Recently we showed that schizophrenia and, especially, deficit schizophrenia is accompanied by neurocognitive impairments as measured with different cognitive batteries. The aim of this study was to examine whether a single trait underpins aberrations in 9 key Cambridge Neuropsychological Test Automated Battery (CANTAB) probes, verbal fluency (VFT), world list memory (WLM), true recall, and the Mini Mental State Examination (MMSE). We recruited 80 patients with schizophrenia and 40 healthy controls. All patients were assessed using CANTAB tests, namely paired-association learning (PAL), rapid visual information (RVP), spatial working memory (SWM), one touch stocking (OTS), intra/extradimensional set shifting (IED), and emotional recognition test (ERT). We found that a single latent trait, which is essentially unidimensional, underlies the CANTAB tests, VFT, WLM, True Recall and MMSE. The latent trait shows excellent psychometric properties and fits a reflective model and, therefore, reflects a generalized cognitive decline (GCoDe), which is the cause of aberrations in semantic and episodic memory, recall, executive functions, strategy use, rule acquisition, visual sustained attention, attention set-shifting and emotional recognition. 40.5% of the variance in GCode was explained by CCL11, IgA to tryptophan catabolites, and increased oxidative toxicity. GCoDe explains 44.8% of the variance in a single latent trait extracted from psychosis, hostility, excitation, mannerism, negative symptoms, formal thought disorders, and psychomotor retardation and 40.9% in quality of life scores. GCoDe is significantly greater in deficit than in nondeficit schizophrenia. In conclusion, GCoDe mediates the effects of neuro-immune and neuro-oxidative toxicity on the phenome of (deficit) schizophrenia.

Ozonated sunflower oil (OSO) is an established therapeutic agent and nutraceutical harboring various therapeutic values, including antiallergic, derma-protective, and broad-spectrum antimicrobial activity. Conversely, the medicinal aspects of OSO for wound healing, tissue regeneration, and treatment of inflammation in dyslipidemia have yet to be fully elucidated. Herein, a comparative effect of OSO and sunflower oil (SO) was investigated to heal cutaneous wound and tissue regeneration of zebrafish impediment by carboxymethyllysine (CML) toxicity, following impact on hepatic inflammation and blood lipid profile. After OSO (final 2%, 1 μL) and SO's (final 2%, 1 μL) treatment, substantial healing was elicited by OSO in the cutaneous wound of zebrafish impaired by CML (final 25 mg). As an important event of wound healing, OSO scavenges the reactive oxygen species (ROS), rescues the wound from oxidative injury, and triggers the essential molecular events for the wound closer. Furthermore, the intraperitoneal injection of OSO was noted to counter the CML-induced adversity and prompt tissue regeneration in the amputated tail fin of zebrafish. Additionally, OSO counters the CML-induced neurotoxicity and rescues the zebrafish from acute mortality and paralysis, along with meticulous recovery of hepatic inflammation, fatty liver changes, and diminished ROS and proinflammatory interleukin (IL)-6 production. Besides, OSO efficiently ameliorated CML-induced dyslipidemia by alleviating the total blood cholesterol (TC), triglyceride (TG) and increasing high-density lipoproteins cholesterol (HDL-C). The outcome of multivariate assessment employing principal component analysis and hierarchical cluster analysis supports a superior therapeutic potential of OSO over SO against the clinical manifestation of CML. Conclusively, OSO owing to its antioxidant and anti-inflammatory potential, counters CML-induced toxicity and promotes wound healing, tissue regeneration, hepatoprotection, improved blood lipid profile, and survivability of zebrafish.

As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxicants to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and/or oral inhalation, which are known to enable the transfer of nanomaterials into the blood stream resulting in rapid distribution in the body. Consequently, mucosal barriers present in nose, buccal and lung have been identified and intensively studied as the key tissue barrier to nanoparticle translocation. Despite decades of research, surprisingly little is known about the differences among various mucosa tissue types to tolerate nanoparticle exposures. One limitation in comparing nanotoxicological data sets can be linked to a lack of harmonization and standardization of cell-based assays, where a) different cultivation conditions such as air-liquid interface or submerged cultures, b) varying barrier maturity and c) diverse media substitutes have been used. The current comparative nanotoxicological study therefore aims at analyzing the toxic effects of nanomaterials on four human mucosa barrier models including nasal (RPMI2650), buccal (TR146), alveolar (A549), and bronchial (Calu-3) mucosal cell lines to better understand the modulating effects of tissue maturity, cultivation conditions and tissue type using standard Transwell cultivations at liquid-liquid and air-liquid interfaces. Overall, cell size, confluency, tight junction localization, and cell viability as well as barrier formation using 50% and 100% confluency was monitored using trans-epithelial-electrical resistance (TEER) measurements and Presto Blue assays of immature (e.g. 5 days) and mature (e.g. 22 days) cultures in the presence and absence of corticosteroids such as hydrocortisone. Results of our study show that cellular responses to increasing nanoparticle exposures are highly cell type specific, where bronchial mucosal cell barriers models cultivated under ALI conditions showed less tolerance to acute ZnO nanoparticle exposures. Additionally, stronger toxicities are found using early mucosa barriers compared to later barrier models being maturated under air-liquid cultivation conditions.

Simple summary This reassessment of the findings from our Phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate-high risk prostate cancer in the absence of androgen-deprivation therapy due to patient’s refusal, with a median follow-up of 6.5 years. Our primary focus is on analysing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade 2 or higher, both genitourinary and gastrointestinal. Abstract Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intraprostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intraprostatic recurrences occurred in 7 patients (21%), with ≥ 75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patient. Notably, 5 patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intraprostatic recurrences. Extended follow-up revealed grade 2 or higher late GU and GI toxicity in 18% (n=6) and 6% (n=2) of the patients. Conclusions: Among patients with intermediate-high risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: focal dose escalated prostate SBRT prevented recurrences in the dominant nodule, however extra-prostatic recurrence sites were frequent.

The antioxidant and anti-inflammatory abilities of beeswax alcohol (BWA) are well reported in animal and human clinical studies, with a significant decrease in malondialdehyde (MDA) in blood, reduction of liver steatosis, and decrease in insulin. On the other hand, there is insufficient information to explain the in vitro antioxidant activity of BWA because it is extremely insoluble in aqueous buffer system. The BWA mixture was incorporated into reconstituted HDL (rHDL) with apoA-I, and the physiological functions of BWA in a water system were evaluated. After synthesis of rHDL with palmitoyloleoyl phosphatidylcholine (POPC), cholesterol, apolipoprotein A-I (apoA-I), and the BWA at molar ratios of 95:5:1:0 (rHDL-0), 95:5:1:0.5 (rHDL-0.5), and 95:5:1:1 (rHDL-1) for POPC:FC:apoA-I:BWA, the particle size of rHDL-1 was increased 15% compared to rHDL-0. rHDL-1 exhibited the strongest anti-glycation activity, up to 18% less glycation than rHDL-0 treated HDL3, with the highest protection of apoA-I from proteolytic degradation: a 28% larger band intensity than that of rHDL-0 treated HDL3 in the presence of fructose (final 250 mM). The antioxidant ability to inhibit cupric ion-mediated LDL oxidation increased as the BWA content in rHDL increased. The rHDL-1-treated LDL exhibited the smallest oxidation extent in electromobility with the least quantification of oxidized species (MDA). The antioxidant activities of HDL, ferric ion reduction ability (FRA), and paraoxonase (PON) were enhanced by the BWA in rHDL treatment with a concomitant increase in the molar ratio. rHDL-1-treated HDL showed 20–22% higher FRA and PON activities than rHDL-0-treated HDL. A microinjection of each rHDL into zebrafish embryos was performed in the presence of carboxymethyllysine (CML). The rHDL-1 injected embryo exhibited the highest survivability (~63%), whereas the CML alone group showed 28% survivability. A higher BWA content in rHDL helped neutralize the CML toxicity, resulting in higher survivability and normal developmental morphology. In contrast, the CML alone injected embryo showed severe retardation of the developmental speed and morphological defect. The CML-alone group showed the highest extent of reactive oxygen species (ROS) production and cellular apoptosis in embryos, but a co-injection of rHDL-1 resulted in a remarkable decrease in ROS and apoptosis. The dermal application of rHDL containing BWA resulted in higher potent wound-healing activity in a dose-dependent manner with decreased reactive oxygen species and cellular apoptosis in the cutaneous wound area in the presence of CML. Conclusively, incorporating BWA in rHDL significantly enhanced the anti-glycation and antioxidant activities in rHDL via more stabilization of apoA-I with a larger particle size. The rHDL containing BWA facilitated enforced inherent antioxidant ability of HDL and anti-inflammatory activity to suppress the CML toxicities in zebrafish embryos and to ameliorate CML-aggravated chronic wounds in adult zebrafish.

Background: Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to increased levels of high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). Objective: The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Methods: Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. Results: HMGB1 and DKK1 are significantly higher in T2DM irrespective of hypertension. T2DM was also accompanied by increased atherogenicity indices. HMGB1 and DKK1 are significantly correlated with HbA1c, glucose, indices of insulin resistance, β-cell function, and glucose toxicity, and different atherogenic indices. A large part of the variance in the β-cell index (30.5%) and glucose toxicity (34.8%) was explained by the combined effects of HMGB1 and DKK1 and hypertension. We found that 18.3% of the variance of the atherogenic index of plasma was explained by HMGB1 and DKK1 levels and that 31.2% was explained by glucose toxicity, HMGB1 and body weight. Conclusion: The higher serum HMGB1 and DKK1 levels in T2DM patients and the associations with atherogenicity indicate that low grade inflammation and disorders in the Wnt pathways are associated with T2DM and that both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are new drug targets in the treatment of T2DM.

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress has a severe effect on low-density lipoprotein (LDL) oxidation, leading to several detrimental health effects. Thereof, in this study, the effect of beeswax alcohol (BWA) was evaluated to prevent LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipoprotein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle and older human subjects (n=50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10-30 μM), which was significantly better them the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails CuSO4 (final 0.5 μM) evoked LDL/apo-B oxidation and a marked reduction of lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 μM). Additionally, BWA counter carboxymethyllysine (CML, 500 ng) induced toxicity and rescued zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blind, placebo-controlled preliminary clinical study on middle and older-aged human subjects (n=50) exhibited that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA), total hydroperoxides, and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in anthropometric profile, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and has a positive impact on the oxidative variables of human subjects.

Hu7691 represents a novel Pan-Akt kinase inhibitor, demonstrating excellent selectivity towards non-AGC kinase families and pronounced inhibitory effects on the proliferation of multiple tumor cell lines. However, there is currently a notable absence of in vivo toxicological research evidence concerning Hu7691. This study represents the first investigation into the 14-day repeated dose toxicity of Hu7691 in male and female Sprague-Dawley (SD) rats. Male rats were administered daily doses of 12.5, 50, 100, and 150 mg/kg, while female rats received doses of 12.5, 25, 50, and 75 mg/kg for 14 consecutive days. Hematological assessments, organ weights, and histopathological examinations revealed corresponding alterations, suggesting potential target organs for toxicity including the spleen, thymus, and gastrointestinal tract. It is worth noting that the test substance may also impact the liver, kidneys, heart, and ovaries. The No Observed Effect Level (NOAEL) was determined to be no greater than 12.5 mg/kg. Based on the observed gender-related toxicity differences in preliminary trials, it is recommended that the high dose reference dose for male animals in formal experiments should not be less than 100 mg/kg, while for female animals, it should be less than 50 mg/kg.

Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, enabling the correlation of the relative abundance of molecular features (representing individual phytochemicals) with the read-outs of bioassays. We applied this strategy for discovering and identifying constituents of Centella asiatica (C. asiatica) that protect against Aβ cytotoxicity in vitro. C. asiatica has been associated with improving mental health and cognitive function, with potential use in Alzheimer’s disease. Human neuroblastoma MC65 cells were exposed to subfractions of an aqueous extract of C. asiatica to evaluate the protective benefit derived from these subfractions against amyloid β-cytotoxicity. The % viability score of the cells exposed to each subfraction was used in conjunction with the intensity of the molecular features in two computational models, namely Elastic Net and selectivity ratio, to determine the relationship of the peak intensity of molecular features and % viability. Finally, the correlation of mass spectral features with MC65 protection and their abundance in different sub-fractions were visualized using GNPS molecular networking. Both computational methods unequivocally identified dicaffeoylquinic acids as providing strong protection against Aβ-toxicity in MC65 cells, in agreement with the protective effects observed for these compounds in previous preclinical model studies.

Microalgae and cyanobacteria are photosynthetic microorganisms with significant biotechnological potential for the production of bioactive compounds, making them a promising resource for diverse industrial applications. This study presents the development and validation of a modular, droplet-based microfluidic photobioreactor (µ-PBR) designed for high-throughput screening and cultivation under controlled light conditions. The µPBR, based on PTFE tubing and a 4-channel LED illumination system, enables precise modulation of light intensity, wavelength, and photoperiod, facilitating dose-response experiments. Synechococcus elongatus UTEX 2973 and Chlorella vulgaris were used to demonstrate the system's capacity to support photosynthetic growth under various conditions. The results indicate that continuous illumination, particularly under blue and mixed blue-red light, promotes higher autofluorescence and chlorophyll-a content in cyanobacteria Synechococcus elongatus UTEX2973, while Chlorella vulgaris achieved optimal growth under a 16:8 light-dark cycle with moderate light intensity. This µ-PBR offers not only a flexible, scalable platform for optimizing growth parameters but also investigating highly resolved dose response screenings of environmental stressors such as salinity. The findings highlight its potential for advancing microalgal biotechnology research and applications.

The increased volume of heavy vehicles and the use of de-icing agents on concrete bridge decks have accelerated their deterioration. Concurrently, the demand for rapid replacement of these structures and research interest in prefabricated bridges have increased. Traditionally, horizon-tal shear connections between girders and precast decks have utilized rebar stirrup shear con-nectors. Although effective for initial construction, this method complicates the dismantling of aged decks because the rebar connectors are fully embedded within the girders. The removal of concrete decks requires cutting, whereas composite decks atop girders must be demolished us-ing breakers. This process generates dust, noise, and vibrations, raising environmental concerns and causing delays in urban demolition projects due to public complaints. This study introduces an embedded separable shear connector that minimizes deck breaking and facilitates easy rein-stallation by allowing simpler separation of the deck from the girder. Horizontal shear and flexural tests on composite girders and comparisons with various design codes were conducted to evaluate this innovative connector. The results show that the proposed connector provides superior horizontal shear strength relative to traditional methods and satisfies modern ductility design criteria. Simulations confirmed that the decks could be easily separated and reassembled, maintaining shear strength under initial construction conditions.

