacco was not an important risk factor among participants (p = 0.529). Conclusions: These findings suggest that the sociodemographics risk factors for cancer among a population of Caribbean immigrants were significantly different between the sexes. However, the use of tobacco and alcohol showed insignificant differences among the immigrants.

Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify and treat patients according to disease stage. LPA is known to target actin-binding protein gelsolin that is a key regulator of actin filament assembly. Previous studies have shown that the phosphate headgroup of LPA alone is inadequate to bind to the short chain of amino acids in gelsolin known as the PIP2-binding domain. Thus, the molecular-level detail of the mechanism of LPA binding is poorly understood. Here, we model LPA binding to the PIP2-binding domain of gelsolin in the gelsolin-actin complex through extensive ten microsecond atomistic molecular dynamics (MD) simulations. We predict that LPA binding causes a local conformational rearrangement due to LPA interactions with both gelsolin and actin residues. These conformational changes are a result of the amphipathic nature of LPA, where the anionic phosphate, polar glycerol and ester groups, and lipophilic aliphatic tail mediate LPA binding via charged electrostatic, hydrogen bonding, and van der Waals interactions. The negatively-charged LPA headgroup binds to the PIP2-binding domain of gelsolin-actin while its hydrophobic tail is inserted into actin, creating a strong LPA-insertion pocket that weakens the gelsolin–actin interface. The computed structure, dynamics, and energetics of the ternary gelsolin–LPA–actin complex confirms that a quantitative OC assay is possible based on LPA-triggered actin release from the gelsolin-actin complex.

Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/- chemotherapy, surgery and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsy in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained samples at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the IsofluxTM CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline, and numbers fell during treatment and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points three microRNAs (hsa-miR-95, hsa-miR-10a and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. They represent potential predictive biomarkers and a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response.

Background: Cancer patients require cross-professional care during the diagnosis and treatment periods. Therefore, methods for effectively carrying out case management are essential to tumor care. Purpose: To investigate the effects of using the community software LINE Official Ac-count on oral cancer case management. Methods: An experimental design was used; 100 patients were randomly divided into two groups by using a computer-generated random number table. The experimental group used LINE Official Account, which gave them self-care information, timely messages, and one-on-one health-care consultations. The control group followed standard healthcare practices. Results: The experimental group was satisfied with the self-care information provided by LINE Official Account (86.9%), patients regularly checked the self-care information (89.4%) and would check the information when receiving a push notification (54.3%). Ten patients used the one-on-one consultation(20.0%). LINE Official Account had a significant effect on the rate of participation in support groups. Generalized estimating equations indicated a significant difference between the two groups regarding the overall quality of life over 7 days (P = 0.023). Conclusion: Community software applications used in oncological case management can improve self-management and empower, also enable tracking of long-term follow-up effectiveness and reinforce the case manager’s role as a family therapist. Therefore, this study recommends that case manager systems be incorporated into mobile applications to increase the sustainable management, accessibility, effectiveness, and satisfaction of oncological management systems. This study also provides the value of Sustainable Development Goals (SDGs) with Good Health and Well-being, and decreased social withdrawal among patients with oral cancer.

Transglutaminase 2 (TG2) is a critical cancer cell survival factor that activates several signaling pathways to foster drug resistance, cancer stem cell survival, metastasis, inflammation, epithelial mesenchymal transition, and angiogenesis. All-trans retinoic acid (ATRA) and chemotherapy have been the standard treatments for acute promyelocytic leukemia (APL), but clinical studies have shown that arsenic trioxide (ATO), alone or in combination with ATRA, can improve outcomes. ATO exerts cytotoxic effects in a variety of ways by inducing oxidative stress, genotoxicity, altered signal transduction, and/or epigenetic modification. In the present study, we showed that ATO increased ROS production and apoptosis ratios in ATRA-differentiated NB4 leukemia cells and that these responses were enhanced when TG2 was deleted. The combined ATRA+ATO treatment also increased the amount of nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor, an adaptive regulator of cellular oxidative stress response, and proteolytic activity of calpain, resulting in TG2 degradation and reduced survival of WT leukemia cells. We further showed that upon ATO treatment, the induced TG2 protein expression was degraded in the MCF-7 epithelial cell line, and primary peripheral blood mononuclear cells, thereby sensitizing these cell types to apoptotic signals.

Prostate cancer (PC) is the most frequently diagnosed non-skin cancer in the world. Previous studies showed that genomic alterations represent the most common mechanism for molecular alterations that cause the development and progression of PC. Great efforts have been done to identify common protein-coding genetic variations; however, the impact of non-coding variations including regulatory genetic variants is not still well understood. To gain an understanding of the functional impact of genetic variants, particularly, regulatory variants in PC, we developed an integrative pipeline (AGV) that used whole genome/exome sequences, GWAS SNPs, chromosome conformation capture data, and ChIP-Seq signals to investigate the potential impact of genomic variants on the underlying target genes in PC. We identified 646 putative regulatory variants, of which 30 of them significantly altered the expression of at least one protein-coding gene. Our analysis of chromatin interactions data (Hi-C) revealed that the 30 putative regulatory variants may affect 131 coding and non-coding genes. Interestingly, our study showed the 131 protein-coding genes are involved in disease-related pathways including Reactome and MSigDB in which for most of them targeted treatment options are currently available. Together, our results provide a comprehensive map of genomic variants in PC and revealed their potential contribution to prostate cancer progression and development.

ABSTRACT Background It is important to be able to predict, for each individual patient, the likelihood of later metastatic occurrence, because the prediction can guide treatment plans tailored to a specific patient to prevent metastasis and to help avoid under- or over-treatment. Deep Neural Network (DNN) learning, commonly referred to as deep learning, has become popular due to its success in image detection and prediction, but questions such as whether deep learning outperforms other machine learning methods when using non-image clinical data remain unanswered. Grid search has been introduced to deep learning hyperparameter tunning for the purpose of improving its prediction performance, but the effect of grid search on other machine learning methods are under-studied. In this research, we take the empirical approach to study the performance of deep learning and other machine learning methods when using non-image clinical data to predict the occurrence of breast cancer metastasis (BCM) 5, 10, or 15-years after the initial treatment. We developed DNN models as well as models using 9 other machine learning methods including Naive Bayes (NB), Logistic Regression (LR), Support Vector Machine (SVM), LASSO, Decision Tree (DT), k-Nearest Neighbors (KNN), Random Forrest (RF), AdaBoost (ADB), and XGBoost (XGB). We used grid search to tune hyperparameters for all methods. We then compared the deep learning models to the models trained using the 9 other machine learning methods. Results Based on the mean test AUC results, DNN ranks 6th, 4th, and 3rd when predicting 5-year, 10-year, and 15-year BCM respectively, out of 10 machine learning methods. The top performing methods in predicting 5-year BCM are XGB(1^st), RF(2^nd), and KNN(3^rd). For predicting 10-year BCM the top performers are XGB (1^st), RF(2^nd), and NB(3^rd) . Finally, for 15-year BCM the top performers are SVM (1^st), LR and LASSO (tied for 2^nd), and DNN (3^rd). The ensemble methods RF and XGB outperform other methods when data are less balanced, while SVM, LR, LASSO, and DNN outperform other methods when data are more balanced. Our statistical testing results show that at a significance level of 0.05 DNN overall performs no worse than other machine learning methods when predicting 5-year, 10-year, and 15-year BCM. Conclusions Our results show that deep learning with grid search overall performs at least as well as other machine learning methods when using non-image clinical data. It is interesting to note that some of the other machine learning methods such as XGB, RF, and SVM are very strong competitors of DNN when incorporating grid search. It is also worth noting that the computation time required to do grid search with DNN is way more than that required to do grid search with the other 9 machine learning methods.

Cancer has emerged as a systemic disease which targets various organs thus challenging the overall physiology of the host. Recently, we have shown that hyperactive neutrophils infiltrate various organs of tumor bearing host and contribute significantly to gradual systemic deterioration. Therefore, taming neutrophils via potent immunomodulators could be an appropriate therapeutic approach in regulating systemic damage. Tinospora cordifolia (TC), an Ayurvedic panacea, is known for its immense medicinal values in traditional literature and recent reports have also documented its strong immunomodulatory potential. However, whether TC can regulate neutrophils to exert its therapeutic effectiveness has not been deciphered so far. To discern this, we utilized murine model of Dalton’s Lymphoma (DL) wherein, we have earlier reported heightened infiltration of neutrophils and their hyperactivation. Our findings showed that TC treatment significantly reduced neutrophil count in peripheral blood and their infiltration in vital organs of tumor bearing host. Further, it ameliorated neutrophil hyperactivation by down regulating the expression of its key cargoes including neutrophil elastase (NE), myeloperoxidase (MPO), MMP-8, MMP-9 and cathepsin G (CSTG) at early and mid stage of tumor growth. In addition, TC treatment prevented histopathological alterations and restored the normal serum enzyme levels at different stages of tumor growth. Importantly, TC treatment also showed significant reduction in tumor burden which was accompanied by a remarkable increase in survival of the tumor-bearing mice. We conclude that Tinospora cordifolia could limit systemic damage via regulating neutrophil infiltration and hyperactivation which can further lead to cancer control at both prophylactic and therapeutic level.

Background: A growing number of clinical practice guidelines (CPGs) with regards to non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistency of recommendations, it remains uncertain how best to design and implement such non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: Clinical practice guidelines which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using the Appraisal of Guidelines for REsearch and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions that were recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: Fourteen CPGs were identified and analysed. Of the 14 CPGs appraised, only five were rated as high quality. The domain with the highest standardised percentage was “scope and purpose” (84.61%), while the “applicability” domain had the lowest standardised percentage (51.04%). Five guidelines were assessed as “recommended”, seven were rated as “recommended with modifications”, and the remaining two were considered “not recommended”. Regarding the content analysis, physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage, and acupressure were the common self-managed non-pharmacological interventions recommended by the 14 CPGs. Physical activity/exercise was the only self-managed non-pharmacological intervention that was mostly recommended for psychological and physical symptom management by the included CPGs. However, there were significant disparities in terms of level of evidence and grade of recommendation in the included CPGs. Conclusion: The recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs in order to guide clinicians in offering high-quality and tailored breast cancer survivorship care.

