Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

Background: Breastfeeding is essential for optimal infant health, offering numerous benefits such as infection prevention and enhanced bonding. Despite its importance, challenges exist, particularly for mothers of preterm and very low birth weight (VLBW) infants, necessitating effective lactation support strategies. Initiatives like the Baby Friendly Hospital Initiative (BFHI) and Kangaroo Mother Care (KMC) aim to promote breastfeeding success, while donor human milk (DHM) serves as an alternative bridge while the mother is supported to build up her supply. Adequate lactation support, counseling, and education are vital antenatally, during NICU stays and after discharge to improve breastfeeding rates and infant health outcomes, ultimately contributing to global efforts to reduce neonatal mortality and achieve sustainable development goals. This study explores existing research on factors influencing mothers’ ability to produce breast milk and sustain breastfeeding, with the aim of enhancing lactation support and improving infant health outcomes.Methods/Design: A systematic review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. Searches will be performed in the following databases: PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE Ovid via EBSCOhost, Google Scholar, and WILEY online Library) to identify and incorporate primary research articles related to the topic published between 2014 and 2024. Authors will search peer-reviewed articles, gray literature sources, and reference lists to identify eligible studies. Independent abstract and full-text screening by two reviewers will follow the title screening. The analysis of data will be carried out using Review Manager software (version 5.3.5). The I² test will be used to quantify the amount of unexplained heterogeneity. Potential biases related to study size (such as publication bias) will be examined through the application of several techniques, including funnel plots, Egger’s test, Begg’s test, and Trim and Fill analysis.Discussion: Our review represents a singular exploration into exclusive breastfeeding among very low birth weight (VLBW) infants in low- and middle-income countries (LMICs), focusing on breastfeeding assistance methods. With VLBW defined as less than 1500 g, and most low birth weight (LBW) babies born in LMICs, there is a critical need to address feeding challenges and promote optimal nutrition. Despite updated WHO guidelines in 2022, there is still a lack of comprehensive advice for this vulnerable population. Peer support interventions and health worker counseling have shown promise in increasing breastfeeding continuation rates in LMICs, but challenges persist due to workforce shortages and inadequate documentation. Promoting early postpartum milk expression is crucial for milk production and infant health. Our review aims to fill the gap in understanding VLBW mothers’ breastfeeding experiences in LMICs, shedding light on the effectiveness of breastfeeding support methods and identifying areas for further research. Systematic review registration: CRD42024547864

Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

In recent years, the consumption of over-the-counter probiotics used to promote health has grown rapidly worldwide and become an industry. In medicine, various studies have proven that probiotics can help improve the immune system and intestinal health. They are usually safe, but in some rare cases, they may cause concerning adverse reactions. Although the use of probiotics has been widely popularized in the public, the results of many probiotics clinical trials are contradictory. Especially for the cancer patients, the feasibility of probiotics management to provide benefits by targeting cancer and lessening anti-cancer side effects requires further investigations. And this review summarizes the interactions between probiotics and the host and current pros and cons of applying probiotics in the cancer patients.

Cancer is a complex and devastating disease that has engaged scientists and researchers for decades. Despite tremendous efforts, previous hypotheses about cancer development have not achieved significant breakthroughs. Evolutionary Cancer Cell Biology (ECCB) is a novel and emerging branch of oncological science that provides an evolutionary perspective on the origin of cancer. It reveals that the cancer genome evolved hundreds of millions of years ago, long before multicellular organisms such as metazoans and humans emerged. ECCB aims to unify all evolutionary insights, hypotheses, and theories into a cohesive framework. It investigates the intricate relationship between cancer genomics and ancient pre-metazoan genes that emerge when normal cells transform into cancer cells. It challenges the conventional wisdom of cancer research by suggesting that cancer could arise through intrinsic cellular mechanisms without genetic alterations and mutations. Furthermore, it postulates that somatic mutations are only secondary, downstream events in the process of oncogenesis.

1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer's disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. 2) Methods: Here, we report the effects of long-term treatment with a SPM, maresin like 1 (MarL1), on AD pathogenesis in a transgenic 5xFAD mouse model. 3) Results: MarL1 treatment reduced Aβ overload, curbed the loss of neurons in brains especially cholinergic neurons associated with cleaved-caspase-3-associated apoptotic degeneration, reduced astrogliosis and microgliosis and the pro-inflammatory M1 polarization of microglia, curbed the AD-associated decline in an-ti-inflammatory Iba1+Arg-1+-M2 microglia, reduced astrogliosis-associated level of neuroin-flammatory TNF-α, inhibited phenotype switching of pro-inflammatory neurotoxic A1 astrocytes and N1 neutrophils, promoted polarization of inflammation-resolving neuroprotective A2 as-trocytes, promoted the blood–brain-barrier-associated tight-junction protein claudin-5 and de-creased neutrophil leakage in 5xFAD brains, and induced the switch of neutrophils toward the inflammation-resolving N2 phenotype. 4) Conclusion: Long-term administration of MarL1 mit-igates AD-related neuropathogenesis in brains by curbing neuroinflammation and neurodegen-eration. These findings provided the preclinical leads and mechanistic insights for the develop-ment of MarL1 into an effective modality to ameliorate AD pathogenesis.

Improving photobioreactor performance for microalgae cultivation has attracted many researchers over the past years. One of the primary challenges associated with existing photobioreactors is the light penetration. An effective photobioreactor design should maximize light penetration, ensuring uniform illumination throughout the reactor. This study aims to assess the impact of light intensity on microalgal growth from the perspective of energy efficiency and productivity in two photobioreactors. A novel cactus-like and a cylindrical photobioreactor were designed and fabricated using 3D printing technology. These two photobioreactors were used to cultivate two strains of microalgae. The novel photobioreactor achieved a maximum biomass productivity of 0.99 g/L/d and a maximum energy efficiency of 0.3139 g/d/kWh. The cylindrical photobioreactor reached a maximum biomass productivity of 0.74 g/L/d and 0.2199 g/d/kWh of energy efficiency. The increase in biomass productivity can be linked to enhancements in the photobioreactor's surface-to-volume ratio and better light utilization.

Tuberculosis (TB) remains a global public health issue, particularly in developing countries. Hematopoietic stem cell transplant (HSCT) recipients are at elevated risk for TB due to immunosuppression. This retrospective study (2005-2022) assessed a preemptive latent tuberculosis infection (LTBI) screening and treatment strategy in 338 HSCT recipients and their donors. Screening included tuberculin skin test (TST) or QuantiFERON-TB Gold (QFT), and pulmonary imaging, with positive cases receiving isoniazid (INH) therapy. Statistical analyses aimed to compare TB reactivation rates, overall survival (OS), and relapse-free survival (RFS) across HSCT groups. Of 338 patients, 92 (27%) were diagnosed with LTBI. Screening involved TST in 325 cases and QFT in 13. INH therapy was completed by 81 patients, with 5 discontinuing due to hepatotoxicity. The cumulative incidence of active TB was 0.6%, and LTBI reactivation rate in patients who received INH was 1.2%. LTBI status did not affect OS or RFS. Our study exemplifies the effectiveness of LTBI protocols incorporating TST/QFT and CT-scan testing, followed by INH therapy, in reducing TB reactivation among HSCT recipients in a high-burden region.

There are clear signs that the COVID-19 pandemic has had a straining impact on the higher education sector in South Africa and the far reaches of the world. This chapter examines (Science, Technology, Engineering, Mathematics) STEM lecturers’ experiences with digital assessments and perspectives on the continuity of digital transformation in the higher education sector in the post-COVID-19 era at one of South Africa’s rural universities. In 2022, a survey of ten (10) lecturers was conducted and the reports were also consulted by four (4) e-learning practitioners to obtain their views on the use of online learning and contact courses in the post-pandemic period. A qualitative research approach was used to understand the puzzling issues faced by STEM lecturers at a previously disadvantaged institution in Limpopo Province. The results of this study show that there is a puzzling conundrum that hinders the integration of effective online learning. Furthermore, online education as the new normal in the post-COVID-19 era seems unattainable due to extremely complex and difficult-to-understand mathematical symbols. Software and tools proved to be limitations in terms of establishing an interactive learning environment for students and lecturers on online learning platforms. Lecturers’ use of learning and teaching platforms deteriorated due to numerous unknown challenges, but also the tightening of COVID-19 restrictions. Furthermore, the results showed that science and mathematics lecturers believe that contact learning remains irreplaceable across generations and eras as some are not technology enthusiasts. This paper recommends that the lack of technological systems as well as technological resistance and reluctance to adopt transformative pedagogy and innovative practices, should not be viewed as a thorny issue to end the dominance of online education in STEM courses. Keywords: connectivism, Learning Management Systems, affordances, technological resistance, Moodle, transformative pedagogy

Almost contact complex Riemannian manifolds, known also as almost contact B-metric manifolds, are equipped with a pair of pseudo-Riemannian metrics that are mutually associated with each other using the tensor structure. Here we consider a special class of these manifolds, those of the Sasaki-like type. They have an interesting geometric interpretation: the complex cone of such a manifold is a holomorphic complex Riemannian manifold (also called a Kähler–Norden manifold). The basic metric on the considered manifold is specialized here as a soliton, i.e. has an additional curvature property such that the metric is a self-similar solution of an intrinsic geometric flow. Almost solitons are more general objects than solitons because they use functions rather than constants as coefficients in the defining condition. A β -Ricci-Bourguignon-like almost soliton ( β is a real constant) is defined using the pair of metrics. The introduced soliton is a generalization of some well-known (almost) solitons (such as those of Ricci, Schouten, Einstein), which in principle arise from a single metric rather than a pair of metrics. The soliton potential is chosen to be pointwise collinear to the Reeb vector field, or the Lie derivative of any B-metric along the potential to be the same metric multiplied by a function. The resulting manifolds equipped with the introduced almost solitons are characterized geometrically. Appropriate examples for two types of almost solitons are constructed and the properties obtained in the theoretical part are confirmed.

Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies resulting in abnormal connection between pulmonary arteries and veins. In 80% of cases, PAVMs are present from birth, but clinical manifestations are rarely seen in childhood. These congenital malformations are typically associated with Hereditary Hemorrhagic Telangiectasia (HHT), a rare disease that affects 1 in 5,000/8,000 individuals. HHT disease is frequently caused by mutations in genes involved in the TGF-β pathway. However, approximately 15% of patients do not have a genetic diagnosis and, among the genetically diagnosed, more than 33% do not meet the Curaçao Criteria. This makes clinical diagnosis even more challenging in the pediatric age group. Here, we introduce an 8 years old patient bearing a severe phenotype of multiple diffuse PAVMs caused by an unknown mutation which ended in lung transplantation. Phenotypically, the case of study follows a molecular pattern HHT-like. Therefore, molecular biology and cellular functional analysis has been performed in primary endothelial cells (ECs) isolated from the explanted lung. The findings revealed a loss of functionality in lung endothelial tissue and a stimulation of endothelial to mesenchymal transition. Understanding the molecular basis of this transition could potentially offer new therapeutic strategies to delay lung transplantation in severe cases.

Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer’s disease (AD). Previous research from our group has demonstrated that herpes simplex virus type I (HSV-1) induces an AD-like phenotype in several cell models of infection. This study explores the interplay between cholesterol and HSV-1-induced neurodegeneration. The impact of cholesterol was determined by modulating its levels with methyl-beta-cyclodextrin (MβCD) using the neuroblastoma cell lines SK-N-MC and N2a. We have found that HSV-1 infection triggers the intracellular accumulation of cholesterol in structures resembling endolysosomal/autophagic compartments, a process reversible upon MβCD treatment. Moreover, MβCD exhibits inhibitory effects at various stages of HSV-1 infec-tion, underscoring the importance of cellular cholesterol levels not only in the viral entry pro-cess but also in subsequent post-entry stages. MβCD also alleviated several features of AD-like neurodegeneration induced by viral infection, including lysosomal impairment and intracellu-lar accumulation of amyloid-beta peptide (Aβ) and phosphorylated tau. In conclusion, these findings highlight the connection between cholesterol, neurodegeneration, and HSV-1 infection, providing valuable insights into the underlying mechanisms of AD.

The therapeutic, attenuative, and morphological effects of proprietary neural stem cell-derived extracellular vesicles (NSC EVs, AB126) produced by Aruna Bio, Inc. were assessed in a range of in vitro and in vivo models of stroke. We emphasize that modulation of neuroinflammation is a key target and suggest further studies to advance our understanding of the mechanisms of action and ultimately how best to dose and monitor the benefits of AB126 in stroke patients.