The exponential growth of publicly available omics data presents both an opportunity and a challenge for biomedical researchers, particularly those in low- and middle-income countries (LMICs). The Collective Omics Data to Knowledge (CD2K) initiative aims to address this challenge by providing an accessible framework for biomedical research training. This review describes the development and implementation of the CD2K program, which comprises three core modules: COD1 (reductionist interpretation of collective omics data), COD2 (creation of curated dataset collections), and COD3 (re-analysis of omics data on a global scale). The CD2K approach emphasizes the reuse and reinterpretation of public data, integrating literature mining and emerging technologies like Large Language Models (LLMs). A key feature of the program is its focus on accessibility, designed to make the exploitation of large-scale datasets amenable to researchers without extensive data science skills. The curriculum aims to equip trainees with a range of skills, from basic data interpretation to more advanced bioinformatics analysis, with an emphasis on producing tangible outputs such as peer-reviewed publications, which directly address career development needs. The CD2K initiative has involved researchers from multiple institutions across several countries, resulting in several publications and publicly available dataset collections. While still in its early stages, the program shows promise in providing a structured framework for leveraging public omics data in biomedical research. This review also discusses the current limitations of the CD2K approach and ongoing efforts to expand its reach. By offering an accessible model for building research capacity, the CD2K initiative represents a step towards fostering data-driven discovery in global biomedical research, particularly in resource-limited settings.

Short-term electrical demand forecasting is crucial for the effective operation of new electrical networks. This necessity arises from the requirement for more timely demand information compared to traditional networks, as well as the integration of new energy sources into the electrical grid. Most existing forecasting methodologies fail because they do not consider the nonlinearities of the system, and because they neglect to represent important external influences on the problem; in other words, they are not based on a holistic approach to electricity demand forecasting. In this study, we present a new approach to developing an electrical demand forecasting model, and consider a case study to evaluate the importance of several factors affecting electricity consumption and forecast accuracy. We use an ISO NE (Independent System Operator New England) dataset that represents the total electrical load of several New England cities from January 2017 to December 2019. This dataset includes 23 independent variables, such as meteorological data, economic indicators and market information. Our study presents a pipeline for building electrical demand forecast models using time series information as input. By carefully selecting variables and representing external factors, we demonstrate the feasibility of generating a more accurate forecasting model with reduced computational resources. Our results show that incorporating external factors can enhance model accuracy by up to 60%. To handle large input datasets, variable selection is crucial for reducing dimensionality while maintaining accuracy, enabling the effective application of deep learning models. Simulations reveal that deep learning models with no more than three intermediate layers and an optimal number of neurons perform efficiently. The CNN+LSTM composite model achieved the lowest error rate at 0.15%, surpassing previously studied models, including standalone CNN and LSTM approaches, which had error rates of 0.8% and 1.44%, respectively. The CNN's feature extraction abilities, combined with the LSTM's strength in handling time-series data, were instrumental in achieving superior performance across most scenarios.

Oenobiol Sun Expert, a food formulation designed to enhance skin health prior to sun exposure, has been optimized by incorporating the OenoGrape Advanced Complex, which includes grape pomace extract, increased selenium content and 10% lycopene-rich tomato extract, these constituents exhibiting high antioxidant potential. To evaluate the effects of those individual ingredients and the overall formulation at the cellular level, the AOP1 cell antioxidant efficacy assay was employed to measure intracellular free radical scavenging activity, while the CAA (DCFH-DA) assay was used to assess peroxidation scavenging at the plasma membrane level. Indirect antioxidant activity was examined using stably transfected cell lines containing a luciferase reporter gene controlled by the Antioxidant Response Element (ARE), which activates the endogenous antioxidant system via the Nrf2/Keap1-ARE pathway. Our results indicate that, among the individual components, grape pomace extract and sodium selenite possess high and complementary antioxidant properties. Grape pomace extract was particularly effective in inhibiting free radicals (AOP1 EC₅₀ = 6.80 mg/ml) and activating the ARE pathway (ARE EC₅₀ = 231.1 mg/ml), whereas sodium selenite exerted its effects through potent ARE activation at sub-microgram levels (EC₅₀ = 0.367 mg/ml). In contrast, the lycopene-rich tomato extract did not show a notable contribution to antioxidant effects. The antiradical activity of the OenoGrape Advanced Complex, comprising these three ingredients, was very efficient and consistent with the results obtained for the individual components (AOP1 EC₅₀ = 15.78 µg/ml and ARE EC₅₀ of 707.7 μg/ml). Similarly, the free radical scavenging activity still persisted in the Oenobiol Sun Expert formulation (AOP1 EC₅₀ = 36.63 µg/ml). In addition, the direct and indirect antioxidant activities of ingredients were confirmed on both hepatocytes and keratinocytes after in vitro intestinal trans-epithelial transfer experiments, demonstrating bioavailability and bioactivity of grape pomace extract and sodium selenite. These finding suggest that the ingredients of this food supplement contribute to enhanced cytoprotection following ingestion.

Background: Previous studies have highlighted that copper supplementation at 200% of the recommended daily dietary allowance modified vascular contraction and relaxation through increased reactive oxygen species (ROS) and prostaglandin formation, which modified the antioxidant status of middle-aged Wistar rats. Methods: In this study, young (1 month old) male Wistar rats (n/group = 10) received a diet supplemented with 6.45 mg copper/kg (100% of daily recommendation—Group A) for 8 weeks. The experimental group received 12.9 mg copper/kg of diet (200% of the daily recommendation—Group B). Results: Experimental supplementation with 200% copper modified the copper concentration in the blood (1.21-fold, p = 0.04), liver (1.15-fold, p = 0.032), and kidneys (1.23-fold, p = 0.045), potentiated the ROS formation in the aortic rings, and enhanced the sensitivity of the aortic rings to the vasodilator acetylcholine. We observed an increased participation of nitric oxide (NO) derived from inducible NO synthase (iNOS) in vascular contraction and a decreased net effect of vasodilator prostanoids derived from cyclooxygenase-2 in vascular relaxation. In rat kidneys, the concentrations of potassium (1.08-fold, p = 0.001) and iron (1.13-fold, p = 0.046) were higher, while, calcium (0.88-fold, p = 0.001) and chromium (0.77-fold, p = 0.005) concentrations were lower. In the rat liver, magnesium (1.06-fold, p = 0.012) was higher. No differences were observed in the concentrations of sodium, zinc, manganese, selenium, cobalt, molybdenum, and vanadium. The antioxidant activity of water- and lipid-soluble compounds; total antioxidant status in the blood; and superoxide dismutase, catalase, and malondialdehyde levels in the heart did not change. Conclusions: In young rats, prolonged supplementation with 200% copper had a lesser effect than anticipated on oxidative stress and vascular reactivity. Detailed data on the status of trace elements and their interactions in patients of different age groups are strongly required for effective nutritional and therapeutic intervention.

ADAM10 is a multi-functional proteinase that can cleave approximately 100 different substrates. Previously, we demonstrated that ADAM10 is expressed by ameloblasts responsible for enamel formation. Here we asked if ADAM10 plays a role in enamel development. Deletion of Adam10 in mice is embryonic lethal and deletion of Adam10 from epithelia is perinatal lethal. We therefore deleted Adam10 from ameloblasts. Here, we confirm ameloblast-specific expression of the Tg(Amelx-iCre)872pap construct. We crossed these mice with Adam10 floxed mice to generate Amelx-iCre; Adam10fl/fl mice (Adam10 cKO). We show that Adam10 cKO mice have discolored teeth with softer than normal enamel. Notably, the Adam10 cKO enamel density and volume were significantly reduced in both incisors and molars. Moreover, the incisor enamel rod pattern became progressively more disorganized moving from the DEJ to the outer enamel surface and this disorganized rod structure created large gaps between and among the rods. ADAM10 cleaves proteins essential for cell signaling and for enamel formation such as RELT and COL17A1. ADAM10 also cleaves cell-cell contacts such as E- and N-cadherins that may support ameloblast movement necessary for normal rod patterns. Here, we show for the first time that ADAM10 expressed by ameloblasts is essential for proper enamel formation.

This article discourses on how the inheritance and innovation in paper-cutting art have taken place through its integration with modern design language. Xuzhou paper-cut is regarded as representative of China's traditional folk art, carrying a rich cultural heritage, but it faces both challenges and opportunities that come with modern society. In the course of reviewing the development history of Xuzhou paper-cutting, the value of Xuzhou paper-cut as intangible cultural heritage was discussed. This paper will seek to find out the possibility of application for Xuzhou paper-cutting in modern design with both qualitative and quantitative methods, including questionnaires and interviews. Successful examples are used in this research to look for evidence that effectively proves traditional paper-cutting combines well with the principles of modern design in developing concepts, artistic expressions, and cultural symbolism. It shows that Xuzhou paper-cutting has a great potential to apply in modern design, and education, exhibitions, and community activities will be also necessary to revive it. On the other hand, traditional craft could adapt to current social needs only when the design language has been innovated. The research brought in new input with regard to integrating traditional culture with modern design from a theoretical and practical point of view, thus serving as an informant for the direction of further research in heritage and design integration.

Background: Cardiovascular comparisons between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium-glucose co-transporter-2 (SGLT-2) inhibitors in type 2 diabetes(T2D) remain an area of interest. Thus, the purpose of this meta-analysis is to compare the impact of these two drug classes on major CV outcomes, such as heart failure hospitalization(HHF), major adverse cardiovascular events (MACE), CV mortality, myocardial infarction, stroke, and all-cause mortality, with an emphasis on heart failure hospitalizations. Methods: PubMed (including MEDLINE), Google Scholar, Cochrane Central Library, PLOSONE, and Science Direct databases were searched for studies that compared GLP-1 RAs and SGLT-2 inhibitors in patients with type 2 diabetes. Six cohort studies were selected for the analysis. Odds ratios (OR) with 95% CI were calculated and a random-effects model was used to estimate the hazard ratios (HR) of the studies. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS), and publication bias was assessed using funnel plots and Egger’s test. Results: Pooled analysis demonstrated a significant reduction in heart failure hospitalizations with SGLT-2 inhibitors compared to GLP-1 RAs (HR: 0.78 [0.62–0.98], I² = 87%, p < 0.01). Cardiovascular mortality was also significantly reduced by SGLT-2 inhibitors (HR: 0.74 [0.31–1.67], I² = 87%, p < 0.01), and a modest reduction was observed for all-cause mortality (HR: 0.85 [0.44–1.64], I² = 17%, p = 0.27). While SGLT-2 inhibitors appeared to slightly reduce the risk of myocardial infarction (HR: 0.83 [0.74–0.92], I² = 0%, p = 0.85), no significant difference was observed for MACE (HR: 0.91 [0.82–1.01], I² = 0%, p = 0.70) or stroke (HR: 0.88 [0.77–1.00], I² = 0%, p = 0.85). Conclusions: Compared to GLP-1 receptor agonists, SGLT-2 inhibitors were more effective in lowering heart failure hospitalizations and cardiovascular mortality in patients with type 2 diabetes. It was also found that all-cause mortality and myocardial infarction were moderately reduced using oral agents. However, the differences were not significant for MACE or stroke. These results imply that SGLT-2 inhibitors may potentially provide better cardiovascular benefits, especially with respect to heart failure and cardiovascular mortality, than GLP-1 RA. Further research should be conducted to determine the effects of the long-term use of these therapies on stroke and other cardiovascular events.

Biowaste sources, like coffee wastes (CWs), are considered for advanced materials. CW was assessed to prepare activated carbon for supercapacitor electrodes, but showed low performance compared to other counterparts. Enhanced CW activation process may help address this limitation. In this study, CW was subjected to two activation methods: physical (pyrolysis) activation and physical-chemical activation using ZnCl2, to determine the more effective approach. Both resulting materials were analyzed using SEM, TEM, BET, Raman spectroscopy and XRD. The physical-chemical activation yielded activated carbon with better characteristics, including a higher specific-surface area (SSA) of ~830 m²/g, compared to 458 m²/g from the physical activation. With its promising potential for supercapacitor electrodes, the former activated carbon was singled out for supercapacitor study. Cyclic voltammetry revealed a specific capacitance of 261 F g-1, and energy density of 18.3 Wh/kg, with power density of 360 W/kg at a current density 0.33 A/g. Charge-discharge studies showed a specific capacitance of 150 F g-1 at the same current density. Electrochemical impedance spectroscopy indicated a specific capacitance of 180 F g-1, with an equivalent series resistance of 0.56 Ω at a low frequency of 0.01 Hz. The electrode exhibited exceptional characteristics, maintaining high stability over 5,000 charge-discharge cycles.

Background/Objectives: Malignant neoplasms represent the most common diseases worldwide, and breast cancer is the most commonly diagnosed cancer type in the female population. One of the critical features of this cancer type is the ability to metastasize. This process is related to adhesion, migration, and invasiveness. As demonstrated, the catalytic telomerase subunit, hTERT, may control these processes. The expression and activity of telomerase in normal somatic cells are very low or absent, which makes it a universal and attractive target for cancer diagnostics and therapy; Methods: In this work, we assessed the influence of telomerase inhibitors TMPyP4, BIBR 1532, or imetelstat on the ability to form spheroids in MCF7 and MDA-MB-231 breast cancer cells. Cells of both lines were treated with specific compounds in concentrations: TMPyP4 - 5, 10, 20 µM; BIBR 1532 - 1, 5, 10 µM or imetelstat 1, 5, 10 µM for 72 hours. Cells were then trypsinized and applied to 96-well low-adhesive plates at 500 cells per well, followed by observation at different time intervals, i.e., 24, 48, and 72 hours; Results: As shown, the applied telomerase inhibitors influenced the ability of MCF7 and MDA-MB-231 breast cancer cells to form spheroids in a concentration- and incubation-time-dependent manner; Conclusions: Although the mechanism of this phenomenon has not been fully understood, it seems that the use of telomerase expression/activity inhibitors to reduce the adhesive capacity and metastatic potential of breast cancer cells may play a significant role in cancer therapy.

The sustainability of social security is increasingly important to countries worldwide, yet the impact of regulation on social security remains controversial. Most scholars and policymakers focus primarily on the influence of social regulation on social security, while to varying degrees neglecting the effects of market regulation. This study employs data on the relaxation of market regulation (RMR) from the Marketization Index of China’s Report (MICR) and balanced panel data for 31 provinces in China from 2008 to 2019. Using instrumental variable methods to address endogeneity issues in the model, we empirically evaluate the impact of China's RMR on the level of social security (SSL) and its underlying mechanisms. The conclusion indicates that for every standard deviation increase in the intensity of RMR by local governments, there is a 2.25% increase in SSL. The study also found that social security expenditure and efficiency serve as mediating variables for the impact of RMR on SSL, but it did not support the mediating role of social security fairness. These findings offer valuable insights for optimizing regulation and social security reform in China, as well as useful references for other emerging market economies in identifying priorities for their coordinated regulatory and social security reform.

