Abstract: Pomegranate peels are important source of polyphenols with remarkable interest in food, pharmaceutical and cosmetic industry. An improved extraction of total polyphenolic com-pounds (TPC) from pomegranate peels by Solid-State Fermentation (SSF) was achieved. A Box Hunter & Hunter (BHH) followed by Central Composite Design (CCD) were performed to assess the effect of the process variables on TPC release. The statistic designs indicate that the best TPC extraction (234.85 mg GAE/gdm) by means of SSF occurs, at 42°C, 50 % moisture, pH 5.0, mineral solution (g/L): NaNO3 (3.83), KH2PO4 (1.52), MgSO4 (4.66) and KCl (1.52) at 36 h. At the best fer-mentation conditions, TPC (248.78±1.24 mgGAE/gdm) increased 5.96-fold than values previously reported and antioxidant activity [AA] increased 5.81-fold than the value obtained before the SSF optimization. High-valued citric acid, α and β punicalin, α and β punicalagin, punigluconin, gal-loyl-HHDP hexoside and ellagic acid molecules were identified. The increased extraction of TPC by SSF provides a suitable alternative for pomegranate peels valorization through the re-covery of molecules with high added value with potential use in food, pharmacy and cosmetic industries; a diversification in the use of food agroindustry by-products is obtained as approach to the circular economy model through biotechnological processes.

Anti-Müllerian hormone (AMH) has been proposed as biomarker for fertility in cattle, yet this associative relationship appears to be influenced by heat stress. Objective was to test serum AMH and AMH-related single nucleotide polymorphisms (SNPs) as markers potentially predictive of reproductive traits in heat-stressed dairy cows. The study included 300 Holstein cows that were genotyped using BovineSNP50 (54,000 SNP) after blood samples were collected and DNA extracted. A genome wide association study was then executed. Nine intragenic SNPs within the pathways that influence the AMH gene were found important with multiple comparisons adjustment test (p<1.09x10-6). A further validation study was performed in an independent Holstein cattle population, which was divided into moderate (MH; n=152) and severe heat-stressed (SH; n=128) groups, and subjected to a summer reproductive management program. Serum AMH was confirmed as a predictor of fertility measures (p<0.05) in MH but not in SH group. Cows were genotyped using the TaqMan allelic discrimination method and qPCR, which revealed four SNPs as predictive markers for serum AMH (p<0.01), reproductive traits (p<0.01) and physiological variables (p<0.05). These SNPs were in the genes AMH, IGFBP1, LGR5 and TLR4. In conclusion, both serum AMH concentrations and AMH-related SNPs appear to be associated with fertility traits in dairy cows managed during summer.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

The number of engineers who are transitioning into environmental sustainability careers is growing, though a gap still exists between supply and demand. This presents an opportunity for undergraduate engineering students to fulfill the demand as environmental sustainability professionals. This qualitative exploratory study investigated environmental sustainability learning experiences and future career interests in environmental sustainability. The social cognitive theory (SCCT) was utilized as a theoretical lens, exploring undergraduate students’ environmental sustainability interests, related learning experiences and their interest in pursuing a future career in environmental sustainability. Twenty-five undergraduate engineering students in various engineering disciplines were interviewed for this study. Data were analyzed to (1) identify students’ interest in pursuing a career in environmental sustainability, (2) determine if students’ interests have changed since they began their undergraduate studies, and (3) explore how learning experiences have impacted students’ future career choice. The findings posit that exposure to environmental sustainability learning experiences is impactful and plays an important role, impacting students' interests in pursuing careers in sustainability. Results reveal that elements such as personal beliefs and salary considerations inspire career choices. This research contributes to addressing the demand for additional working professionals who are prepared to tackle environmental sustainability issues, highlighting the role of learning experiences in shaping students' career interests.

Traumatic brain injury (TBI) affects millions of people each year. Previous studies using the central fluid percussion injury (CFPI) model in adult male rats indicated that elevated intracranial pressure (ICP) was associated with long-term effects, including neuronal cell loss and increased sensory sensitivity post-injury and secondary ICP elevation, that were not seen following injury alone. Investigations also indicated that Cathepsin B (Cath B), a lysosomal cysteine protease, may play a role in the pathological progression of neuronal membrane disruption; however, the specific impact of Cath B inhibition following CFPI remains unknown. Thus, the focus of this study was to evaluate the effects of Cath B inhibition via intracerebroventricular infusion of CA-074Me 2w following injury with or without secondary elevation of ICP. This was accomplished using adult male rats continuously infused with CA-074Me or 10% DMSO as a vehicle control for 2w following either sham injury, a CFPI only, or a CFPI with subsequent ICP elevation to 20mmHg. We assessed Cath B activity in the lateral neocortices and liver, evaluated protein levels of Cath B and Cath B binding partners AIF, Bcl-XL, and Bak. We also conducted histological analyses of total cell counts to assess for cell loss, membrane disruption, and Cath B localization. Finally, we investigated somatosensory changes with the whisker nuisance task. Overall, this study demonstrated that Cath B is not a direct driver of membrane disruption, however, administration of CA-074Me alters Cath B localization and reduced hypersensitivity, emphasizing Cath B being an important component in late secondary pathologies.

Climacteric fruits undergo a characteristic ripening process regulated by ethylene, a key plant hormone. Extending the shelf life of these fruits while preserving their postharvest quality poses a significant challenge for the food industry. This review provides a comprehensive overview of physiological and molecular strategies to delay ethylene-mediated ripening in climacteric fruits and their impact on shelf life, postharvest quality, sensory attributes, and volatile compounds. Additionally, it examines the role of ethylene in fruit ripening analysing various ethylene managing strategies including ethylene inhibitors, ethylene adsorbents and ethylene scavengers by catalytic oxidation The review concludes with future research directions including integrated strategies, environmental considerations and commercial applications for improving postharvest handling and fruit quality.

The integration of robotic devices into healthcare settings for rehabilitation purposes represents a rapidly advancing field with significant benefits for both therapists and patients. However, standalone robot systems face limitations such as inefficient processing of patient data and logistical challenges for patients, such as travel time to rehabilitation centers. To address these shortcomings, this paper proposes the integration of cyber-physical systems into rehabilitation robotics. Cyber-physical systems leverage network connectivity and real-time data processing to enhance the efficiency and convenience of robot-based rehabilitation. By seamlessly integrating sensors, actuators, and computational algorithms, cyber-physical rehabilitation systems empower therapists to more effectively treat patients by providing actionable insights derived from comprehensive data analysis. This enables therapists to tailor treatment plans precisely to each patient’s unique needs, ultimately leading to improved outcomes. Additionally, cyber-physical rehabilitation systems facilitate remote monitoring and intervention, allowing therapists to oversee patient progress and make timely adjustments to treatment protocols without the need for in-person visits. This not only saves patients valuable time and resources but also ensures continuity of care, particularly for individuals residing in remote or underserved areas. Furthermore, cyber-physical rehabilitation systems enable collaborative decision-making by facilitating communication and information sharing among healthcare professionals, further enhancing the quality and efficacy of rehabilitation services. In summary, integrating cyber-physical systems into rehabilitation robotics represents a significant advancement in leveraging technology to optimize patient care and outcomes, promising to revolutionize rehabilitation therapy.