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

Dietary pattern (DP) and its relationship with disease biomarkers has received recognition in nutritional epidemiology investigations. However, DP relationships with adipokines (i.e., adiponectin and leptin) among breast cancer survivors remain unclear. Therefore, we assessed relationships between DP with high molecular weight (HMW) adiponectin and leptin concentration among breast cancer survivors. This cross-sectional study involved 128 breast cancer survivors who attended the oncology outpatient clinic at two main government hospitals in East Coast of Peninsular Malaysia. The serum concentration of HMW adiponectin and leptin were measured using enzyme-linked immunosorbent assay (ELISA) kits. Reduced rank regression method was used to analyze DP. Relationships between DP with HMW adiponectin and leptin were examined using regression models. Findings showed that a one-unit increase in the ‘energy-dense, high-saturated fat and low-fiber’ DP z-score was associated with a 0.41 µg/mL lower HMW adiponectin (95% CI: -0.806, -0.014) which was independent of age, BMI, cancer stage, duration since diagnosis, education level and occupation status. A similar relationship with leptin concentration was not observed. In conclusion, ‘energy-dense, high-saturated fat and low-fiber’ DP, which is characterized by high sugar-sweetened drink and fat-based spread but low intake of fruits and vegetables, is an unhealthy dietary pattern and unfavorable for HMW adiponectin concentration but not for leptin. These findings could serve as a basis in developing specific preventive strategies that are tailored to the growing population of breast cancer survivors.

Cervical cancer is a worldwide public health problem with a high rate of illness and mortality among women. In this study, we proposed a novel framework based on Faster RCNN-FPN ar-chitecture for the detection of abnormal cervical cells in cytology images from cancer screening test. We extended the Faster RCNN-FPN model by infusing deformable convolution layers into the feature pyramid network (FPN) to improve scalability. Furthermore, we introduced a global contextual aware module alongside the Region Proposal Network (RPN) to enhance the spatial correlation between the background and the foreground. Extensive experimentations with the proposed deformable and global context aware (DGCA) RCNN were carried out using the cer-vical image dataset of “Digital Human Body" Vision Challenge from the Alibaba Cloud TianChi Company. Performance evaluation based on the mean average precision (mAP) and receiver operating characteristic (ROC) curve has demonstrated considerable advantages of the proposed framework. Particularly, when combined with tagging of the negative image samples using tra-ditional computer-vision techniques, 6-9% increase in mAP has been achieved. The proposed DGCA-RCNN model has potential to become a clinically useful AI tool for automated detection of cervical cancer cells in whole slide images of Pap smear.

Ovarian cancer (OC) represents the most common and lethal gynecologic malignancy, due to its increased incidence and mortality rate. It is usually diagnosed in advanced stages and, even though surgery and platinum-based treatment are initially efficient, recurrences emerge in over 70% of cases. Although there are multiple options of chemotherapy drugs from which to choose, little is known regarding the best strategy for prolonged survival. Thus, the aim of this study was to assess the effect that most frequently used chemotherapeutic regimens have upon time-to-treatment-failure (TTF) from the first line and beyond, considering clinical and biological factors which influence the treatment outcome of platinum-resistant recurrent OC. We retrospectively analyzed data from 78 patients diagnosed with platinum-resistant OC, who underwent chemotherapy-based treatment with or without anti-angiogenic therapy at OncoHelp Oncology Center, Romania (January 2016 - February 2021). Our study identified positive predictive factors for TTF related to anthropometry (age over 60 for patients treated with topotecan with or without bevacizumab), renal function (creatinine levels between 0.65 and 1 mg/dl for patients treated with regimens containing bevacizumab and pegylated liposomal doxorubicin) and treatment choice (bevacizumab in combination with pegylated liposomal doxorubicin or topotecan used from the first line and beyond).

Background: Cancer patients may fail to distinguish COVID-19 symptoms such as anosmia, dysgeusia/ageusia, anorexia, headache, and fatigue, which are frequent after cancer treatments. We aimed to identify symptoms associated with COVID-19 and to assess the strength of their association in cancer and cancer-free populations. Methods: The prospective multicenter cohort study PAPESCO-19 included 878 cancer patients and 940 healthcare workers (HCWs) systematically tested for SARS-CoV-2-specific antibodies. Participants reported the results of routine screening RT-PCR and thirteen COVID-19 symptoms. Backward logistic regression identified the symptom combinations significantly associated with COVID-19. Results: COVID+ proportions were similar in patients (8%) and HCWs (9.5%, p=0.26), whereas symptomatic proportions were lower in patients (32%) than HCWs (52%, p<0.001). Anosmia, anorexia, fever, headache, and rhinorrhea together accurately discriminated (c-statistic=0.7027) COVID-19 cases in patients. Anosmia, dysgeusia/ageusia, muscle pain, intense fatigue, headache, and chest pain better discriminated (c-statistic=0.8830) COVID-19 cases in HCWs. Anosmia had the strongest association in patients (OR=7.48, 95% CI: 2.96–18.89) and HCWs (OR=5.71, 95% CI: 2.21–14.75). Conclusions: COVID-19 symptoms and their diagnostic performance differ in cancer patients and HCWs. Anosmia is associated with COVID-19 for patients, while dysgeusia/ageusia are not. Cancer patients deserve tailored preventive measures due to their particular COVID-19 symptom pattern.

Instead of tissue-based detection, blood-based tumor mutation burden (bTMB) is becoming an alternative promising alternate to predict the response of immune checkpoint inhibitor in cancers, especially non-small-cell lung cancer. Although bTMB is more convenient and less invasive, many evidences identified its limited predictive ability and less accurate discrimination of candidates to receive immunotherapy. Several ways of adjustments have been applied to improve the clinical usefulness of bTMB, such as setting restriction for threshold of allele frequency to exclude some unwanted mutations. But many questions remained to be explored such as the number and the type of mutations that should be incorporated into the bTMB estimation. This viewpoint summarized the current attempts to modify bTMB and provided granular aspects that have implications for further enhancement of bTMB’s predictive capability.

Complex diseases such as cancer are caused by changes in the Gene Regulatory Networks. Systems that model the complex dynamics of these networks along with adapting to real gene expression data are closer to reality and can help understand the creation and treatment of cancer. In this paper, for the first time, modelling of gene regulatory networks is performed using delayed nonlinear variable order fractional systems in the state space by a new tool called GENAVOS. This tool uses gene expression time series data to identify and optimize system parameters. This software has several tools for analyzing system dynamics. The results show that the nonlinear variable order fractional systems have very good flexibility in adapting to real data. We found that regulatory networks in cancer cells actually have a larger delay parameter than in normal cells. It is also possible to create chaos, periodic and quasi-periodic oscillations by changing the delay, degradation and synthesis rates. Our findings indicate a profound effect of time-varying order on these networks, which may be related to a type of cellular memory due to epigenetic and environmental factors. We showed that by changing the delay parameter and the variable order function for a normal cell system, its behavior changes and becomes quite similar to the behavior of a cancer cell. This work also confirms the effective role of the miR-17-92 cluster in the cancer cell cycle. GENAVOS is available at https://github.com/hanif-y/GENAVOS with its user guide and MATLAB codes.

We use a system biology approach to translate the interaction of Bacillus Calmette-Gurin (BCG) + interleukin 2 (IL-2) for the treatment of bladder cancer into a mathematical model. The model is presented as a system of differential equations with the following variables: number of tumor cells, bacterial cells, immune cells, and cytokines involved in the tumor-immune response. This work investigates the delay effect induced by the proliferation of tumor antigen-specific effector cells after the immune system destroys BCG-infected urothelium cells following BCG and IL-2 immunotherapy in the treatment of bladder cancer. For the proposed model, three equilibrium states are found analytically. The stability of all equilibria is analyzed using the method of Lyapunov functionals construction and the method of linear matrix inequalities (LMIs).

Although oncolytic viruses are currently being evaluated for cancer treatment in clinical trials, systemic administration is hindered by many factors that prevent them from reaching the tumor cells. When administered systemically, mesenchymal stem cells (MSCs) target tumors, and therefore constitute good cell carriers for oncolytic viruses. Methods: MSCs were primed with trichostatin A under hypoxia, which upregulated the expression of CXCR4, a chemokine receptor involved in tumor tropism, and coxsackievirus and adenovirus receptor that plays an important role in adenoviral infection. After priming, MSCs were loaded with conditionally replicative adenovirus that exhibits limited proliferation in cells with a functional p53 pathway and encodes Escherichia coli nitroreductase (NTR) enzymes (CRAdNTR) for targeting tumor cells. Results: Primed MSCs increased tumor tropism and susceptibility to adenoviral infection, and successfully protected CRAdNTR from neutralization by anti-Adenovirus antibodies both in vitro and in vivo, and specifically targeted p53-deficient colorectal tumors when infused intravenously. Analyses of deproteinized tissues by UPLC-MS/QTOF revealed that these MSCs converted the co-administered prodrug CB1954 into cytotoxic metabolites, such as 4-hydroxylamine and 2-amine, inducing oncolysis and tumor growth inhibition without being toxic for the host vital organs. Conclusion: This study shows that the combination of oncolytic viruses delivered by MSCs with the activation of prodrugs is a new cancer treatment strategy that provides a new approach for the development of oncolytic viral therapy for various cancers.

Does cell clustering influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naïve (intrinsic MDR) and drug-exposed (acquired MDR) lines of ovarian cancer A2780 cells by cytometry of reaction rate constant (CRRC). MDR efflux was characterized by accurate and robust “cell number vs. MDR efflux rate constant (kMDR)” histograms. Both drug-naïve and drug-exposed monolayer cells presented unimodal histograms; the histogram of drug-exposed cells was shifted towards higher kMDR value suggesting greater MDR activity. Spheroids of drug-naïve cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of drug-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of drug-exposed cells but with a moderate shift towards greater MDR activity. The observed greater effect of cell clustering on intrinsic than on acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells.