The recycling of lithium-ion batteries (LIBs) has become increasingly important due to the rising demand for energy storage solutions and the need to mitigate environmental impacts. Among the valuable materials within spent LIBs, lithium metal oxide is particularly sought after for its role in battery production. This review explores the application of microwave technology in combination with froth flotation and magnetic processes for the recovery of lithium metal oxide from spent LIBs. Microwave technology has emerged as a promising method for LIB recycling due to its ability to selectively heat materials and accelerate chemical reactions. In the context of lithium metal oxide recovery, microwave irradiation offers advantages such as rapid and uniform heating, selective heating of target compounds, and enhanced reaction kinetics. These attributes contribute to reduced processing times, lower energy consumption, and improved recovery efficiency. Froth flotation is a widely used separation technique that exploits differences in surface hydrophobicity to separate minerals. In LIB recycling, froth flotation has been adapted to recover lithium metal oxide from electrode materials. The incorporation of microwave technology into froth flotation processes provides several benefits. Microwaves selectively heat lithium metal oxide particles, facilitating their detachment from the electrode surface and enhancing their recovery. Additionally, microwave-assisted pretreatment promotes the liberation of active materials, leading to increased exposure to flotation reagents and improved recovery rates. Moreover, microwave-assisted froth flotation requires lower temperatures and shorter flotation times, resulting in energy savings and reduced operating costs. Magnetic separation is another method commonly used in LIB recycling to recover magnetic materials such as cobalt and nickel. By exploiting the magnetic properties of these materials, magnetic separation enables their separation from non-magnetic components. Integrating microwave technology into magnetic separation processes offers opportunities for enhanced efficiency and selectivity. Microwave irradiation can assist in the liberation of magnetic materials from electrode materials, promoting their separation. Furthermore, microwave-assisted magnetic separation can operate at lower temperatures and shorter processing times, contributing to energy efficiency and cost-effectiveness. The application of microwave technology in conjunction with froth flotation and magnetic processes shows promise for the efficient recovery of lithium metal oxide from spent LIBs. The synergistic effects of microwave irradiation with these separation techniques lead to improved recovery rates, reduced energy consumption, and lower environmental impact. However, further research is needed to optimize process parameters, scale up operations, and address challenges such as material heterogeneity and equipment design. With continued innovation and collaboration, microwave-assisted recycling processes have the potential to play a significant role in advancing sustainable battery recycling practices.

Recent studies with ApoE knockout (ApoE-/-) mice deficient for PACAP (pituitary adenylate cyclase-activating polypeptide) or its receptor PAC1 provide evidence for a possible involve-ment of immune- and vasoregulatoy PACAP signaling at the PAC1 receptor in atherogenesis and plaque associated vascular inflammation. Therefore, we tested the PAC1 receptor agonist Maxadilan and the PAC1 selective antagonist M65 on plaque development and lumen stenosis in the ApoE-/- atherosclerosis model for possible anti-atherogenic effects. Adult male ApoE-/- mice were fed a cholesterol-enriched diet (CED) or standard chow (SC) treat-ed with Maxadilan, M65 or Sham. Effects of treatment on atherosclerotic plaques, lumen stenosis, apoptosis and pro-inflammatory signatures were analyzed in the brachiocephalic trunk (BT). The percentage of Maxadilan treated mice exhibiting plaques under SC and CED was lower than that of Sham or M65 treatment indicating opposite effects of Maxadilan and M65. Maxadilan ap-plication inhibited lumen stenosis under SC and CED compared to Sham. In spite of significantly increased cholesterol levels, lumen stenosis of Maxadilan-treated mice was similar under CED and SC. In contrast, M65 under SC or CED did not reveal a significant influence on lumen steno-sis. Maxadilan significantly reduced the TNF-α+ area in the plaques under CED, but not under SC. In contrast, the IL-1β+ area was reduced after Maxadilan treatment under SC, but remained unchanged under CED compared to Sham. Maxadilan reduced the caspase-3+ area in the media under both SC and CED without affecting lipid content in plaques. Despite persisting hypercholesterolemia, Maxadilan reduces lumen stenosis, apoptosis and TNF-α driven inflammation. Our data suggest that Maxadilan provides atheroprotection by act-ing downstream of cholesterol-induced vascular inflammation. This implicates the potential of PAC1-specific agonist drugs against atherosclerosis even beyond statins and PCSK-9.

This paper uses a Vector Autoregression (VAR) model and linear regression to analyze the effects of aggressive monetary policies (such as RRR cuts and interest rate reductions) and fiscal measures (like government bond issuance) on household wealth in China, with a focus on housing assets. A comparative analysis with Japan is conducted to explore the transmission mechanisms and the policies’ impacts on housing prices, wealth distribution, and economic growth. The findings highlight the significant role of monetary and fiscal interventions in shaping the housing market dynamics across different economic contexts.

Objectives: Marburg virus disease (MVD), caused by the Marburg virus, is a severe zoonotic viral hemorrhagic fever with high mortality that threats the Global Health Security. Marburg virus is on the WHO list for the next pandemic-prone pathogens it always emerges in outbreaks. Considering it is current involvement in outbreak in Rwanda, there is an urgent need for up to date information to inform policymaking, resources mobilization, strategic planning and guide the implementation of cost-effective response strategies. Methods: Through technical and scientific consultancies with experts and reviewing publicly existed knowledge, we collected and synthesized available information about the disease and summarized it into a brief evidence to inform policymakers, public health leaders, and frontline responders in developing and implementing cost-effective prevention and control measures. Results: We have identified the historical outbreaks and geographical distribution of MVD, main clinical signs and diagnostic tools, primary reservoir, transmission dynamics and case management protocol. More importantly, we summarized the best practices for multisectoral One Health strategy for the prevention and control of MVD outbreaks including strict implementation of WASH and infection prevention measures, isolation of infected humans and animals, contact tracking for confirmed cases, and International Health Regulations (IHRs 2005). High risk populations such as frontline responders including healthcare providers and community health worker should be prioritized for the experimental vaccination. Conclusions: In lack of licensed treatment or vaccine, cost-effective preparedness and response strategy to MVD should focus on preventive measures including community engagement, reduced contact between humans and reservoirs, supportive care and isolation of patients, and proper waste management.

The study explores the link between corporate social responsibility (CSR) and the financial performance of listed firms in the Philippines. This research used a longitudinal approach to investigate data from the Philippine Stock Exchange Index (PSEi) from 2019 to 2022. The environmental, social, and governance (ESG) framework assessed CSR performance, while financial performance was measured using return on equity and stock return. Firm profiles such as industry type, firm size, firm age, and auditor type were used as control variables. The researchers used firms' sustainability, annual, and governance reports as the primary data sources. The regression analysis results show insufficient data to support the idea that CSR performance affects the firm’s financial performance. It shows that only governance performance is positively correlated and significant with return on equity. Other components and overall CSR performance were found insignificant with return on equity and stock return. This study provides preliminary information on the link of CSR to the financial performance of listed firms in the Philippines. It extends the current literature on CSR performance and its link to financial performance in an emerging economy setting.

Phosphorus (P) is an essential element in food production, but it is often largely unavailable for plants as it persists in soils in immobilized forms. Farmers have been using P fertilizers extensively to overcome this unavailability, leading to the exhaustion of non-renewable deposits of phosphorite, rising fertilizers prices and causing several environmental impacts such as eutrophication. Its large-scale utilization is also inefficient since most of the added P becomes quickly unavailable for the plants. Therefore, farming solutions that improve P uptake, P use efficiency of plants and P mobilization in soils are highly important. In this narrative review, we summarized and explored the link between the Silicon (Si) and P cycles in soils. Silicon is quasi-essential for plants, and it has been established that its presence in soil and uptake by plants has several benefits, especially in toxic and nutrient-deficient conditions. Here, we established that Si in soils can affect crop production in P-deficient conditions through: 1) the pH effect – Si improves organic matter decomposition and decreases Al3+ availability; the Si uptake effect – the deposited Si in the plant improves its photosynthetic performance, improves the root ability to uptake P, improves organic matter decomposition and increases P/Mn ration in plant, improving P use; and 3) the Si soil effect – Si stimulates phosphorite rocks weathering and competes with P for the binding places at the surface of Ak and Fe hydroxides, releasing P into soil solution. This positive effect of Si on P mobilization in soils and consequent use by crops should be further disseminated to farmers and other relevant stakeholders.

Agricultural intensification through simplification and specialisation has homogenised diverse landscapes, reducing their heterogeneity and complexity. While the negative impact of large, simplified fields on biodiversity is well-documented, the role of landscape structure in mitigating and stabilising climate is becoming increasingly important. Despite considerable knowledge of landscape cover types, the understanding of how landscape structure influences climatic characteristics remains limited. To explore this further, we studied an area along the Czech-Austrian border, where socio-political factors have created stark contrasts in landscape structure, despite similar topography. Using Land Parcel Information System (LPIS) data, we analysed the landscape structure on both sides, and processed eight Landsat 8 and 9 OLI/TIRS scenes from the 2022 vegetation season to calculate vegetation indices (NDVI, NDMI) and microclimatic features (surface temperature, albedo, and energy fluxes). Our findings reveal significant differences between the two regions. Czech fields, with their larger, simpler structure and lower edge density, experience more extreme temperatures and fluctuating energy fluxes, while Austrian fields exhibit greater stability. These patterns are consistent across landscape classes, with Austria’s finer landscape structure providing higher stability throughout the vegetation season. In light of climate change and biodiversity conservation, these results emphasise the need to protect and restore landscape complexity to enhance resilience and environmental stability.

The central of this article is to present a hypothesis that can solve the long-standing question of how ball lightning arises.

Quenchbody (Q-body), a new type of fluorescent immunosensor, is an antibody fragment labeled with a fluorescent dye. When Q-body binds to its antigen, the fluorescence intensity increases. Highly sensitive detection of antigens by changes in fluorescence intensity is performed in a single step by mixing sample and reagent. In this study, to reveal the structural basis for Q-body, we solved the crystal structures of antigen-binding fragment (Fab) of an anti-osteocalcin antibody KTM219, which is applicable to Q-body, and its complex with the antigen osteocalcin C-terminal peptide (BGP-C7). Also, we solved the structure of a KTM219 Fab crystal grown in the presence of a fluorescent dye 5(6)-carboxytetramethylrhodamine (TAMRA), however, a tightly bound TAMRA was not found in the electron density map. We predicted the binding site of TAMRA by docking simulations. These results support the structural basis for the Q-body mechanism as follows. In the absence of the antigen, the fluorophore located near tryptophan residues is quenched in the hydrophobic pocket of the antigen binding site between VH and VL. In association with the competitive binding of the antigen, the fluorophore is released from the antigen binding pocket and emits fluorescence. The crystal structures of KTM219 Fab and the structural basis of Q-body would be useful for further development and improvement of Q-body fluorescent immunosensors.

Ramsey theory enables re-shaping of the basic ideas of the quantum mechanics. Quantum observables, represented by linear Hermitian operators are seen as the vertices of the graph. Relation of commutation define coloring of the edges linking the vertices: if the operators commute, they are connected with the red link; if they do not commute they are connected with the green link. Thus, a bi-colored, complete, Ramsey graph emerges. According to the Ramsey theorem, complete, bi-colored graph built of six vertices, will inevitably contain at least one monochromatic triangle; in other words, the Ramsey number R(3,3)=6. In our interpretation, this triangle represents the triad of observables, which could or, alternatively, could not be established simultaneously in a given quantum system. The Ramsey approach to the quantum mechanics is illustrated with the numerous examples, including the motion of a particle in a centrally symmetrical field.

Nowadays bioeconomy and sustainability trend drive food technology in the development of novel biobased edible food preservatives to enhance food shelf-life and safety. This study explored the development, characterization, and application of novel polysaccharide-based nanogels enhanced with essential oil derivatives carvacrol and citral, investigating their potential synergistic effects as active edible coatings for extending the shelf life of Chalkidiki PDO green table olives. Nanogels were formulated using xanthan gum and kappa-carrageenan and tested in various ratios (25:75, 50:50, 75:25). Physicochemical characterization of nanogels was done via zeta potential dynamic light scattering measurements and scanning electron microscopy images, while preliminary tests demonstrated high antioxidant activity. Antimicrobial assessments revealed significant bactericidal effects, with FIC results confirming a synergistic effect of NGCTCV 50:50 against Staphylococcus aureus and NGCTCV 25:75 and 75:25 against. The nanogel coatings were applied to Chalkidiki green table olives and evaluated over a 21-day storage period. The NGCTCV 50:50 and 25:75 coatings effectively reduced weight loss, maintained stable pH levels, and preserved visual quality, while inhibiting spoilage microorganisms without affecting beneficial lactic acid bacteria crucial for fermentation. Lab colorimetry confirmed the ability of these nanogels to prevent discoloration, maintaining the olives' characteristic green color. Sensory analysis indicated that NGCTCV 50:50 and 25:75 outperformed both individual nanogels and uncoated samples, effectively extending shelf life by over 14 days. Finally, this study demonstrates the potential of polysaccharide-based nanogels, particularly in the 50:50 and 25:75 ratios, for improving the shelf life of perishable food products, with promising applications in fermented food preservation.

This study compares the photogrammetric performance of three multi-camera systems—two spherical cameras (INSTA 360 Pro2 and MG1) and one multi-camera rig (Ant3D)—to evaluate their accuracy and precision in confined environments. These systems are particularly suited for indoor surveys, such as narrow spaces, where traditional methods face limitations. The instruments were tested for the survey of a narrow spiral staircase within Milan Cathedral and the results were analyzed based on different processing strategies, including different relative constraints between sensors, various calibration sets for distortion parameters, interior orientation (IO), and relative orientation (RO), as well as two different ground control solutions. The study also included a repeatability test. The findings showed that, with appropriate ground control, all systems achieved the target accuracy of 1 cm. In partially unconstrained scenarios, instead, the drift errors ranged between 5 and 10 cm. Performance varied depending on the processing pipelines, but the results suggest that imposing a multi-camera constraint between sensors and estimating both IO and RO parameters during the Bundle Block Adjustment yields the best outcomes. In less stable environments, it might be preferable to pre-calibrate and fix the IO parameters.