The development of a rapid, sensitive, specific method for detecting foodborne pathogens is paramount in supplying safe food to enhance public health safety. Despite the significant improvement in pathogen detection methods, key issues are still associated with rapid methods, such as distinguishing living cells from dead, pathogenic potential or health risk of the analyte at the time of consumption, detection limit, and sample-to-result. The mammalian cell-based assays analyze pathogens' interaction with the host cells and are responsive to only live pathogens or active toxins. In this study, a human embryonic kidney (HEK293) cell line expressing Toll-Like Receptor 5 (TLR-5) and chromogenic reporter system (HEK dual hTLR5) was used for the detection of viable Salmonella in a 96-well tissue culture plate. This cell line responds to low concentrations of TLR5 agonist flagellin. Stimulation of TLR5 ligand activates nuclear factor-kB (NF-κB) - linked alkaline phosphatase (AP-1) signaling cascade inducing the production of secreted embryonic alkaline phosphatase (SEAP). With the addition of a ρ-nitrophenyl phosphate as a substrate, a colored end product representing a positive signal is quantified. The assay's specificity was validated with the top 20 Salmonella enterica serovars and 19 non-Salmonella spp. The performance of the assay was also validated with spiked food samples. The total detection time (sample-to-result), including shortened pre-enrichment (4 h) and selective enrichment (4 h) steps with artificially inoculated outbreak-implicated food samples (chicken, peanut kernel, peanut butter, black pepper, mayonnaise, and peach) was 15 h when inoculated at 1–100 CFU/25 g sample. These results show the potential of HEK-DualTM hTLR5 cell-based functional biosensors for rapid screening of Salmonella.

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell culture due to various limitations of in vivo testing. Unfortunately, in vitro cell culture fails to provide an accurate microenvironment, and in vivo cell culture is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The key component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

While there are millions of reptile images available online, they are not well organized and not easily findable, accessible, interoperable, or reproducible (FAIR). More importantly, they are not standardized and thus hardly comparable. Here we present a reference database of more than 14,000 standardized images of 1,045 reptile species (969 lizard and 76 snake species), that are based on preserved specimens in 20 different collections, including 533 type species of genera and type specimens of 72 species. All images were taken with standardized views, including dorsal and ventral body shots as well as dorsal, ventral, and lateral views of the heads and other body parts. Although only 11 out of the 20 collections are cross-referenced in Vertnet, some others are indexed in GBIF, and this fraction will certainly grow in the near future. The utility of this and similar image collections will further grow with additional material and further cross-referencing, e.g., to DNA sequence databases or citizen science projects. The images are searchable and freely available on Morphobank.org (Project 5121) and on Figshare.com.

A single water pollution by dyes is a huge environmental problem; there is a necessity to produce new decolorization methods that are effective, cost-attractive, and suitable in industrial use. Magnetic chitosan polymers offer the advantage of easy separation from the dye solution. In this work, a Chitosan-Fe polymer was synthesized, characterized, and tested for removal of the azo dye Direct Red 83:1 from water. The polymer was characterized in terms of surface morphology (SEM), elemental analysis (EA), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), infrared spectrophotometry (IR), X-ray powder diffraction (XRD) and density functional theory (DFT). The reported results hint that 1 g and pH 7.0 were the best conditions to carry out both kinetic and isotherm models. To understand the adsorption behavior of Direct Red 83:1 onto the polymers, adsorption rate and maximum adsorption capacity were calculated using kinetic tests and isotherm curves respectively. The kinetic data and mechanism of the adsorption process were analyzed by three models and the equilibrium data by three adsorption isotherms. The results indicated that the adsorption process follows a pseudo-second-order kinetics (R2= 0.999) and fits the Temkin isotherm (R2= 0.946), indicating that the adsorption occurred on heterogeneous surfaces. The newly synthesized Chitosan-Fe polymer exhibited good adsorption properties and easy separation of cleaned water.

The COVID-19 pandemic period, from 2020 - 2022 had a significant impact on maternal infant health with mothers impacted more than their infants. We questioned whether there have been any lingering effects from the pandemic. We examined intermediate and long-term pandemic effects of maternal and neonatal outcomes before, during and after the COVID-19 pandemic period. We reviewed mother-infant pairs from three epochs: 1) the pre-COVID-19 period, 2) the COVID-19 pandemic period, and 3) the post-pandemic period. The Case Mix Index (CMI) for the neonates from all 3 epochs were detailed. Post-pandemic we noted a rising trend of LGA infants (10%), and an increase in SGA infants (13%). For women in 2023 we noted an increase in hypertension, preeclampsia, diabetes, and a higher BMI than the pre- pandemic period. There have also been more congenital anomalies (9%), and neonatal CMI increased in the post-pandemic period. Well after the pandemic period, maternal-infant health continues to be affected. For women, increase in hypertension and diabetes during pregnancy is concerning. For the infants, being LGA or SGA may have long-term consequences. The post-pandemic increase in infants with congenital anomalies compared to the pre-pandemic era is an area that needs ongoing review.

(1) Background: Considering the autoimmune nature with genetic predisposition of alopecia areata, and the immunomodulatory properties of some probiotics, the present study was conducted in patients with alopecia areata. (2) Method: A 24-weeks randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of an oral probiotic intake in severity of alopecia areata and the effect on skin and gut microbiota. 3) Results: The number of alopecia areata plaques decresed in 56% of patients in the probiotic group vs. 30% in the placebo group. Patients with improvement on the affected skin surface area, showed a results of 45% and 20% in probiotic and placebo groups, respectively. For "activity", "inactivity” and "regrowth", an improvement in 55%, 67% and 55% of patients was respectively observed in the probiotic group, compared to 50%, 40% and 30% in the placebo group. No changes were observed in the gut microbiota during the intervention period. Regarding skin microbiota, changes were detected in the probiotic group, with reductions in characteristic genera during the study. (4) Conclusions: To our knowledge, this is the first clinical trial assessing the efficacy of a probiotic in patients with alopecia areata. This probiotic mixture improves the course and modify the skin microbiota of these patients.

The contribution of readymade garment (RMG) industry is immense behind the rapid development of some countries with emerging economies. This industry is empowering these countries to provide employment opportunities for millions of people. However, the health as well as safety issues of the workers in this industry are often ignored, particularly in these developing countries. In recent times, because of the several undesirable and obnoxious conditions that exist in their working environments, they are vulnerable to various health related problems which are increasing at a staggering rate. The main purpose of this paper is to assess and prioritize the major health related problems faced by these garment workers in these countries where the economy is flourishing. In addition, the main hazards responsible for these health perils are also quantified. Data were collected from three different garment factories situated in different locations of Bangladesh. Thirty workers from each factory rated the frequency and severity of 14 health related issues. The health risks were then assessed and prioritized through risk priority number (RPN). Afterwards, three experts provided their opinion on the main hazards prevalent in the workplace of almost every garment factory in this country. These hazards were grouped into four main classes which are: 1) Physical 2) Ergonomic 3) Chemical and 4) Psychological hazards. The main classes were later divided into sub classes also. Best-worst method (BWM) was then applied to analyze these hazards by assessing their relative weights depending on the experts’ judgement. The results showed that the health issues faced by the workers in three different garment factories varied to some extent. The results obtained from the experts’ opinion indicated that physical hazards in the workplace are the most detrimental ones whereas the chemical hazards were the least harmful.