Preventing muscle wasting in certain chronic diseases including cancer is an ongoing challenge. Studies have shown that polyphenols derived from fruits and vegetables show promise in reducing muscle loss in cellular and animal models of muscle wasting. We hypothesized that polyphenols derived from plum (Prunus domestica) could have anabolic and anti-catabolic benefits on skeletal muscle. The effects of a polyphenol-enriched plum extract (PE60) were evaluated in vitro on C2C12 and Colon-26 cancer cells. Treatment of myocytes with plum extract increased the cell size by ~3-fold (p<0.05) and stimulated myoblast differentiation by ~2-fold (p<0.05). Plum extract induced total protein synthesis by ~50% (p<0.05), reduced serum deprivation- induced total protein degradation by ~30% (P<0.05), and increased expression of IGF-1 by ~2-fold (p<0.05). Plum extract also reduced TNFα-induced NFkB activation by 80% (p<0.05) in A549/NFkB-luc cells. In addition, plum extract inhibited growth of Colon-26 cancer cells, and attenuated cytotoxicity in C2C12 myoblasts induced by soluble factors released from Colon-26 cells. In conclusion, our data suggest that plum extract may have pluripotent health benefits on muscle based on its demonstrated ability to promote myogenesis, stimulate muscle protein synthesis, and inhibit protein degradation. It also appears to protect muscle cell from tumor-induced cytotoxicity.

The rapid expansion of transcriptomics from increased affordability of next-generation sequencing (NGS) technologies generates rocketing amounts of gene expression data across biology and medicine, and notably in cancer research. Concomitantly, many bioinformatics tools were developed to streamline gene expression analysis and quantification. We tested the concordance of NGS RNA sequencing (RNA-seq) analysis outcomes between the two predominant programs for reads alignment, HISAT2 and STAR, and the two most popular programs for quantifying gene expression in NGS experiments, edgeR and DESeq2, using RNA-seq data from a series of breast cancer progression specimens, which include histologically confirmed normal, early neoplasia, ductal carcinoma in situ and infiltrating ductal carcinoma samples microdissected from formalin fixed, paraffin embedded (FFPE) breast tissue blocks. We identified significant differences in aligners’ performance: HISAT2 was prone to misalign reads to retrogene genomic loci, STAR generated more precise alignments, especially for early neoplasia samples. edgeR and DESeq2 produced similar lists of differentially expressed genes in stage comparisons, with edgeR producing more conservative, though shorter, lists of genes. Albeit, Gene Ontology (GO) enrichment analysis revealed no skewness in significant GO categories identified among differentially expressed genes by edgeR vs DESeq2. As transcriptome analysis of archived FFPE samples becomes a vanguard of precision medicine, identification and fine-tuning of bioinformatics tools becomes critical for clinical research. Our results indicate that STAR and edgeR are well-suited tools for differential gene expression analysis from FFPE samples.

Bidirectional gene promoters affect the transcription of two genes, leading to the hypothesis that they should exhibit protection against genetic or epigenetic changes in cancer. Therefore, they provide an excellent opportunity to learn about promoter susceptibility to somatic alteration in tumors. We tested this hypothesis using data from genome-scale DNA methylation (14 cancer types), simple somatic mutation (10 cancer types), and copy number variation profiling (14 cancer types). For DNA methylation, the difference in rank differential methylation between tumor and tumor-adjacent normal matched samples based on promoter type was tested by Wilcoxon rank sum test. Logistic regression was used to compare differences in simple somatic mutations. For copy number alteration, a mixed effects logistic regression model was used. The change in methylation between non-diseased tissues and their tumor counterparts was significantly greater in single compared to bidirectional promoters across all 14 cancer types examined. Similarly, the extent of copy number alteration was greater in single gene compared to bidirectional promoters for all 14 cancer types. Furthermore, among 10 cancer types with available simple somatic mutation data, bidirectional promoters were slightly more susceptible. These results suggest that selective pressures related with specific functional impacts during carcinogenesis drive the susceptibility of promoter regions to somatic alteration.

This paper aims to demonstrate that, beyond the small world of Riemann-Liouville and Caputo derivatives, there is a vast and rich world with many derivatives suitable for specific problems and various theoretical frameworks to develop, corresponding to the different paths taken. Notions of time and scale sequences are introduced and general associated basic derivatives, namely right/stretching and left/shrinking, are defined. A general framework for fractional derivative definitions is reviewed and applied to get both known and new fractional order derivatives. Several fractional derivatives are considered, mainly: Liouville, Hadamard, Euler, bilinear, tempered, q-derivative, and Hahn.

Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

'Cv 'Doña María' table grape is a high-quality table grape variety included in the Protected Designation of Origin (PDO) of the European Union "The bagged grape of the Vinalopó." The PDO stipulates that grape clusters must be protected with paper bags from inclement weather and insects, which helps enhance the final grape quality. However, 'Doña María' is a variety prone to high shattering in the late stages of ripening on the vine and during postharvest. Inorganic calcium treatments are one of the most commonly used tools to reduce this disorder, but the translocation of this mineral from veraison onward has been questioned. In this study, five applications were performed, from veraison to harvest, using sorbitol-chelated calcium (0.7 % + 1.0 %), Ca(NO3)2 (Ca) at 0.7% and sorbitol at 1%. It was observed that bagged grapes (not wetted with the solutions) only increased the concentration of total and bound calcium when treated with Sorbitol-Ca. This resulted in reduced berry drop during cultivation and postharvest and improved fruit firmness. Additionally, it reduced grape metabolism indicators such as respiration rate, weight loss, malic acid degradation, prevented abscisic acid (ABA) and malondialdehyde (MDA) accumulation, and favored the accumulation of secondary metabolites such as total polyphenols, increased antioxidant activity, and sugar content. The application of sorbitol-chelated calcium is an effective and safe tool that enhances fruit quality and prevents losses due to shattering during postharvest.

Listeria monocytogenes is an emerging pathogen responsible for serious foodborne disease, listeriosis. Commensal gut microbiota is the first line of defense against pathogen internalization. Gut microbiome can be modified by prebiotic substrates, which are among others frequently added to food products and dietary supplement. Prebiotics should selectively support the growth of beneficial microbes and thus improve host health. Nevertheless, little is known about their effect on growth of L. monocytogenes. The aim of this study was to evaluate the growth ability of four L. monocytogenes strains, representing the most common serotypes, on prebiotic oligosaccharides: beta(1,3)-D-glucan, inulin, fructooligosaccharides, galactooligosaccharides, lactulose, raffinose, stachyose, 2´-fucosyllactose and mixture of human milk oligosaccharides as a sole carbon source. The results showed that only beta(1,3)-D-glucan was metabolized by L. monocytogenes. Therefore, the health-safety of beta(1,3)-D-glucan in respect to listeriosis development should be furthermore studied.

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin from plant origin reveals that the search for new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of extracts from Lippia adoensis. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using the resazurin colorimetric assays. The phytochemical analysis of the extracts was performed using a liquid chromatography-mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS). As a result, the crude extracts from L. adoensis inhibited growth of P. falciparum (3D7 and Dd2) (IC50s; (3D7): 10.008 and 97.467 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. Donovani (IC50s: 22.879-10.522 μg/mL), and T. brucei brucei (IC50s: 2.3085-55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC50s) above 100 μg/mL. The LC-MS tandem molecular networking flow predicted that the extracts contain valsafungin A and bacillamidin on the first cluster, and fatty acids, ketone and aldehyde derivatives on the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds.

Compared to the general population, patients with inflammatory bowel disease (IBD) are less likely to be vaccinated, putting them at an increased risk of vaccine-preventable illnesses. This risk is further compounded by the immunosuppressive therapies commonly used in IBD management. Therefore, developing new treatments for IBD that maintain immune function is crucial, as successful management can lead to better vaccination outcomes and overall health for these patients. Here, we investigate the potential of recombinant banana lectin (rBanLec) as a supporting therapeutic measure to improve IBD control and possibly increase vaccination rates among IBD patients. By examining the therapeutic efficacy of rBanLec in a murine model of experimental colitis, we aim to lay the foundation for its application in improving vaccination outcomes. After inducing experimental colitis in C57BL/6 and BALB/c mice with 2,4,6-trinitrobenzene sulfonic acid, we treated animals orally with varying doses of rBanLec 0.1-10 µg/ml (0.01 – 1 µg/dose) during the course of the disease. We assessed the severity of colitis and rBanLec’s modulation of the immune response compared to control groups. rBanLec administration resulted in a dose-dependent reduction in colitis severity (less pronounced weight loss, less shortening of the colon) and an improved recovery profile, highlighting its therapeutic potential. Notably, rBanLec-treated mice exhibited significant modulation of the immune response, favoring anti-inflammatory pathways (primarily reduction in a local [TNFα]/[IL-10]) crucial for effective vaccination. Our findings suggest that rBanLec could mitigate the adverse effects of immunosuppressive therapy on vaccine responsiveness in IBD patients. By improving the underlying immune response, rBanLec may increase the efficacy of vaccinations, offering a dual benefit of disease management and prevention of vaccine-preventable illnesses. Further studies are required to translate these findings into clinical practice.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

Pipeline conflicts arising from data dependencies are a common issue encountered in the hardware implementation of layered QC-LDPC decoders. This paper proposes an efficient layered decoding architecture to reduce pipeline conflicts without introducing stall cycles, by reordering the processing order offline and using the patch method based on variable-to-check message. The experimental results on the LDPC code of the IEEE802.16 standard in the OFDM-PON system demonstrate that the proposed architecture has a sensitivity improvement of 0.125 dBm and 0.375 dBm, respectively, compared with our previous work and the method described in the other work.

Abstract: Field studies with large-stemmed plants Artemisia dubia (wormwood) have been carried out at Vėžaičiai Branch LAMMC since 2018. According to three years of experimental results, annual dry matter (DM) yield varied from 7.94 to 10.14 t ha-1. Growing conditions, nitrogen ap-plication level and harvesting time had significant impacts on Artemisia dubia productivity. This article presents the results of research on preparation and use of Artemisia dubia biomass for en-ergy conversion and evaluation of technological-technical and environmental parameters of these plants utilization for solid biofuel. For experiments were used 6 variants of Artemisia dubia samples, which were grown in 2021: plants were cut three times and two fertilization options were used: (1) no fertilization and (2) fertilization with 180 kg ha-1 of nitrogen fertilizer. These harvested plants were chopped, milled and were pressed into the pellets. The physi-cal-mechanical characteristics (mоisture content, density and strength) of Artemisia dubia pellets were investigated. During this study, it was found that the density in dry mass (DM) of pellets ranged from 1119.86 to 1192.44 kg m-3. The pellet moisture content ranged from 8.80 to 10.49%. After testing of pellet strength, it was found that the pellets which were made from plant bio-mass PK-1-1, were the most resistant to compression, they withstood 560.36 N of pressure. Dry fuel lower heating value (LHV) of pellets was sufficiently high and was very close to pine saw-dust pellets, it varied from 17.46±0.25 MJ kg-1 to 18.14±0.28 MJ kg-1. The ash content of burned pellets ranged from 3.62±0.02% to 6.47±0.09%. Emissions of harmful pollutants – CO2, CO, NOx and unburnt hydrocarbons (CxHy) did not exceed the maximum permissible levels. Summariz-ing the results of investigated properties, cоmbustion and emissiоns of Artemisia dubia pellets, it can be concluded that this biofuel can be used for production of pressed biofuel and it is charac-terized by sufficient high quality, efficient combustion and permissible emissions to the envi-ronment.