In principle, weak sustainability, WS, requires that inclusive wealth, IW, be non-decreasing. WS provides a more complete account of the sustainability of a geographical entity (e.g., the world, a nation, or a sub-national region) than sustainability indicators, SIs, on one hand, and conventional economic accounts (e.g., gross domestic product, GDP) on the other. We briefly summarize WS theory, noting that it was developed, implicitly, for a geographical space without internal boundaries. Empirical WS assessment was developed by international bodies (the World Bank and the UN Environmental Program) to shine light upon national governments that might be maintaining the current welfare of their citizens, but investing insufficiently in national assets to maintain intertemporal wealth. In so doing, the need arose to address a suite of issues stemming from national boundaries that may limit the mobility of people, resources, goods and services. WS assessment at sub-national levels (states and counties, in the case of the US) has similar motivations – to provide more complete accountability for regional officials who may be maintaining welfare by consuming assets – but the implications of cross-boundary flows are much greater given the porosity of regional boundaries. WS scholars and practitioners have arrived at a consensus that the appropriate criterion for WS status is IW/capita, i.e. the welfare of people should be sustained. Regional economists and economic geographers tend to associate regional success with population growth, which may increase total IW at some cost to individual welfare. We consider this issue in some depth – what is at issue, and how any conflict might be resolved – ultimately concluding that IW/capita is the appropriate criterion for WS assessment, while leaving broader questions of population ethics unresolved. We summarize recent research [1] that starts with the Arrow et al framework [2] and improves methods of assessing IW, especially its health capital component, and assesses IW/capita for all states and counties in the US. These improved methods reveal substantially more not-WS states and counties than the Arrow et al framework [2]. The not-WS counties exhibit a distinct rural bias, consistent with the hypotheses and empirical findings of regional scientists. Our work demonstrates that regional WS assessment is feasible, produces results that are consistent with prior expectations based on reasoning and empirical research, and has the potential to provide fresh insights into longstanding questions of regional development.

Chronic neck and back pain is prevalent among dental professionals, stemming from the static and often awkward positions required during clinical practice. This longitudinal study investigates the effectiveness of Refractive loupes, an ergonomic intervention, in mitigating such musculoskeletal issues among undergraduate dental students. Despite being advocated for posture improvement, traditional loupes may exacerbate neck pain due to prolonged static neck positions. However, the impact of ergonomic loupes, designed to maintain neutral neck positions, remains unexplored.This study enrolled undergraduate dental students from the UK and Australia, provided them with Refractive loupes, and tracked their neck and back pain scores over two years. Participants completed pre- and post-intervention questionnaires assessing pain levels, posture, and loupe use history. Results indicate a significant reduction in pain incidence (15.5%) post-refractive use, with 30.6% of participants reporting pain at the study's end compared to 46.1% at the beginning of the study. Notably, 92.3% reported improved posture ratings despite 39.1% experiencing increased pain, suggesting additional factors contributing to pain development beyond posture alone.Further analysis reveals that later adoption of Refractive loupes correlates with increased pain, suggesting a potential preventive benefit if initiated earlier in dental education. Additionally, a comparison of traditional loupe users with their non-loupe-using counterparts indicates more significant pain reduction among the loupe-using cohort post-refractive use, highlighting the need for more extensive studies in this area.In conclusion, Refractive loupes effectively reduce musculoskeletal pain among undergraduate dental students. Nevertheless, challenges persist, warranting continued research into optimal intervention timing and the role of the loupe type used in pain mitigation.

This research introduces a novel approach to improving wind energy's LCOE (Levelised Cost of Energy). Specifically, this research aims to reduce the LCOE from wind turbines by investigating a novel Active Axis Wind Turbine (AAWT) design. The turbine is neither a horizontal nor vertical axis wind turbine but has an axis of operation that can actively change during operation. The design features a rotor with a single blade capable of dynamic pitch and tilt control during a single rotor rotation. This study examines the potential to balance the centrifugal and aerodynamic lift forces acting on the rotor blade assembly, significantly reducing blade, tower, foundation and infrastructure costs in larger-scale devices and decreasing the LCOE for wind. The design of a laboratory prototype rotor assembly is optimised by varying the masses and lengths in a lumped mass model to achieve equilibrium between centrifugal and lift forces acting on the turbine's rotor assembly. The method involves an investigation of the variation of blade pitch angle to provide a balance between centrifugal and aerodynamic forces, thereby facilitating the cost advantages and opening the opportunity to improve the turbine efficiency across a range of operation conditions. The implication of this study extends to different applications of wind turbines, both onshore and offshore, introducing insight into innovation for sustainable energy and cost-effective solutions.

Computer vision-based gait recognition (CVGR) is a biometric technology that has gained considerable attention in recent years due to its non-invasive, unobtrusive, and difficult-to-conceal nature. Current CVGR systems often transmit collected data to a cloud server for machine-learning-based gait pattern recognition. While effective, this cloud-centric approach can lead to increased system response times. Alternatively, the emerging paradigm of edge computing, which involves moving computational processes to local devices, offers the potential to reduce latency, enable real-time surveillance, and eliminate reliance on internet connectivity. Furthermore, recent advancements in low-cost, compact microcomputers capable of handling complex inference tasks (e.g., Jetson Nano, Xavier NX, AGX Xavier, Raspberry Pi, and Khadas) have created exciting opportunities for deploying CVGR systems at the edge. This paper reports the state of the art in gait data acquisition modalities, feature representations, models, and architectures for CVGR systems amenable for edge computing. Moreover, this paper addresses the general limitations and highlights new avenues for future research in the promising intersection of CVGR and edge computing.

This study presents a bibliometric analysis of thermogravimetric pyrolysis of carnauba biomass (Copernicia prunifera), a palm tree native to northeastern Brazil, belonging to the Arecaceae family. The objective was to analyze the scientific production and methods used to evaluate the kinetic parameters of biomass pyrolysis. A bibliographic survey was conducted using the Scopus, ScienceDirect, and Web of Science databases. The results were analyzed using VOSviewer and Bibliometrix software, which facilitated the generation of clusters and tables of scientific production. The analyses covered a range of variables, including authors, co-authors, countries of affiliation, academic institutions, journals, and keywords. The search yielded 1,983 articles, and after the application of exclusion criteria, 919 articles were retained, forming the basis for the bibliometric analysis. The data provided a more detailed and accurate overview of thermogravimetric pyrolysis of carnauba research and identified areas for further study. Furthermore, it was possible to ascertain which universities and researchers have devoted the most effort to this line of research, the principal findings, and areas that require further investment to complement existing research. Additionally, the study indicated the suitability of the Friedman kinetic method for determining kinetic parameters in biomass pyrolysis.

Lung cancer treatment has long been a major field of study in research due to the com-plexity and variability of cancer. Because drug resistance is a major hurdle for lung cancer treat-ment, in this article, we will review the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) used for the treatment of Non Small Cell Lung Cancer (NSCLC) and the EGFR mutations that cause resistance to them. Then, we will discuss the applications of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) genome ed-iting in medical treatment. The proposed treatment is specifically for NSCLC patients who have acquired resistance to EGFR TKIs due to mutations to EGFR such as T790M and C797S and would make these TKIs become effective once again. Currently, there is no treatment targeting C797S on the market, but fourth-generation EGFR-TKIs are currently in trial [1,2]. (Figure 1) This proposal will review the potential steps and options available as well as some challenges that may complicate the process.

Objectives: The purpose of this clinical study is to compare full-arch intraoral scans taken immediately after implant placement with those obtained after tissue healing in patients rehabilitated with implant-supported fixed prosthesis. Methods: Between September 2023 and March 2024, a total of 19 patients with compromised residual dentition (6 women, 13 men) were rehabilitated using 4 to 6 immediately loaded post-extraction implants. These implants supported fixed full-arch screw-retained prostheses in the lower jaw (9 patients) or upper jaw (10 patients). Intraoral scans were taken immediately after implant placement (termed ‘immediate scan’). After a healing period of four months, the provisional prosthesis was removed and a second intraoral scan was performed using the same scan bodies and scan pattern as the initial scan (termed ‘delayed scan’). The two scans were overlaid and discrepancies between them were measured. Results: The average discrepancy between the immediate and delayed scans was 0.1905 mm. Statistical analysis revealed larger discrepancies for implants placed in the posterior areas, with the implant in site 1.6 ( implant 1 ) showing a discrepancy of 0.2326 mm and the implant in site 2.6 (implant 4) showing 0.2124 mm (P = 0.05). No statistically significant difference was observed when comparing patients treated in the upper and lower jaws. Conclusions: Within the limitations of this study, overlapping digital scans of post-surgical and healed tissues revealed discrepancies that could be attributed to the more difficult conditions present in the post-surgical scenario or operator factors. Further studies are needed to assess the accuracy of post-surgical scans from a clinical point of view.

The modern economic landscape, now more competitive than ever, compels companies to create increasingly innovative, cutting-edge, and cost-effective products. In this regard, design and development phases play a crucial role, since they closely determine the final satisfaction of the customer. As a consequence, the need for a structured approach is evident, since it allows the companies to identify product key characteristics. With the purpose of creating a new product with an extended horizon to various markets, this work is based on the use of Design for Six Sigma (DFSS) methodology for the identification and optimization of Critical-To-Quality (CTQ) features, aiming at making the project as responsive as possible to customer needs. Two main themes are addressed. The first one is the analysis of the integrated product development process with the Six Sigma methodology for achieving design excellence; the second one is the application of the Identify phase of the IDOV (Identify, Design, Optimise, Validate) approach through a DFSS case study.

Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves extracts contain high amounts of flavonoids and terpenoids, endowed with potential antioxidant, anti-inflammatory, anticancer, antidiabetic and antimicrobial effects. Re-cently, many in vitro and in vivo studies have assessed different potential health benefits of per-simmon leaves; however, its anticancer activity towards colorectal cancer (CRC), the second deadliest cancer in Western countries, has not been investigated in depth. Since CRC current therapies are associated with serious side effects and show no efficacy towards patients carrying RAS/BRAF mutations, the search for new and more effective therapies has turned to plant extracts, which could help reduce conventional drugs dosages and toxicity. The effect of Diospyros kaki al-coholic extract has been investigated on E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS activating mutation. This extract is effective in reducing tumor cells viability, without affecting the healthy mucosa cell line CCD 841, and it triggers apoptosis in CRC cells, by disrupting mitochondrial functionality and increasing oxidative stress.

Molecular inhibitors added to the corrosive medium attacking metallic materials are a well-established way of combating corrosion. The inhibitive action proceeds via adsorption of the inhibitor on the surface to be protected. Aromatic building blocks in the inhibitor play a major role in their protective action, further details like substituents, heteroatoms and molecular geometry contribute. An overview is provided focused on aromatic inhibitors aiming at the identification of particularly promising inhibitors and their mode of action. Directions of further research and development are pointed out in conclusion.

Einstein equation approximated to second order in Newton constant G is quantized and applied to a large region of the universe. The two-point correlations of the vacuum energy density and pressure are included and the resulting metric agrees with the one derived from the $\Lambda CDM$ cosmological model plus an additional contribution of the quantum vacuum. The conclusion is that at least a part of the acceleration in the expansion of the universe is due to the vacuum fluctuations.

This study evaluated the neuroprotective potential of peptain-1 conjugated to a cell-penetrating peptide (CPP-P1) in an ocular hypertension model of glaucoma. Brown Norway (BN) rats were subjected to intraocular pressure (IOP) elevation via intracameral injection of silicone oil (SO), with concurrent intravitreal injections of either CPP-P1 or a vehicle. Retinal cross-sections were analyzed for markers of neuroprotection, including cAMP Response Element-Binding Protein (CREB), phosphorylated CREB (p-CREB), growth-associated protein-43 (GAP43), synapsin-1 (SYN1), and superoxide dismutase 2 (SOD2). Hematoxylin and eosin staining was used to assess retinal layer thickness. SO-treated rats exhibited significant reductions in the thickness of the inner nuclear layer (INL, 41%, p=0.016), inner plexiform layer (IPL, 52%, p=0.0002), and ganglion cell layer (GCL, 57%, p=0.001). CPP-P1 treatment mitigated these reductions, preserving INL thickness by 32% (p=0.059), IPL by 19% (p=0.119), and GCL by 31% (p=0.057). Increased levels of CREB and p-CREB were observed in IOP-elevated, CPP-P1-treated retinas compared to IOP-elevated vehicle-treated retinas. Although overall GAP43 levels were low, there was a modest increase in expression within the IPL and GCL in SO- and CPP-P1-treated retinas (p=0.15 and p=0.09, respectively) compared to SO- and vehicle-treated retinas. SO injection reduced SYN1 expression in both IPL and GCL (p=0.01), whereas CPP-P1 treatment significantly increased SYN1 levels in the IPL (p=0.03) and GCL (p=0.002). While SOD2 expression in the GCL was minimal across all groups, a trend toward increased expression was observed in CPP-P1-treated animals (p=0.16). The SO model was replicated with SO removal after 7 days and monitored for 21 days followed by retinal flat-mount preparation to assess retinal ganglion cell (RGC) survival. A 42% loss in RGCs (p=0.009) was observed in SO-injected eyes, which was reduced by approximately 37% (p=0.03) with CPP-P1 treatment. These findings suggest that CPP-P1 is a promising neuroprotective agent that promotes retinal ganglion cell survival and the preservation of other retinal neurons, potentially through enhanced CREB signaling in a rat model of SO-induced ocular hypertension.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in premenopausal women. Although the etiology of PCOS remains uncertain, the role of single nucleotide polymor-phisms (SNPs) in its pathogenesis has been extensively described. The second large genome-wide association study (GWAS) conducted in a Chinese population identified that variants in the INSR (rs2059807), TOX3 (rs4784165), YAP1 (rs1894116), HMGA2 (rs2272046), and ERBB3 (rs2292239) genes are associated with PCOS. In this exploratory study, we evaluated the genetic contribution of five polymorphisms in these genes in a sample of Colombian women. Forty-nine control women and forty-nine women with PCOS were included. Genotypic and allelic frequencies were calcu-lated under different inheritance models, and genotype/phenotype analysis was performed. We found that rs4784165-TOX3 was negatively associated with PCOS risk. Additionally, the GG+AA genotypes at rs2059807-INSR were linked to higher fasting blood glucose levels, while the GA genotype was associated with a greater number of total antral follicles. The AC genotype at rs2272046-HMGA2 was associated with older age and larger total ovarian volume. This is the first pilot study in Colombia to explore the relationship between these gene polymorphisms and PCOS, providing the first insights for the country.

The revolution of physiotherapy is achieved by the application of artificial intelligence (AI) in medical rehabilitation programs. While the integration of virtual reality (VR) and robotics has already marked significant strides in the industry, AI is taking patient rehabilitation to new heights. The integration of AI, VR and robotics in physiotherapy linked to a significant leap forward in patient rehabilitation. These technologies not only increase the effectiveness of the treatment, but also make it more accessible and attractive. In this article, we propose to study the use of AI in the management of medical rehabilitation programs, and we present a comprehensive survey of the latest empirical studies, highlighting AI-based technologies that facilitate the rehabilitation process, trying to demonstrate that the integration of AI in medical rehabilitation programs offers a transformative approach to patient care.