Sediment cores were collected from a mudflow lobe (80 m water depth) offshore of the Mississippi River’s Southwest Pass in 2017 to better understand the sedimentology near the lobe entraining the SS Virginia shipwreck (sunk by a German U-Boat in 1942) and surrounding Mississippi River Delta Front. Core analyses included 210Pb/137Cs geochronology, granulometry, and X-radiography. Sediment accumulation rates (SAR) calculated from excess 210Pb activity in multicores are 0.22–0.29 cm/yr at seabed depths less than 20 cm and 0.29–0.51 cm/year at depths greater than 20 cm. 137Cs accumulation rates are ~0.15 to ~ 0.37 cm/year since 1954 and 1963 respectively. Sediment accumulation rates from 210Pb and 137Cs geochronology and indicators of relative sedimentation and bioturbation from X-radiographs suggest that rates of sediment accumulation near Virginia have declined since ca. the mid-20th century. This may be explained by the multi-decade downslope mass transport of the mudflow lobe in which the shipwreck is embedded, and decreases in sediment supply delivered offshore from the Mississippi River. Mass-transport calculations of the Virginia lobe derived from core properties and published lobe advection rates suggest downslope mass transport is far higher than sediment resupply from the Mississippi River, consistent with recent studies of delta retreat.

Recent literature has seen a rapid expansion in the reference to front-end forensics as an indication of the untapped value of forensic science. While some of these contributions have centered on development of forensic intelligence from a single area of investigation, others call for a more fundamental change in the relationship between crime laboratories and policing, particularly relating early laboratory analysis with big datasets to provide leads to investigators. We highlight several recently implemented tactical strategies of crime laboratories that contribute to the body of forensic intelligence. Beyond the scientific gains from these tactical applications, the corresponding details on associated efficiencies, costs, time savings, and quality improvements offer insights towards patterns of success for the community of crime laboratories. Further details expand an interpretation of what constitutes success with an eye on the contributions of the crime laboratory towards public health, safety, and protection of the innocent in addition to societal gains from conviction of the guilty. The economic interpretation of the value provided by the forensic laboratory assists in the cost-benefit review of strategic and tactical decisions and supports the justification for laboratory public funding with measures of the return on investment from public support of the forensic laboratory

This review provides insight into the role that obesity, but especially mediators of the adipose tissue, have in both renal disease and transplantation. In particular, we focus on the functions of leptin and adiponectin, inflammatory mediators with widely known clinical implications, as well as on the role of arachidonic acid-derived eicosanoid metabolites. These latter compounds, epoxyeicosatrienoic (EETs) and hydroxyeicosatetraenoic (HETEs) acids, which modulate the liberation of cytokines in the adipose tissue, are generated in the epoxygenase pathway of arachidonic biotransformation via CYP450 enzymes. There is accumulating evidence suggesting that EETs and HETEs may have a critical role in the onset and outcome of chronic kidney disease and renal transplantation. Finally, we also discuss the reported effect that the presence of genetic variants in leptin, adiponectin, EETs and HETEs-related genes may cause in renal patients and recipients. The levels of cytokines of the adipose tissue and related compounds play a remarkable role in both renal disease and transplant. Accordingly, novel therapeutic strategies are being developed based on the modulation of their concentrations in patients with various diseases.

Strong-aroma Baijiu is a traditional Chinese spirit distilled from grains that undergo solid-state fermentation. At the end of each fermentation cycle, a significant quantity of Huangshui accumulates at the bottom of the fermentation pit, constituting one of the primary by-products in the brewing process of strong-flavor liquor. In this report, the chemical component analysis of Huangshui obtained from a strong-flavor liquor factory revealed a diverse array of organic acids, alcohols, esters, starch, reducing sugars, amino acids, and other compounds present in Huangshui. Additionally, two specialized solid-state fermentation models were developed to investigate the formation process of Huangshui. Our findings demonstrate a positive correlation between the yield of Huangshui and the initial moisture content of fermented grains. It is concluded that Huangshui is the percolate produced during the solid-state brewing process of strong-flavor liquor, with its water content originating from the initial moisture of fermented grains.

Predictive biomarkers for immune checkpoint inhibitors (ICI), such as PD-L1 expression (TPS), remain limited in clinical applications. Improved novel ICI predictive biomarkers are urgently needed. We evaluated a live single-cell functional liquid biopsy cytokine profiling platform to track immunotherapy treatment response and outcomes. Peripheral blood mononuclear cell samples of healthy donors and NSCLC patients undergoing ICI-based therapies were collected longitudinally pre-/post-treatment under IRB-approved protocols. Samples were enriched for CD4+ and CD8+ T-lymphocytes and analyzed on the IsoLight platform. The single T-cells were captured in microchambers on IsoCode chips for cytokines profiling. Functional polyfunctionality data from 55,775 single cells were analyzed using the IsoSpeak software, kappa coefficient, and Kaplan-Meier survival plots. We found a significant difference between responders and non-responders in CD8+ T-cells’ changes in overall polyfunctionality and polyfunctional strength index (ΔPSI). ΔPSI score in CD8+ T-cells performed better than PD-L1 TPS and, when combined with PD-L1 TPS, strongly correlated with early ICI treatment response with a kappa coefficient of 1.0 (p=0.003). High CD4+ T-cells ΔPSI predicted a strong trend of improved PFS (3.9-fold) and OS (3-fold). In conclusion, single peripheral T-cell polyfunctionality dynamics analysis is a promising liquid biopsy profiling platform as NSCLC ICI predictive biomarker regardless of oncogene-addiction status.

Wood is very susceptible to the action of biotic agents. There is a growing interest in the protection of wood and wood artworks to extend their life, using environmentally friendly preservatives. The aim of this paper was the study of nano/siliconate impregnation system for wood protection to control biological colonization. The biotic agents studied have been wood decay fungi. In conclusion, this paper has shown that all the treatments have presented an excellent protective performance against biotic agents. Is important to mention that a synergistic effect can be observed when generating the siliconate/nanoparticle mixtures, resulting in protective systems with excellent efficiency for all the degrading agents. Moreover, it presents an easy application, which represents not only a watertight protective system, but also a set of systems that may be used and managed according to the availability of the active components, the costs, and, most importantly, without having to modify the form of application.

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored because of their complexity, are invasive, and time-consuming. We propose the evaluation of social nesting, a species-typical behavior naturally occurring in standard housing conditions, for such behavioral monitoring. We provide an example of its use to evaluate social deficits and the long-term effects of neonatal sensorial stimulation in male and female adult 3xTg-AD mice for Alzheimer's disease compared to sex- and age-matched NTg counterparts with normal aging. Social nesting was sensitive to genotype (worse in 3xTg-AD mice), sex (worse in males), profile, and treatment (distinct temporal patterns, time to observe the maximum score and incidence of the perfect nest). Since social nesting can be easily included in housing routines, this neuroethological approach can be useful for animal's welfare, monitoring the disease's progress, and evaluating potential risk factors and effects of preventive/therapeutical strategies. Finally, the non-invasive, painless, simple, short time and low-cost features of this home-cage monitoring are advantages that make social nesting feasible to be successfully implemented in most animal department settings.