Low efficiency of in vivo transfection of a few fibers revealed a novel tissue network which temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibers began to grow after complete fiber degradation, synchronous inflammation, myoblast and myotube formation. The first detection of neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) has been made in this system. The neonatal, fast and slow SERCA isoforms displayed consequent change with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that the expression of the slow myosin heavy chain and the slow muscle type SERCA2a are dif-ferently regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SER-CA1b shRNA stimulated fiber size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished in co-transfection with Cain or in case of perimuscular injection with IL4 antibody. This revealed a novel signalling network resembling to scale-free networks which, starting from transfected fiber myonuclei as “hubs”, can amplify growth stimula-tion uniformly in the entire regenerating muscle.

A novel educational platform called Shared Modeling and Simulation Environment (SMSE) was initiated in the ERASMUS+ “CybPhys” project. It integrates the Jupyter platform, including Ju-pyter Notebooks, for e-learning in the STEM field. A novel platform enhances e-learning by combining Moodle with Jupyter's capabilities to create virtual labs. A survey was conducted in the spring of 2023 among bachelor and master students of Chernihiv National Polytechnic Uni-versity aimed to gather feedback from students using SMSE in their e-learning process. Two student groups were involved: one of them consisted of students using SMSE in both the autumn and spring semesters and another represented the students starting with SMSE in the spring se-mester. The survey based on the adjusted Technology Acceptance Model (TAM) was conducted to understand the acceptance of this e-learning approach. A comprehensive analysis of students’ answers based on the TAM approach revealed the inside of the process of transformation of stu-dents’ perceptions during the acquisition of the SMSE platform. Our research demonstrates that SMSE effectively merges Moodle's online learning capabilities with Jupyter notebooks, provid-ing a flexible and interactive learning experience for both in-class and remote students. It pro-vides a web-based, multifunctional e-learning environment that combines a variety of tools and technologies, giving students the possibility to be involved in all sorts of teaching activities, such as lectures, exercises, simulations, etc., through the use of one single online environment.

The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

Cissus populnea Guill. & Perr. (Vitaceae) is used in traditional medicine to treat microbial infec-tions, venereal diseases, and infertility, among others. The aim of the research is to isolate and characterize the antimicrobial constituent(s) from the stem of C. populnea. The n-butanol fraction of C. populnea being most active was subjected to silica gel column chromatography which led to the isolation of a white solid and white crystalline substances coded compounds C1 and C4C5, respectively. Spectral analysis (1D & 2D-NMR) of the isolated compounds and comparison with literature data indicated C1 to be Bis-(2-ethyloctyl)-phthalate and C4C5 to be a mixture of stig-masterol and β-sitosterol; C4C5 exhibited zone of inhibition ranging from 24 – 29 mm against the test organisms with Candida albicans being the most sensitive organism while Trichophyton rubrum was the least sensitive organism. The standard drugs, Ciprofloxacin had 27 – 37 mm while Flu-conazole and Fulcin exhibited zone of inhibition ranging from 34 mm and 29 – 32 mm, respec-tively. The MIC and MBC/MFC values for C4C5 ranges from 12.5 – 25.0 µg/cm3 and 25.0 – 50.0 µg/cm3 against MRSA, S. aureus, E. coli, C. albicans, T. rubrum, and T. mentagrophyte, respectively. In conclusion, three bioactive compounds were identified for the first time from the stem of C. populnea

Keywords: Wall-like RC columns; Strengthening; FRP; NSM rebars; Steel plates; Testing; FE modeling; Preloading.

As drone technology is rapidly becoming accessible to school children in terms of both low cost and ease-of-use, primary and secondary school teachers are beginning to consider where modern drones can play an important role in schooling. To date, there is very little empirical education research printed in the education research literature guiding innovative curriculum developers in the incipient domain of drone education. As a result, teachers interested in including emerging technologies in their classrooms are often at a loss of where to begin. Through clinical interviews with schoolteachers in the United States, our study identified five readily accessible “departure points” to include drones in contemporary STEM & vocational technology (CTE) school classrooms that help teachers address common curricular goals. Taken together, these interviews reveal that teachers using drones follow one of several distinct pathways as a first step toward achieving a widespread goal of teaching students to use modern technologies to construct, pursue, and communicate findings of fruitful research inquiries—the prevalence of which is not reflected in a comprehensive literature review. The five pathways for starting a successful drone education emerging from the interview data as dominant were: timed-racing trials; precision-flight obstacle courses; computer coding; videography; and domain-specific knowledge of drone operations laws and ethics.

The present study investigated the insulin-like growth factors (IGFs) and their receptors and binding proteins among different pig breeds during weaning. Sixty Duroc (DR), Taoyuan black (TB), and Xiangcun black (XB) piglets (20 piglets per breed) were selected at 21 and 24 days of age (three days of post-weaning) to analyze organ indices, plasma concentrations of IGF and IGF-binding proteins (IGFBPs) using ELISA kits, and gene expression of IGF system-related components in different tissues. The plasma IGFBP-3 level in TB piglets was higher (P > 0.05) than in the XB and DR piglets at 21 days of age. At 21 days of age, compared with the DR piglets, the IGF-1 expression was lower (P < 0.05) in the kidney but was higher (P < 0.05) in the spleen of XB and TB piglets. At 24 days of age, the IGF-1 expression was higher (P < 0.05) in the kidney of TB piglets than in the XB and DR piglets, while IGFBP-3 in the stomach and IGFBP-4 in the liver of XB and TB piglets were lower (P < 0.05) compared with the DR piglets. Weaning down-regulated (P < 0.05) the IGF-1 expression in the jejunum, spleen, and liver of piglets, while up-regulated (P < 0.05) IGFBP-3 expression in the stomach, IGFBP-4 in the liver, IGFBP-5 in the ileum, and IGFBP-6 in the jejunum of DR piglets. Spearman’s correlation analysis showed a negative correlation (P < 0.05) between plasma IGFBP-2 and IGFBP-5 and the organ index of piglets. Collectively, there were significant differences in IGF system components among different pig breeds. The IGF system components were altered during weaning, which might be involved in weaning stress to decrease the growth of piglets.

The study of mechanical properties of rock mass can be effectively carried out through rock-like material model test. The similarity of mechanical properties between rock-like material and protolith is dependent on the appropriate selection of composition and content of rock-like materials. In this research, X-Ray diffraction test was conducted to analyze the composition of deep rock, which confirmed silica, quartz, and dolomite as the primary components of deep sandstone. An orthogonal design test was used to execute the ratio test of rock-like material. River sand was used as an aggregate, cement as a binder, gypsum powder as a regulator, and polystyrene foam (EPS) as rock damage simulation material. The influencing factors considered in the orthogonal mechanical tests were the proportion of aggregate and binder, ratio of binder and regulator, quantity of damage simulation material, and size of damage simulation material. Three levels were set for each factor, and mechanical parameters such as compressive strength, tensile strength, elastic modulus, axial strain, and Poisson's ratio were tested for each group of samples. The changes of those parameters with the levels of the above four factors were studied. The study revealed that adjusting the size of polystyrene foam (EPS) can adjust the values of elastic modulus, tensile strength, and Poisson's ratio of rock-like material. Similarly, changing the ratio of binder and regulator can adjust the values of axial strain and compressive strength of rock-like material. The rock-like material developed in the study can simulate the mechanical properties of different rock masses such as granite, sandstone, shale, and limestone.

Purpose: Inflammation of various degrees is common among humans. There are associated side effects with orthodox delivery systems and anti-inflammatory agents hence the study investigated the characteristics of herbal lipospheres and the anti-inflammatory potency of the lipospheres formulated from Pentaclethra macrophylla with the view to having a drug with a better delivery system and lesser side effects.Methods: Herbal lipospheres were formulated using solidified reverse micellar solutions (SRMS) of P90H and goat fat and characterized for particle size and morphology, pH – time dependent analysis, encapsulation efficiency (EE%) and Fourier Transform infrared spectroscopy. The in vitro antinociceptive and anti-inflammatory study were carried out using membrane stabilization by hypotonicity induced haemolysis and determination of anti-platelet aggregatory activity models. The in-vivo anti-nociceptive and anti-inflammatory studies on egg albumin and formaldehyde induced arthritis models were done. Total white blood cell count and differential blood count were carried out on the rats. Results: The results showed that there was no change in pH for the PM unloaded lipospheres and 2.5g of PM-loaded lipospheres from Day 1 to Day 7, but mild variation in the rest of the formulations. The EE ranged from 35.2% to 94% increasing according to the drug concentration. The photomicrographs of the lipospheres showed that the particles were spherical in shape. The particle sizes were within the acceptable range for lipospheres. FTIR showed no interaction. In the arthritis study, PM-loaded lipospheres inhibited edema consistently throughout the duration of observation. Inhibition of membrane increased steadily with an increase in concentration of PM in the lipospheres and the standard drug. The platelet aggregatory inhibition decreased steadily with an increase in concentration of the PM in the lipospheres as well as the standard. The T50 dose of PM had the highest percentage of WBC and it decreased as the treatment doses increased from T100 to T200. There was no significant differences among the Neutrophil counts of the different groups.Conclusion: The study, therefore, showed that the methanol extract of Pentaclethra macrophylla formed efficient herbal lipospheres with antinociceptive and anti-inflammatory activities.

Infective endocarditis is a rare and challenging diagnosis, Q fever endocarditis being a major cause of culture-negative endocarditis (IE). The presence of multiple cerebral microbleeds (CMBs) suggests a particular vascular frailty and could be correlated to potential emergence of a haemorrhagic stroke in IE. We report a case of a 45 years-old patient with Coxiella burnetii endocarditis, with a brainstem hemorrhage and cerebral MRI CMBs resembling those of CAA. However the systemic inflammatory tests, the splenic infarct and kidney pathology could not be explained by a variant of CAA, neither the normal initial cerebral CT scan when the patient had already the brainstem clinical signs without evidencing the hemorrhage. Transthoracic and transesophageal echocardiogram revealed only calcified bicuspid aortic valve with moderate stenosis and regurgitation, without any vegetations and the blood cultures on conventional media were negative. Serology for Coxiella burnetii was positive. Inclusion of CMBs as a new minor imaging criteria for infective endocarditis could upgrade the diagnosis in almost 50% of patients.

Peroxiredoxins play central roles in the detoxification of reactive oxygen species and have been modelled across multiple organisms using a variety of kinetic methods. However, the peroxiredoxin dimer-to-decamer transition has been underappreciated in these studies despite the 100-fold difference in activity between these forms. This is due to the lack of available kinetics and theoretical framework for modelling this process. Using published isothermal titration calorimetry data, we obtained association and dissociation rate constants of 93.0 µM-4·s-1 and 102 s-1, respectively, for the dimer-decamer transition of human PRDX1. We developed an approach that greatly reduces the number of reactions and species needed to model the peroxiredoxin decamer oxidation cycle. Using these data, we simulated horse radish peroxidase competition and NADPH-oxidation linked assays and found that the dimer-decamer transition had an inhibition-like effect on peroxidase activity. Further, we incorporated this dimer-decamer topology and kinetics into a published and validated in vivo model of PRDX2 in the erythrocyte and found that it almost perfectly reconciled experimental and simulated responses of PRDX2 oxidation to hydrogen peroxide insult. By accounting for the dimer-decamer transition of peroxiredoxins, we were able to resolve several discrepancies between experimental data and available kinetic models.

Respiratory tract infections (RTIs) are one of the main causes of hospitalization and mortality causing substantial economic burden to healthcare systems globally. As opposed to the previous belief that respiratory infections are caused by a single pathogen, studies have shown that most RTIs are a result of a combination of bacterial and/or viral pathogens infecting the host. The clinical manifestation of RTIs is very similar (i.e., syndrome), often showing Influenza-like illness (ILI) symptoms. While COVID-19 has dominated ILI over the past few years, there are many other pathogens that are responsible for ILI. In addition, it is not uncommon to have coinfections with multiple pathogens in patients presenting with ILI and that such coinfections can even exacerbate the disease severity of RTIs. Therefore, an insight into coinfections can help with accurate disease prognosis, patient care management and outcomes. The goal of this study was to identify the different organisms in symptomatic patients presenting with ILI.

The injectable hydrated calcium phosphate bone-like paste (hCPP) have been developed with suitable nanoscale characteristics and unindered injection through 23G standard needles. In vitro assays showed the cytocompatibility of hCPP with mesenchymal embryonic C3H10T1/2 cell cultures. The hCPPs were identified to be composed of aggregated nano-sized particles with sphere-like shapes with low crystallinity. The ability of serum proteins (FBS) to adsorb on hCPP particles was also studied. The hCPP demonstrated high protein adsorption capacity, thereby indicating its potential in various biomedical applications. The results of the in vivo assay upon subcutaneous injection in Wistar rats indicated the nontoxicity and biocompatibility of experimental hCPP, as well as the gradual resorption of hCPP, comparable to the period of bone regeneration. The data obtained are of great interest for the development of commercial highly effective osteoplastic materials for bone tissue regeneration and augmentation.