The pervasive use of screens, averaging nearly 7 hours per day globally across mobile phones, computers, notebooks and TVs, has sparked a growing desire to minimize reflections from ambient lighting and enhance readability in harsh lighting conditions, without the need to increase screen brightness. This demand highlights a significant need for advanced anti-glare (AG) technologies, to increase comfort and eventually reduce energy consumption of the devices. Currently used production technologies are limited in their texture designs, which can lead to suboptimal performance of the anti-glare texture. To overcome this design limitation and improve performance of the anti-glare feature, this work reports a new, cost-effective high-volume production method that enables the much needed design freedom on a large area. This is achieved by combining mastering via large-area Laser Beam Lithography (LBL) and replication by Nanoimprint Lithography (NIL) processes. The environmental impact of the production method, such as material consumption, are considered and the full cycle from design to final imprint is discussed.

Wastewater-based epidemiology (WBE) is a promising approach that has been used to monitoring the exposure to pathogens and understanding the status of disease outbreaks in defined population groups. Viral RNAs of SARS-Cov-2 and influenza A and B were detected and quantified by two commercial kits in three wastewater treatment plants (WWTP) selected in different regions of Canton Ticino (Switzerland). We have monitored the presence of SARS-CoV-2 during two big waves of pandemic, from March 2021 until June 2023, when number of confirmed cases and tests decreased. The presence of influenza A and B viruses was investigated from October 2022 to June 2023. We confirmed the presence of SARS-CoV-2 and influenza A and B in all the WWTP monitored; RNA concentration in wastewater could be correlated with clinical cases confirming that WBE is a powerful tool to monitor diseases dissemination supporting the management of an epidemic.

Tick-borne encephalitis virus is a pathogen endemic to northern Europe and Asia, transmitted through bites from infected ticks. It is a member of the Flaviviridae family, possesses a positive-sense, single-stranded RNA genome encoding a polypeptide that is processed into seven non-structural and three structural proteins, including the envelope (E) protein. The glycosylation of the E protein, a single N-linked glycan at position N154, plays a critical role in viral infectivity and pathogenesis. Here, we dissected the entire glycosylation profile of the E protein using liquid chromatography tandem mass spectrometry and identified three novel O-linked glycans which were found at relatively low frequency. One of the O-linked glycans was positioned close to the highly conserved N-linked glycan site and structural analysis indicated that it may be of relevance for viral maturation. The N154 site was found to be glycosylated with a high frequency, containing oligomannose or complex-type structures, some of which are fucosylated. An unusually high portion of oligomannose N-linked glycan structures exhibited compositions that are normally observed on proteins while they are translocated from the endoplasmic reticulum to the trans golgi network, suggesting disruption of the glycan processing pathway in the infected cells from which the E protein was obtained.

The novel phosphor Eu3+ doped Na5Zn2Gd(MoO4)6 triple molybdate were prepared by the sol-gel method. The structure, morphology, and luminescent properties have been characterized by X-ray diffraction, thermogravimetry-differential thermal analysis, scanning electron microscopy, FTIR spectroscopy and Luminescence spectroscopy. The results indicated that the synthesized Na5Zn2Gd1-x(MoO4)6: xEu3+phosphor consisted of a pure phase with monoclinic structure. Under excitation at 465 nm, the Na5Zn2Gd1-x(MoO4)6: xEu3+ phosphor exhibits intensive red emission band around 610 nm corresponding to the transition of 5D0→7F2 is much higher than that 5D0→7F1 at 594 nm, which was appropriate for blue LED. According to the influence of the synthesis conditions, the phosphors show the highest emission intensity as the doping concentration of Eu3+ was 25 mol.% and the molar ratio of citric acid to metal ions was 2:1. Na5Zn2Gd0.75(MoO4)6: 0.25 Eu3+ with the color coordinates (x= 0.658, y= 0.341) is a stable red phosphor for blue-based white LEDs due to it is closer to the NTSC standard values (0.670, 0.330) comparing with the color coordinates (0.48, 0.50) of the commercial Y2O2S: Eu3+ red phosphor.

Objective: To analyze the relationship and predictive value of Netrin-1 expression and ultrasonic blood flow parameters with the severity of cervical intraepithelial neoplasia (CIN). Methods: The receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of Netrin-1 expression and ultrasonic blood flow parameters for the severity of cervical intraepithelial neoplasia. Results: FI, VI, and VFI levels increased sequentially, and the differences in levels between grade II, III patients, and the control group were statistically significant (P < 0.05). Netrin-1 was negatively correlated with ultrasonic blood flow parameters FI, VI, and VFI (r = -0.287, -0.309, -0.298, P < 0.05). The results of multifactorial logistic regression analysis showed that Netrin-1 positivity was a protective factor for CIN III lesions, while FI, VI, and VFI were risk factors for CIN III lesions. The AUC area of Netrin-1 was 0.712, with a sensitivity and specificity of 76.4% and 79.5%, respectively, which were higher than those of other indicators (P < 0.05). Conclusion: Netrin-1 is under-expressed in CIN patients, while ultrasonic blood flow parameters FI, VI, and VFI are over-expressed, and both are closely related to the severity of the patient's lesions. Netrin-1 is negatively correlated with ultrasonic blood flow parameters FI, VI, and VFI. Netrin-1 positivity is a protective factor for CIN III lesions, while FI, VI, and VFI are risk factors for CIN III lesions. The expression levels of both have a certain predictive guiding role in the early screening, diagnosis, and prevention of cervical cancer.

In this paper, we present a comparative analysis of seventeen different approaches to optimizing Euclidean distance computations, a core mathematical operation that plays a critical role in a wide range of algorithms, particularly in machine learning and data analysis. The Euclidean distance, being a computational bottleneck in large-scale optimization problems, requires efficient computation techniques to improve the performance of various distance-dependent algorithms. To address this, several optimization strategies can be employed to accelerate distance computations. From spatial data structures and approximate nearest neighbor algorithms to dimensionality reduction, vectorization, and parallel computing, various approaches exist to accelerate Euclidean distance computation in different contexts. Such approaches are particularly important for speeding up key machine learning algorithms like K-means and K-nearest neighbors (KNN). By understanding the trade-offs and assessing the effectiveness, complexity, and scalability of various optimization techniques, our findings help practitioners choose the most appropriate methods for improving Euclidean distance computations in specific contexts. These optimizations enable scalable and efficient processing for modern data-driven tasks, directly leading to reduced energy consumption and a minimized environmental impact.

Microfluidic systems offer controlled microenvironments for cell-to-cell and cell-to-stromainteractions, which have precise physiological, biochemical, and mechanical features. The opti-mization of their conditions to best resemble tumor microenvironments constitutes an experimentalmodeling challenge, particularly regarding carcinogenesis in the central nervous system (CNS), giventhe specific features of the blood–brain barrier (BBB). Gel-free 3D microfluidic cell culture systems(gel-free 3D-mFCCSs), including features such as self-production of extracellular matrices, providesignificant benefits, including promoting cell–cell communication, interaction, and cell polarity. Theproposed microfluidic system consisted of a gel-free culture device inoculated with human brainmicrovascular endothelial cells (HBEC5i), glioblastoma multiforme cells (U87MG), and astrocytes(ScienCell 1800). The gel-free 3D-mFCCS showed a diffusion coefficient of 4.06 × 10−9 m2·s−1, and itreconstructed several features and functional properties that occur at the BBB, such as the vasculo-genic ability of HBEC5i and the high duplication rate of U87MG. The optimized conditions of thegel-free 3D-mFCCS allowed for the determination of cellular proliferation, invasion, and migration,with evidence of both physical and biochemical cellular interactions, as well as the production ofpro-inflammatory cytokines. In conclusion, the proposed gel-free 3D-mFCCSs represent a versatileand suitable alternative to microfluidic systems, replicating several features that occur within tumormicroenvironments in the CNS. This research contributes to the characterization of microfluidicapproaches and could lead to a better understanding of tumor biology and the eventual developmentof personalized therapies. (PDF) A Versatile Microfluidic Device System that Lacks a Synthetic Extracellular Matrix Recapitulates the Blood-Brain Barrier and Dynamic Tumor Cell Interaction. Available from: https://www.researchgate.net/publication/384802118_A_Versatile_Microfluidic_Device_System_that_Lacks_a_Synthetic_Extracellular_Matrix_Recapitulates_the_Blood-Brain_Barrier_and_Dynamic_Tumor_Cell_Interaction#fullTextFileContent [accessed Oct 10 2024].

Severe seasonal droughts driven by global climate change significantly alter the cycling of carbon and nutrients in forest ecosystems through disturbing plant physiology and phenology, soil physicochemical properties, and soil microbial activity. While, the investigation into the impacts of floor mass and plant roots on soil microbial biomass within the context of recurrent seasonal droughts is still rare. To investigate the environmental determinants governing soil microbial biomass with the escalating severity of seasonal droughts, we conducted a study on soil microbial biomass in a comprehensive block experiment, which was manipulated to explore the interplay between floor mass and plant roots contributions, crossed with a factorial irrigation treatment, in a montane subtropical moist evergreen broad–leaved forest of southwestern China. Within control and watered plots, we respectively established four experimental subplots with plant roots and floor mass included (R+F+), plant roots included but floor mass excluded (R+F−), plant roots excluded but floor mass included (R−F+), and plant roots and floor mass excluded (R−F−) from June 2019 to May 2023. The study results revealed that soil microbial biomass as well as soil moisture, floor mass, and plant roots showed an apparent single–hump modal within one year. In the comparative analysis of soil microbial biomass fluctuation amplitudes across control and watered plots, a discernible disparity was observed, indicating that significant differences in microbial biomass dynamics between the respective experimental conditions. The pooled data revealed a statistically significant influence of seasonal drought, floor mass, plant roots, and their reciprocal interactions on the soil microbial biomass, highlighting these factors as pivotal determinants of microbial community dynamics. This study elucidates the interactive regulatory mechanisms by which seasonal drought, floor mass, and plant roots collectively modulate soil microbial biomass within tropical and subtropical forests, offering insights into the complex ecological processes governing microbial community dynamics. This interactive regulation might influence the trajectory of plant species and soil microbial communities, facilitating their adaptive development and evolutionary responses.

Regulation (EU) 2016/429 establishes new extensive guidelines for managing transmissible animal diseases, including zoonoses. The Commission Implementing Regulation 2018/1882 classifies diseases into five categories based on their prevalence and the required response, ranging from eradication to surveillance. Key aspects of the regulations concern emphasis on animal traceability, biosecurity, wildlife pathogen control, sustainable farming, and the reduction of the impact of diseases on both public and animal health, as well as on the environment. These align with the European Green Deal, the Farm to Fork Strategy and the One Health approach. In Italian inner areas—similarly to other European regions that are fragile, remote from major service centers, and often neglected—agropastoral and agri-food activities are beneficial for tourism, commercialization of typical foods, and recreational activities. In these areas including the Molise Region, the activation of optional programmes within the framework of the aforementioned regulations could help control infectious animal diseases that are not subject to mandatory eradication but cause income loss and trade restrictions, such as infectious bovine rhinotracheitis and paratuberculosis, a suspected zoonosis potentially linked to Crohn's disease in humans. These programmes could boost the economic income of local extensive breeding, counteract depopulation, and protect human and animal health.

Dielectrophoresis (DEP) cell-separation technology is an effective means of separating rare cells. To develop highly efficient cell-separation devices, detailed analysis of the nonuniform electric field’s intensity distribution within the device is needed, as it affects separation performance. Here we analytically expressed the distributions of the electric field and DEP force in a parallel-plate cell-separation DEP device by employing electrostatic analysis through the Fourier series method. The solution was approximated by extrapolating a novel approximate equation as a boundary condition for the potential between adjacent fingers of interdigitated electrodes and changed the underlying differential equation into a solvable form. The distributions of the potential and electric fields obtained by the analytical solution were compared with those from numerical simulations using finite element method software to verify their accuracy. The results showed excellent agreement. Three-dimensional fluorescence imaging analysis used live non-tumorigenic human mammary (MCF10A) cells. The distribution of cell clusters adsorbed on the interdigitated electrodes was compared with the analytically obtained distribution of the DEP force, and the mechanism underlying cell adsorption on the electrode surface was discussed. Furthermore, parametric analysis using the width and spacing of these electrodes as variables revealed that spacing is crucial for determining DEP force. The results showed that, by optimizing cell-separation devices using interdigitated electrodes, adjusting electrode spacing significantly enhances device performance.

Oxidative stress (OS) plays a crucial role in placental pathogenesis and pregnancy-related complications. This review explores OS's impact on placental development and function, focusing on novel biomarkers for early detection of at-risk pregnancies and emerging therapeutic strategies. We analyzed recent research on OS in placental pathophysiology, examining its sources, mechanisms, and effects. While trophoblast invasion under low-oxygen conditions and hypoxia-induced OS regulate physiological placental development, excessive OS can lead to complications like miscarriage, preeclampsia, and intrauterine growth restriction. Promising OS biomarkers, including malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, show potential for early detection of pregnancy complications. Therapeutic strategies targeting OS, such as mitochondria-targeted antioxidants, Nrf2 activators, and gasotransmitter therapies, demonstrate encouraging preclinical results. However, clinical translation remains challenging. Future research should focus on validating these biomarkers in large-scale studies and developing personalized therapies to modulate placental OS. Emerging approaches like extracellular vesicle-based therapies and nanomedicine warrant further investigation for both diagnostic and therapeutic applications in pregnancy-related complications. Integrating OS biomarkers with other molecular and cellular markers offers improved potential for early identification of at-risk pregnancies.

Nipa palm is a plant of great value to communities due to its social, environmental, and economic benefits. Effective management of the supply chain for products derived from nipa palm resources is essential to provide communities with suitable channels for selling each type of product. This study aims to map the supply chain structure of six different nipa palm products. Data were collected through semi-structured interviews with 100 households engaged in nipa palm cultivation. The analysis focused on the characteristics of the products, existing challenges, and the current supply chain dynamics. The findings revealed that among the six products, palm sugar had the highest production volume. The most significant challenges identified were related to labor shortages and limited marketing channels. To achieve sustainable supply chain management, it is crucial to maintain a balance between supply and demand. The study recommends exploring appropriate marketing channels for each product, with particular emphasis on online platforms that allow communities to sell directly to consumers.