Shared micromobility has gained significant attention in the field of transportation engineering in recent years as an environmentally friendly, convenient, and easily accessible transportation mode. Like other medium-sized cities, Birmingham, Alabama implemented a shared micromobility pilot program in 2021 that captured the attention of local travelers. This study examined shared e-scooter usage and associated travel patterns in Birmingham using 2021-2022 field data. From these data, ArcGIS maps were used to showcase trip origins and destinations. To gain a further understanding of e-scooter travel patterns in the study area, zip code and block group densities were calculated. Additionally, a negative binomial regression model was constructed to identify determinants of shared e-scooter trips. The analysis results showed that the usage of shared e-scooters was the highest during the nighttime, on weekends, and in the fall season. Furthermore, the research findings indicated that shared e-scooters experienced their highest utilization rates in areas with a higher proportion of educated and higher-income individuals. These findings suggest that travelers’ mode choice related to the use of micromobility modes is influenced by environmental and demographic factors. Overall, this case study offers valuable contributions to the understanding of the role of shared e-scooters in Birmingham's transportation landscape and can guide transportation authorities in other medium-sized cities in their efforts to plan for micromobility options.

The rapid advancement of large language models (LLMs), such as ChatGPT, has revolutionized natural language processing, enabling these models to generate coherent and contextually relevant text. These capabilities hold significant potential for various applications, particularly in the medical field. LLMs can assist healthcare professionals by providing accurate information, supporting diagnostic processes, and enhancing medical education. However, the implementation of LLMs in clinical settings faces several barriers, including technical limitations, ethical concerns, regulatory constraints, and practical challenges. Ensuring accuracy, reliability, and interpretability is crucial, along with addressing biases, ensuring data privacy, and establishing ethical guidelines. Future research should focus on improving training techniques, developing explainable AI methods, and creating efficient, resource-saving models. Expanding applications through domain-specific models and multi-modal integration can further unlock the potential of LLMs. By addressing these challenges and prioritizing responsible development, LLM technology can be safely and effectively integrated into various domains, driving innovation and improving outcomes. This paper explores the current state of LLM technology, its medical applications, barriers to implementation, and directions for future research and development

Solving environmental odor issues can be confounded by many analytical, technological, and socioeconomic factors. Considerable know-how and technologies can fail to properly identify odorants responsible for the downwind nuisance odor and mitigate it for the affected citizenry. We propose enabling solutions to environmental odor issues by utilizing troubleshooting techniques developed for the food, beverage, and consumer products industries. We showed that the downwind odorant impact-priority ranking process can be definable and relatively simple. The initial challenge is the prioritization of environmental odor character from the perspective of the impacted citizenry downwind. In this research, we aim at summarizing three natural models of the rolling unmasking effect (RUE) and discuss them more systematically in the context of the proposed downwind environmental odor prioritization approach. Regardless of the size and reach of an odor source, a simplification of odor character and composition typically develops with downwind dilution. The extreme odor simplification-upon-dilution was demonstrated for two plant varieties, prairie verbena and Virginia pepperweed. Their downwind odor frontal boundaries were dominated by single, character-defining odorants; p-cresol-dominated ‘barnyard’ odor, and benzyl mercaptan-dominated ‘burnt match’ odor, respectively. The P.T. porcupine downwind odor frontal boundary was dominated by two potent, character-defining odorants: (1) ‘onion’/‘body odor’ odorant #1 and (2) ‘onion’/‘grilled’ odorant #2. In contrast with their downwind boundary simplicities, each odor source presented considerable compositional complexity and composite character difference near the source. The proposed RUE approach’s ultimate significance is the illustration of naturally occurring phenomena that explain why some environmental odors and their sources can be challenging to identify and mitigate using the analytical only approach (focused on compound identities and concentrations). These approaches rarely move beyond comprehensive lists of compounds being emitted by the source.

Oxidative stress has been implicated in cellular senescence and aging, as well as in the onset and progression of many diverse genetic and acquired diseases and conditions. The search for biomarkers of oxidative stress has become relevant to many biomedical fields using many different methods and approaches. Fluorescence methodology is advantageous because of its simplicity and high sensitivity. Fluorescent probes are frequently used to investigate the role of reactive oxygen species in oxidative stress in experimental or clinical settings, often involving the use of flow cytometry and related single-cell based technologies. To assess the specific role of reactive oxygen species in oxidative stress studies by cytometric methodologies, it is essential to detect and characterize these species accurately. However, the detection and quantitation of individual intracellular ROS is still a challenge, but different and complementary strategies may focus on other endpoints of oxidative stress. In this review we present and discuss briefly the limitations and perspectives of such approaches. Based on our results, we also provide recommendations for proper design of cytometric studies of oxidative stress in order to prevent or minimize experimental errors..

Background/Objectives Recurrent shoulder instability following Bankart lesion repair often necessitates surgical revision. Identified risk factors include young age, glenoid bone loss, and off-track Hill-Sachs lesions. This systematic review aims to understand failure rates of arthroscopic revision Bankart repair and if these aforementioned factors influence its success. Methods Following PRISMA guidelines, this systematic review, registered on PROSPERO, included twenty-four articles. Two independent reviewers assessed eligibility across three databases, focusing on recurrent instability as the primary endpoint, while also noting functional measures, adverse events, revision operations, and return-to-sport rates when available. Results Key surgical techniques for recurrent instability post-Bankart repair were identified, with revision arthroscopic Bankart being the most common (685/1032). Despite generally endorsed effectiveness, recurrence rates have increased over the past four years. Comparative analysis revealed significantly lower recurrence for open Latarjet compared to revision arthroscopic Bankart (p

Many drastic actions are taken by cocaine users for the sake of experiencing high dopamine levels, which depends on iron for its synthesis. Dopamine depletion and iron deficiency are also involved in the symptoms of restless leg syndrome (RLS). The intersecting biochemical pathways of cocaine use, iron deficiency, and RLS have not been adequately investigated. This case report reveals the successful treatment of a patient with these conditions. A 63-year-old male with a history of cocaine use disorder, insomnia, and RLS sought emergency care for suicidality. Upon admission, he was also found to be iron-deficient. He revealed that his RLS worsened when he attempted to abstain from cocaine. He also used alcohol to sustain the effects of cocaine when the cost of cocaine was too high. During hospitalization, his mood, cravings, and RLS were resolved with adjunctive iron supplementation as well as 300 mg of Wellbutrin. If iron-deficient, replenishment of adequate dopaminergic receptor density and function via supplementation may play an essential role in the prevention of cocaine use and cessation of cocaine withdrawal. Further research is warranted to validate these findings and understand the implications of iron supplementation in addiction medicine.

Glioblastoma is a central nervous system cancer type with a poor prognosis. One of its main features is the constant change of metabolism phenotype to support its development and progression. Mitochondria play a critical role in cellular metabolism. Acetylation on lysine residues of mitochondrial enzymes is a mechanism for regulating protein function. This modification negatively affects the mitochondrial proteome function and is counteracted by the enzyme sirtuin 3 (SIRT3). To better understand how SIRT3 regulates mitochondrial metabolism, we inhibited SIRT3 and examined by high-resolution mass spectrometry analysis the proteome and acetylome of two glioblastoma cell lines with different metabolic preferences. Our results indicate that protein synthesis machinery is regulated by lysine acetylation and plays a role in the metabolic phenotype. We also identified new SIRT3 targets not previously associated with specific functions, highlighting their potential as future targets for further study. This study shed light on the role of SIRT3 in mitochondria and its implication for cellular metabolism. We have generated knowledge at the proteome and acetylome levels on the dynamics between two glioblastoma cell lines with opposing metabolic phenotypes. Our results might guide in searching for biomarkers at both proteome and acetylome levels in glioblastoma.