Erectile dysfunction (ED) is a common and feared complication of radical prostatectomy (RP) for prostate cancer. Recently, tissue engineering is being attempted for post-prostatectomy ED, with controlled interactions between cells, growth factors, and extracellular matrix (ECM) being important for nerve regeneration's structural integrity. In this study, we evaluated the effects of biomechanical ECM patch on human bone marrow-derived mesenchymal stem cells (hBMSCs) morphology and behavior in bilateral cavernous nerve injury (BCNI) rat model. The ECM patch, made of decellularized human fibroblast-derived ECM (hFDM) and a biocompatible polyvinyl alcohol (PVA) hydrogel, was tested with human bone marrow-derived mesenchymal stem cells (hBMSCs) on a bilateral cavernous nerve injury (BCNI) rat model. In vitro analysis showed that the hFDM/PVA + hBMSCs patches significantly increased neural development markers. In vivo experiments demonstrated that the rats treated with the hFDM/PVA patch had higher ICP/MAP ratio, a higher ratio of smooth muscle to collagen, increased content of nNOS, higher levels of eNOS protein expression, and a higher cGMP level compared to the BCNI group. These results indicate that the hFDM/PVA patch is effective in promoting angiogenesis, smooth muscle regeneration, and nitrergic nerve regeneration, which could contribute to improved erectile function in post-prostatectomy ED.

Existence of carcinogenic nitrite in food has attracted much attention, however, it is still a challenge to develop nitrite sensor with higher sensitivity and selectivity to enlarge its applications in daily life. Herein, one-dimensional honeycomb-like carbon nanofibers (HCNFs) were synthesized with an electrospun technology, and its specific structure enables the controlling growth and highly dispersed bismuth nanoparticles (Bi NPs) on its surface, which endows the obtained Bi/HCNFs with excellent electrocatalytic activity toward nitrite oxidation. By modifying Bi/HCNFs on screen-printed electrode, the constructed Bi/HCNFs electrode (Bi/HCNFs-SPE) can be used for nitrite detection in one drop of solution, and exhibits higher sensitivity (1269.9 μA mM-1 cm-2) in a wide range of 0.1~800 μM with lower detection limit (19 nM). Impressively, the Bi/HCNFs-SPE has been successfully used for nitrite detection in food and environment samples, the satisfactory property and recovery indicates its feasibility in further practical applications.

In the context of the Education-2030 Framework for Action, an important goal for initial STEM teacher education is to provide professional development on equality and gender awareness. This study explored whether STEM prospective secondary teachers are prepared to implement a sustainable gender-sensitive practice upon graduation. To this end, we cross-culturally validated the TEGEP (Teacher Self-Efficacy for Gender Equality practice) scale and compared STEM student teachers’ perceptions of self-efficacy by country and sex. Participants were 205 STEM (science, technology, engineering, and mathematics) secondary school student teachers (136 Greek and 69 Spanish) drawn from seven public universities (six Greek, one Spanish). Statistical analysis confirmed the structure and factor invariance of the TEGEP across country and between sexes showing evidence that gender equality self-efficacy level is only moderate and that perceived competence in gender knowledge was significantly higher in Greek than in Spanish STEM student teachers, while the latter felt more competent than the Greek in developing values and attitudes in regards to gender. The study provides a cross-validated instrument to measure gender equality self-efficacy in STEM teacher education and evaluate sustainable changes after planned interventions.

This paper attempts to describe the large-scale (solar system-like, astronomical-scale) systems of the known world using the physical models and mathematical tools of relativistic quantum mechanics. The value of H_x can be introduced and approximated as an analogue of the constant ℏ. Based on the quantum mechanical approach, the proper time scale of the solar system can be determined.

Porcine epidemic diarrhea virus (PEDV) causes severe enteric disease in pigs, particularly neonatal piglets. Attempts to develop a safe and effective vaccine have been unsuccessful. Ginseng stem-leaf saponins (GSLS), a promising oral adjuvant candidate, can improve intestinal immune responses in poultry and mice. However, the low stability limits the further use. Poly lactic-co-glycolic acid (PLGA), a biocompatible and biodegradable nanoparticle, have been widely used in biomedicine for stable and targeted drug delivery. In this study, we developed GSLS-PLGA nanoparticles (GSLS-NPs) and evaluated the mucosal adjuvant efficacy in vitro and in vivo. GSLS-NPs significantly enhanced antigen internalization and pro-inflammatory cytokine secretion by DC2.4 cells. Mice orally administered GSLS-NPs before intramuscular inoculation generated CD11b+CD8α- and CD11b-CD103+ dendritic cells in the spleen and draining mesenteric lymph nodes, respectively, which are the types mainly responsible for antigen presentation. Additionally, enhanced neutralizing and non-neutralizing antibody responses and expanded activities of specific effector and memory CD4+ and CD8+ T cells were also observed in mice immunized with PEDV vaccines plus GSLS-NPs compared to mice receiving the vaccines alone. Furthermore, GSLS-NPs showed a good safety profile and presented great advantages over GSLS aqueous solution. Collectively, our results highlight the potential of GSLS-NPs as a mucosal adjuvant and provide an attractive vaccination strategy for combatting PEDV. Further study is required to evaluate the efficacy of this mucosal adjuvant in swine.

In this paper, we study the deflection angle for wormhole-like static aether solution by using Gibbons and Werner technique in non-plasma, plasma and dark matter mediums. For this purpose, we use optical spacetime geometry to calculate the Gaussian optical curvature, then implement the Gauss-Bonnet theorem in weak field limits. Moreover, we compute the deflection angle by using a technique known as Keeton and Petters technique. Furthermore, we analyze the graphical behaviour of the bending angle ψ with respect to the impact parameter b, mass m as integration constant and parameter q in non-plasma and plasma mediums. We examine that deflection angle is exponentially increasing as direct with charge. Also, we observe that for small values of b, ψ increases and for large values of b the angle deceases. We also considered an analysis to the shadow cast of the wormhole relative to an observer at various locations. Comparing it the the Schwarzschild shadow, shadow cast is possible for wormhole as r<2m. At r>2m, the Schwarzschild is larger. As r → ∞, we have seen that the behavior of the shadow, as well as the weak deflection angle, approaches that of the Schwarzschild black hole. Overall, the effect of plasma tends to decrease the value of the observables due to the wormhole geometry.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), etiological agent of the novel coronavirus disease 2019 (COVID-19), has spread since December 2019, resulting in massive health and economic crisis worldwide. While efforts to stop the pandemic are crucial, collecting epidemiological data to help manage current and future pandemics will be important. In addition to humans, serological and molecular based studies have demonstrated SARS CoV-2 exposure in several wild, domestic and farmed animals. For examples Shriner and the team showed serologically an exposure of 40% to the white deer living in close proximity to urban centers. Additional reports have also emerged of susceptibility of animal’s species like cats, ferrets, raccoon dogs, cynomolgus macaques, rhesus macaques, white-tailed deer, rabbits, Egyptian fruit bats, and Syrian hamsters to SARS-CoV-2 infection.. It’s worth emphasizing that these reports are based on experimental data mostly derived from Europe, USA, South America and parts of Asia. In limited instances natural infections of SARS-CoV-2 have been reported in pet dogs, cats, tigers, lions, snow leopards, pumas, gorillas at zoos and farmed mink and ferrets. The presence of the virus in animal species and an understanding of whether these are natural or recent human to animal transmissions is important. It’s possible that such transmission could passage the virus or subject the virus to a different immunological pressure thereby helping with the development of viral variants in addition to being a host for future reservoirs of the virus. In Kenya SARS-CoV-2 was first detected on March 12th 2020 from imported human cases of persons who had travelled from the United States. This was followed by detection of imported cases majorly from China, Sweden and United Kingdom. Later infections were confirmed in Nairobi and Mombasa suggesting further cases of disease importations through the major ports of entry. However, no comparable data on animal exposure have hitherto been generated in Kenya. To address this key concern, we focused on three objectives; 1) development of a robust antibody ELISA based on crude SARS-CoV-2 lysate. 2) SARS-CoV-2 serology of domestic animals in Kenya. 3) Corroboration of the crude lysate based seroprevalence data and a commercial ELISA kit based on the Spike receptor binding domain (RBD) antigen. Our sample set included camel sera (both pre- & post outbreak sera), as well as sera from cats and dogs collected at the peak of the pandemic. Our results using the ELISA based on crude SARS-CoV-2 lysate indicated SARS-CoV-2 antibodies in camels (71%, N=145), cats 11% (N=16) and dogs (81%, N=36) with varying titer levels. These findings were comparable to those obtained using the commercial ELISA kit based on the spike RBD antigens. In summary, the data warrants two key conclusions: (i) we have demonstrated that the crude lysate ELISA allows for SARS-CoV-2 antibody detection, and given its potential to offer robust detection could be applied for initial mass screening (ii) although the current study cannot disentangle the relative contributions of antigenic cross-reactivity, pre-pandemic exposure to SARS-CoV-2 or human-animal transmission, it nonetheless demonstrates for the first time the prevalence of SARS-CoV-2 like antibodies in domestic and wild animals in Kenya. Our findings set the scene for further research into the prevalence of SARS-CoV-2 in domestic and wild animals to understand their potential epidemiological implications.

Neutrophils as innate immune cells primarily act as first responders in acute infection and directly maintain inflammatory responses. However, a growing body of evidence suggests that neutrophils also bear the potential to mediate chronic inflammation by exhibiting memory-like features. We recently showed that priming by serial doses of lipopolysaccharide (LPS) from gram-negative bacteria can trigger opposing memory-like responses (exaggerated inflammation, i.e. trained sensitivity or suppression of inflammation, i.e. tolerance) depending on the LPS-dose. We now asked whether this observation could also hold true for lipoteichoic acid (LTA) from gram-positive S. aureus. We found comparable effects of LTA on neutrophil priming as seen for LPS. Low-dose (1 ng/mL) LTA-priming promoted increased production of pro-inflammatory mediators (i.e., TNF-α, IL-6, ROS), whereas high-dose (10 µg/mL) results in contrary reactions supporting anti-inflammatory responses by increased IL-10 and declined pro-inflammatory capacity. In vitro neutrophil recruitment was similarly regulated by LTA -priming. Investigation of signalling patterns revealed TLR2/MyD88-mediated regulation of NFκB-p65 through intermediate PI3Ks/MAPK. Collectively, our data suggest a previously unknown capacity of neutrophils to be differentially primed by varying doses of LTA, endorsing memory-like features in neutrophils.

Neural stem cell (NSC) based therapies are at the forefront of regenerative medicine strategies to combat illness and injury of the central nervous system (CNS). In addition to their ability to produce new cells, NSCs secrete a variety of products, known as the NSC secretome, that have been shown to ameliorate CNS disease pathology and promote recovery. As pre-clinical and clinical research to harness the NSC secretome for therapeutic purposes advances, a more thorough understanding of the endogenous NSC secretome can provide useful insight into the functional capabilities of NSCs. In this review, we focus on research investigating the autocrine and paracrine functions of the endogenous NSC secretome across life. We also compare the NSC secretome across species, finding signs of conserved parallels between rodent, human and zebrafish NSC secretomes. Throughout development and adulthood, we find evidence that the NSC secretome is a critical component of how endogenous NSCs regulate themselves and their niche. We also find gaps in current literature, most notably in the clinically relevant domain of endogenous NSC paracrine function in the injured CNS. Future investigations to further define the endogenous NSC secretome and its role in CNS tissue regulation are necessary to bolster our understanding of NSC-niche interactions and to aid in the generation of safe and effective NSC-based therapies.

Cordia dichotoma Forst. (F. Boraginaceae) has been traditionally used for the management of a variety of human ailments. In our earlier work, the antidiabetic activity of methanolic bark extract of C. dichotoma (MECD) has been reported. In this paper, two flavonoid molecules were isolated (by column chromatography) and identified (by IR, NMR and Mass spectroscopy/spectrometry) from the MECD with an aim to investigate their antidiabetic effectiveness. Molecular docking and ADMET studies were carried out using AutoDock Vina software and Swiss ADME online tool, respectively. The isolated flavonoids were identified as 3,5,7,3’,4’-tetrahydroxy-4-methoxyflavanone-3-O-L-rhamnopyranoside and 5,7,3’-trihydroxy-4-methoxyflavanone-7-O-L-rhamnopyranoside (quercitrin). Docking and ADMET studies revealed the promising binding affinity of flavonoid molecules for human lysosomal alpha-glucosidase and human pancreatic alpha-amylase with acceptable ADMET properties. Based on computational studies, our study reports the antidiabetic potential of the isolated flavonoids with predictive pharmacokinetics profile.