Cahuachi (Nazca River Valley, South Peru) was the major ceremonial center of the Nasca civilization. According to previous studies, it was struck and destroyed by three El Niño-Southern Oscillation events, which would have occurred around 100 BCE, 600 CE and 1000 CE, respectively. At the end of the series of events, the ceremonial center would have been buried by a cap of conglomerates. Despite this hypothesis raised well-founded doubts regarding its geochronological and paleoenvironmental implications, it is uncritically used as a reference in geoarchaeological research. In the present study, optically stimulated luminescence (OSL) dating results of some samples taken from alluvial deposits at Cahuachi are reported, with the aim to evaluate the literature’s hypothesis. Since the obtained ages are older than the Holocene epoch, such a hypothesis must be rejected. A number of field evidences corroborate this result. Finally, the advancement in fluvial geomorphology knowledge of the Nazca River Valley is briefly discussed.

Background: wildfire modelers rely on Monte-Carlo simulations of wildland fire to produce burn-probability maps. These simulations are computationally expensive. Methods: we study the application of Importance Sampling to accelerating the estimation of burn probability maps, using L2 distance as the metric of deviation. Results: assuming a large area of interest, we prove that the optimal proposal distribution re-weights the probability of ignitions by the square root of expected burned area divided by expected computational cost, then generalize these results to assets-weighted L2 distance. We also propose a practical approach to searching for a good proposal distribution. Conclusion: these findings contribute quantitative methods for optimizing the precision/computation ratio of wildfire Monte Carlo simulations without biasing results, offer a principled conceptual framework for justifying and reasoning about other computational shortcuts, and can be readily generalized to a broader spectrum of simulation-based risk modeling.

The intricate orchestration of molecular events that constitutes life, as we know it, is oftentimes ascribed to an intelligent design motive. It is portrayed as if a paranormal watch maker has engineered the assemblage of parts and events that eventually manifests as the clockwork precision with which ontogeny and evolution operate within the boundary conditions imposed by what we know as life. The debate between those who advocate evolution versus intelligent design as the shaping force for modern life forms persists. However, that is not the motive for this essay. Though there has been several studies and scholarly articles that aspire to decipher and present the complexity of the molecular events that constitutes life in an insular fashion, there is a paucity of resources for undergraduates that summarizes the complexity cogently, as parts of a whole, for appreciating the enormity of the multidimensional nature of biological information and the inherent contradictions that are embedded therein. The fluidity inherent in the way information flows through signalling networks, the way biomolecular architectures maintain homeostasis in the ying-yang of life and the way multicellular complexity evolves through precise cell-cycle control is inherent in the evolution, maintenance and reproduction of biological systems. The matrix of events that encode information at the sequential and structural level across different macromolecules is a fascinating jungle of information. Combining these with how small-molecule metabolites interact with macromolecules in a spatially and temporally coordinated manner to evolve signal over random noise generates a staggering picture of informational organization and relays that, most often, defies human comprehension. This perspective is an attempt to array the various sources of information and put them together in context to appreciate the nuances of how information is stored and relayed within the biological systems. Further, it speculates on how these multitiered organization of biological information could be adapted to guide synthetic biology approaches and the future of information storage and organization.

Diabetic retinopathy is the most common retinal vascular disease, affecting the retina's blood vessels and causing chronic inflammation, oxidative stress, and ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, the main pathway for methylglyoxal (MGO) formation. MGO is a highly reactive dicarbonyl and the most rapid glycation compound to form endogenous advanced glycation end products (AGEs). MGO can act both intra- and extracellularly by glycating molecules and activating the RAGE pathway. This review summarizes the sources of MGO formation and its actions on various cell pathways in retinal cells such as oxidative stress, glycation, autophagy, ER stress, and mitochondrial dysfunction. Finally, the detoxification of MGO by glyoxalases is discussed.

We investigated theoretically the electron-surface optical phonon interaction across the long-range Fröhlich coupling in monolayer transition metal dichalcogenides such as WS2, WSe2, MoS2, and MoSe2 monolayers on SiC and hexagonal BN dielectric substrates. We employed the effective Hamiltonian in the 〖K_(+ ) (K〗_-) valley of the hexagonal Brillouin zone, to assess electronic energy shifts induced by the interaction between electronic states and surface polar optical phonons. Our results indicate that the interaction between electron and surface optical phonon depends upon the polar nature of the substrate. We have also calculated the polaronic oscillator strength as well as the polaronic scattering rate of the lower polaron state in monolayer WS2, WSe2, MoS2, and MoSe2 on SiC and hexagonal BN dielectric substrates. As a result, we have proved theoretically; firstly, the enhancement of polaronic scattering rate with temperature, and secondly, the notable influence of the careful selection of surrounding dielectrics on both Polaronic oscillator strength and polaronic scattering rate. Thus, the optimal dielectrics would be those exhibiting both elevated optical phonon energy and a high static dielectric constant.

Keywords: Raman scattering; Rayleigh scattering; Zero-Shot Deconvolution Networks, denoising, Fluorescence, Light sheet, Microscopy, Spheroid, Multimode, Hyperspectral, Deep Learning, super-resolution

The axon initial segment (AIS) region is crucial for action potential (AP) initiation due to its molecular organization especially voltage gated ion channels and Ankyrin-G (AnkG). AnkG act as recruiter and restrict almost all the proteins at AIS in order to maintain the AIS assembly. Voltage gated sodium channels (Nav channels) are enriched at AIS with high density and independently responsible for the AP initiation. Moreover, AIS also contains voltage gated potassium channels (Kv channels) for repolarization phase of AP, microtubules (MTs) responsible for the proper protein trafficking through molecular motors. AIS also acts as a cytoplasmic filter and diffusion barrier, responsible for the selective entry of the proteins into axon. Mutation of AIS related protein can cause various neurological dysfunction including Alzheimer’s disease. This review also reflects the role and importance of computational modelling in the understanding of action potential mechanisms mathematically.

Ultrasonic nondestructive testing is widely used not only in the laboratory, but also in industry. The tests use various types of ultrasonic waves, diverse measurement techniques and different apparatus. One of the problems encountered is the high susceptibility of the surface wave to interference. Some of the interference is random in nature and can be minimized (e.g., contamination of the surface, resting a finger on the surface under study). Some of the interference is permanent in nature, such as variable surface roughness. The aim of the conducted research was to evaluate the influence of roughness on ultrasonic wave propagation. The study used samples with surface roughness Sa from 0.28 to 219µm, and ultrasonic surface wave probes with frequencies from 1.41 to 8.02 MHz. It was observed that roughness significantly affects the attenuation of the ultrasonic wave, and the differences in signal amplification reached more than 15dB. Similarly, the effect of the ultrasonic wave's transit time through surfaces of different roughness was noted. It was found that the difference in the ultrasonic wave transition time was more than 50 µs. The results of the study can be helpful, for ultrasonic testing of materials with different surface conditions.

Globally, there is increasing prevalence of non- communicable chronic diseases (NCCD) like obesity, metabolic syndrome, type2 diabetes mellitus (T2DM), hypertension, allergic asthma and neuro-developmental/psychiatric problems making NCCD a leading cause of disability, morbidity and mortality . Some of these NCCD are presenting at a younger age especially in the socio-economically disadvantaged communities of affluent countries, and in low and middle -income countries undergoing industrialization and socioeconomic transition.to more economic prosperity. NCCD are often attributed to unhealthy personal lifestyles, but there may be more at play. Through a case report-based discussion, I will illustrate how environmental exposures during the critical window of life, including in utero and early infancy, can significantly influence health as an adult . I will discuss how establishment of a rich and diverse symbiotic gut microbiota in the first three years of life promotes health while a loss of diversity and abundance of beneficial symbiotic gut microbes can predispose to aforementioned NCCD , and the best practices to establish a symbiotic gut.

Currently available seasonal influenza vaccines confer variable protection due to antigenic changes resulting from accumulation of diverse mutations. Analysis of new seasonal influenza vaccines is challenging in part due to limitations of the traditional hemagglutination inhibition (HAI) assay with A/H3N2 strains. An improved and objective novel HAI assay was developed using recombinant virus-like particles (VLPs) and egg-derived virus as agglutinins, oseltamivir treatment of VLPs, human red blood cells, and using an automated image reader-based analysis of hemagglutination. HAI validation was demonstrated using four VLP and egg-derived strains, with 46–56 serum samples tested 12 times in duplicate per strain. The validated HAI assay was precise as indicated by the percent geometric coefficient of variation for intra-, inter-, and total-assay precision, and accurate as evidenced by % bias measurements. The assay exhibited linearity, specificity for homologous type/subtype strains, and sensitivity with a starting dilution of 1:10. Assay robustness and sample stability were demonstrated as a % difference compared to reference condition. Validated HAI results were equivalent for singleton and duplicate sample testing and correlated well with a qualified live wild-type influenza microneutralization assay. These findings demonstrate the suitability of this high-throughput novel modified validated HAI assay, for evaluating vaccine immunogenicity and efficacy.

The composition of the gut microbiota varies significantly among healthy individuals and insomniacs, hypersomniacs and healthy people. On the other hand, there is a substantial bacterial strain shared across these populations with distinct intra-population, mother-to-infant and intra-household transmission patterns. Based on these premises, we propose a hypothesis stating that person-to-person bacterial transmission can change the sleep pattern in couples. In this pilot study, 157 couples who had been married and living together for an average of 5.91 months were enrolled. A wide range of questionnaires were administered to participants to measure sleep patterns. Gut microbiota composition was analyzed at two time points: baseline and 3 months. We found that sleep disturbances in couples can be partially explained by changes in gut microbiota.

The present review is related to the novel approach for improvement of the optical properties of wide bandgap metal oxides, in particular TiO2, based on the formation of the inorganic-organic hybrids that display absorption in the visible spectral range due to the formation of interfacial charge transfer (ICT) complexes. We outlined the property requirements of TiO2-based ICT complexes for efficient photo-induced catalytic reactions, emphasizing the simplicity of the synthetic procedure, the possibility of the fine-tuning of the optical properties supported by the density functional theory (DFT) calculations, and the formation of a covalent linkage between inorganic and organic components of hybrids, i.e., the nature of the interface. In addition, this study provides a comprehensive insight into potential applications of TiO2-based ICT complexes in photo-driven catalytic reactions (water splitting and degradation of organic molecules), including the identification of reactive species that participate in photocatalytic reactions by the spin-trapping electron paramagnetic resonance (EPR) technique. Considering the practically limitless number of combinations between inorganic and organic components capable of forming oxide-based ICT complexes and with the knowledge that this research area is unexplored, we are confident it is worth studying, and we emphasized some further perspectives.

Background: Avaram Amrit, derived from a traditional medicinal plant, has shown potential in diabetes management. This study aimed to evaluate its clinical efficacy in glycemic control. Methods: A 12-week, open-label clinical trial was conducted with 9 type 2 diabetes patients. Participants received Avaram Amrit extract daily. Fasting and postprandial glucose levels were measured bi-weekly, with HbA1c assessed at baseline and week 12. Results: Fasting glucose levels decreased significantly from 252.54 ± 71.99 mg/dL at baseline to 195.50 ± 55.01 mg/dL at week 12 (p<0.001), representing a 22.6% reduction. Mean HbA1c decreased by 1.25 percentage points. Postprandial glucose levels showed consistent improvement across the study period. A strong positive correlation was observed between initial HbA1c and fasting glucose (r=0.89). Conclusion: Avaram Amrit demonstrated significant improvement in glycemic control over 12 weeks. The consistent decrease in both short-term (glucose levels) and long-term (HbA1c) measures indicates a positive response to the intervention. While promising, larger randomized controlled trials are necessary to confirm these findings and establish Avaram Amrit's role in diabetes management.

Novel double-impurity doping process for silicon (Si) surfaces was developed, utilizing nanosecond-laser melting of a top 11-nm thick gold (Au) film and a Si wafer substrate in a laser plasma-activated liquid-nitrogen (LN) environment. Scanning electron microscopy revealed the fluence- and exposure-independent surface micro-spike topography, while energy-dispersive x-ray spectroscopy identified minor Au (0.05 at. %) and major N (1-2 at. %) dopants, localized within a 0.5-m thick surface layer, and slight surface post-oxidation of the micro-relief (oxygen (O), 1.5-2.5 at. %). X-ray photoelectron spectroscopy identified bound surface (SiNx) and bulk doping chemical states of the introduced nitrogen (10 at. %), metallic (&lt;0.01 at. %) and cluster (&lt;0.1 at. %) forms of gold dopant, and evaluated their depth distributions, strongly affected by the competition between gold dopant in its marginal local concentrations and other more abundant dopants (N, O). 532-nm Raman micro-spectroscopy indicated the slight reduction of the crystalline order revealed in the second-order Si phonon band, nanoscale dimensions of the resolidified Si nano-crystallites envisioned by the main Si optical-phonon peak, negligible a-Si abundance and a low-wavenumber peak of Si3N4 structure. In contrast, Fourier-transform infrared (FT-IR) 2D-mapping exhibited the only broad structureless absorption bands in the range of 600-5500 cm-1 related to dopant absorption and light-trapping in the surface micro-relief. The room-temperature electrical characteristics of the laser-double-doped Si layer – carrier mobility of 1050 cm2/Vs and background carrier sheet concentration 21010 cm-2 (bulk concentration 1014-1015 cm-3) – are superior regarding previously reported parameters of nitrogen-implanted/annealed Si samples. This novel facile double-element laser-doping procedure paves the way toward local mask-less on-demand introduction of multiple intra-gap intermediate donor and acceptor bands in Si, providing its related multi-wavelength IR photoconductivity for optoelectronic applications.

Handmade papers, as carriers of paper-based cultural relics, have played a crucial role in the development of human culture, knowledge, and civilization. Understanding the intricate relationship between the structural properties and degradation mechanisms of handmade papers is essential for the conservation of historical documents. In this work, an artificial dry-heat accelerated ageing method was used to investigate the interplay between the mechanical properties of paper, the degree of polymerization (DP) of cellulose, chemical composition, hydrogen bond strength, crystallinity, and degree of hornification. The results show that the mechanical properties of handmade bamboo paper exhibited a first plateau region, a rapid decline region, and sometimes a second plateau region. A critical point in the mechanical properties of the paper occurs when the cellulose DP decreases to a range of 400-600, signifying a shift from the initial plateau to a sharp decline phase. The strengthening of intermolecular hydrogen bonds and the hornification process help counteract the embrittlement of fibers caused by cellulose chain scission due to DP reduction. A secondary plateau emerges when the DP is smaller than 400, cellulose degradation is slow, and the component content, hydrogen bond strength, crystallinity, and degree of hornification reach a secondary plateau.