There is a restricted knowledge about the potential impact of the use of different wood species on color and anthocyanin changes during the red wine aging process. This lack of knowledge is even greater when no oak wood species are used. Thus, the aim of this study was to carry out a comparative analysis of the impact of wood chip extracts from oak, acacia and cherry species on the chromatic characteristics and anthocyanins changes by the use of model wine solutions. In this context, several methodologies were used to quantified, color and anthocyanins changes during the aging time studied. The results indicated that the contact between wood chip extracts and grape skin isolated anthocyanin extracts induced a decrease of color intensity, particularly red color, and also the anthocyanin content in the different experimental model wine solutions studied. All chromatic modifications are potentially detected by human eyes because ΔE values were much higher than 3 CIELab units. These tendencies seems to be independent of the wood species used, but more pronounced for higher contact time between wood chip extracts and anthocyanins. The obtained results may contribute to a better understanding of the chromatic changes of red wines when aged in contact with different wood chips species.

Background: Infections are a major cause of morbidity and mortality in patients with pemphigus vulgaris (PV). One of the most common infections in these patients is candidiasis. This is probably due to the use of systemic immunosuppressant, including oral and intravenous corticosteroids, mainly in megadoses (pulse therapy), although it is unknown if there are other associated factors in addition to immunosuppressive treatment. We determine the factors associated with candidiasis in PV patients in two Second-Care hospitals in Mexico. Methods: We reviewed 100 cases with PV. Cases were randomly selected from the databases of two second-care hospitals between January 2010 and December 2019 (10 years). The primary endpoint was the incidence of candidiasis in patients with PV. Results: One hundred patients with PV were enrolled in this retrospective study. Candidiasis was observed in 79 patients (79%). A maximum corticosteroid dose of 55 mg/day during the last year (p = 0.001) and higher neutrophil/lymphocyte ratio were associated with candidiasis in patients with PV (p = 0.001). Conclusion: Risk factors favoring candidiasis in patients with PV are not only related to the use of corticosteroids, but also to demographic factors, the activity of the disease, and the systemic inflammation associated with autoimmunity.

Developed countries have shown a time trend towards a younger age at menarche (AAM), which is associated with increased risk of later obesity and non-communicable diseases. We aimed to assess whether a time trend in AAM with associated disease risk is also present in Mexico. For this, we used data of 30,826 women from the Mexican National Health Survey (2000). Linear and log binomial regression was used for nutritional and disease outcomes, whereas Welch-ANOVA was used to test for a time trend. AAM decreased over time (p < 0.001), with a maximal difference of 0.99 years between the 1920s (13.6 years) and 1980s (12.6 years). AAM (in years) was negatively associated with weight (β = -1.01 kg; 95 % CI -1.006, -1,004) and BMI (β = -1.01 kg/m2; -1.007, -1.006), and positively with height (β = 0.18 cm; 0.112, 0.231). AAM was associated with diabetes (RR = 0.95; 0.93, 0.98) and hypercholesterolemia (RR = 0.93; 0.90, 0.95), but not with hypertension, breast cancer or arthritis. In Mexico, AAM decreased significantly during the 20th century. AAM was inversely associated with adult weight and BMI, and positively with height. Women with a later AAM had a lower risk of diabetes and hypercholesterolemia.

Human societies demand sustainable alternatives for goods and services. Plants are sustainable sources of important metabolites with beneficial impacts on human health. There are many reported methodologies and commercial suppliers for extract preparations from the plant Mucuna sp. They usually claim to be enriched in L-dopa, their distinctive metabolite. However, there are poor characterizations of the metabolite's components in that extracts. Here, we present the metabolite characterization of a Mucuna seed extract, emphasizing the L-dopa identification and quantification. To obtain the extracts, we follow a green and sustainable extraction protocol. The lyophilized extract was subject to liquid chromatography and mass spectrometry to identify its primary metabolites. Additionally, we follow thin-layer chromatography to identify some carbohydrates in the sample. The resultant extract has a 56% L-dopa. Other main components in the extract were arginine, stizolamine, and the fructooligosaccharides sucrose and nystose. The characterized Mucuna extract can be easily standardized as powder presentation and used in several biomedical applications.

Contamination of soil and crops with heavy metals (HMs) poses a significant environmental challenge in the United States. Hence, this study aimed to assess HM contamination levels from sampled Ohio and West Virginia soils using various pollution indicators analyses, including Enrichment Factor (EF), Geo-accumulation index (lgeo), Contamination Factor (CF), and Pollution Load Index (PLI) and identify the Translocation Factor (TF) of HMs in the edible part of the vegetables and further evaluate health risks associated with dietary exposure through estimations of Estimated Daily Intake (EDI), Hazard Index (HI), Target Hazard Quotient (THQ), Cancer Risk (CR) and Target Cancer Risk (TCR) on adults and children. In this study, Fe was the most predominant contaminant, ranging from 28.41 to 67.36 g/kg in the soil. Cancer risk assessment revealed that Ni poses significant risks. Therefore, regular monitoring of metal concentrations in soil and vegetables grown in these regions might mitigate potential health hazards in the future.

The large quantity of information retrieved from communities, public data repositories, web pages, or data mining can be sparsed and poorly classified. This work shows how to employ unsupervised classification algorithms such as K-means proper to classify user reviews into their closest category, forming a balanced data set. Moreover, we found that the text vectorization technique significantly impacts the clustering formation, comparing TF-IDF and Word2Vec. The value for mapping a cluster with movie genre was 81.34% ± 20.48 of the cases when the TF-IDF was applied, whereas Word2Vec only yielded a 53.51% ± 24.1. In addition, we highlight the impact of the removal of stop-words. Thus, we detected that pre-compiled lists are not the best method to remove stop-words before clustering because there is much ambiguity, centroids are poorly separated, and only 57% of clusters could match a movie genre. Thus, our proposed approach achieved a 94% of accuracy. After analyzing the classifiers’ results, we appreciated a similar effect when divided by the stop-words method removal. Statistically significant changes were observed, especially in precision metric and Jaccard scores in both classifiers, using custom-generated stop lists rather than pre-compiled ones. Reclassifying sparse data is strongly recommended as using custom-generated stop lists.

A single-center, randomized, double-blind, placebo-controlled clinical trial with two arms was conducted in 71 healthy subjects suffering from sleep disturbances, which were treated with a dietary supplement based on an extract of Aloysia citrodora (or Lippia citriodora, lemon verbena) (n = 33) for 90 days. Subjects in the placebo group (n = 38) received capsules of microcrystalline and maltodextrin with the same organoleptic properties. Between-group significant differences in favor of the experimental group were found in the visual analogue scale (VAS) score rating sleep quality; overall score, sleep latency and sleep efficiency of the Pittsburg Sleep Quality Index (PSQI); and sleep latency, sleep efficiency, wakefulness after sleep onset and duration of awakening assessed by actigraphy. Plasma nocturnal melatonin levels also increased significantly in the experimental group. Changes in anthropometric parameters and physical activity levels were not found. This study shows that the administration of a dietary supplement comprised lemon verbena administered for 3 months was associated with a significant improvement of sleep quality as compared with placebo in a population of healthy subjects with sleep problems. Improvements were also apparent at the mid-study visit after 45 days of supplementation.