High-resolution K-shell photoionization cross-sections for the C-like atomic nitrogen ion (N+) are reported in the 398 eV (31.15 Å) to 450 eV (27.55 Å) energy (wavelength) range. The results were obtained from absolute ion-yield measurements using the SOLEIL synchrotron radiation facility for spectral bandpasses of 65 meV or 250 meV. In the photon energy region 398 eV - 403 eV, 1s⟶2p autoionizing resonance states dominated the cross section spectrum. Analyses of the experimental profiles yielded resonance strengths and Auger widths. In the 415 eV - 440 eV photon region 1s⟶1s2s22p2 4Pnp and 1s⟶1s2s22p2 2Pnp resonances forming well-developed Rydberg series up n=7 and n=8 , respectively, were identified in both the single and double ionization spectra. Theoretical photoionization cross-section calculations, performed using the R-matrix plus pseudo-states (RMPS) method and the multiconfiguration Dirac-Fock (MCDF) approach were bench marked against these high-resolution experimental results. Comparison of the state-of-the-art theoretical work with the experimental studies allowed the identification of new resonance features. Resonance strengths, energies and Auger widths (where available) are compared quantitatively with the theoretical values. Contributions from excited metastable states of the N+ ions were carefully considered throughout.

Dynamic analyses and seismic assessments of multi-storey buildings at urban level require large-scale simulations and computational procedures based on simplified but accurate numerical models. At this aim the present paper propos-es an equivalent non-uniform beam-like model, suitable for the dynamic analysis of buildings with asymmetric plan and non-uniform vertical distribution of mass and stiffness. The equations of motion of this beam-like model, which pre-sents only shear and torsional deformability, are derived through the application of Hamilton’s principle. The linear dy-namic behaviour is evaluated by discretizing the continuous non-uniform model according to a Rayleigh-Ritz approach based on a suitable number of modal shapes of the uniform shear-torsional beam. In spite of its simplicity, the model is able to reproduce the dynamic behaviour of low- and mid-rise buildings with a significant reduction of the computa-tional burden with respect to that required by more general models. The efficacy of the proposed approach has been tested, by means of comparisons with linear FEM simulations, on three multi-storey buildings characterized by different irregularities. The satisfactory agreement, in terms of natural frequencies, modes of vibration and seismic response, proves the capability of the proposed approach to reproduce the dynamic response of complex spatial multi storey frames.

Ixodes scapularis is the major vector of Lyme disease in the eastern United States. Each active life stage (larva, nymph, and adult) takes a blood meal either for developing and molting to the next stage (larvae and nymphs) or for oviposition (adult females). This protein-rich blood meal is the only food taken by Ixodes ticks and therefore blood digestion is very important for tick survival. Most studies on blood digestion in ticks have shown that the initial stages of digestion are carried out by cathepsin proteases within acidic digestive cells. However, most of these studies have focused on partially engorged ticks. In other hematophagous arthropods, the serine proteases play an important role in blood protein degradation. In this study, we determined transcript expression of four I. scapularis serine proteases with previously characterized roles in blood digestion. RNA interference was used for functional analysis and a trypsin-benzoyl-D, L-arginine 4-nitoanilide assay was used to measure active trypsin levels. An in vitro hemoglobinolytic assay was performed with or without serine protease inhibitor. Our data suggest that trypsin levels increase significantly after blood feeding and peaked in larvae, nymphs, and adults at 3, 1, and 1 day post host detachment, respectively. The knockdown of three previously identified serine proteases by RNAi negatively impacted blood intake, survival, fecundity, levels of active trypsin in the gut and resulted in lower hemoglobin degradation in vitro. A trypsin inhibitor, PMSF, blocked the action of trypsin in the gut extract resulting in 65% lower hemoglobin degradation. We provide evidence of the serine proteases as digestive enzymes in fully engorged, replete females. Our data also demonstrated that in addition to blood digestion, these serine proteases might have a role in blood feeding success in I. scapularis.

Schistosomiasis, a crippling ailment that afflicts over 220 million people worldwide. Yet or up till now, there is no vaccine for schistosomiasis, and chemotherapy relies heavily on a single drug, the praziquantel. The present study was undertaken to investigate the therapeutic effect of Monophosphoryl Lipid A (MPLA) as an adjuvant in soluble egg antigen (SEA) vaccinated mice against the deleterious pathological impacts induced in hepatic tissues of mice by Schistosoma mansoni infection. In addition, to study the associated parasitological, immunological and biochemical parameters. Parasitological parameters showed that intraperitoneal injection of MPLA into SEA-vaccinated and S. mansoni-infected mice was effective to a significant degree in reducing the worm and egg burden, granuloma count and diameter as well as the total area of infection in their livers versus SEA-untreated but infected ones. In addition, MPLA showed ameliorative action on the elevated liver oxidative stress marker, including malondialdehyde (MDA) and decrease in the level of the antioxidant enzymes, reduced glutathione (GSH) and catalase (CAT) which may have a role in the liver damage and fibrosis due to S. mansoni infection. In conclusion, treatment with MPLA has multi-functions in attenuating the deleterious impacts of S. mansoni infection in mice livers. Its effects are mediated through a reduction of ova count, worm burden, granuloma diameter and amelioration of antioxidant defense systems, and liver function biomarkers.

To evaluate whether autologous mesenchymal cells, adipose derived stem cells and platelet-rich plasma, grafted into the supracoroideal space by surgical treatment according to Limoli retinal restoration technique (LRRT), can produce growth factors in order to exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and divided based on retinal foveal thickness ≤ 190 or >190 µm into group A and group B, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed an improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of RP, it can be confirmed that further research is needed on tapeto-retinal degenerations both from a clinical and molecular point of view to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation times, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering.

Satellite-based remote sensing technologies are utilized extensively to investigate urban thermal environments under rapid urban expansion. Current MODIS data is, however, unable to adequately represent the spatially detailed information because of its relatively coarser spatial resolution, while Landsat data can’t explore temporally the refined analysis due to the low temporal resolution. In order to resolve this situation, we used MODIS and Landsat data to generate “Landsat-like” data by using the flexible spatiotemporal data fusion method (FSDAF), and then studied spatiotemporal variation of land surface temperature (LST) and its driving factors. The results showed that 1) The estimated “Landsat-like” data have high precision; 2) By comparing 2013 and 2016 datasets, LST increases ranging from 1.8°C to 4°C were measurable in areas where the impervious surface area (ISA) increased, while LST decreases ranging from -3.52°C to -0.70°C were detected in areas where ISA decreased; 3) LST has a strongly negative relationship with the Normalized Difference Vegetation Index (NDVI), and a strongly positive relationship with Normalized Difference Built Index (NDBI) in summer; and 4) LST is well correlated with Building density (BD), in a complex conic mode, and LST may increase by 0.460°C to 0.786°C when BD increases by 0.1. Our findings can provide information useful for mitigating undesirable thermal conditions and for long-term urban thermal environmental management.

Background: diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause for end stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. The mesenchymal stem cells (MSCs) derived exosomes are currently considered as a new promising therapy in chronic renal injury. However, the renal protective mechanism of exosomes on DN has not been completely understood. We examined the potential role of MSCs derived exosomes in enhancement of autophagy activity and its effect on DN. In our study we used five groups of rats; control, DN, DN treated with exosomes, DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy) and DN treated with 3-methyladenine (3-MA) and chloroquine and exosomes groups. We assessed renal functions, morphology and fibrosis. Moreover, autophagy markers; mTOR, Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I ratio were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved the renal functions and showed histological restoration of renal tissues with significant increase in LC3 and Beclin-1 besides the significant decrease in mTOR and fibrotic markers expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitor, chloroquine and 3-MA. Conclusions: we conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

Despite the progress achieved regarding survival rates in childhood B-acute lymphoblastic leukemia, relapsed and/or refractory disease still poses a therapeutic challenge. Inotuzumab ozogamicin is a CD22-directed monoclonal antibody conjugated to calicheamicin, which has been approved for adults with CD22+ refractory/relapsed B lineage acute lymphoblastic leukemia and has already demonstrated promising results in the pediatric setting. The Food and Drug Administration approved inotuzumab ozogamicin (Besponsa, Pfizer) for pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia. Herein, we present the case of a 23-month-old girl with high-risk B-acute lymphoblastic leukemia, who experienced very early isolated medullary relapse and invasive pulmonary aspergillosis. She was finally successfully transplanted upon achieving remission and minimal residual disease negativity with two cycles of inotuzumab ozogamicin after failure of three lines salvage treatment with conventional chemotherapy, blinatumomab and bortezomid.

To clarify whether changes in biological features of breast tumor cells and intra-tumor immunity after neoadjuvant chemotherapy (NAC) may correlate with pathological responses and prognosis in breast cancer patients treated with NAC, we investigated various biomarkers using both pre- and post-NAC tumor samples. The study subjects were 24 primary breast cancer patients, who were treated with NAC at the Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital between 2010 and 2011. All of them had a non-pathological complete response (pCR) to NAC and their pre- and post-NAC tumor samples were available for biomarker assays. Ki67 labeling index, apoptosis, factors related to cancer stem cells and epithelial-mesenchymal transition, tumor infiltrating lymphocytes (TILs), and expression levels of CD-8, CD-4, FoxP3, PD-L1, and PD-1 were studied using the paired samples. Biological characteristics of residual tumors such as nuclear grade (NG) and vascular invasion (v) were also investigated. The median age was 53 years-old and 14 patients had stage III tumors, while 10 had stage II tumors. A higher expression level of CD8, CD4, or PD-1 in pre-NAC samples and of CD8, CD4 or PD-L1 in post-NAC samples was significantly correlated with a better pathological response to NAC. Positivity of ZEB1, vimentin, and v or NG 3 in post-NAC samples was significantly correlated with either worse disease-free survival (DFS) or worse overall survival (OS) by univariate analyses. Multivariate analyses for DFS and OS revealed that positivity for v and vimentin expression in residual tumors were independent prognostic factors in this study. These findings indicate that activated intra-tumor immune microenvironments may play significant roles in pathological responses to NAC, and that the up-regulation of vimentin and v-positivity in residual tumors may be pivotal prognostic factors in non-pCR cases to NAC.

The integration of Artificial Intelligence (AI) in healthcare has transformed clinical practices by improving the accuracy of diagnosis, optimizing surgical procedures, improving the patient experience, and accelerating drug development. This article provides a comprehensive overview of the many applications of artificial intelligence (AI) across several industries, including fast diagnostics, where ML algorithms greatly enhance the accuracy and velocity of disease diagnosis. State-of-the-art robotic-assisted minimally invasive surgical procedures that shorten patients' hospitalization and improve their chances of recovery, cutting-edge AI applications in healthcare monitoring, and medication development. The article also looks at the primary challenges that AI in healthcare will inevitably encounter, such as differences in product quality, a shortage of skilled workers, privacy and ethical issues, and the need for improved regulatory frameworks. Despite the challenges, AI contributes significant advantages to the healthcare industry, providing novel and remarkable contributions to the efficiency of medical procedures and the progress of medical outcomes. The paper emphasizes the importance of cooperation in overcoming current challenges and enhancing the acceptability of AI technology in clinical settings. This will ensure that AI-driven innovations continue to enhance the standards of patient care.

Introduction: The World Health Organization (WHO) recommends visual inspection with acetic acid (VIA) for cervical cancer screening (CCS) in lower-resource settings; however, quality varies widely, and it is difficult to maintain a well-trained cadre of providers. The Smartphone-Enhanced Visual Inspection with Acetic acid (SEVIA) program was designed to offer secure sharing of cervical images and real-time supportive supervision to health care workers providing screening in semirural Tanzania, in order to improve quality and accuracy of visual assessment of the cervix for treatment. The purpose of this evaluation was to document early learnings from patients, providers, and higher-level program stakeholders, on barriers and enablers to program implementation. Methods: From September 9th to December 8th, 2016, observational activities and open-ended interviews were conducted with image reviewers (n= 5), providers (n=17), community mobilizers (n=14), patients (n=21), supervisors (n=4) and implementation partners (n=5) involved with SEVIA. Sixty-six interviews were conducted at 14 facilities, in all 5 of the program regions. Results SEVIA was found to be a highly regarded tool for the enhancement of CCS services in Northern Tanzania. Acceptability, adoption, appropriateness, feasibility, and coverage of the intervention were highly recognized. It appeared to be an effective means of improving good clinical practice among providers and fit seamlessly into existing roles and processes. Barriers to implementation included network connectivity issues, and community misconceptions and adoption of CCS more generally. Conclusion: SEVIA is a practical and feasible mobile health intervention and tool that easily integrated into the National CCS program to enhance quality of care. With the introduction of HPV DNA testing as a primary screening strategy for cervical cancer prevention in settings such as Tanzania, the role of a mobile health platform for program surveillance, tracking follow-up care, and quality assurance of visual assessment of the cervix for treatment (in women who test positive for high-risk HPV) further supports the importance of programs, such as SEVIA, in low resource contexts. Further expansion of the program, especially to rural areas where screening providers can benefit from virtual support for screening services through the use of the mobile App, could strengthen the delivery of services within the national cervical cancer prevention program.