Field of ResearchThis research study investigates the role of distributed leadership and culture within small enterprises in Malta, an area in which there has been very limited research. It focuses on the interaction between these two elements and their impact on organizational behaviour and effectiveness. Several studies (Jardon et al 2019; Cope et al., 2011; de Oliveira et al., 2015; Mohanty et al., 2012;) suggest that effective leadership and culture are vital elements in the successful endeavours of small organizations. Schein (2006) further asserts that they are two different faces on the same coin and the dyadic interaction characterizes “how leaders create culture and how culture defines and creates leaders”. Distributed Leadership is a systematic practice of interactions and synergies between leaders, followers, and the situation (Spillane 2013). It is different from traditional leadership, which involves top-down management because it tends to be more democratic and participatory, whereby influence and decision-making are shared among multiple individuals rather than being controlled by a single leader. (Xhemajli et al. 2022) MethodologyAdopting a naturalistic approach and guided by an interpretivist, constructivist epistemological stance, this research delves into the intricate interplay between leadership and culture within small businesses. The chosen research methodology employs Grounded Theory, recognized for its robust and systematic process facilitating the observation of patterns through intensive iterative and highly analytical procedures (Charmaz, 2015).In the initial stages of field research, characterized by 'responsive interviewing' (Rubin and Rubin, 2012), data sampling commenced with convenience sampling. This initial phase gradually evolved into a refined strategy incorporating selective sampling and theoretical sampling (Corbin and Strauss, 2015). The shift in sampling approaches reflects a deliberate focus on collecting data based on its specific contribution to the development and comprehension of the dimensions, properties, and characteristics of key concepts.The induction of theory is a product of successive comparative analyses, involving the systematic comparison of data points to identify both similarities and variations. Abductive reasoning is integral throughout the analytical process, with particular emphasis during constant comparative analysis of categories, leading to theoretical integration (Charmaz, 2006). This meticulous approach aligns with the assertion of Strauss and Corbin (2015) that grounding theory in data enhances the likelihood of deriving theories that authentically reflect reality.The key advantage of using this approach is that the analysis carried out goes beyond deep exploration and rich description and actually develops a framework that explains the phenomena observed (Parker and Roffey, 1997, p.218). This is very important if the findings are to contribute to the knowledge enhancement of any field of practiceThe culmination of this research effort is the presentation of a set of interconnected concepts, intricately woven together into an emergent parsimonious model (Corbin and Strauss, 2015). This model serves to explain the dynamic interplay between leadership and culture, elucidating its tangible impact on the effectiveness of small enterprises. Research Contribution:Implications for PracticeThis research contributes to the literature on leadership and organizational culture in small enterprises, particularly in the context of Malta where such studies are scarce. By providing an initial exploration of these phenomena and their impact on organizational behavior, this paper lays the groundwork for further inquiry into this important area. Furthermore, the study offers practical insights for leaders of small enterprises by elucidating leadership behaviors observed in established organizations. Through applied cases, it demonstrates how the abstract concept of culture can be translated into a practical instrument that supports leadership and organizational development. This not only enriches the understanding of leadership dynamics but also provides tangible strategies for implementation. Moreover, the research contributes empirical evidence on the development of leadership functions within small enterprises, emphasizing the potential of shared and distributed leadership models. By grounding its findings in data, the study equips leaders with a deeper understanding of how these leadership approaches can shape organizational development, fostering more effective management practices in small businesses. Methodologically, the adoption of Grounded Theory methodology showcases its efficacy in exploring complex management phenomena. By employing this approach, the researchers were able to gather rich descriptions and develop an explanatory framework, highlighting its applicability in studying nuanced organizational dynamics. Implications for Policy and TheoryThis research also holds significant implications for policymakers, academic researchers and institutions involved in supporting small businesses. By providing insights into distributed leadership and cultural influences on organizational effectiveness, it offers a basis for informed policy formulation and support mechanisms. The conceptual model emerging from this study serves as a foundation for designing more targeted policies that cater to the unique needs of small enterprises. By understanding the intricacies of leadership dynamics and cultural contexts, policymakers can develop interventions that foster a conducive environment for small business growth and sustainability. Additionally, academic researchers can use these findings to further refine theoretical frameworks and empirical studies in the field, contributing to ongoing scholarly dialogue and knowledge advancement.

Ever since Varela and Maturana proposed the concept of autopoiesis as the minimal requirement for life, there has been a focus on cellular systems that erect topological boundaries to separate themselves from their surrounding environment. Here we reconsider whether the existence of such a spatial boundary is strictly necessary for self-producing entities. This work presents a novel computational model of a minimal autopoietic system inspired by dendrites and molecular dynamics simulations in three-dimensional space. A series of simulation experiments where the metabolic pathways of a particular autocatalytic set are successively inhibited until autocatalytic entities that could be considered autopoietic are produced. These entities maintain their distinctness in an environment containing multiple identical instances of the entities without the existence of a topological boundary. This gives rise to the concept of a metabolic boundary which manifests as emergent self-selection criteria for the processes of self-production without any need for unique identifiers. However, the adoption of such a boundary comes at a cost, as these autopoietic entities are less suited to their simulated environment than their autocatalytic counterparts. Finally, this work showcases a generalized metabolism-centered approach to the study of autopoiesis that can be applied to both physical and abstract systems alike.

Silicon carbide single crystal (SiC) has been widely used in the field of power devices, while it is difficult to fabricate ultra-flat surface by traditional manufacturing technologies due to its difficult-to-machine property. This paper investigates the interaction process during femtosecond laser ablation of crystalline silicon carbide based on the two-temperature model simulation and experimental study. The findings reveal that parameters such as laser pulse energy, scanning interval, and defocus amount exert significant influence on ablation depth, roughness, and surface morphology. The femtosecond laser proves effective in removing surface defects from cut SiC substrates, albeit resulting in increased surface roughness. However, subsequent polishing treatment of the laser-ablated silicon carbide surface can mitigate this roughness, underscoring the feasibility of laser surface ablation for silicon carbide single crystals.

Phyllanthus emblica (P. emblica) has been described in many studies to have multiple therapeutic activities and is considered an important part of Ayurvedic and Unani medicinal systems. This study successfully synthesized P. emblica loaded polyvinylalcohol/gelatin based cryogels (PVA/Gel/P.emblica) to examine their potential in wound dressing applications. Swelling tests, Brunauer-Emmett-Teller (BET) and morphology analysis were conducted within the scope of characterization studies. In vitro cell culture studies were performed using HaCaT cells to illustrate the suitability of the synthesized cryogels as wound dressing material. The swelling tests and BET analysis results showed that swelling and surface area properties of cryogels increased with increasing P. emblica amounts. Morphological results displayed that the cryogels had a dense, interconnected pore morphology and a macroporous structure. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results revealed that adding of P. emblica into cryogels led to enhanced cell proliferation, increased cell number, and improved cell viability. Based on the phase contrast microscope, scanning electron microscope (SEM), immunofluorescence and giemsa staining images, it was observed that P. emblica promoted cell attachment, proliferation and penetration. In conclusion, it has been shown that PVA/Gel/P.emblica cryogels are suitable for use as wound dressing materials and can be developed with further studies.

To improve carbon efficiency for urban logistics service system composed of a third-party logistics service provider (3PLs) and an e-business enterprise, low-carbon operation game between them was studied. Considering low carbon technology investment cost and sales expansion effect of low carbon level, profit functions for both players were constituted. Based on their different bargaining capabilities, totally 5 types of game scenarios were designed. Through analytical solution, Nash Equilibria under varied scenarios were obtained. By analyzing these equilibria, 4 major propositions were given, in which, some key variables and system performance index were compared. Results show that the best system yields could only be achieved under the fully cooperative situation; limited cooperation only for carbon emission reduction would not benefit the system performance improvement; E-business enterprise-leading game’s performance overtook 3PLs-leading ones.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

This paper, from the perspective of Mode 3 of knowledge production, takes the important carrier of knowledge, scientific research papers, as the research object. The mainstream databases (SCIE and SSCI) are chosen as the data sources. Firstly, bibliometric methods are applied to analyze the cooperation status among the main bodies of paper production, including authors and their affiliated institutions, countries, and disciplines; secondly, the Analytic Hierarchy Process (AHP) is used to construct a comprehensive evaluation model for the state of research cooperation in carbon neutrality. Based on the evaluation model, the cooperation characteristics of different disciplinary fields and the relationship between paper cooperation status and high-impact research papers are comparatively analyzed. At the same time, an analysis is conducted on the support from the government, the sponsorship from enterprises, and the participation of the public in the process of paper production. Finally, some suggestions are put forward on how to build an innovative ecosystem for carbon neutrality research from the perspective of Mode 3 of knowledge production.

Background This study aimed to identify the prominent risk factors that may trigger danger signals of early onset of vascular deregulation in T1D. The risk factors we have identified may serve as dual-purpose biomarkers of rapid diagnosis that offer prospective tailor-made resolution therapeutics. Methods The healthy control (HC) was compared with individuals diagnosed with T1D for the risk factors of vascular deregulation in published research studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, which is relevant to clinical subjects. A random effect model for continuous data was followed and analysed by RevMan 5.4 and GraphPad Prism software. Results 80 relevant case-control studies having 5293 HC and 7492 T1D patients were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of all age groups were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Conclusions Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-C, and AI% which the clinicians could evaluate using a simple blood test or non-invasive techniques. (Protocol registered at https://www.crd.york.ac.uk/prospero/ CRD42022384636).