The FTF (Fusarium Transcription Factor) gene family is composed of two members (FTF1 and FTF2) with high sequence homology. Both genes encode Zn(II)2Cys6 binuclear zinc finger transcription factors involved in the modulation of virulence in the F. oxysporum species complex (FOSC). While FTF1 is a multicopy gene exclusive of highly virulent strains of FOSC and is located in the accessory genome, FTF2 is a single copy gene, located in the core genome, and well conserved in all filamentous ascomycete fungi, except yeast. The involvement of FTF1 in the colonization of the vascular system and regulation of the expression of SIX effectors has been stablished. To address the role of FTF2 we generated and characterized null FTF2 mutants in a F. oxysporum f. sp. phaseoli weakly virulent strain and analyzed them together with the equivalent mutants formerly obtained in a highly virulent strain. The results obtained highlight a role for FTF2 as a negative regulator of the production of macroconidia and demonstrate that it is required for full virulence and positive regulation of SIX effectors. In addition, gene expression analyses provide compelling evidence that FTF2 is involved in the regulation of hydrophobins likely required for plant colonization.

E-scooters are a micromobility transportation option for completing short trips. In recent years, many ‎cities welcomed shared e-scooters in an effort to offer more mode choices, increase travelers' ‎convenience, and reduce automobile use in their service areas. However, a knowledge gap still remains ‎regarding the acceptability of shared e-scooters as a transportation option, which motivates additional ‎research on user and non-user preferences and attitudes toward e-scooter use. This study investigates ‎latent variables impacting the adoption of shared e-scooters in urban areas, focusing on mode choice ‎factors and attitudes towards e-scooter use and car use. The study utilizes machine learning (ML) ‎techniques and SHAP analysis to analyze survey data (N=1196) collected from travelers in Washington, ‎D.C., Miami, FL, and Los Angeles, CA, in 2021 and 2022. A comparative analysis is performed to develop ‎comprehensive demographic profiles of e-scooter users. The analysis reveals gender (male), age (25-39 ‎years age group), higher income, and educational background as the most relevant factors toward e-‎scooter use. Attitudinal variations among e-scooter users and non-users underscore the complexity of ‎perceptions toward e-scooter use, with significant differences in mode choice factors and attitudes ‎toward the use of e-scooters and private vehicles. Notably, educational background ranked as a significant ‎factor in Washington, D.C., and Miami, while Factor 3, derived from factor analysis and encompassing car ‎use attitudes and the utilization of technology, emerged as influential in Los Angeles. This research ‎contributes fresh insights into factors shaping e-scooter adoption, offering a foundation for informed ‎urban transportation planning and policymaking. The holistic approach showcased in this study enhances ‎understanding of shared micromobility and its implications for urban mobility.

Building deep learning models proposed by third parties can become a simple task when specialized libraries are used. However, a great deal of mystery still surrounds the design of new models or the modification of existing ones. These tasks require in-depth knowledge of the different components or building blocks as well as their dimensions. This information is limited and broken up in different literature. In this article, we collect and explain in-depth the building blocks to design deep learning models, starting from the artificial neuron to the concepts involved in building deep neural networks. Furthermore, the implementation of each building block is exemplified using the Keras library.

The smoke house works as a tourism model that will directly impact women living across Quintana Roo communities and small towns, with the idea that this project will empower them, and provide them with a more dignified income, with the end goal to reduce the poverty rates in the state Likewise, to introduce an adequate formula of cuisine that promotes the regional gastronomic identity, since this typology of cultural heritage is linked to the experience of enjoying the state's native food. (Carrillo, J. and Vazquez, L., 2018) It should be noted that the main representatives and transmitters of gastronomy are women, usually housewives. Therefore, a methodology based on the qualitative approach was designed, taking as a basis the ethnographic method, which allows understanding the behavioral patterns of a society. In the first instance, a gastronomic laboratory is proposed for the university, which will later be used as a business model within the tourism industry, directed at people who seek to enjoy cultural and ex-periential tourism. And at the same time, it will benefit communities across the state by generating more income for them. In addition, the project of model smoke kitchen is oriented to go in accordance with the 2030 agenda. Which includes 17 objectives and 169 goals; six of those objectives are directly aligned with this project, and the rest can be observed to relate it in a more indirectly manner. In the same way, a summary of the results obtained by the five-year groundwork is presented, as well as the division of the gastronomy in the state according to the characteristics that conform the gastronomic region.

Inherent in every Active Magnetic Bearing (AMB) are differences between the expected geometric axes and the actual magnetic axes due to a combination of discrepancies, including physical variation from manufacturing tolerances and misalignment from mechanical assembly, fringing and leakage effects, as well as variations in magnetic material properties within a single AMB. A method is presented here for locating the magnetic axes of an AMB that will facilitate the accurate characterization of the bearing air gaps for potential improvement in field tuning, performance analyses and certain shaft force measurement techniques. This paper presents an extension of the application of the bias current perturbation method for the determination of the magnetic center [4] to the determination of magnetic axes for the further development of accurate current-based force measurement techniques [1].

The architectural configuration of the space plays a crucial role in the acoustics of Neonatal Intensive Care Units (NICUs). The design of the environment, the materials used in construction, and the organisation of noise sources within the room significantly influence the noise levels present in these critical areas. For this research, noise levels found in two hospitals, with different architectural configurations and sizes but similar construction materials, have been analyzed. Data were recorded at 1-second intervals over a period of more than 24 hours. The data collected in these hospitals confirm the magnitude of the noise problem in NICUs, highlighting the urgent need to address it effectively to ensure an appropriate and safe environment for the recovery of neonates. Good architectural planning can help mitigate noise, while poor configuration can exacerbate acoustic problems, negatively affecting both patients and healthcare staff. It is crucial to involve architects, acoustic engineers, and healthcare staff in the design and renovation of NICUs to create spaces that not only meet medical needs but also consider the auditory well-being of neonates.

In many regions where drinking water supply is intermittent and unreliable, households adapt by storing water in cisterns or rooftop tanks. Both intermittent supply and stored water can be vulnerable to contamination by microorganisms with deleterious health effects. The Guadalajara Metropolitan Area is a rapidly growing urban center with over five million residents where household storage is nearly ubiquitous. This pilot study was conducted in July 2018 to examine the microbiological quality of drinking water in Guadalajara. Samples were tested for free available chlorine residual, total coliform bacteria, and E. coli. A survey on access to water and public perspectives was also conducted. Water exiting rooftop tanks exceeded regulatory limits for total coliform levels in half of the homes studied. Piped water arriving at two homes had total coliform levels that far exceeded regulatory limits. No E. coli were detected in any of the samples. Only 35% of homes had a chlorine residual between the recommended 0.2 and 1.5 mg/L. Many homes reported unpleasant odors and colors. Only 7% of residents drank the piped water. Future studies are needed, especially during April and May when many homes reported a higher disruption to water service.