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1&gt;49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p&lt;0.05). In addition, patients diagnosed with adenocarcinoma, PDL1&lt;49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p&lt;0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Small and Medium Enterprises (SMEs) are recognized as the main drivers of economic growth and development in many countries throughout the world. SMEs represent about 90% of the manufacturing sector and contribute about 14% of the total manufacturing contribution to GDP. Despite SMEs’ potential to change Nigeria’s status from a consumer economy to a production economy, policies that will ensure that environmentally- friendly manufacturing processes and production technology are not implemented or complied with. SMEs’ operational activities may be deleterious to human health and the ecosystem if environmental management practices are not adopted or prioritized. This paper evaluated the perception and adoption of the Environmental Management System, mainly ISO 14001, by SMEs in Nigeria. One hundred and fifty (150) SMEs in the manufacturing sector in Lagos and Ogun State, Southwestern Nigeria, were randomly selected for this study. The paper posits that environmental management literacy and advocacy should be carried out in SMEs. Environmental management practices involve engaging both industries and product end-users in sustainable practices. The paper concludes that the implementation of environmental management practices and culture by SMEs will abate environmental pollution and its concomitant health risks to humans, the environment, flora, and fauna. Mandatory and voluntary environmental measures are suggested as a means of engendering eco-friendly innovation for sustainable development, triggering employment, job security, and gross domestic product.

Based on non-invasive neuroimaging techniques and graph theory-based network analyses, many researchers have tried to use small-world network model to elucidate sex differences in the brain. This manuscript aims to compile the related research findings from the past few years and summarize the sex differences in human brain networks from the perspective of small-world properties. We reviewed published reports examining altered small-world properties in both the functional and structural brain networks between males and females. Based on four patterns of altered small-world properties proposed--randomization, regularization, stronger small-worldization and weaker small-worldization, we found that current results point to a significant trend toward more regularization in females and more randomization in males in the functional brain networks. As for particular topological properties, the most consistent findings include a significant shift toward higher global efficiency in males and higher local efficiency in females in the functional network studies. On the other hand, there seems to be no consensus to date on the sex differences in small-world properties of the structural brain networks. Nevertheless, we noticed that the sample sizes in many published studies are limited, and future studies with larger samples are warranted to obtain more reliable results. We anticipate that the conclusions in this manuscript will contribute to a deeper understanding of neurobiological mechanisms underlying the sex differences in the brain.

In the modern power grid, characterized by the increased penetration of power electronics and extensive utilization of renewable energy, inverters-based power plants play a pivotal role as the principal interface of renewable energy sources (RESs) and the grid. Considering the stability characteristics of grid-following (GFL) inverters when the grid is relatively weak, the application of grid-forming (GFM) controls becomes imperative to enhance the stability of the entire power plant. Thus, there is an urgent need for suitable and effective models to study the interaction and stability of the paralleled inverters employing GFL and GFM controls. Thus, the small-signal modeling with full-order state space model and eigenvalues analysis is presented in this paper. First, the small-signal state-space model of the individual GFL and GFM inverters is obtained considering the control loop, interaction, reference frame, transmissions, and time delays. Then, the models of the individual inverter are extended to the hybrid inverters to study the effects of the GFM inverters on the small- signal stability of the entire system. And, the impacts of the inertia and damping are analyzed by the eigenvalues of the state-transition matrix. Case comprising three parallel GFL inverters and two GFL inverters with one GFM inverter, respectively, are studied to examine the effectiveness and accuracy of the model. Finally, the stability margin obtained from the eigenvalue analysis of the entire system is verified by time-domain simulations.

Metabarcoding of prokaryotic and fungal ribosomal DNA was used to describe the microbial communities in soils of remnant equatorial rainforest, maize-bean intercrop, and sugarcane in western Kenya. Cropping systems influenced the microbial community composition and functional traits (energy source and nutrient cycling) of bulk soil in each crop. Microbial richness and diversity tended to increase with cultivation intensity. Soil of maize-bean intercrop had lower percentages and sugarcane had higher percentages of unique amplicon sequence variants of both bacteria and fungi compared to the remnant forest. Functional traits were altered by cultivation intensity. Compared to remnant forest soils, maize-bean intercrop soil had lower percentages of aerobic chemoheterotrophic bacteria and higher percentages of N-cycling bacteria, while sugarcane had higher percentages of aerobic chemoheterotrophic bacteria and lower percentages of N-cycling bacteria. In the face of increasing forest loss and pressures for agricultural productivity, this landscape provides a rich site for studying the impacts of cropping systems on soil health.

Unmanned aerial vehicle (UAV) photogrammetry allows the generation of orthophoto and digital surface model (DSM) rasters of a terrain. However, DSMs of water bodies mapped using this technique often reveal distortions in the water surface, thereby impeding the accurate sampling of water surface elevation (WSE) from DSMs. This study investigates the capability of deep neural networks to accommodate the aforementioned perturbations and effectively estimate WSE from photogrammetric rasters. Convolutional neural networks (CNNs) were employed for this purpose. Two regression approaches utilizing CNNs were explored: direct regression employing an encoder and solution based on prediction of the weight mask by an encoder-decoder architecture, subse-quently used to sample values from the photogrammetric DSM. The dataset employed in this study comprises data collected from five case studies of small lowland streams in Poland and Denmark, consisting of 322 DSM and orthophoto raster samples. Each sample corresponds to a 10 by 10 meter area of the stream channel and adjacent land. A grid search was employed to identify the optimal combination of encoder, mask generation architecture, and batch size among multiple candidates. Solutions were evaluated using two cross-validation methods: stratified k-fold cross-validation, where validation subsets maintained the same proportion of samples from all case studies, and leave-one-case-out cross-validation, where the validation dataset originates entirely from a single case study, and the training set consists of samples from other case studies. The proposed solution was compared with existing methods for measuring WSE in small streams using a drone. The results indicate that the solution outperforms previous photogrammetry-based methods and is second only to the radar-based method, which is considered the most accurate method available. The solution is characterized by a high degree of explainability and generalization.

Food and nutrition insecurity, affecting 30% of the global population in 2020, poses a significant challenge to achieving Sustainable Development Goal (SDG) 2 - Zero Hunger. Urbanization, particularly in sub-Saharan African cities e.g. Lagos, Nigeria, exacerbates these issues, impacting resources and contributing to informal settlements. There is emphasis on innovative solutions in urban farming, with Recirculating Aquaculture Systems (RAS) emerging as one of the promising approach due to its efficiency in space and capital utilization. However, maintaining optimal conditions in RAS, crucial for SDG 2 and 11, requires robust water quality monitoring. This study explores the availability of digital tools for water quality monitoring in small-scale urban RAS, evaluating handheld devices and IoT sensors' reliability through t-test statistical method. The results aim to guide practitioners in selecting effective monitoring tools, contributing valuable insights for sustainable aquaculture in urban areas, particularly in sub-Saharan Africa, where access to affordable digital solutions is pivotal for success and can attract youth to agri-food technologies.

For equivalent modeling of mixed wind farms (WFs), existing clustering indicators cannot consider the complex coupling characteristics between different types of wind turbines (WTs). This paper proposes a refined equivalent modeling method for mixed WFs based on artificial intelligence technology. Firstly, the electromechanical transient performance of mixed WFs is analyzed. The WT type, wind speed and direction, and voltage dip are considered the main factors affecting the external dynamic response of mixed WFs. Secondly, the equivalent node model is established, including the selection of independent and dependent variables. Then, the multiple artificial neural networks (ANNs) are trained one by one based on sample data, to explore the nonlinear relationship between the dependent variables and the independent variables. Finally, the electromechanical transient simulations of the power systems with a mixed WF is carried out by using the MATLAB platform. Simulation results show that the proposed model can reflect the external characteristics of the mixed WF in different wind scenarios and voltage dips.

Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabo-lism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, albeit 10-year clinical trial data in Duchenne muscular dystrophy patients suggests a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD50> 5000mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.

The genetic diversity of coronavirus (CoV) is high, and its infection in animals has not yet been fully revealed. By RT-PCR detection of partial RNA dependent RNA polymerase (RdRp) gene of CoV, we screened a total of 502 small mammals belonging to 18 species in 12 genera and 4 orders collected in Dali and Nujiang Prefecture of Western Yunnan Province, China. The prevalence of β-CoV in Chevrieri's field mouse (Apodemus chevrieri) and Lancangjiang field mouse (A. ilex) were 3.54% (4/113) and 6.67% (6/90), respectively; the prevalence of α-CoV in White-footed Indochinese rat (Rattus nitidus) and long-tailed red-toothed shrew (Episoriculus leucops) was 75% (3/4) and 5.88% (1/17), respectively. The co-infection rates of β-CoV and α-CoV in Kachin red-backed vole (Eothenomys cachinus), Norway rat (R. norvegicus) were 2.22% (2/90), 3.85% (1/26) respectively. The identity of the partial RdRp genes obtained of 13 strains of β-CoV was 83.42%-99.23% at nucleotide level, and it is worth noting that the two strains from Kachin red-backed vole showed highly homology to BOV-36/IND/2015 from Indian bovine and DcCoV-HKU23 from one-humped camel (Camelus dromedarius) in Morocco, the nucleotide similarity between 97.86%-98.33%. Similarly, the identity of the 7 strains of α-CoV among the partial RdRp sequences was 94.00%-99.18% at nucleotide levels. The viral load in different tissues was measured by quantitative RT-PCR (qRT-PCR). The average CoV viral load in small mammalian intestinal tissue was 1.25×106copies/g, differently, the mean CoV viral load in liver, heart, lung, spleen and kidney tissue was from 1.29×103 to 4.02×103copies/g, which revealed that CoV has extensive tropism of intestinal tissue in small mammals (P &lt; 0.0001). This result revealed the genetic diversity, epidemiology, and infective tropism of α-CoV and β-CoV in small mammals from Dali and Nujiang, which deepens the comprehending of the retention and infection of coronavirus in natural hosts.

Mercury emissions from small-scale coal-fired boilers are still a serious environmental problem in Poland and the Czech Republic. The publication presents the results of mercury emission tests conducted using five different small-scale coal-fired boilers and five different coal fuels. The research was carried out under laboratory conditions, but also using residential users' heating devices. They covered a wide range of operational parameters, both energy and emission. It was shown that more than 94% of the mercury contained in coal fuel undergoing combustion is emitted into the atmosphere with the volatile products of combustion (including dust), and the amount of emissions is strongly dependent on the original mercury content of the fuel. One solution to the problem of mercury emissions from small-scale coal-fired boilers may be to replace traditional coal with low-emission carbon fuels. The paper shows that mercury emissions from burning such fuels are many times lower than from burning coal. The widespread use of low-emission carbon fuels in individual heating systems in Poland and the Czech Republic would reduce mercury emissions to the atmosphere by up to 90% compared to the current level of emissions generated by individual heating systems in these countries.

This research aims to examine the level of readiness of the community to carry out sustainable tourism development, especially community-based tourism on small islands, such as Lombok Island, Indonesia. More specifically, the objectives of this study are as follows: (1) Knowing the level of community readiness in carrying out sustainable tourism development. (2) Knowing the various dimensions that influence sustainable tourism development. (3) Knowing the role of stakeholders in sustainable tourism development. The method applied in this research is mixed methods, a combination of quantitative and qualitative approaches. Quantitative methods are used to determine community readiness for sustainable tourism development. A qualitative approach is used to determine the various factors that influence the development of community-based tourism and to determine the role of stakeholders in the development of community-based tourism. The level of community readiness for sustainable tourism development is high in terms of economic, social, cultural, environmental, and symbolic capital aspects. Aspects that influence the development of sustainable tourism are economic, social, and cultural. Stakeholders who play a role in developing sustainable tourism in the research area are the government, the private sector, universities, non-governmental organizations, and the media.