Vitamin A, or retinol, is one of the most effective anti-ageing molecules, but it presents issues with photo-sensitivity and irritation. Retinol-like alternatives are emerging, but have so far been less effective. Here, we present a Silibum marianum extract (SME) as a retinol-like ingredient providing both safety and efficacy. SME was compared to the reference compound, retinol, and to the main alternative, bakuchiol. In ex vivo tests, skin explants from a 58-year-old donor were treated with pure retinol (0.1%), bakuchiol (0.2%) or SME (0.8%). After 5 days, collagen and hyaluronic acid levels were analysed. A placebo-controlled study involving 57 volunteers (ages 45-73 years) was also conducted, with products applied twice-daily for 56 days. Results were measured by AEVA-HE and VISA. Levels of collagen III were significantly increased by SME, by 23% and 16% compared to bakuchiol and retinol, respectively. Compared to bakuchiol, SME treatment increased hyaluronic acid production by 36%. In clinical tests, SME had a significantly stronger anti-wrinkle effect than bakuchiol – reducing the number of wrinkles on the forehead by 21%, and their circumference by 17% – producing effects similar to retinol, and better than bakuchiol. In the self-assessment, 43% of volunteers reported discomfort while using retinol, as compared to 0% for the SME formulation. By enhancing levels of collagen III – the youth collagen – and hyaluronic acid in the skin, SME paves the way for the maturation of collagen I fibrils and skin plumping. With its stronger efficacy compared to bakuchiol and enhanced safety profile compared to retinol, SME may be the next-generation of natural alternatives to retinoids.

To make wind power more competitive, it is necessary to reduce turbine downtime and reduce costs associated with wind turbine Operation and Maintenance (O&amp;M). Incorporating machine learning in developing condition-based predictive maintenance methodologies for wind turbines can enhance their efficiency and reliability. This paper presents a monitoring method that utilizes Base Density for the Support Vector Machine (BDSVM) and the evolutionary Fourier spectra of vibrations. This method allows smart monitoring of the function evolution of the turbine. A complex optimal function (FO) for 5-degree order has been developed that will be the boundary function of the BDSVM to timely determine the magnitude, frequency, and place of the failure occurring in wind turbine drive.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

As companies increasingly undergo digital transformation, the role of talent management pro-cesses becomes pivotal in enhancing overall organizational performance. The research addresses the significance of talent management in corporate digital transformation, examining whether variations in the digitalization of these processes can be attributed to company size. A qualitative approach was employed, utilizing a questionnaire, collecting responses from 202 organizations across diverse sectors. Findings reveal disparities in digitalization throughout the talent man-agement process, with pronounced presence in the attracting, selecting, and rewarding phases, but diminishing in deployment and development, further declining in planning. A positive cor-relation between company size and adoption of specific digital platforms was observed. Larger enterprises exhibit greater utilization of digital platforms in talent deployment and development. Moreover, corporate communication tools are consistently utilized in the rewarding phase, irre-spective of company size. These findings offer practical insights for organizations to optimize their digitalization strategies based on their scale, thereby contributing to more effective and tailored digitalization endeavors. The uniqueness of this research lies in its exploration of the in-fluence of company size on the digitalization of talent management processes and its potential to explain variations across different stages of these processes.

A great deal of studies have assessed the expression of noncoding RNAs (ncRNAs) as well as their relevant molecular functions and biological mechanisms in the individuals of alcohol dependence. Alcohol dependence is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is intricate and inadequately understood. There is considerable evidence demonstrating substantial links between multiple genetic factors and the development of alcohol dependence. Critical roles of ncRNAs have been emphasized in the pathophysiology of mental diseases including alcohol dependence. In the comprehension of ncRNAs action and their mechanisms of modification, they have emerged as therapeutic targets for a variety of psychiatric illness including alcohol dependence. Worth mentioning, dysregulated expression of ncRNAs has been regularly detected in individuals of alcohol dependence. An in-depth knowledge of roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a deeper comprehension of functional roles ncRNAs may make significant contributions to the precise diagnosis and/or actual treatment of alcohol dependence. Here in this review, we mostly focused on the up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in alcohol dependence, and then, presented their prospects for future research and therapeutic application with a novel concept of engram-system.

To address the insufficient mechanical properties of calcined phosphogypsum, this research aims to investigate the utilization of basalt fiber and calcium carbonate whiskers as reinforcing agents. The study examines their impact on the flexural and compressive strength, toughness, water resistance, and tensile strength of calcined phosphogypsum. In the individual tests, basalt fibers with different lengths (3 mm, 6 mm, 9 mm, and 18 mm) were added at dosages of 0%, 0.5%, 1.0%, and 1.5% respectively. The findings demonstrate that basalt fiber effectively enhances the flexural and compressive strength, toughness, and tensile strength of calcined phosphogypsum, albeit potentially compromising water resistance. Among the various fiber lengths, the 6 mm fibers exhibit the most advantageous influence on the performance of calcined phosphogypsum. A subsequent test was conducted to investigate the impact of cross-scale fibers on the properties of calcined phosphogypsum by mixing 6 mm basalt fibers and calcium carbonate whiskers. The results illustrate that calcium carbonate whisker refines the pores, thereby improving the flexural strength and toughness of calcined phosphogypsum. Furthermore, it compensates for the water resistance limitations associated with the sole utilization of basalt fiber while further augmenting the tensile strength and strain capacity. However, it should be noted that increasing the dosage of both calcium carbonate whiskers and basalt fibers concurrently leads to increased porosity of phosphogypsum and reduced compressive strength.

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

This paper illustrates an experimental activity for the closed-loop position control of an actuator made using shape memory alloy (SMA) wire. A solution with the self-sensing effect was implemented to miniaturize the systems, i.e., without external sensors. A proportional control algorithm was initially used, demonstrating the idea's feasibility: the wire can behave simultaneously as an actuator and sensor. An experimental investigation was subsequently conducted for the optimization of the developed actuator. As for the material, a Flexinol wire, Ni-Ti alloy, with a diameter of 0.150 mm and a length of 200 mm, was used. Preliminarily, a characterization of the SMA wire at constant and variable loads was carried out: the characteristics detected are elongation vs. electric current and elongation vs. electrical resistance. The control system is PC-based with a data acquisition card (DAQ). A drive board has been designed and built to read the wire's electrical resistance and power it by pulse width modulation (PWM). A notable result is that the actuator works with good precision and in dynamic conditions, even when it is called to support a load up to 65% different from that for which the electrical resistance-length correlation has previously been experimentally obtained, on which the control is based. This opens up the possibility of using the actuator in a counteracting configuration with a spring, which makes hardware implementation and control management simple.

This study investigates cloud cavitation suppression around a model scale NACA66 hydrofoil using active water injection and explores the effect of multiple injection parameters. Numerical simulations and a mixed-level orthogonal test method are employed to systematically analyze the impact of jet angle αjet, jet location Ljet, and jet velocity Ujet on cavitation suppression efficiency and hydrofoil energy performance. The study reveals that jet location has the greatest influence on cavitation suppression, while jet angle has the greatest influence on hydrofoil energy performance. The optimal parameter combination (Ljet = 0.30C, αjet = +60 degrees, Ujet = 3.25 m/s) effectively balances energy performance and cavitation suppression, reducing cavitation volume by 49.34% and improving lift-drag ratio by 8.55%. The study found that the jet's introduction not only enhances vapor condensation and reduces the intensity of the vapor-liquid exchange process but also disrupts the internal structure of cavitation clouds and elevates pressure on the hydrofoil suction surface, thereby effectively suppressing cavitation. Further analysis shows that positive-going horizontal jet components enhance the lift-drag ratio, while negative-going components have a detrimental effect. Jet arrangements near the trailing edge negatively impact both cavitation suppression and energy performance. These findings provide valuable reference for selecting optimal injection parameters to achieve a balance between cavitation suppression and energy performance in hydrodynamic systems.

Drowsiness is a main factor for various costly defects, even fatal accidents in areas such as construction, transportation, industry and medicine, due to the lack of monitoring vigilance in the mentioned areas. The implementation of a drowsiness detection system can greatly help to reduce the defects and accident rates by alerting individuals when they enter a drowsy state. This research proposes an Electroencephalography (EEG) based approach for detecting drowsiness. EEG signals are passed through a preprocessing chain composed of artifact removal and segmentation to ensure accurate detection followed by different feature extraction methods to extract the different features related to drowsiness. This work explores the use of various machine learning algorithms such as Support Vector Machine (SVM) the K Nearest Neighbor (KNN) the Naive Bayes (NB) the Decision Tree (DT) and the Multilayer Perceptron (MLP) to analyze EEG signals sourced from the DROZY database, carefully labeled into two distinct states of alertness (awake, and drowsy). Segmentation into 10-second intervals ensures precise detection, while a relevant feature selection layer enhances accuracy and generalizability. The proposed approach achieves high accuracy rates of 99.84% and 96.4% for intra (subject by subject) and inter (cross-subject) modes, respectively. SVM emerges as the most effective model for drowsiness detection in the intra mode, while MLP demonstrates superior accuracy in the inter mode. This research offers a promising avenue for implementing proactive drowsiness detection systems to enhance occupational safety across various industries.

Introduction: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may cause acute respiratory failure but also remains responsible for many other pathologies, including electrolyte disorders. SARS-CoV-2 infection can cause dysfunction of the renin-angiotensin-aldosterone system and disrupt water hemostasis with thirst and appetite abnormalities. Dysnatremia affects prognosis and may be associated with mortality in patients admitted to SARS-CoV2 intensive care. Patients and Methods: The study included 209 patients admitted to the Intensive Care Unit between April 12, 2021, and March 1, 2022 who were over 18 years old and diagnosed with SARS-CoV-2 infection by clinical and thoracic tomography findings or with a positive reverse transcription polymerase chain reaction (RT-PCR) test result. The laboratory markers, treatment modalities, nutritional, and respiratory support also for outcome evaluation, length of stay in the ICU, total hospitalization duration, and mortality in ICU were recorded.The laboratory marker comparison was made admission with the final assessment performed before the time of mortality in ICU or discharge. Results: Inotropic requirements among patients were high which was reflected in the first-month mortality. Hypernatremia presence was associated with an increase in enteral support and inotropic support requirement and mortality. Hypernatremia was correlated with diabetes mellitus, chronic renal failure, and a longer duration under mechanical ventilation. Discussion: Hypernatremia was an important risk factor in ICU patients hospitalized for SARS-CoV-2 infection, which was also affected by the treatment regimens given itself. This complex relationship underlies the importance of proper electrolyte management, especially in patients who were under severe stress and organ failure.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

A new quinazolinone alkaloid, named peniquinazolinone A (1), as well as eleven known com-pounds, 2-(2-hydroxy-3-phenylpropionamido)-N-methylbenzamide (2), viridicatin (3), viridicatol (4), (±)-cyclopeptin (5a/5b), dehydrocyclopeptin (6), cyclopenin (7), cyclopenol (8), methyl-indole-3-carboxylate (9), 2,5-dihydroxyphenyl acetate (10), methyl m-hydroxyphenylacetate (11), conidiogenone B (12), was isolated from the endophytic Penicillium sp. HJT-A-6. The chemical structures of all compounds were elucidated by comprehensive spectroscopic analysis, including 1D, 2D NMR, and HRESIMS. The absolute configuration at C-13 of peniquinazolinone A (1) was established by applying the modified Mosher’s method. Compounds 2, 3, and 7 exhibited an op-timal promoting effect on the seed germination of Rhodiola tibetica at a concentration of 0.01 mg/mL, while the optimal concentration for compounds 4 and 9 to promote Rhodiola tibetica seed germination was 0.001 mg/mL. Compound 12 showed optimal seed-germination-promoting activity at a concentration of 0.1 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compounds 2, 3, 4, 7, 9, and 12 could extend the seed-germination period of Rhodiola tibetica up to the 11th day.