The numbness to human loss becomes ordinary. Indifference to human affairs seems normal after experiencing the global lockdown. Bringing up empathy becomes the most challenging task in architectural design studios after COVID pandemic. Examining otherness solidified after global pandemic would be a way to revive the empathy to engage more in architecture design studios. The physiological disparity between the modern and the vernacular environments narrows down with the revival of Najd architecture, Salmani architecture style and Diriyah Gate Project in Riyadh, KSA. The disparity is caused by intangible factors such as speed and density, but the revival focuses heavily on the tangible, formal expression. The architectural elements in the vernacular, Najd architecture, have different meanings and roles more than being a decorative motif. The feeble values of the vernacular undermined by touristic images are challenged by a series of radical design projects not to be generalized again by picturesque replicas of the past. Seeing the lost, the ecological sensibility of a community or collective will that embraced the harshest land with full respect, might not be visual but radically experiential like a serendipitous breeze in Riyadh. This paper introduces a series of studio works that challenged how to bring back the living structure in the harshest environment to daily lives through experimental and speculative design processes. It proposes how a community is called onto guard the environmental landscape again defying the visual interpretation of Najd architecture in the political landscape dominated by high fence walls.

Free vibration calculations of Sandwich plates with curvilinear fiber variable stiffness composite face sheets usually require a significant computing effort to obtain a high computational accu-racy. In order to get the natural frequencies of sandwich plates with high computational accuracy and low computational cost, an improved approach integrating the differential quadrature method (DQM) and first-order shear deformation theory (FSDT) is introduced in this work. The skins of sandwich plates are composed of one or several layers of variable stiffness composite laminates (VSCL) with fiber paths assumed to follow a specific linear pattern. The FSDT and von Kármán strain–displacement relationship were used to derive the governing equations of the sandwich plate, and DQM was applied to discretize such governing equations and solve for the fundamental frequency of the sandwich plate. The computational results were verified and compared with other FSDT–based computational results, and there was good agreement with the suggested model. Also, the variation patterns of the natural frequency under different pa-rameters such as fiber orientation angles, boundary conditions, number of layers, and core/skin thickness were investigated. This study entailed the development of an efficient solution to the problem of the fundamental frequency of VSCL sandwich plates, and the outcomes could pro-vide a basis for future dynamics comparative studies.

The low coefficient of thermal expansion of Invar 36 represents a significant consideration in light of its potential effects, particularly in industrial applications where thermal stability is of paramount importance. In light of this, a three-step heat treatment was employed, to reduce the thermal expansion coefficient, and enhance the thermal dimensional stability. The ingots produced by vacuum induction melting were subjected to a warm rolling process at 900 °C, followed by a three-step heat treatment consisting of water quenching at 850 °C, tempering at 350 °C with a holding time of 1 hour, and aging at 100 °C for 24 hours. This process enabled the coefficient of thermal expansion to remain almost unchanged, exhibiting values between 0.5 and 0.6 x10-6/°C up to 150 °C. Following the heat treatment, the total elongation increased up to 40% as a natural consequence of the reduction of residual stresses, while a slight decrease in tensile strength was observed. The implementation of a three-step heat treatment process has facilitated an enhancement of the soft magnetic property, which has exhibited a decline in coercivity and an increase in saturation magnetization. As a consequence, three-step heat-treated invar 36 alloys are emerging as a potential candidate for utilization in the aerospace and precision electronics industries, given their satisfactory physical and mechanical characteristics.

A new compounded distribution called the Topp-Leone-Lomax Poisson is developed. The statistical properties of this model are derived. The model parameters are estimated via the maximum likelihood technique. The performance of the estimation techniques was assessed by means of simulation studies. The new model was exposed to three data sets and compared to other models within the same class and the evidence supports the importance of the new model in data modelling.

One of the most important aspects in the fabrication of car seats is the quality of its welded joints. In this proposal, a design of experiments (DoE) approach is used to improve the actual process capability (Cpk) of weld penetration depth in automotive seat adjusters using a laser beam welding (LBW) machine TRUMPF TruDiode 3006. Welding speed effects, laser power, and focal position in the Z axis were considered to determine the optimal welding penetration depth conditions, which is a minimum of 1.20 mm in cold rolled steel metal sheets ZE 790 with a thickness of 1.60 mm. The initial process capability evaluation indicated a Cpk value of 0.50, considering the initial process parameters. The proposed design was modeled using the response surface methodology, stepwise reduction technique, F-test, and before and after process capability evaluation for validation purposes. After applying the proposed methodology, a Cpk of 1.81 was obtained, resulting in a significant improvement of the process, reducing defective parts from 6.51% to 0.00%.

We study the collapse of spherical cold clouds beyond black hole (BH) formation to investigate the possibility of a bounce in the in-falling matter when a critical density or pressure is reached. As a first step, we analyze the pressureless collapse in general relativity (GR), where an analytic solution exists, and demonstrate that an equivalent Newtonian solution can be derived. Such equivalence also holds for spherically symmetric perfect fluids with uniform density and non-vanishing pressure. We numerically investigate the Newtonian collapse of such clouds with masses of $5$, $20$, and $1000$ M$_\odot$ obeying a polytropic equation of state (EoS). By choosing EoS parameters inspired by typical neutron star conditions, we observe bounces at and above nuclear saturation density. Assuming approximate uniformity, we explore the equivalent GR behaviour of the matter during the bounce. Our findings are: i) A GR bounce occurs around the ground state of the matter, characterized by $P = -\rho$. ii) The GR solution significantly differs from the Newtonian result due to the presence of curvature ($k \neq 0$). iii) Both the curvature and the ground state are crucial factors in allowing a GR bounce to occur.

Background CDK4/6 inhibitors are the standard of care for HR+/HER2-negative metastatic breast cancer in combination with endocrine therapy. However, the real-world efficacy and safety of standard versus reduced doses in elderly patients remain unclear. This study aims to compare the clinical outcomes of standard versus reduced doses of CDK4/6 inhibitors in elderly patients with metastatic breast cancer. Methods This multicenter retrospective cohort study included 158 patients aged ≥70 years diagnosed with HR+/HER2-negative metastatic breast cancer who received either standard or reduced doses of CDK4/6 inhibitors (Ademaciclib, Ribociclib, Palbociclib) as first-line therapy. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. PFS and OS were estimated using the Kaplan-Meier method, and comparisons between groups were performed using the log-rank test. Results Of the total population, 108 patients (68.4%) received the standard dose, and 50 patients (31.6%) received a reduced dose. The standard dose group had significantly longer median PFS compared to the reduced dose group (21.3 vs. 15.2 months, p = 0.014), while median OS did not differ significantly (37.2 vs. 37.2 months, p = 0.103). Subgroup analyses revealed no significant differences in PFS or OS between standard and reduced doses for Ademaciclib and Ribociclib, while Palbociclib at standard dose showed superior PFS (21.9 vs. 12.7 months, p = 0.029) and OS (50.5 vs. 28.6 months, p = 0.026). The incidence of Grade 2-4 AEs was higher in the standard dose group (74.2% vs. 56.8%, p = 0.044). Conclusions Dose reduction of CDK4/6 inhibitors, particularly Ademaciclib and Ribociclib, is a viable option in elderly patients, maintaining comparable OS outcomes to standard dosing while reducing the risk of adverse events. Palbociclib at standard dose may offer superior outcomes. These findings support personalized dosing strategies to optimize efficacy and tolerability in frail or elderly patients.

This case report describes the application of the REAC (Radio Electric Asymmetric Conveyer) Gamma Brain Wave Optimization (BWO-G) treatment in a 16-year-old female with a history of emotional trauma, depressive symptoms, and gender dysphoria. The patient underwent 18 sessions of REAC NPPO BWO-G, with quantitative electroencephalography (QEEG) conducted pre- and post-treatment. Initial QEEG analyses indicated altered brainwave activity, with peaks in alpha rhythm frequencies in occipital and right posterior temporal areas. Following treatment, significant improvements were observed, including a reduction in delta and theta rhythms and increased alpha and gamma rhythms, corresponding to enhanced cognitive clarity and emotional regulation. Clinically, the patient experienced reduced anxiety, improved mood, heightened social engagement, better auditory tolerance, and resumed weight management. These findings suggest that the REAC NPPO BWO-G treatment may be an effective, non-invasive approach to enhancing cognitive and neuropsychological resilience in individuals with complex psychosocial challenges.

Lidocaine, a commonly used local anesthetic, has demonstrated modulatory effects in various cells. This study investigates the impact of lidocaine on cytokine production in peripheral blood mononuclear cells (PBMCs) from healthy donors and tumor-infiltrating immune cells (TIICs) from gastric cancer patients. Flow cytometry and cytokine assays revealed that lidocaine inhibited IFN-γ and IL-12 production in CD8+ and CD14+ PBMCs, respectively, while enhancing anti-inflammatory cytokines IL-10, TGF-β, and IL-35 in CD4+CD25+ and CD14+ PBMCs. In contrast, lidocaine promoted the secretion of pro-inflammatory IFN-γ and IL-12 in CD8+ and CD14+ TIICs, while reducing IL-10, TGF-β, and IL-35 levels, thus shifting CD14+ macrophages toward an M1-like phenotype. Additionally, lidocaine decreased PD-1 expression and increased IFN-γ production in CD8+ TIICs via NF-κB activation, enhancing their cytotoxicity against primary gastric cancer cells (PGCCs). Importantly, lidocaine did not affect the viability of normal PBMCs, TIICs, or PGCCs at concentrations up to 1.5 mM. These findings suggest that lidocaine reprograms the tumor immune microenvironment, supporting its potential as an adjunct therapy in gastric cancer by enhancing anti-tumor immunity.

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, influenced by dietary and environmental factors that can modify the intestinal microbiota. The aim was to evaluate changes in composition and diversity of the intestinal microbiota, associated with carbohydrate (CH) consumption in T2DM patients. Forty patients participated, with and without T2DM. Feces samples were collected for the characterization of microbial diversity from the massive sequencing of the 16S rRNA gene. Carbohydrate consumption was quantified from the FCF, the groups were categorized according to BMI and BMI + CH consumption. The group without T2DM showed normal biochemical and anthropometric parameters, although it had high carbohydrate consumption compared to the group with T2DM. At the Phylum level, there were differences in relative abundance, Control overweight group (CL–OW&gt;CH) and T2DM-Normal Weight &gt; CH patients, had increased Bacteroides and decreased Firmicutes. In contrast, CL–OW&gt;CH and T2DM-OW&lt;CH, showed reduced Bacteroidetes and elevated Firmicutes amount. At the genus level, the differences were in the relative abundance of Roseburia, Clostridium_IV, Prevotella, and Sporobacter, associated with the consumption of carbohydrate. The groups that consumed high amounts of carbohydrates, regardless of whether they had diabetes mellitus and overweight, had a significantly reduced proportion of Faecalibacterium, an altered proportion of Bacteroides. The high consumption of carbohydrate showed considerable modifications in the composition and diversity of the bacterial communities.

Alzheimer’s disease (AD) is a predominant and incurable chronic debilitating neuro-degenerative disorder occupying more than 60% of all types of dementias. It is inaugurating by a cascade of events initiating from amnesic-type memory impairment and by gradually loss of cognitive and executive capacities, which is an intolerable problem for the patients and their familiars. Pathologically, there is overwhelming evidence that clumps of misfolded amyloid-β (Aβ) and hyperphosphorylated Tau protein aggregate in the brain. These pathological processes leading to synapse loss, neuronal loss, brain atrophy and gliosis culminating in neurodegeneration and fuelling AD. Thus, at a basic level, abnormality in brain proteins function is observed, causing disruption in the brain network and loss of neural connectivity. Nevertheless, AD is a multifactorial disorder, caused by a combination of age-related changes, genetic, environmental and lifestyle factors that affect the brain over time, its mysterious pathology seems non limited to senile plaques (Aβ) and neurofibrillary tangles (tau), but plethora of substantial and biological processes have been also emerged in its pathogenesis such as — breakdown and/or dysfunction of the blood–brain barrier (BBB); patients’ carriers of the gene variant APOE4; and the immunosenescence of the immune system. Furthermore, type 2 diabetes (T2DM) and metabolic syndrome (MS) whose have also observed as early markers that may provoke pathogenic pathways that lead or aggravate AD progression and pathology. Notwithstanding, of various pathological pathways, there are numerous substantial AD features that require shedding light on, such as chronic neuroinflammation, decrease glucose utilization and energy metabolism as well as brain insulin resistance (IR). Herein, we come to broadened our understanding & to connect the dots of the multiple comorbidities and their cumulative impact that may have synergistic effects on BBB dysfunction and AD pathology. We shed light on the path-physiological modifications in the cerebral vasculature that may contribute to AD pathology and cognitive decline prior to clinically detectable changes in amyloid beta (Aβ) and tau pathology, diagnostic biomarkers of AD, neuroimmune involvement and the role of APOE4 allele and AD-IR pathogenic link - the shared genetics and metabolomics biomarkers between AD and IR disorders. Investment in the future researches brings us closer to know the pathogenesis of AD, and paves the way to build preventive and treatment strategy.

The Oscillating Water Column (OWC) represents a highly promising approach for wave energy conversion. This study presents laboratory experiments conducted on a fixed, bottom-detached OWC device to evaluate the impact of various geometric parameters (specifically, turbine damping, front wall draft, and chamber length in the direction of wave propagation) on the device's capture width ratio. Despite the extensive research over the past few decades on OWC devices, most studies and field-tested prototypes have been designed for long-fetch sea conditions. Consequently, these devices tend to be larger in size and have higher rated power outputs. In contrast, short-fetch sea conditions necessitate tuning the OWC to the shorter dominant wave frequencies, which calls for the development of smaller devices and specialized turbines, highlighting the need for focused research. This work specifically addresses short-fetch sea conditions, which are representative of moderate wave climates, such as those found in the Central Mediterranean region. The study identifies a maximum capture width ratio of approximately 73%. The experimental dataset generated can serve as a benchmark for numerical models under these specific conditions and assist in the development of air turbines optimized for effective performance in short-fetch wave climates.

Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the linker histones H1.2 and/or H1.4 from chromatin fraction. Chromatin remodeling or multiH1 knocking-down is known to promote the upregulation of repetitive elements, ultimately triggering an interferon response. Herein, using HeLa cells and applying fluorescent reporter assay with flow cytometry and quantitave RT-PCR, we found that among PSMs depleting linker histones, 8 compounds significantly activate type I interferon signaling pathway. Out of these compounds resveratrol, berberine, genistein, delphinidin, naringenin and curcumin also caused LINE1 expression detected by quantitate RT-PCR and by immunefluorescent staining analysis of ORF1 LINE1 and γ-H2AX. Fisetin and quercetin, which also induced linker histone depletion, significantly activated only type I interferon signaling, but not LINE1 expression. Curcumin, sanguinarine and kaempferol, causing depletion of the linker histone H1.4 more intensively respectively to H1.2, activate interferon signaling less intensively without any changes of LINE1 expression. For 4 PSMs, which did not cause linker histone depletion, we did not observe effects of interest. Thus, we have shown for the first time that activation of type I interferon signaling accompanies chromatin remodeling caused by PSMs, and LINE1 expression often impacts this activation.