We examine a nonlinear initial value problem both singularly perturbed in a complex parameter and singular in complex time at the origin. The study undertaken in this paper is the continuation of a joined work with A. Lastra published in 2015. A change of balance between the leading and a critical subdominant term of the problem considered in our previous work is performed. It leads to a phenomenon of coalescing singularities to the origin in the Borel plane w.r.t time for a finite set of holomorphic solutions constructed as Fourier series in space on horizontal complex strips. In comparison to our former study, an enlargement of the Gevrey order of the asymptotic expansion for these solutions relatively to the complex parameter is induced.

Export participation and restricted access to external formal credit are two factors attracting meticulous attention from researchers and policymakers, especially in developing countries. Exploring the interactive relationship of these factors in both the static and dynamic models is the purpose of this study. The study uses data sets from small and medium-sized manufacturing enterprises (SMEs) in Vietnam for the period 2009 - 2015. The instrumental variable approach is implemented to deal with the endogenous variable problem in the model. The results show an effect of credit constraint on the firms’ exporting status, and continuous exports are likely to reduce the limit of credit constraint.

Despite several decades of research, the physics underlying translation – protein synthesis at the ribosome – remains poorly studied. For instance, the mechanism coordinating various events occurring in distant parts of the ribosome is unknown. Very recently, we have suggested that this allosteric mechanism could be based on the transport of electric charges (electron holes) along RNA molecules and localization of these charges in the functionally important areas; this assumption was justified using tRNA as an example. In this study, we turn to the ribosome and show computationally that holes can also efficiently migrate within the whole ribosomal small subunit (SSU). The potential sites of charge localization in SSU are revealed, and it is shown that most of them are located in the functionally important areas of the ribosome – intersubunit bridges, Fe4S4 cluster and the pivot linking the SSU head to the body. As a result, we suppose that hole localization within the SSU can affect intersubunit rotation (ratcheting) and SSU head swiveling, in agreement with the scenario of electronic coordination of ribosome operation. We anticipate that our findings will improve the understanding of the translation process and advance the molecular biology and medicine.

Recently, there has been renewed interest in the performance, functionality, and sustainability of traditional small-scale storage interventions (check dams, farm bunds and tanks) used across India for the improvement of local water security. The Central Groundwater Board of India is en-couraging the construction of such interventions for the alleviation of water scarcity. It is of critical importance to understand the hydrological effect of these interventions at basin scales to maximise their effectiveness. The quantification of small-scale interventions in hydrological modelling is often neglected, especially in large-scale modelling exercises. A bespoke version of the GWAVA model was developed to assess the impact of interventions on the water balance of the Cauvery Basin and two smaller sub-catchments. Model results demonstrate that farm bunds appear to have a negligible effect on the estimated average annual simulated streamflow at the outlets of the two sub-catchments and the basin whereas tanks and check dams have a more significant effect. In-terventions generally were found to increase evaporation losses across the catchment. The model adaption used in this study provides a step-change in the conceptualisation and quantification of the consequences of small-scale storage interventions in large- or basin-scale hydrological models.

Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research.

this review summarizes current knowledge of the hydrogen sulfide role in cardiovascular system, the proposed mechanisms of its action and the prospects for its applicability in the treatment of cardiovascular diseases. Hydrogen sulfide was recently recognized as gasotransmitter – simple signaling molecule which freely penetrates the cell membrane and regulates a number of biological functions. In humans endogenous H2S is generated via enzymatic and non-enzymatic pathways and its content varies in different tissues and is strictly regulated. In cardiovascular system H2S is produced by myocardial, vascular and blood cells and regulates a number of vital functions. Numerous experimental data prove that endogenously generated as well as exogenously administered H2S exerts a wide range of actions in cardiovascular system, including vasodilator/vasoconstrictor effects, regulation of blood pressure, pro-apoptotic and anti-proliferative effects in the vascular smooth muscle cells, influence on angiogenesis and erythropoiesis, myocardial cytoprotection in ischemia-reperfusion injury, oxygen sensing, inhibition of platelet aggregation and blood coagulation, modification of erythrocyte microrheological properties (aggregability and deformability). Understanding of molecular mechanisms of H2S action and molecular crosstalk between H2S, NO, and CO is essential for the development of its diagnostic and therapeutic potential.

Small Island States (SIDS) are among the nations most exposed to climate change (CC) and are characterised by a high degree of vulnerability. Their special nature means there is a need for more studies focused on the limits to CC adaptation on such fragile nations, particularly in respect of their problems and constraints. This paper addressed a perceived need for research into the limitations of adaptation on SIDS, focusing on the many restrictions which are unique to them. The main research question raised by this study was that how and to what extent the challenges by human activities (e.g., agriculture and tourism) posed to coastlines of SIDS could be addressed. This paper identified and described the adaptation limits they have, by using a review of the literature and an analysis of case studies from a sample of five SIDS in the Caribbean and Pacific regions (Barbados, Trinidad and Tobago, Cook Islands, Fiji, Solomon Islands, and Tonga). The findings of this research showed that an adaptable SIDS is characterised by awareness of various values, appreciation and understanding of a diversity of impacts and vulnerabilities, and acceptance of certain losses through change. The implications of this paper are two-fold. It explains why island nations continue to suffer from the impacts of CC, and suggest some of the means via which adequate policies may support SIDS in their efforts to cope with the threats associated with a changing climate. This study concluded that, despite the technological and ecological limits (hard limits) affecting natural systems, adaptation to CC is not only limited by such complex forces, but also by societal factors (soft limits) that could potentially be overcome by more adequate adaptation strategies.

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Hyperhomocysteinemia (HHcy) is typically defined as levels >15 micro mols/L. Elevated plasma levels of Hcy can be caused by the deficiency of either vitamin B12 or folate. The active role of homocysteine is quite ambivalent: many studies detected its potential impact on neurological events; others try to identify it as one of the possible risk factors of cardiovascular events, but with a complementary and secondary role. HHcy has been reported in many neurologic disorders, including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Nowadays, homocysteine could be considered as a possible link between a common vascular risk factor and potential alterations in degenerative neuronal disorders. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum stress; all these aspects have been considered to play an essential role in the pathogenesis of several diseases, including atherosclerosis, major stroke, and vascular dementia. Specific models of astrocytes impairment in HHcy-mice, which mimic small vessel disease, have been developed with a three-step investigation (at 6, 10, 14 weeks of B6, B9, and B12 detrimental diet in wild type HHcy mouse). These studies found out that after ten weeks on a diet (at the most after 14 weeks), end-feet disruption occurs. This phenomenon is concomitant to reduced vascular labeling for aquaporin -4-water channels, lower protein/mRNA levels for Kir4.1, and BK potassium channels, associated with a higher expression of MMP-9. The most exciting finding is that microglial activation in this mice model was evident since the precocious time of observation (6-week time) and precedes astrocytic changes. Our research aims to review the possible role of HHcy in neurodegenerative disease and small-vessel disease and to understand its pathogenic impact.

In the last decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) which are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e. GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation and also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.

In general, remote sensing has proven to be a powerful tool in the overall understanding of natural and anthropogenic phenomena. Satellites have become useful tools for tasks such as characterization, monitoring, and the continuous prospecting of natural resources. This research aims to analyze spatial dynamic and destructive on coral reefs area and correlation between live coral reduction and population on small islands. Landsat MSS, TM, ETM, and OLI-TIRS are used to spatial analyze of coral reef dynamics from 1972 to 2016. The image processing includes gap-filling, atmospheric correction, geometric correction, image composite (true color), water column correction, unsupervised classification, reclassification, accuracy assessment. The statistical analysis identifies the relationship between dynamic population data with a reduction of live coral, namely Principal Component Analysis (PCA) and Multiple Regression Analysis. The effect of the population shows a positive correlation with the reduction in the area of live coral, although it is significant. The fact is the practice of coral destruction on an island; it is usually not only caused or carried out by residents who live on the island but also carried out by other residents of different islands.

Understanding the spatially varying effects of demographic factors on the spatio-temporal variation of intestinal parasites infections is important for public health intervention and monitoring. This paper presents a hierarchical Bayesian spatially varying coefficient model to evaluate the effects demographic factors on intestinal parasites morbidities in Ghana. The modeling relied on morbidity data collected by the District Health Information Management Systems. We developed Poisson and Poisson-gamma spatially varying coefficient Models. We used the demographic factors, unsafe drinking water, unsafe toilet and unsafe liquid waste disposal as model covariates. The models were fitted using the Integrated Nested Laplace Approximations (INLA). The overall risk of intestinal parasites infection was estimated to be 10.9 per 100 people with a wide spatial variation in the district-specific posterior risk estimates. Substantial spatial variation of increasing multiplicative effects of unsafe drinking water, unsafe toilet and unsafe liquid waste disposal occurs on the variation of intestinal parasites risk. The structured residual spatial variation widely dominates the unstructured component, suggesting that the unaccounted-for risk factors are spatially continuous in nature. The study concludes that both the spatial distribution of the posterior risk and the associated exceedance probability maps are essential for monitoring and control of intestinal parasites.

The advent of RNA-sequencing (RNA-Seq) technologies has markedly improved our knowledge and expanded the compendium of small non-coding RNAs, most of which derive from the processing of longer RNA precursors. In this review article, we will discuss about the biogenesis and function of small non-coding RNAs derived from eukaryotic ribosomal RNA (rRNA), called rRNA fragments (rRFs), and their potential role(s) as regulator of gene expression. This relatively new class of ncRNAs remained poorly investigated and underappreciated until recently, due mainly to the a priori exclusion of rRNA sequences—because of their overabundance—from RNA-Seq datasets. The situation surrounding rRFs resembles that of microRNAs (miRNAs), which used to be readily discarded from further analyses, for more than five decades, because we could not believe that RNA of such a short length could bear biological significance. As if we had not yet learned our lesson not to restrain our investigative, scientific mind from challenging widely accepted beliefs or dogmas, and from looking for the hidden treasures in the most unexpected places.

This study investigated the roles of transactions cost in MSMEs access to finance. This was done by investigating the impact of transactions cost on access to credit from both MSMEs and financial institutions (commercial banks and microfinance banks). From the MSMEs’ side, borrowing experience, decision lag, firm size and borrowers’ distance to the loan office were investigated. On the financial institution’s side, the costs of information gathering, loan administration, monitoring and loan enforcement were investigated. We used the questionnaire survey method, in-depth interviews and case studies, as well as the annual financial statements of the banks. We identified interest rate and collateral value as constraints to access to finance for MSMEs. We also found financial institutions’ attitude to MSMEs access to credit was not friendly. Financial institutions need to do more to bring down transaction cost of lending. This hopefully can be achieved by investing more in agent banking which would lower operating costs, as well as spreading risk, and ultimately increase credit intermediation to small businesses.

Microbial contamination is now more common than chemical contamination in Tibet, and water-borne microbes can cause a number of diseases that threaten public health. Thus, in order to clarify the spatiotemporal distribution of bacteria in small watersheds for which there is no data in Tibet, we set up four sampling points along an upstream-downstream transect of the Xincang River Basin. We collected 239 water samples in 2014 and 2015, and evaluated their total constituent numbers of bacteria (TB) and coliforms (TC). The results of this study show that the microbial contamination of the Xincang River Basin is mild-to-moderate in terms of TB and TC contents, and that these concentrations vary significantly in different seasons. Results show that in summer TB and TC concentrations in the downstream section of this river were highest and that microbial contamination was most serious. Data also demonstrate that precipitation is the most important factor underlying increases in TB and TC concentrations during the summer months; both these variables are significantly correlated with precipitation, while animal husbandry and domestic sewage are the main sources of microbial contamination overall. The results of this study are likely to reflect the basic characteristics of small watersheds for which there is no data to some extent, and are thus of significant practical importance for protecting their ecological environments and promoting sustainable development.

This thesis completion works it out to deepen into diverse modeling techniques for Point Absorbers. A combined frequency-time domain model is conceived, designed and developed in Matlab with Fortran as a base, leading to obtain physical variables of primary importance, namely position, velocity and power to energy net balance relationships of absorption. Integration of different degrees of freedom with heave as main executable leads in turn to a single buoy motion focus. Acquisition of the needed hydrodynamic coefficients is provided through application of NEMOH \& BEMIO solvers due to the Boundary Element Methodology. Initially, this Wave-to-motion model is validated by comparison with previous experimental results for a floating cone cylinder shape (Buldra-FO3). A single, generic, vertical floating cylinder is contemplated then, that responds to the action of the passing regular waves excitation. Later, two equally sized vertical floating cylinders aligned with the incident wave direction are modeled for a variable distance between the bodies. For both unidirectional regular and irregular waves as an input in deep water, we approximate the convolutive radiation force function term through the Prony method. By changing the spatial disposition of the axisymmetric buoys, using for instance triangular or rectangular shaped arrays of three and four bodies respectively, the study delves into motion characteristics for regular waves. The results highlight efficient layouts for maximizing the energy production whilst providing important insights into their performance, revealing displacement amplification- and capture width-ratios, while deriving in possible interpretations of scenarios related to the the known park effect. These terms are encompassed by the novelty of a new conceptual Post-Processing methodology in the field, which leads to obtain an optimal distance for the separated bodies with effective energy absorption in a regular wave regime. In conclusion, this computational excursion envisions and proposes potential fields of study, which will surely enhance new connections and link this renewable energy form.