The branch prediction units (BPUs) generally have security vulnerabilities, which can be used by attackers to obtain the execution status, jump directions, and jump address of conditional branches, and the existing protection methods cannot defend against these attacks. Therefore, this article proposes a hardware security protection method for conditional branches of embedded systems. This method calculates the number of updates to the branch target buffer (BTB). When it exceeds the threshold, BTB is locked to prevent attackers from analyzing the execution status of branches based on the time difference of whether BTB is updated. Moreover, the hybrid physical unclonable function (PUF) circuit is designed to provide confidentiality protection for the jump directions, jump addresses, and their indexes, preventing attackers from stealing these critical data. If these mechanism fails and attackers successfully tamper with conditional branches, this paper proposes a control flow integrity (CFI) protection mechanism based on branch labels to timely detect tampering with instruction codes, jump addresses, and jump directions. The proposed method is implemented and tested on FPGA. The experimental results show that this method can achieve fine-grained security protection for conditional branches, with about 5.4% resource overhead and less than 5.5% performance overhead.

Mannosylerythritol lipids (MELs), one of the most promising biosurfactants (BS), are glycolipids produced by yeasts or fungi, with great environmental performance and a high compatibility with the human body. MELs besides working as typical surfactants, can form diverse structures when in the critical aggregation concentration (CAC), reducing the surface tension of water and other solutions, and being stable over a wide range of conditions. Among others, MELs present anti-microbial, antitumor, antioxidant and anti-inflammatory activity, skin and hair repair capacity, which opens possibilities for their use in applications from cosmetics and pharmaceutics to bio-remediation and agriculture. However, their market share is still low when compared to other glycolipids, due to their less developed production process and higher production cost. This re-view gathers information on the potential applications of MELs mentioned on the literature since 1993. Furthermore, it is also explored the current strategies being developed to enhance the market presence of MELs, in parallel with the ones developed for rhamnolipids and sophorolipids.

The wellness economy has developed rapidly recently, particularly in wellness tourism. Wellness tourism transforms sustainable strategy through the availability of extended multi-actor engagement in service innovation to further the tourism experience. Therefore, when operating a wellness tourism destination, it is necessary to encourage multi-actor engagement in service innovation to achieve sustainable development. This paper introduces a mixed research method with the SWOT-AHP-QSPM, as it qualitatively analyzes the advantages, disadvantages, opportunities, and threats, constructs an evaluation index system, conducts quantitative analysis using the analytic hierarchy process, determines the index weight and weighted score, and calculate the sustainable development strategy, which is appropriate for wellness development of Chongqing Tea Mountain and Bamboo Forest National Forest Park. Purposive field surveys and personal interviews were conducted in Chongqing forest tourism destinations, involving 356 effective respondents. The research reveals that multi-actor engagement significantly enhances sustainable development. These findings bridge service innovation knowledge gaps and provide valuable insights for forest tourism destination management and sustainable policy strategies to elevate multi-actor engagement in forest sites.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p &lt; 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

Lignin fibers typically influence the mixture performance of stone matrix asphalt (SMA), such as strength, stability, durability, noise level, rutting resistance, fatigue life, and water sensitivity. However, limited studies were conducted to analyze the influence of fibers on the percent voids in mineral aggregate in bituminous mixture (VMA) during the mixture design. This study analyzed the effect of different fibers and fiber contents on the VMA in SMA mixture design. A surface-dry condition method test and Marshall Stability test were applied on the SMA mixture with four different fibers (i.e., flocculent lignin fiber, mineral fiber, polyester fiber, blended fiber). The test results indicated that the bulk specific gravity of SMA mixtures and asphalt saturation decreased with the increasing fiber content, whilst the percent air voids in bituminous mixtures (VV), Marshall Stability and VMA increased. Mineral fiber had the most obvious impact on the bulk specific gravity of bituminous mixtures, while flocculent lignin fiber had a minimal impact. The mixture with mineral fiber and polyester fiber had significant effects on the volumetric properties, and, consequently, exhibited better VMA over the conventional SMA mixture with lignin fiber. Modified fiber content range was also provided, which will widen the utilization of mineral fiber and polyester fiber in the applications of SMA mixtures. The mixture evaluation suggested no statistically significant difference between lignin fiber and polyester fiber on the stability. The mineral fiber required a much larger fiber content to improve the mixture performance than other fibers. Overall, the results can be a reference to guide SMA mixture design.

In this paper, a semi-empirical model of air waves induced by falling rock is described. The model is composed of a uniform motion phase (velocity close to 0 m·s^-1) and an acceleration movement phase. The uniform motion phase was determined based on experimentally and the acceleration movement phase was derived by theoretical analysis. A series of experiments were performed to verify the semi-empirical model and elucidated the law of the uniform motion phase. The acceleration movement phase accounted for a larger portion with a greater height of the falling rock. Experimental results of different falling heights of the goaf showed close agreement with theoretical analysis values. The semi-empirical model could accurately and conveniently estimate the velocity of air wave induced by falling rock. Thus, the semi-empirical model can provide a reference and basis for estimating the speed of air waves and designing protective measures in mines.

Exosomes are produced by all cell types, their biogenesis is of endosomal origin, originating as a result of cell membrane invagination. Furthermore, physiochemical characteristics are important prerequisites for their commercial application. The representative size range of exosomes is 50-200 nm. Whereas, comparative to animal cell, exosomes from plant cell sources have a relatively larger size range, moreover, exhibit broader therapeutic potential. In this review study, we have briefly discussed the research potential of plant-derived exosomes. Including their earlier studies on biogenesis, characterization, isolation methods, and possible therapeutic applications. Additionally, we have quoted targeted drug delivery for targeted therapies and have provided insights of methods for customizing exosomes produced from plants with various drugs. Most-importantly, here we have embodied exosomes from plant sources are natural nano-inducers possessing the ability for inter-kingdom communication, resulting in cross-kingdom regulations.

The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it is related to the loss of a suppressing protein called merlin. At the same time, alterations in energy production are visible in cancer cells where increased demand for energy is observed. Fatty acid oxidation could be one of the ways cancer cells obtain energy. This metabolic pathway uses the acylcarnitine shuttle system, which is responsible for the acylation of fatty acids and their transport through mitochondria. Therefore, this study aimed to profile acylcarnitines with short-, medium- and long-acyl chain length in meningiomas to assess their changes in tumors with different NF2 mutation statuses. For the analysis, solid-phase microextraction (SPME) coupled with liquid chromatography high resolution mass spectrometry (LC-HRMS) was used. The presented sampling method enables low invasive and easy collection of the analytes from the studied lesions, which can be crucial for future analysis of potential biomarkers in the surgery room. It was observed that higher levels of these analytes characterized meningiomas with NF2 mutation. Moreover, increased energy consumption and elevated levels of acylcarnitines show that these analytes can be considered as a marker of increased fatty acid oxidation in NF2 mutated cells.

This study addresses the importance of conducting mass movement susceptibility mapping and hazard assessment using quantitative techniques, including machine learning, in the Northern Lima Commonwealth (NLC). Previous exploration of the topographic variables revealed high correlation and multicollinearity among some of them, which led to dimensionality reduction through principal component analysis (PCA). Six susceptibility models were generated using weights of evidence, logistic regression, multilayer perceptron, support vector machine, random forest, and naive Bayes methods to produce quantitative susceptibility maps and assess the hazard associated with two scenarios: the first being an El Niño phenomenon and the second being an earthquake exceeding 8.8Mw. The main findings indicate that machine learning models exhibit excellent predictive performance for the presence and absence of mass movement events, as all models surpassed an AUC value of &gt;0.9, with the random forest model standing out. In terms of hazard levels, in the event of an El Niño phenomenon or an earthquake exceeding 8.8Mw, approximately 40% of the NLC area would be exposed to the highest hazard levels. It also highlights the importance of integrating methodologies to reduce model uncertainty, such as comprehensive analysis of variables supported by high quality data and organized workflows. The findings of this research are expected to serve as a supportive tool for land managers in formulating effective disaster prevention and risk reduction strategies.

SOC stock (SOCS) changes caused by land use changes are still unclear, and understanding this response is essential for many environmental policies and land management practices. In this study, we investigated the temporal-spatial and vertical distribution characteristics of SOCS on the Western Sichuan Plateau (WSP) using the sparrow search algorithm-random forest regression (SSA-RFR) models with excellent model applicability and accuracy. The temporal-spatial varia-tions in the SOCS were modeled using 1080 soil samples and a set of nine environmental covariates. We analyzed the effect of land use changes on the SOCS on the WSP. The total SOCS increased by 18.03 Tg C from 1990 to 2020. The results of this study confirmed that the SOCS in the study area has increased significantly since 2010, with an increase of 27.88 Tg C compared to the total SOCS in 2010. We found that the spatial distribution of the SOCS increased from southeast to northwest, and the vertical distribution of the SOCS in the study area decreased with increasing soil depth. Forest and grassland are the main sources of SOCS, the total SOCS in the forest and grassland accounted for 37.53 and 59.39% of the total SOC pool in 2020, respectively. Expansion of the wetlands, forest, and grassland areas could increase SOCS in the study area.