Peripheral artery disease (P.A.D.) is a significant health issue in developed countries. Stenosis of an artery produces substantial changes in blood flow and, consecutively, in its hemodynamics. By simulating the stenosis (obstruction) - arterial environment, valuable insights are obtained. Various methodologies are used to simulate an arterial flow distribution. In this study, a 0D model using a printed circuit board (P.C.B.) is proposed. The model mimics a medium-sized single artery stenosis. Various degrees of stenosis are simulated. Results show that the P.C.B. model accurately predicts the hemodynamic changes produced by stenosis of a medium-sized artery. Also, the model is sensitive to the arterial wall stats. In conclusion, the P.C.B. design is a viable method for hemodynamic simula-tions. Moreover, to enhance the precision and intricacy of the simulation, the complexity and design of the P.C.B. must be augmented. Additionally, alongside subsequent computational fluid dynamics (C.F.D.) studies, the model will extract significant insights into the vascular dynamics of arterial stenosis

Background: Endurance athletes require personalized nutrition strategies to optimize performance, recovery, and training adaptations. While traditional sports nutrition guidelines provide a foundation for personalization, individual variability in metabolic responses underscores the need for precision nutrition, tailored to genetic, biological, and environmental factors. This scoping review evaluates the application of systems biology-driven sports nutrition for endurance athletes, focusing on ‘omics’ and wearable technologies. Methods: A scoping review of the literature was conducted following PRISMA guidelines across PubMed, Scopus, and Web of Science with the following inclusion criteria: original research in English, involving endurance athletes, systems biology approaches, and nutritional interventions or continuous glucose monitoring (CGM). Relevant data were extracted in a systematic way. Results: Forty-eight reports were included with running as most studied sport. Eleven reports used metabolomics, ten nutrigenetics, nine metagenomics, nine CGM, six multi-omics, one proteomics, one epigenomics, and one lipidomics. Over half (62%) were randomized controlled trials (RCTs). Most studies were proof-of-concept investigations aimed at assessing biomarkers; however, the evidence linking these biomarkers to performance, recovery, and long-term health outcomes in endurance athletes remains insufficient. Significant inter-individual variability in responses to exercise and nutritional interventions was observed. Furthermore, many studies were constrained by small sample sizes and inadequate reporting of training status. Conclusions: While evidence is limited, some of the reviewed papers suggest a potential utility of systems biology-driven nutritional recommendations for endurance athletes. Future research should focus on well-powered replicated crossover RCTs, 360-degree systems-wide approaches, and validation of genetic impacts on nutritional interventions to refine dietary guidelines.

Background: Rabies, a zoonotic disease caused by the lyssavirus genus, is widely distributed and a significant cause of human death in Africa and Asia. The study aimed to investigate human rabies exposure and associated risk factors in Northwest Ethiopia. Methods: The study encompassed four zones, seven districts, and four kebeles from each district. Result: A total of 642 households were interviewed. In the current study, rabies exposure was revealed 10.47%. Over 98% of respondents displayed a strong understanding of rabies, with 99.69% correctly identifying rabies as a zoonotic disease. But, 80% of the interviewees trusted traditional medicine could treat rabies. Only 21.93% of the victims were taken post-exposure to prophylaxis. Dogs were the primary affected animals; (87.73%) of these 48.70% were bitten by their own dogs. Metema district was at a higher risk (p < 0.001) compared to the other six districts. Dog ownership (p

The complex dielectric permittivity, ε (f, H) = εʹ (f, H)- i εʺ (f, H), in the microwave frequency range f, of (0.1 - 3) GHz and polarizing field values H, in the range of (0 - 135) kA/m, was measured for a kerosene-based ferrofluid with magnetite particles. A relaxation process attributed to interfacial type relaxation was highlighted, determining for the first time in the microwave field, the activation energy of the dielectric relaxation process in the presence of the magnetic field, EA(H), in relation to the activation energy in zero field, EA(H=0). Based on the complex permittivity measurements and the Claussius-Mossotti equation, the dependencies on frequency (f), and magnetic field (H), of the polarizability (α) and electrical conductivity (σ), were determined. From the dependence of α(f,H), the electric dipolar moment, p, of the particles in the ferrofluid, was determined. The conductivity spectrum, σ(f,H), was found to be in agreement with Jonscher's universal law and the electrical conduction mechanism in the ferrofluid was explained using both Mott's VRH (variable range hopping) model and CBH (correlated barrier hopping) model. Based on these models and conductivity measurements, the hopping distance, Rh, of the charge carriers and the maximum barrier height, Wm, for the investigated ferrofluid was determined for the first time in the microwave field. Knowledge of these electrical properties of the ferrofluid in the microwave field is useful for explaining the mechanisms of polarization and control of electrical conductivity with an external magnetic field, in order to use ferrofluids in various technological applications in microwave field.

Sphingosine-1-phosphate (S1P) is a sphingolipid metabolic product produced via the phosphorylation of sphingosine by sphingosine kinases (SPHKs), serving as a powerful modulator of various cellular processes through its interaction with S1P receptors (S1PRs). Currently, the incompletely understood of mechanism in pancreatic diseases including pancreatitis and pancreatic cancer, largely limits therapeutic therapy options for these disorders. Recent evidence indicates that S1P significantly contributes to pancreatic diseases by modulating inflammation, promoting pyroptosis in pancreatic acinar cells, regulating the activation of pancreatic stellate cells, and affecting organelle functions in pancreatic cancer cells. Nevertheless, no review has encapsulated these advancements. Thus, this review compiles information about the involvement of S1P signaling in exocrine pancreatic disorders, including acute pancreatitis, chronic pancreatitis, and pancreatic cancer, as well as prospective treatment strategies to target S1P signaling for these conditions. The insights presented here possess the potential to offer valuable guidance for the implementation of therapies targeting S1P signaling in various pancreatic diseases.

This study uses Historical Geographic Information Systemsand spatial analysis methods like Space Syntax and Kernel Density Estimation to examine the urban spatial evolution of Xi'an from the Five Dynasties (907 CE) to the early People's Republic of China (1949 CE). By focusing on six historical periods, it reveals the city's transition from a centralized layout to a decentralized, multi-center form. The research shows that Xi'an's spatial structure was shaped by political, economic, cultural, and environmental forces. The Ming and Qing dynasties, in particular, saw economic diversification and the influence of the Silk Road, driving the city's outward expansion and the formation of multiple functional zones. The study also discusses how these historical changes offer valuable lessons for modern urban planning, particularly in balancing cultural heritage preservation with modernization. Overall, the findings provide fresh insights into the long-term urban development of historic cities and offer practical strategies for modern urban planning.

Acute kidney injury (AKI) in children is a critical medical condition characterized by a sudden decline in kidney function. This article provides a comprehensive overview of AKI in pediatric populations, exploring its pathophysiology, the role of various drugs, and the long-term implications for kidney health. Key topics include oliguria, anuria, urine output, hypervolemia and interactions among them as well as role of diuretic nephrotoxicity and glomerular filtration rate. Concepts of electrolytes, acid-base balance and renal perfusion assessment are presented. Basic principles of intensive care unit (ICU) management, renal replacement therapy, and the association with multiorgan failure are described. Additionally, the article discusses the potential long-term outcomes of AKI, including the risk of chronic kidney disease, hypertension, and proteinuria.

In recent years, the decline of birth rate in China has made the enhancement of willingness to have additional children an urgent social issue. Utilizing data from the 2021 China General Social Survey (CGSS 2021) and employing Logit regression models, Poisson regression models, and Lewbel models, this study analyzes the impact of physical exercise on Chinese residents' willingness to have more children. The results indicate that: (1) Physical exercise has a significant positive effect on the willingness to have additional children, and this finding remains robust after controlling for other variables; (2) Among samples from high-income families and individuals with shorter working hours, physical exercise positively influences the willingness to have more children, suggesting that economic and time factors affect the relationship between physical exercise and fertility intentions. This research is the first to explore the impact of physical exercise on the fertility intentions of Chinese residents, aiming to provide theoretical reference and policy implication for enhancing the willingness to have additional children, effectively unleashing fertility potential, and promoting the construction of a fertility-friendly society.

The sediments deposited at the lower reaches of 90 medium and minor rivers from 5 states along western India were analysed for mineralogy and, major and trace elements chemistry. Kaolinite followed by minor illite and gibbsite and traces of goethite and, smectite followed by minor kaolinite, illite and chlorite are characteristic of the clays from Archean-Proterozoic (A-P) terrain and Deccan Trap (DT) terrain, respectively. The sediments were depleted with Si, Ca, Mg, Na and K relative to that of Post Archean average Australian Shale. The SiO2/Al2O3 ratio suggests the sediments from A-P terrain resemble lateritic soils, while those from DT terrain are non-lateritic, chemically weathered soils. The weathering indices indicate intensely weathered and compositionally mature sediments from Kerala, Karnataka and Maharashtra and, intermediate to intensely weathered sediments from Goa and Gujarat. The sediments exhibit relatively high Th, U, La, Zr and Hf from A-P terrain and, high Sc, Cr, Co, Ni, V and Ga from DT terrain. The total trace element content (∑TE) was lower for the clay than silt fractions of sediments. The peak high ∑TE occur in the silt fraction of sediments from Kerala and Maharashtra. The Th/U and Rb/Sr ratios are controlled by the intensity of weathering and lithology of source rocks. The standard plots using trace elements reveal intermediate provenance between felsic and mafic source. Clay fractions from both terrains are more mafic implying mafic-component dominated sediments are transported to the adjacent Seas and Oceans. Therefore, it would be challenging to identify the clays transported from granitic terrain in the Oceans, using trace element chemistry.

This study examines Cambodian higher education teachers' readiness for online teaching and learning (OTL) using a structural equation modeling (SEM) approach. The framework centers around three key dimensions: teachers' self-efficacy in technological, pedagogical, and content knowledge (TPACK), their perceived online teaching presence, and the institutional support they receive. A quantitative survey was administered to 140 teachers at the university level. Teachers' online teaching experience positively influenced their TPACK self-efficacy. Online teaching experience also had a significant positive impact on teachers perceived online teaching presences. Furthermore, teachers' perceptions of institutional support were positively associated with their online teaching experience. These results highlight the critical role of teachers' online teaching experience in shaping their readiness for OTL. The findings suggest that targeted professional development programs and institutional support mechanisms can effectively enhance teachers' self-efficacy, online teaching presence, and perceptions of institutional support in Cambodian higher education.

This study presents an innovative, dynamic model for predicting typhoon track deflections over complex terrain. Based on potential vorticity conservation, the model incorporates a topographic adjusting parameter (α) and a meridional adjusting velocity (MAV) to capture the vortex’s response to terrain variations. Simulations using an idealized bell-shaped mountain and Taiwan's realistic topography reveal that steeper terrain gradients consistently deflect typhoon tracks southward. This steering effect intensifies with increasing vortex strength due to a larger α, leading to enhanced MAV. Shallower approach angles also amplify deflections due to prolonged terrain interaction. Results highlight the significant role of Taiwan's Central Mountain Range in shaping typhoon trajectories. This model offers a refined approach for predicting typhoon behavior near complex terrain, advancing forecasting capabilities, and enhancing disaster preparedness strategies.

This paper discusses an improved XGBoost model based on four-vector optimization algorithm to improve the accuracy of loan approval prediction. Through the analysis of correlation heat maps, we found that there were significant positive and negative correlations among some variables, which laid the foundation for subsequent machine learning analysis. Based on this, we compare the traditional machine learning algorithm with the improved model to evaluate its performance in loan approval forecasting. In the confusion matrix analysis of the training set, the improved XGBoost model demonstrated excellent performance, with all loan approval predictions being correct with 100% accuracy. However, the performance in the test set was slightly different, with 1,182 projects receiving correct loan approval predictions and 99 projects forecasting errors. Of these, 26 projects that should have been predicted to be "unapproved" were incorrectly labeled as "approved," while 73 projects that should have been predicted to be "approved" were incorrectly labeled as "unapproved." These results suggest that we still need to pay attention to the misjudgment of the model in practical application. By synthesizing all model evaluation indicators, we found that the improved XGBoost model based on the four-vector optimization algorithm has a higher accuracy in loan approval prediction than the traditional XGBoost model, with an increase of 1.5%. In addition, the other evaluation indicators also show a trend of significantly better than the traditional model. This study shows that the four-vector optimization algorithm can effectively improve the application effect of XGBoost model in the field of loan approval, and provide more accurate data support and decision-making basis for the financial industry. In the future, we will continue to explore the potential and application prospects of this algorithm in other fields.

The construction of artificial grasslands using native species is an effective measure to restore degraded grassland. In this study, three native grass species, Elymus nutans, Elymus tangutorum and Poa litwinowiana, domesticated in the northern Tibetan Plateau, were used as test subjects. Three monocultures El. N, El. T and Po. L and four mixed combinations El. N+El. T, El. N+Po. L, El. T+Po. L and El. N + El. T + Po. L were set up, with 7 sowing combinations as the main zones, and nested fertilization and non-fertilization as the secondary zones. The optimal sowing combinations were selected to clarify the community growth dynamics of different grass pasture, and to investigate the transgressive overyielding and diversity effects of artificial grassland and the response of soil chemometrics to fertilizer application, with a view to providing a scientific basis for ecological restoration of degraded grassland in the northern Tibetan Plateau. The results show that the different sowing combinations of grassland all exhibit significant growth, with aboveground biomass peaking on 20 September. The type of El. N is the dominant community of the mixed combinations. The forage yield was highest in the combination, and the fertilization treatment significantly increased the forage yield. El. N + El. T + Po. L mixed sowing with fertilizer application is the recommended methodology to establish artificial grassland in the northern Tibetan Plateau. The relative yield totals of the mixed combinations were all greater than 1, and all were transgressive overyielding. Combined with the analysis of the distribution of soil ecological stoichiometric characteristics under fertilizer and non-fertilizer treatments, it was found that aboveground biomass and transgressive overyielding coefficients responded to soil ecological stoichiometry in completely different ways. Under the unfertilized treatment, soil C, N and P are regulated primarily through microbial stoichiometry under the resource dependence of soil dissolved nutrient stoichiometry, which affected aboveground of artificial grassland. Under the fertilizer treatment, microbially mediated extracellular enzyme stoichiometry was dynamically changing to regulate the new substrate environmental supply and demand balance derived from fertilizer application. Future research should further explore the long-term effects of these combinations under different environmental conditions and integrate other ecological restoration techniques to enhance the sustainability and ecological benefits of artificial grasslands. This will help achieve ecological balance and efficient utilization of forage resources in the Tibetan Plateau region, providing a more comprehensive scientific basis for regional environmental protection.