One of the major concerns in structural health management (SHM) is the early detection of a growing crack. Using this, future damage due to crack propagation can be mitigated or eliminated by implementing proper repair and maintenance. Acoustic Emission (AE) is a non-destructive testing (NDT) method with potential applications for locating and monitoring fatigue cracks. The research presented in this paper focuses on SHM using AE. A novel AE signal analysis approach was proposed in order to detect crack initiation and assess small crack lengths. Experimental investigation indicated that initiation of a crack could be identified through the statistical analysis of the resulting features of the AE signals. A probabilistic AE-based model for small fatigue crack sizing was developed and the uncertainties of the model were estimated. In addition, a probabilistic model validation approach was implemented to confirm accurate estimation of the results. The outcome of this research can be used to evaluate the integrity of structures under fatigue loading. The proposed approach can also be applied as an approach to manage health and assess prognosis of structures.

Leishmaniasis is a complex infectious parasitic disease caused by protozoa of the genus Leishmania, belonging to a group of neglected tropical diseases. It poses significant global health challenges, particularly in socio-economically disadvantaged regions. Macrophages, as innate immune cells, play a crucial role in initiating the inflammatory response against the pathogens responsible for this disease. Macrophage polarization, the process of differentiating macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, is essential for the immune response in leishmaniasis. The M1 phenotype is associated with resistance to Leishmania infection, while the M2 phenotype is predominant in susceptible environments. Notably, various immune cells, including T cells, play a significant role in modulating macrophage polarization by releasing cytokines that influence macrophage maturation and function. Furthermore, other immune cells can also impact macrophage polarization in a T-cell-dependent manner. Therefore, this review comprehensively examines macrophage polarization's role in leishmaniasis and other immune cells' potential involvement in this intricate process.

Recently, two pig-to-human kidney transplants and a pig-to-human heart transplant were completed. The kidney trials involved a patient who was deceased and a patient who was brain dead. They seemed to indicate that pig kidneys can be at least somewhat functional in humans. However, patients still have to be under severe immunosuppression - and the first patient to receive a porcine heart passed away after two months. It is difficult to know exactly which proteins we need to overexpress or underexpress/knockout in a porcine organ to negate the human recipient’s immunological response to it. And testing different porcine organ genetic modifications in baboons can cost around $500,000 per transplant. But there might be a way to decrease immunogenicity where we don’t have to worry so much about modifying the animal’s organs genetically. First, however, we would have to prevent complement factor-mediated lysis of the porcine vascular endothelial cells, which we have made much progress on with triple knockout animals. Then, we could modify the porcine organ so that the cells of said organ secrete a small molecule or peptide that acts as a chemorepellent for the host immune cells. The host immune cells can be modified via bone marrow transplant or vector delivery to express the chemorepulsion receptor.

Laser patterning of implant materials for bone tissue engineering purposes has shown to be a promising technique to control cell properties such as adhesion or differentiation, resulting in an enhanced osteointegration. However, the perspective of patterning the bone tissue side interface to generate microstructure effects has never been investigated. In the present study, three different laser-generated patterns were machined on the bone surface with the aim to identify the best surface morphology compatible with osteogenic-related cells recolonization. The laser patterned bone tissue was characterized by electron scanning microscopy and confocal microscopy in order to obtain a comprehensive picture of the bone surface morphology. Cortical bone patterning impact upon cell compatibility and cytoskeleton rearrangement to the patterned surfaces was performed with Stromal Cells from Apical Papilla (SCAPs). Results indicated that laser machining had no detrimental effect upon consecutively seeded cells metabolism. Orientation assays revealed that surface patterning characterized by larger hatch distances was correlated with a higher cell cytoskeletal conformation to the laser-machined patterns. For the first time, to our knowledge, bone is considered and assessed here as a potentially engineered-improvable biological interface. Further studies shall focus on in vivo implications of this direct patterning.

Metastasis is the leading cause of cancer death and can be realized through the phenomenon of tumor cell fusion. The fusion of tumor cells with other tumor or normal cells leads to the appearance of tumor hybrid cells (THCs) exhibiting novel properties such as increased proliferation and migration, drug resistance, decreased apoptosis rate and avoiding immune surveillance. Experimental studies showed the association of THCs with a high frequency of cancer metastasis; however, the underlying mechanisms remain unclear. Many other questions also remain to be answered: the role of genetic alterations in tumor cell fusion, the molecular landscape of cells after fusion, the lifetime and fate of different THCs, and the specific markers of THCs, and their correlation with various cancers and clinicopathological parameters. In this review, we discuss the factors and potential mechanisms involved in the occurrence of THCs, the types of THCs, and their role in cancer drug resistance and metastasis, as well as potential therapeutic approaches for the prevention and targeting of tumor cell fusion. In conclusion, we emphasize the current knowledge gaps in the biology of THCs that should be addressed to develop highly effective therapeutics and strategies for metastasis suppression.

Complex dynamical fluctuations, from molecular noise within cells, collective intelligence, brain dynamics or computer traffic have been shown to display noisy behaviour consistent with a critical state between order and disorder. Living close to the critical point can have a number of adaptive advantages and it has been conjectured that evolution could select (and even tend to) these critical states. One way of approaching such state is by means of so-called self-organized criticality (SOC) where the system poises itself close to the critical point. Is this the case of living cells? It is difficult to test this idea given the enormous dimensionality associated with gene and metabolic webs. In this paper, we present an alternative approach: to engineer synthetic gene networks displaying SOC behaviour. This is achieved by exploiting the presence of a saturation (congestion) phenomenon of the ClpXP protein degradation machinery in E. coli cells. Using a feedback design that detects and then reduces ClpXP congestion, a {\em critical motif} is built from a two-gene network system, where SOC can be successfully implemented. Both deterministic and stochastic models are used, consistently supporting the presence of criticality in intracellular traffic. The potential implications for both cellular dynamics and designed intracellular noise are discussed.

Normally, the Nernst voltage calculated from the concentration of the reaction gas in the flow channel is considered to be the ideal voltage (reversible voltage) of the oxyhydrogen fuel cell, but actually it will cause a concentration gradient when the reaction gas flows from the flow channel through the gas diffusion layer to the catalyst layer. The Nernst voltage loss in fuel cells in most of the current literature is thought to be due to the difference in concentration of reaction gas in the flow channel and concentration of reaction gas on the catalyst layer at the time when the high net current density is generated. Based on the Butler-Volmer equation in oxyhydrogen fuel cell, this paper demonstrates that the Nernst voltage loss is caused by the concentration difference of reaction gas in flow channel and on the catalytic layer at the time when equilibrium potential (Galvanic potential) of each electrode is generated.

We simulate elementary calcium release events (sparks) in a single calcium release unit in ventricular myocyte. Previously developed and tested electron-conformational model of the stochastic dynamics of RyR-channels is integrated to the calcium dynamics model in the cardiac cell. This approach allows to observe RyRs opening/closing in details on the macromolecular level during the calcium dynamics course. We simulate calcium diffusion in the dyadic space and “domino-like” RyR’s activation during the so-called “calcium induced-calcium release process”. Ca²⁺ sparks initiation, spread and termination are investigated in the computer experiments. Sparks’ initiation and termination rate dependence on the Ca²⁺ diffusion velocity is observed. We show that sarcoplasmic reticulum lumen local depletion and RyR’s stochastic attrition could be the reasons of Ca²⁺ spark termination.

Currently available COVID-19 mRNA vaccines have demonstrated high efficacy in clinical trials.1-3 However, cancer patients, including those with hematological malignancies, were largely excluded from these trials. In this prospective, observational study we measured anti-S protein IgG titers as well as avidity in lymphoma patients (n=67) vaccinated with a COVID-19 mRNA vaccine. Serological response rates in lymphoma patients who were treatment naïve (100% in CLL, 88.9% in other, non-CLL non-Hodgkin lymphoma patients), or who were last treated more than 24 months prior to vaccination (100% in CLL, 90% in other-NHL), were similar to healthy controls (100%). Patients on active therapy, however, had a diminished response rate (40% in CLL, 21.0% in other-NHL). No patient who received anti-CD20 monoclonal antibodies (mAb) within six months of vaccination responded. Thus, the utility of testing anti-S titers should be explored in patients on active therapy or with recent anti-CD20 mAb exposure, to assess their response to vaccination. We also propose studying passive protection with S-protein mAbs as an alternative prophylactic strategy for patients who respond poorly to vaccination.

The recent COVID-19 pandemic has significantly challenged Blood Transfusion Services (BTS) for providing blood products and for keeping blood supplies available. The possibility that similar pandemic event may occur again has induced researchers and transfusionists to investigate the adoption of new tools to prevent and reduce these risks. Similarly, increased donor travelling and globalization, with consequent donor-deferral and donor pool reduction, have contributed to raise awareness on this topic. Although recent studies have validated the use of pathogen reduction technology (PRT) for the control of Transfusion Transmitted Infections (TTI) this method is not a standard of care despite increasing adoption. We present a critical commentary on the role of PRT for platelet and on associated problems for blood transfusion services (BTS). The balance of cost effectiveness of adopting PRT is also discussed.

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment - surgery, radiation, and chemotherapy - on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

Pancreatic cancer is an intractable disease with the worst prognosis of all cancers. The currently used treatment regimens do not significantly impact patient survival, and therefore, effective treatment strategies are urgently needed. Drug repurposing, which identifies new indications for existing and approved drugs, has proven to be a promising approach to anti-cancer drug discovery. Indeed the antihelmintic drug, pyrvinium pamoate has shown promise as an anti-pancreatic cancer drug, but to date, the inhibition of mitochondrial function is the only mechanism of action described in pancreatic cancer. This study showed, using pancreatic cancer 2D cell cultures and 3D spheroids, that pyrvinium pamoate exhibited short- and long-term cytotoxicity, inhibited epithelial-to-mesenchymal transition and cell invasion and migration. Mechanistically, pyrvinium pamoate induced DNA damage, inhibited the PI3K/AKT cell survival pathway, and triggered cell cycle arrests, as well as apoptotic and autophagic cell death. Importantly, pyrvinium pamoate acted synergistically with the first-line drug, gemcitabine in 2D and 3D pancreatic cancer cell culture models. This study provided evidence that pyrvinium pamoate is effective as a single agent and in combination with gemcitabine for the treatment of pancreatic cancer.

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. We also used multivariable analyses to identify factors associated with patient interest in test use. In 2023, we surveyed 159 (32%) of 500 identified patients. Among respondents, 125 (79%) reported a high level of interest in having an MCED test. Interest was not associated with personal background characteristics, but was positively associated with the following expectations: testing would be recommended for cancer screening, be convenient, and be effective in finding early-stage disease (OR=11.70, 95% CI: 4.02, 34.04, p < 0.001). Research is needed to assess patient interest and actual uptake when detailed information on testing is presented in routine care.

Strawberry fruit is highly appreciated worldwide for its organoleptic and healthy properties. However, this plant is attacked by many pathogenic fungi, which significantly affect fruit production and quality at pre- and post-harvest stages, making chemical applications the most effective but undesirable strategy to control diseases, so far. Alternatively, genetic manipulation employing plant key genes involved in defense, such as members of the NPR-like gene family, has been successful in many crops to improve resistance. The identification and use of the endogenous counterpart genes in the plant of interest (as it is the case of strawberry) is desirable as it would increase the favorable outcome and requires prior knowledge of their defense related function. Using RNAi technology in strawberry, we show that transient silencing of Fragaria ananassa NPR3 members in fruit significantly reduces tissue damage after Colletotrichum acutatum infection whereas the ectopic expression of either FaNPR3.1 or FaNPR3.2 does not have an apparent effect. Furthermore, the ectopic expression of FaNPR3.2 in Arabidopsis thaliana double mutant npr3npr4 reverts the disease resistance phenotype to Pseudomonas syringe to wild type levels. Therefore, our results reveal that members of the strawberry FaNPR3 clade negatively regulate the defense response to pathogens, as do their Arabidopsis AtNPR3/AtNPR4 orthologs. Also, we provide evidence that FaNPR3 members act in strawberry (F. ananassa) as positive regulators of WRKY genes, FaWRKY19 and FaWRKY24, and that in Arabidopsis, FaNPR3.2 negatively regulates its orthologous genes AtNPR3/AtNPR4. We report for the first time the functional characterization of FaNPR3 members in F. ananassa which provides a relevant molecular basis for the improvement of resistance in this species through new breeding technologies.