Introduction: Cleft lip with or without cleft palate (CL/P) is the most common congenital face anomaly in the world of multifactorial etiology. Objective: To determine the prevalence and characteristics of cleft palate. To identify associated risk factors to guide prevention and/or prenatal detection for early intervention and better health outcomes. To assess the rehabilitation protocols after operations in cleft palate. Design: Retrospective descriptive and clinical study. Patients: One hundred and three children with cleft palate treated in the Department of Head and Neck Surgery Clinic for Children and Young Adults, Department of Clinical Pediatrics, University of Warmia and Mazury, were included in the study. Methods: Records evaluation was conducted regarding sex, cleft type, mother occupation, parents education, histories of cleft in any of parents. The data were analyzed using R (R core team 2021) and the ordinal logistic regression analyses. Results: Children of stressed mothers during pregnancy had 9.4 times higher odds of having bilateral cleft. While there was no evidence that children sex, order of birth, and body mass as well as risk of maternal toxicity at work or reporting infections or drugs toxicity had a significant effect on the dependent variable. Conclusions: Children of parents with cleft history and having low educated mothers had higher probability of bilateral cleft palate. Children of stressed mothers during pregnancy had higher odds of having bilateral cleft. In literature, there is a lack of reports about rehabilitation in different operations methods in children with cleft palates.

Bacteriophages (phages) are potential alternatives to chemical antimicrobials against pathogens of public health significance. Understanding the diversity and host specificity of phages is important for developing effective phage biocontrol approaches. Here, we assessed the host range, morphology, and genetic diversity of eight Salmonella enterica phages isolated from a wastewater treatment plant. The host range analysis revealed that six out of eight phages lysed more than 81% of the 43 Salmonella enterica isolates tested. The genomic sequences of all phages were determined. Whole genome sequencing data (WGS) data revealed that phage genome sizes ranged from 41 to 114 kb with GC contents be-tween 39.9 and 50.0 %. Two of the phages SB13 and SB28 represent new species Epsep-timavirus SB13 and genera Macdonaldcampvirus, respectively as designated by the In-ternational Committee for the Taxonomy of Viruses (ICTV) as per genome based taxonomic classification. One phage (SB18) belonged to the Myoviridae morphotype while the re-maining phages belonged to the Siphoviridae morphotype. The gene content analyses showed that none of the phages possessed virulence, toxin, antibiotic resistance, type I-VI toxin-antitoxin modules or lysogeny genes. Three (SB3, SB15 and SB18) out of the eight phages possessed tailspike proteins. Whole genome-based phylogeny of the eight phages with their 113 homologs revealed three clusters A, B, C and seven subclusters (A1, A2, A3, B1, B2, C1 and C2). While cluster C1 phages were predominantly isolated from animal sources, cluster B contained phages from both wastewater and animal sources. The broad host range of these phages highlights their potential use to control the presence of S. enterica in foods.

A low-cost bio-mass-derived carbon substrate has been employed to synthesize MoS₂@carbon composites through a hydrothermal method. Carbon fibers derived from natural cotton provide a three-dimensional and open framework for the uniform growth of MoS₂ nanosheets, thus constructing hierarchically coaxial architecture. The unique structure could synergistically benefit fast Li-ion and electron transport from the conductive carbon scaffold and porous MoS₂ nanostructures. As a result, the MoS₂@carbon composites, when served as anodes for Li-ion batteries, exhibit a high reversible specific capacity of 820 mAh g^-1, high-rate capability (457 mAh g^-1 at 2 A g^-1), and excellent cycling stability. The superior electrochemical performance makes the MoS₂@carbon composites to be low-cost and promising anode materials for Li-ion batteries.

Source water quality is a key determinant of drinking water quality. The recast European Union 2020/2184 drinking water directive (DWD) introduced the obligation for comprehensive risk assessment in drinking water supplies, including the water source and incorporated new elements of natural origin in the list of parameters to be monitored. The current study is the first comprehensive assessment of 15 natural elements (B, Ba, Be, Ca, Co, K, Li, Mg, Mo, Na, Se, Sr, Ti, U and V) in 1155 (82%) Hungarian drinking water sources, including surface water, bank filtered and groundwater sources. Parameters posing a risk to health (Se, V and U) were typically below the lower limit of quantification (LOQ), but higher concentrations (max. 7.0, 17 and 41 µg/L, respectively) may occur in confined locations, the latter exceeding the DWD parametric value in one water supply. Li in a small geographical area, Mg and Ca in the majority of the water supplies reached the concentration range assumed to be protective to health. Water sources were grouped in 6 clusters based on their element distribution, some of them also showing clear geographical patterns. Water types were not differentiated, with the exception of karstic waters (dominated by Ca and Mg). None of the investigated parameters are expected to be a source of public health concern.

The intranasal route of drug administration is characterized by high bioavailability and is considered promising for rapid delivery of drugs with systemic action to the central nervous system, bypassing the blood-brain barrier. This is particularly important for the use of neuroprotective drugs in the treatment of brain tissue damage in infants caused by the effects of intrauterine hypoxia. Creation of new dosage forms for neonatology with the use of software and mathematical technologies in pharmaceutical development allows to create cerebroprotective drugs with controlled pharmaco-technological properties, thus reducing time and resources for necessary research. We developed a formulation of a new nasal gel formulation with Angiolin using Box-Benken experiment design for the therapy of prenatal CNS damage. It was found that the consistency properties of the nasal gel were significantly influenced by the gelling agent and mucoadhesive component - sodium salt of carboxymethylcellulose. We have optimized the composition of nasal gel formulation with Angiolin using the formed models and relationships between the factors. The optimized composition of the obtained nasal gel has satisfactory parameters of thixotropic properties. The developed 1% gel for neuroprotection with Angiolin meets all the requirements for harmlessness and safety to drug forms of this group - low toxicity, absence of local irritant and allergic effect.

In this paper, based on our previous expertise on ceramic artifacts, several archaeometric methods applied to some samples collected from the Dudești archaeological site (Oltenia region, Romania) are reported for the first time in the literature. The chemical composition and microstructural and morphological characterization of these samples offer important conclusions about the processing conditions. Some specific techniques such as X-ray diffraction (XRD), wave-length-dispersive X-ray fluorescence (WDXRF), Optical microscopy (OM), stereomicroscopy, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy, provide composition information about pigments and their decay processes. Additionally, the Brunauer-Emmett-Teller (BET) method helps to estimate pore sizes and specific surface areas. Thermal analysis (TGA) was used to establish details regarding the production technology and the raw materials source used to make the ceramics, too. The obtained results indicated that the ceramics are based on a paste of muscovite, feldspar, with high plasticity, quartz, melanterite, and calcite, the latter in very low concentrations. According to the obtained results, we could assume that non-calcareous clays are present in the investigated samples because calcium exists in low concentrations. Gypsum is present, too, in very low concentration, identified by the presence of sulfate group in WDXRF. In the same context, iron oxides significantly impact the firing atmosphere of iron-rich clay, resulting in blackening under reducing conditions and reddish coloration under oxidative conditions. Using hematite and gypsum as pigments further contributes to the color variations in the pottery. The consistent firing temperature range of 200-600 °C in Dudești pottery implies a standardized production process, the variation in color being dependent on the specific reducing/oxidative regime conditions. This relationship between clay composition and local sources suggests a connection to Neolithic pottery production in the region and their color depending on the reducing/oxidative regime conditions.

Abstract: Short-chain fatty acids (SCFAs) are the major microbial metabolites produced in the gut through the fermentation of non-digestible fibers. SCFAs act through free fatty acid receptor 2 and 3 (FFAR2 and 3), which are known to be expressed on glucagon-like peptide-1 (GLP-1)-secreting L-cells. This pathway is suggested to protect the intestinal mucosa. We aimed to investigate how lack of fiber affects the production of SCFAs and the vulnerability of the co-lon. Additionally, the involvement of FFAR2 and 3 in GLP-1 secretion and intestinal protection. SCFA concentrations in luminal contents from chow- or fiber-free diet-fed mice were analysed by LC‒MS. SCFAs were applied to isolated perfused colons from FFAR2/3 double KO and WT mice, and the secretion of GLP-1 was measured. Dextran sulfate sodium (DSS) colitis was induced in chow- or fiber-free diet-fed mice as well as in FFAR2/3 KO and WT mice. The removal of die-tary fiber significantly decreased total colonic SCFA concentrations, with specific decreases in acetate, propionate, and butyrate. SCFAs significantly increased colonic GLP-1 secretion but not in FFAR2/3 KO mice. In the DSS model, the removal of dietary fiber increased the severity and delayed recovery. Colitis severity was independent of FFAR2 and FFAR3 signaling.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Hybrid reinforcement in a composite material (CM), in many situations, allows better govern material mechanical properties. Polymer matrix CM plate is reinforced with small particles and macro-fibers. Particles are oil shale ash (OSA) powder, macro-fibers – basalt fiber threads im-pregnated by matrix material. With the goal to find out elastic properties of the matrix- polymer with OSA, samples with its different concentrations were experimentally fabricated and their elastic properties were experimentally measured. Obtained data were used in numerical model-ling. Was observed polymer matrix composite slab, reinforced with OSA and three-dimensional (3D) basalt fiber fabric. Fabric are forming threads impregnated by matrix (polymer resin mixed with OSA particles). Damage accumulation in the stretched slab was modelled. Impregnated thread, in the modelling, is observed as a macro-fiber (MF) with averaged elastic properties. With the load increase MF in the material began to break. At first, appeared isolated single breaks. A probabilistic sequential MF rupture accumulation model was accepted and numerical-ly realized. The geometry of the reinforcing knitted fabric was modeled using the Leaf and Glaskin approach. In the knitted fabric highly, stressed MF cross-sections are observed as po-tential location where thread breakage can occur. If one thread breaks, the cross-sections of the adjacent threads experience the overload caused by this rupture. More overloaded crossection in the adjacent overloaded thread breaks and we obtain two adjacent broken MF designated as a defect with the size j=2. The probabilities of obtaining defect consisting of at least 2, 3, … j adjacent broken MF in the plate were calculated. The calculations continued until the rupture process becomes unstable (j→∞). The overstresses on adjacent threads in the CM were calculat-ed using the FEM three-dimensional numerical approach. Analytical and stochastic methods were used for the load-carrying capacity determination and different size defects accumulation in the hybrid composite material (HCM) plate. Also, was calculated the probability of the plate rupture.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.