Serelaxin (RLX), the recombinant form of human Relaxin-2 hormone, protects the heart from the ischemia/reperfusion (I/R)-induced damage due to its anti-inflammatory, anti-apoptotic and antioxidant properties. RLX exerts its actions by binding to its specific RXFP1 receptor whereby it regulates multiple cellular transduction pathways. In this in vitro study we offer first evidence for the involvement of AMP kinase/Sirtuin1 (AMPK/SIRT1) pathway in the protection afforded by RLX against H/R-induced damage in H9c2 cells. Treatment of the H/R-exposed cells with RLX (17 nmol L−1) enhanced SIRT1 expression and activity. Inhibition of SIRT1 signaling with EX527 (10 µmol L-1) reduced the beneficial effect of the hormone on mitochondrial efficiency and cell apoptosis. Moreover, RLX upregulated AMPK pathway, as shown by the increase in the expression of phospho-AMPK active protein. Finally, AMPK pathway inhibition by Compound C (10 and 20 μmol L−1) abrogated the increase in SIRT1 expression induced by RLX, thus suggesting the involvement of AMPK pathway in this effect of RLX. The results of this study strengthen the concept that RLX exerts its cardioprotective effects against H/R-induced injury by multiple pathways which also include AMPK/SIRT1.

Personalized cancer vaccines have emerged as a promising avenue for cancer treatment or prevention strategies. This approach targets the specific genetic alterations in individual patient’s tumors, offering a more personalized and effective treatment option. Previous studies have shown that generalized peptide vaccines targeting a limited scope of gene mutations are ineffective, emphasizing the need for personalized approaches. While studies have explored personalized mRNA vaccines, personalized peptide vaccines have not yet been studied in this context. Pancreatic ductal adenocarcinoma (PDAC) remains challenging in oncology, necessitating innovative therapeutic strategies. In this study, we developed a personalized peptide vaccine design methodology, employing RNA sequencing (RNAseq) to identify prevalent gene mutations underlying PDAC development in a specific patient solid tumor tissue. We performed RNAseq analysis for trimming adapters, read alignment, and somatic variant calling. We also developed a Python program, called GeneFinder, which validates the alignment of the RNAseq analysis. The Python program is freely available to download. Using chromosome number and locus data, GeneFinder identifies the target gene along the UCSC hg38 reference set. Based on the gene mutation data, we developed a personalized PDAC cancer vaccine that targets 100 highly prevalent gene mutations in the individual patient. We predicted peptide-MHC binding affinity, immunogenicity, antigenicity, allergenicity, and toxicity for each epitope. Then, we selected the top 50 and 100 epitopes based on our previously published vaccine design methodology. Finally, we generated pMHC-TCR 3D molecular model complex structures which are freely available fo download. The designed personalized cancer vaccine contains epitopes commonly found in PDAC solid tumor tissue. Our personalized vaccine was composed of neoantigens, allowing for a more precise and targeted immune response against cancer cells. Additionally, we identified mutated genes which were also found in the reference study where we obtained the sequencing data, thus validating our vaccine design methodology. This is the first study designing a personalized peptide vaccine using human patient data to identify gene mutations associated with the specific tumor of interest.

Plant-based alternative medicine is normally grounded on empiric cultural perception, as the main objective, these practices intent to either maintain good health or to provide a route to turn-the-tide on a specific disease or ailment. Amongst the thousands of plants that have been used and studied, Neem (Azadirachta indica) seems to have a very interesting tale to tell, since its properties to ward-off certain diseases have overtime, and in a rigorous way, been proven. The preceding concise review is a collection of some of the most relevant studies today, not only focusing on the health benefits obtained by its use, but digging into the molecular mechanisms of how the properties come about. In particular, we take a look over antioxidant properties and how these mediate and mitigate important molecules such as IL-6 and TNF-, leading the way in reducing systematic damage by oxidative stress. Further, we relate this oxidative reduction to other systemic diseases such as cancer and diabetes, as these are currently becoming the most rampant killers. As of yet not all is known about the different ways of extracting or the total composition of an extract, as these may be from different parts of the plant. Therefore, we also allude to an important cautionary view where toxicological effects and conflicting outcomes arise. Overall, presented results show a great potential for the different extracts of Neem as their antioxidant activity can be taken advantage off, and potentially used in modern medicine.

This article propose a didactic, through games, tool based on information and communication technologies, in order to eliminate possible communication barriers and to promote the inclusion of students with hearing impairment in Physical Education classes. To this end, a dossier of traditional games has been developed. These are structured in turn into objectives, materials, organisation, graphic description and a QR code for each game. These codes are linked to different videos hosted on the YouTube platform, in which the explanation of the games, mentioned above, can be visualised graphically using sign language. The whole creative process is described in the article, as well as possible pedagogical applications of the use of the tools created for this purpose in other educational contexts.

This study investigates the utilization of innovative green composites made from hemp shiv, a waste by-product of hemp cultivation, with the aim of promoting sustainability within the construction industry. The manufacturing method involve the application of pressure in a mold to create the samples. These materials were produced using an environmentally friendly binder consisting of colophony, arabic gum and corn starch, moreover white glue and bioepoxy are also used to compare with the green resins. Three different binder compositions for the specimens. The samples underwent mechanical testing through tensile and bending assessments, and their performance was compared to that of non-green binders to validate the effectiveness of the manufacturing processes. The study revealed that decreasing the moisture content during the curing process is crucial for improving the mechanical properties. The best results were achieved when using arabic gum as a binder, yielding a tensile strength of 2.16 MPa and a bending strength of 5.25 MPa, with a composition of 62.5% hemp shiv and a manufacturing process involving a pressure of 5 MPa.

New technologies have resulted in a better understanding of blood and lymphatic vascular heterogeneity at the cellular and molecular levels. Meanwhile, we still need to learn more about the heterogeneity of the cardiovascular and lymphatic systems between different species at the anatomical and functional levels. Even the deceptively simple question of the functions of fish lymphatic vessels has yet to be conclusively answered. The most common interpretation assumes a similar dual setup of the vasculature in zebrafish and mammals: on the one hand, there is the cardiovascular, circulatory system, and on the other hand, the lymphatic vascular system, in which the unidirectional flow is derived from surplus interstitial fluid and returned into the cardiovascular system. A competing interpretation questions the identity of the lymphatic vessels in fish as at least some of them receive their flow from arteries via specialised anastomoses, neither requiring an interstitial source for the lymphatic flow nor stipulating unidirectionality. In this alternative view, the “fish lymphatics” are a specialised subcompartment of the cardiovascular system, called the “secondary vascular system” (SVS). Many of the contradictions found in the literature appear to stem from the fact that the SVS develops in part or its entirety from an embryonic lymphatic vascular system by transdifferentiation. Future research needs to establish the extent of embryonic transdifferentiation of lymphatics into SVS blood vessels. Similarly, more insight is needed into the molecular regulation of vascular development in fish. Most fish do feature more than the five VEGF genes and three VEGF receptor genes that we know from mice or humans, and the relative tolerance of fish to whole genome and gene duplications could underlie the evolutionary diversification of the vasculature. This review discusses the key elements of the fish lymphatics versus the SVS and attempts to draw a picture coherent with the existing data, including the phylogenetic knowledge.