Exosomes are nano-sized extracellular vesicles released by cells that contain nucleic acids, proteins, lipids, and other bioactive compounds that play a role in the body's physiological and pathological processes. Exosomes have significant and distinct benefits over synthetic carriers such as liposomes and nanoparticles in the realm of illness diagnostics and therapy due to their endogeneity and heterogeneity. Exosomes are classified as either natural or designed, depending on whether they have been deliberately altered. Natural exosomes are further classified as either animal-derived or plant-derived exosomes. Plant-derived exosome-like nanoparticles (PDENs) are comprised of numerous kinds of bioactive biomolecules. As an alternative cell-free therapeutic strategy, they have the ability to transfer nano-bioactive chemicals to the human body, resulting in diverse anti-inflammatory, antioxidant, and anti-tumour effects. This review focuses on the beneficial effects of plant-derived exosomes against a range of inflammatory conditions, including as periodontitis, inflammatory bowel disease (IBD), autoimmune skin disorders, and inflammation of the liver, lungs, and intestines. Inflammatory disorders are a major issue because of their widespread influence on both personal health and public healthcare systems. Since these illnesses are persistent, the affected people's quality of life is negatively impacted and long-term morbidity is exacerbated. The complicated interaction of genetic, environmental, and immunological variables in the development of various disorders makes effective prevention and therapy more challenging. Plant exosomes present a promising avenue for developing novel therapeutic strategies against inflammatory diseases, offering unique advantages over other alternatives. In order to exploit this efficient carrier, future research will concentrate on creating a PELNV delivery system with high stability, transdermal volume, and ease of administration. Plant exosomes have the potential to become reliable therapeutic agents for a range of common disorders if they are targeted and generated with interdisciplinary expertise.

MicroRNAs are small ribonucleotides which act as key gene regulators. Their altered expression is often associated with onset and progression of several human diseases, including cancer. Given their potential use as biomarkers, there is a need to find detection methods of microRNAs suitable for use in clinical setting. Field Effect Transistor based biosensors (bioFETs) appear to be valid tools to detect microRNAs, since they may reliably quantitate the specific binding between the immobilized probe and free target in solution through an easily detectable electrical signal. We have investigated the detection of human microRNA 155 (miR-155) using an innovative cap-turing probe constituted by a synthetic peptide nucleic acid (PNA), which has the advantage to form a duplex even at ionic strengths approaching the physiological conditions. With the aim to develop an optimized BioFET setup, the interaction kinetics between miR-155 and the chosen PNA was preliminary investigated by Surface Plasmon Resonance (SPR). By exploiting both these results and our custom-made bioFET system, we were able to attain a low-cost, real-time, label-free, highly specific detection of miR-155 in the nano-molar range.

We evaluated diagnostically differential radiological findings between focal nodular hyperplasia (FNH)-like lesions and hepatocellular carcinoma (HCC). We studied pathologically confirmed FNH-like lesions in 13 alcoholic-cirrhosis patients who were negative for hepatitis-B surface antigen and hepatitis-C virus antibody and underwent dynamic computed tomography (CT) and magnetic resonance imaging (MRI), including superparamagnetic iron oxide (SPIO) and/or gadoxetic acid-enhanced MRI. Seven patients underwent angiography-assisted CT. Evaluated lesion features included arterial enhancement pattern, washout appearance (low density compared to surrounding liver parenchyma), signal intensity on T1-weighted image (T1WI) and T2-weighted image (T2WI), central scar presence, chemical shift on in- and out-of-phase images, and uptake pattern on gadoxetic acid-enhanced MRI hepatobiliary phase and on SPIO-enhanced MRI. Eleven patients had multiple small lesions (&lt;1.5 cm). Radiological features of FNH-like lesions included hypervascularity despite small lesion, lack of “corona-like” enhancement in the late phase on CT during hepatic angiography (CTHA), high-intensity on T1WI, slightly high- or iso-intensity on T2WI, no signal decrease in out-of-phase images, and complete SPIO uptake or incomplete/partial uptake of gadoxetic acid. Pathologically, like HCC, FNH-like lesions showed many unpaired arteries and sinusoidal capillarization. In summary, FNH-like lesions have unique radiological findings useful for differential diagnosis. Specifically, SPIO- and/or gadoxetic acid-enhanced MRI and CTHA features might facilitate differential diagnosis of FNH-like lesions and HCC.

Bottlebrush (BB) elastomers with water-soluble side chains and tissue-mimetic mechanical properties are promising for biomedical applications like tissue implants and drug depots. This work investigates the microstructure and phase transitions of BB elastomers with crystallizable polyethylene oxide (PEO) side chains by real-time synchrotron X-ray scattering. In the melt, the elastomers exhibit the characteristic BB peak corresponding to the backbone-to-backbone correlation. Upon crystallization of the side chains, the intensity of the peak decays linearly with crystallinity, and eventually vanishes due to BB packing disordering within intercrystalline amorphous gaps. This behavior of the bottlebrush peak differs from an earlier study of BBs with poly(ε-caprolactone) side chains, explained by stronger backbone confinement in the case of PEO, a high-crystallinity polymer. Microstructural models based on 1D SAXS correlation function analysis suggest crystalline lamellae of PEO side chains separated by amorphous gaps of monolayer-like BB backbones.

The Totiviridae family of viruses has a unique genome consisting of double-stranded RNA with two open reading frames that encode the capsid protein (Cap) and the RNA-dependent RNA polymerase (RdRpol). Most virions in this family are isometric in shape, approximately 40 nm in diameter, and lack envelope. There are five genera within this family, including Totivirus, Victorivirus, Giardiavirus, Leishmaniavirus, and Trichomonasvirus. While Totivirus and Victorivirus primarily infect fungi, Giardiavirus, Leishmaniavirus, and Trichomonasvirus infect diverse hosts, including protists, insects, and vertebrates. Recently, new totivirus-like species have been discovered in fish and plant hosts, and through metagenomic analysis, a novel totivirus-like virus (named Tianjin totivirus) has been isolated from bat guano. Interestingly, Tianjin totivirus causes cytopathic effects in insect cells but cannot grow in mammalian cells, suggesting that it infects insects consumed by insectivorous bats. In this study, we used next-generation sequencing and identified totivirus-like viruses in liver tissue from Molossus molossus bats in the Amazon region of Brazil. Comparative phylogenetic analysis based on the RNA-dependent RNA polymerase region revealed that the viruses identified in Molossus bats belong to two distinct phylogenetic clades, possibly comprising different genera within the Totiviridae family. Notably, the mean similarity between Tianjin totivirus and the totiviruses identified in Molossus bats is less than 18%. These findings suggest that the diversity of totiviruses in bats is more extensive than previously recognized and highlight the potential for bats to serve as reservoirs for novel toti-like viruses.

Due to the complexity of the microstructure of porous media, it is of great significance to explore the heat transport mechanism in porous media in many engineering applications. In this study, an expression for effective thermal conductivity（ETC） of porous media with randomly distributed damaged tree-like bifurcation networks is derived based on the theory of thermodynamics and fractal features of tree-like bifurcation networks. We investigate the effect of heat conduction and heat convection in porous media with randomly distributed damaged tree-like bifurcation networks on the ETC of the porous media. It is found that our fractal model is in good consistency with the existing available experimental data. In addition, the influence of the micro-structural parameters of the model on heat transfer in the porous media have been analyzed in detail. The research results can provide significant theoretical guidance for the development and design of heat transfer systems.

Incobotulinumtoxin A and Yoga-like Isometric Exercise in Adolescent Idiopathic Lumbar Scoliosis – a randomized pilot study Abstract: Background: Approximately 90% of scoliosis is adolescent idiopathic (AIS). From its first appearance at 10-14 until age 18 it is most vulnerable to deterioration; young people are most susceptible to the condition worsening. An effective non-surgical means of remediation would be welcome. Design: Randomized control two-arm study, assessing the safety and efficacy of combining incobotulinum injections with yoga to reverse lumbar and thoracolumbar AIS. Methods: In a private clinic setting, non-pregnant healthy 12 – 18 year-olds were either taught a symmetrical “placebo” yoga pose (control sub-group 1), given the side plank (Vasisthasana) done thrice daily with placebo injection (control sub-group 2) or given the thrice-daily side-plank with botulinum injection (Intervention group 3). Injection: 33 IU of incobotulinum toxin type A (Xeomin) injected into concave-side lumbar paraspinals and quadratus lumborum at L2-3 and the psoas muscle at L3-4, or injected similarly with placebo. Randomization by Random.com. Objective: Assess whether muscular asymmetry treated with botulinum toxin injection and the side-plank are safe and effective in AIS.Results: Outcome: Twelve intervention and 12 placebo patients (Groups 1 + 2), 12 -18 years old completed the three-month study period. Mean daily side-plank time = 165 seconds. Mean initial lumbar curvature was 36.9 degrees (SD 14.36), (p<0.0001); mean curvature at 3 weeks was 29.5 degrees. (SD 14.23) (p<0.0001); mean curvature at 3 months was 26.0 degrees (SD 12.81) Onset vs 3-month value: p<0.0001. Two patients in Group 3 complained of shoulder pain, and 2 of wrist pain that resolved when the side-plank was done on the elbow. Conclusion: Muscle asymmetry appears relevant to AIS treatment. Incobotulinum injections combined with the side-plank done with the convex side downward may be safe and helpful in adolescent idiopathic lumbar scoliosis.

Incobotulinumtoxin A and Yoga-like Isometric Exercise in Adolescent Idiopathic Lumbar Scoliosis – a randomized pilot study Abstract: Background: Approximately 90% of scoliosis is adolescent idiopathic (AIS). From its first appearance at 10-14 until age 18 it is most vulnerable to deterioration; young people are most susceptible to the condition worsening. An effective non-surgical means of remediation would be welcome. Design: Randomized control two-arm study, assessing the safety and efficacy of combining incobotulinum injections with yoga to reverse lumbar and thoracolumbar AIS. Methods: In a private clinic setting, non-pregnant healthy 12 – 18 year-olds were either taught a symmetrical “placebo” yoga pose (control sub-group 1), given the side plank (Vasisthasana) done thrice daily with placebo injection (control sub-group 2) or given the thrice-daily side-plank with botulinum injection (Intervention group 3). Injection: 33 IU of incobotulinum toxin type A (Xeomin) injected into concave-side lumbar paraspinals and quadratus lumborum at L2-3 and the psoas muscle at L3-4, or injected similarly with placebo. Randomization by Random.com. Objective: Assess whether muscular asymmetry treated with botulinum toxin injection and the side-plank are safe and effective in AIS. Results: Outcome: Twelve intervention and 12 placebo patients (Groups 1 + 2), 12 -18 years old completed the three-month study period. Mean daily side-plank time = 165 seconds. Mean initial lumbar curvature was 36.9 degrees (SD 14.36), (p<0.0001); mean curvature at 3 weeks was 29.5 degrees. (SD 14.23) (p<0.0001); mean curvature at 3 months was 26.0 degrees (SD 12.81) Onset vs 3-month value: p<0.0001. Two patients in Group 3 complained of shoulder pain, and 2 of wrist pain that resolved when the side-plank was done on the elbow. Conclusion: Muscle asymmetry appears relevant to AIS treatment. Incobotulinum injections combined with the side-plank done with the convex side downward may be safe and helpful in adolescent idiopathic lumbar scoliosis.

Abstract: It has been shown that three-dimensional self-assembled multicellular structures derived from human pluripotent stem cells show electrical activity similar to EEG. More recently, neurons were successfully embedded in a digital game-worlds (Kagan, et al. 2022). The biologically inspired neural network (BNN), expressing human cortical cells, was able to show internal modification and learn the task at hand (predicting the trajectory of a digital ball while moving a digital paddle). In other words, the system allowed to read motor information and write sensory data into cell cultures. In this article, we discuss Neural Correlates of Consciousness (NCC) theories, and their capacity to predict or even allow for consciousness in a BNN. We found that In-formation Integration Theory (IIT) is the only NCC that offers the possibility for a BNN to show consciousness. IIT argues that any system capable of integrating information will have some degree of phenomenal consciousness. The pattern of activity appearing in the BNN, with increased density of sensory information leading to better performance, implies that the BNN could be conscious. This may have profound implications from a physiological, philosophical, and ethical perspective.