In this paper, a generic fractional derivative is defined as a set of the linear operators left-inverse to the Riemann-Liouville fractional integral. Then the theory of the left-invertible operators developed by Przeworska-Rolewicz is applied for derivation of its properties. In particular, we characterize its domain, null-space, and projector operator, establish the interrelations between its different realisations, and present a generalized fractional Taylor formula involving the generic fractional derivative. Then we consider the fractional relaxation equation containing the generic fractional derivative, derive a closed form formula for its unique solution, and study its complete monotonicity.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

This article delves into the enduring relevance of Liberal International Relations (IR) Theory amidst persistent criticisms regarding power dynamics and its applicability in emerging states. Despite its detractors, Liberal IR Theory offers a nuanced understanding of state behavior, blending social contexts with power dynamics. It recognizes the intricacies of economic interdependence and advocates for a balanced approach in advancing democracy and human rights. While nationalism poses challenges to international institutions, their adaptability endures. Leaders, albeit constrained, retain the capacity to foster peace through visionary leadership and global cooperation. By acknowledging its limitations and fostering open dialogue, Liberal IR Theory continues to evolve, poised to contribute to a just and peaceful global order.

Systematic reviews represent a powerful instrument to summarize the existing evidence in medical literature. However, articles for a systematic review are hard to identify, and mostly require a structured search of the literature through a number of databases, using keyword-based search strategies, followed by the painstaking manual selection of pieces of evidence that are pertinent to the query. A.I. algorithms may offer solutions to reduce the workload on investigators. We applied BERTopic, a newer and much-recognized transformer-based topic-modeling algorithm, to two datasets of 6137 and 5309 articles of newly published systematic reviews in the area of peri-implantitis and bone regeneration in implant dentistry. In the two datasets, BERTopic identified 14 and 22 clusters, respectively, and it automatically created labels describing the nature of the topics for each individual cluster based on semantic interpretation of their titles. Most themes regarded the query theme, but in both conditions, BERTopic also uncovered articles related to off-themes, which composed around 30% of the dataset—with sensitivity up to 0.79 and specificities of at least 0.99. Our results suggest that adding a topic-modeling step to the screening process could potentially save working hours for researchers involved in systematic reviews of the literature.

Soft magnetic composites cores were produced by Spark Plasma Sintering (SPS) from Ni3Fe@ZnFe2O4 and NiFeMo@ZnFe2O4 pseudo-core-shell powders. In the Fe-Ni alloys@ZnFe2O4 pseudo-core-shell composite powders, the core is a large nanocrystalline Permalloy or Supermalloy particle obtained by mechanical alloying, and the shell is a pseudo continuously layer of Zn ferrite particles. The pseudo-core-shell powders have been compacted by SPS at temperatures between 500-700 ºC, with a holding time of 0 minutes. Several techniques were used for the characterisation of the powders and sintered compacts: X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, magnetic hysteresis measurements (DC and AC) and electrical resistivity. The electrical resistivity is stabilised at values of about 7·10-3 Ω·m for sintering temperatures between 600-700 °C and this value is 3 orders of magnitude higher than the electrical resistivity of sintered Fe compacts. The best relative initial permeability was obtained for the Supermalloy/ZnFe2O4 composite compacts sintered at 600 ºC, which decreases linearly for the entire frequency range studied, from around 95 to 50. Up a frequency of 2,000 Hz the power losses are lower than 1.5 W/kg. At the frequency of 10 kHz, the power losses are larger, but they remain at a low level. In the case of Supermalloy/ZnFe2O4 composite compact SPS-ed at 700 °C, the specific power losses are even lower than 5 W/kg. The power losses decomposition proved that intra-particles losses give the main part of the losses.

Geothermal energy, being a clean energy source, has immense potential, and accurate wellbore modeling is crucial for optimizing the drilling process and ensuring safety. This paper presents a novel geothermal wellbore model based on the drift-flux approach, tested under three different temperature and pressure well conditions. The proposed model integrates the conservation equations of mass, momentum, and energy, incorporating the gas-liquid two-phase flow drift-flux model and heat transfer model. Key features include handling heat transfer between the for-mation and the wellbore, addressing the slip relationship between gas and liquid phases, and accounting for wellbore friction. The nonlinear equations are discretized using the finite differ-ence method, and the highly nonlinear system is solved using the Newton-Raphson method. Numerical simulation, validation, and comparison with existing models demonstrate the en-hanced accuracy of this model. In our tests, the model achieved high accuracy in calculating bottom hole pressure and temperature, with Mean Relative Errors (MRE) significantly lower than those of other models. These results offer valuable insights for optimizing drilling parameters and ensuring drilling safety. Comparisons indicate that this approach significantly outperforms others in capturing the complex dynamics of geothermal wellbores, making it a superior tool for geo-thermal energy development.

Nanocellulose (CNC) seems to be a promising surfactant, which, together with expandable graphite (EG), forms the essence of an effective natural-based fire retardant wood coating. In our research, the most suitable composition of the mixture was tested concerning good solubility, dispersion, and consistency. Favorable results were achieved with the formulation composed of a 4% CNC alkaline solution with 80 wt.% of selected EG. Subsequently, six different EG were used to prepare these wood fire retardant coatings. The effectiveness of treatments was verified using a test with a radiant heat source, where the test samples' relative weight loss, relative burning rate, and surface temperature during 600 sec were evaluated. All prepared formulations can be characterized as more or less equally effective. However, the best results were obtained with EG of GG 200 – 100 N, where the mass loss of the sample was 8.10 ± 1.24%. Very good results were also achieved by graphite 25 E + 180 HPH (8.70 ± 0.89%), which is similar to the previous one, even according to the microscopic assessment of the coating as well as the expanded layer. Graphite type 25 K + 180 (8.86 ± 0.65 %) shows the expanded layer's best cohesion, coating uniformity, and ease of application. The results of this work confirmed that the CNC coating itself has significant retardation effects.

The article presents the results of studies aimed to identify the effect of foliar treatments of winter wheat, sugar beets and soybeans with mineral and bioorganic fertilizers. Their positive effect on increasing the concentration of mineral forms of nitrogen in soil was revealed. The crop types have a greater influence on the size of nitrous oxide emissions: in winter wheat crops - 679 µg/m3, soybeans - 637.2 µg/m3, sugar beets - 576.8 µg/m3. The amounts of nitrous oxide emissions were lower in the variants without the use of phosphorus-potassium fertilizers. The Ruter AA fertilizer showed the greatest efficiency on winter wheat crops - 42.7 c/ha. Soybean grain yield of 44.2 c/ha was also achieved by using Ruter AA, as well as Geo-humate together with phosphorus-potassium fertilizers. On the background of the actual supply of phosphorus and potassium, maximum yield was obtained when using N30 on the leaf - 39.3 c/ha. Foliar feeding ensured a yield of sugar beet root crops of up to 67.1-77.4 c/ha on the backdrop of the application of phosphorus-potassium fertilizers with the advantage of using Amino turbo. The largest yield of sugar beet roots without use of mineral phosphorus and potassium was ensured by N30 treatment of the leaf in the phases of 4-6 and 8 leaves - 63.2 t/ha. Of the organo-mineral fertilizers and biostimulants, the best result was shown by the use of Ruter A - 62.6 t/ha. We believe that foliar feeding of crops can be a sustainable farming method that can increase crop yields and reduce N2O emissions.

MicroRNAs (miRNA) exert regulatory actions via base-pairing with their binding sites on target mRNAs. Cooperative-binding, i.e., synergism, among binding sites on a mRNA is biochemically well-characterized. We studied whether this synergism is reflected in global relationship between miRNA-mediated regulatory activity and miRNA-binding-site count on the target mRNAs, i.e., leading to a non-linear relationship between the two. Recently, using our own and public datasets, we have enquired into miRNA regulatory actions: first, we analyzed the power-law distribution pattern of miRNA binding sites; second, strikingly, mRNAs for core miRNA regulatory apparatus proteins have extra-ordinarily high binding site counts, forming self-feedback-control loops; third, we revealed that tumor suppressor mRNAs generally have more sites than oncogene mRNAs; and fourth, we characterized enrichment of miRNA target mRNAs in translationally less-active polysomes relative to more-active polysomes. In these four studies, obvious correlation was observed qualitatively between the extent to which a mRNA is miRNA-regulated and its binding sites count. This paper summarizes the used datasets. We also re-analyzed the correlation by comparative linear and non-linear regression analyses. The results support a non-linear, instead of linear, relationship between the two parameters, conceivably a transcriptome-level reflection of cooperative-binding/synergism among miRNA binding sites on a target mRNA.

Background: In response to inflammation, the absorption of nutritional iron is restricted. Multiple inflammation-related signaling pathways can lead to ferroptosis, an iron-dependent mechanism of programmed cell death. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). Methods: Six- to eight-week-old male DBA/1 mice were fed either a normal or a low iron diet starting three weeks before arthritis induction. From day four after the collagen-booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. The complete blood count was determined as well as Fe2+, Fe3+, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) in whole paw tissue by ELISA. Quantitative PCR was performed from whole paw tissue for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to com-pare markers of iron metabolism and ferroptosis as well as nonlinear regression models for longitu-dinal data for signs of arthritis. Results: Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (p

The kinase pathway plays a crucial role in blood vessel function. Particular attention is paid to VEGFR-type 2 angiogenesis and vascular morphogenesis as the tyrosin kinase pathway is preferentially activated. In silico studies were performed on several peptides that affect VEGFR2 in both stimulating and inhibitory ways. This investigation aims to examine the molecular properties of VEGFR2, a molecule primarily involved in the processes of vasculogenesis and angiogenesis. These relationships were defined by the interactions between vascular endothelial growth factor receptor 2 (VEGFR2) and the structural features of the systems. The chemical space of the inhibitory peptides and stimulators was described using topological and energetic properties. Furthermore, chimeric models of stimulating and inhibitory proteins (for VEGFR2) were computed using the protein system structures. The interaction between the chimeric proteins and VEGFR was computed. The chemical space was further characterized using complex manifolds and high-dimensional data visualization. The results show that a slightly similar chemical area is shared by VEGFR2 and is shared by stimulating and inhibitory proteins. On the other hand, the stimulator peptides and the inhibitors have distinct chemical spaces.