The objective of this work was to analyze the potential of Rhizophora mangle as a bioindicator of seven heavy metals, Fe, Cu, Zn, Mn, Ni, Cr, and Cd, in the mangrove sediments of the Navachiste lagoon complex (NAV). The concentration of trace metals (TM) in sediments and tis-sues (leaf, stembark, and root of R. mangle) were determined by digestion with nitric acid (HNO3), whereas the metal absorbance was measured by atomic absorption spectrophotometry with an air-acetylene flame. The enrichment factor, the bioavailable fraction, the seasonal varia-tion of heavy metal concentrations and their correlation with those determined in R. mangle tissues were assessed. Metal concentrations found in sediments were as following: Fe>Mn>Zn>Cr>Ni>Cu>Cd, and for tissues: Mn>Fe>Zn>Cu>Cr>Ni>Cd, and regarding the roots, the findings were as following: Fe>Mn>Zn>Cu>Cr>Ni>Cd. The highest trace metal concentra-tions were correlated with silt, clay, and organic matter in sediments with basic pH. The highest salinities were found adjacent to R. mangle trees. Of all the trace metals analyzed, there was only a positive linear regression between the bioavailability of Mn in the sediment with the concen-tration of Mn in leaf tissue consistently throughout the year. The Cu bioavailability in the sedi-ment showed similar positive linear regressions except for winter, where it did not show this pattern. These results suggest that the concentrations of Mn and Cu in the R. mangle leaf could be a potential bioindicator of environmental exposure to anthropogenic sources of contamination by these trace metals in sediments

We present a numerical calculation of the heat transport in a Bragg mirror configuration made of materials that do not obey Fourier's law of heat conduction. The Bragg mirror is made of materials that are described by the Cattaneo-Vernotte equation. By analyzing the Cattaneo-Vernotte equation's solutions, we define the thermal wave surface impedance to design highly reflective thermal Bragg mirrors. Even for mirrors with a few layers, very high reflectance is achieved ($>90\%$). The Bragg mirror configuration is also a system that makes evident the wave-like nature of the solution of the Cattaneo-Vernotte equation by showing frequency pass-bands that are absent if the materials obey the usual Fourier's law.

Oxidative stress plays an essential role in the pathological processes that trigger various chronic liver diseases and contributes to the development of hepatocarcinogenesis. Antioxidants from natural sources trap free radicals by converting them into non-harmful products and minimize oxidative stress, playing a crucial function in the treatment of free radical-induced diseases. However, the activity of these antioxidants is limited due their poor bioavailability, which is why various nano-drug delivery systems have been developed to improve their stability, promote smooth release, and targeted delivery for liver cancer treatment. Specifically, this review aims to report recent scientific findings of novel nano-formulations containing natural antioxidant molecules targeted for the treatment of liver cancer.

From their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses [1]. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3 to 10% of reported cases [2-5]. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches have been taken for the treatment of BRAF mutant cancers. In this review we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.

Scientists, politicians, and practitioners are debating the current structure of pig farms in Lithuania, as medium and small farms have almost disappeared over the past decade. The debated problem is whether the revitalization of medium and small pig farms would sustainably contribute to self-sufficiency in pork? Therefore, this research aims to determine which farms in terms of size could be the most perspective. In order to achieve this aim the multi-criteria evaluation method TOPSIS was used. The economic, production and environmental indicators of Lithuanian pig farms and pig farming sector in Lithuania and selected EU countries: Latvia, Estonia, Poland, Germany, and Denmark were analyzed in this research. The multi-criteria evaluation led to the conclusion that Danish pig farms were the best managed. Germany occupied the second place. The industrial large farms were found as dominated in those countries. Large pig farms (approximately two thousand sows) appeared most perspective in Lithuania: they took the first place in the years examined (2016–2021). The criterion estimate of their assessed indicators was much higher than of the medium (100 sows) and small (20 sows) farms. The main reasons: significantly higher labour productivity, lower cost, lower price, and better production indicators.

Grape pomace is one of the main by-products in the wine industry and contains some high added-value compounds such as polysaccharides. Considering the wide application possibilities of polysaccharides in wine and in the food industry, the revalorization of grape pomace to extract polysaccharides presents itself as an opportunity for by-product management. Therefore, the aim of this study was to characterize polysaccharide extracts obtained from pomace by-products of different white grape varieties. The type and content of polysaccharides, proteins and phenols were analyzed. Statistically significant differences were found between the varietal extracts in the types and concentrations of polysaccharides. The extracts obtained from the Verdejo and Puesta en Cruz varieties showed the highest polysaccharide purity and contents, but the type of polysaccharides was different in each case. The Verdejo provided extracts richer in non pectic polysaccharides, while the Puesta en Cruz in pectic polysaccharides. Protein and polyphenol contents were low in all extracts, below 2.5% and 3.7%, respectively. These results open up a new possibility for the revalorization of grape pomace by-products to obtain polysaccharide-rich extracts, although it would be interesting to improve both the yield and the purity of the extracts obtained by studying other extraction techniques or processes.

The present study aimed to investigate the effects of a 10-week online high-intensity interval training (HIIT) on body composition and aerobic performance in physically sedentary women. A parallel two-group, longitudinal (pre, post) design was used with physical tests performed before (preintervention) and after (postintervention) the 10-week intervention period. A total of for-ty-eight healthy and physically sedentary women were recruited to participate in this study. Par-ticipants were distributed in two groups: The experimental group (EG) with 24 women (n = 24, age 21.21 ± 2.15 years, weight 61.16 ± 8.94 kg, height 163.96 ± 4.87 cm, body mass index body weight 22.69 ± 2.49 kg/m2), and the control group (CG) with another 24 women (n = 24, age 20.50 ± 1.29 years, weight 62.0 ± 6.65 kg, height 163.92 ± 4 .89 cm, body mass index 23.04 ± 1.74 kg/m2). The EG performed an online HIIT program for 10 weeks, while CG continued with their daily life routines. The repeated measures ANCOVA indicated a significant effect in the within-group analysis for weight (p=0.001; d=-0.96), demonstrating a significant decrease in the Experimental Group (EG) while the Control Group (CG) did not show a significant decrease in body mass in-dex (p=0.15; d=-0.11). Regarding maximal oxygen uptake (VO2 max) values, the EG exhibited a significant improvement (p=0.001; d=-1.07), whereas the CG did not demonstrate a significant improvement (p=0.08; d=-0.37). A new within-group analysis with power output (W) revealed that EG significantly improved (p=0.01; d=-0.96), while CG did not show a significant improve-ment in power output (W/kg) (p=0.20; d=-0.11). Lastly, the within-group analysis with Load re-vealed that EG significantly improved (p=0.001; d=-0.50), while CG did not show a significant improvement in Load (p=0.10.; d=-0.10). The present study showed that 10 weeks of HIIT in an online environment during the Covid-19 lockdown significantly improved maximum oxygen consumption, and caused weight loss and a significant decrease in body mass index in physically sedentary women. These results suggest HIIT may be used as a time-efficient strategy to improve body composition and cardio-respiratory fitness in sedentary women.

In this paper, we study the problem of controllability of impulsive neutral evolution integrodifferential equations with state dependent delay in Banach spaces. The main results are completely new and are obtained by using Sadovskii's fixed point theorem, theory of resolvent operators, and an abstract phase space. An example is given to illustrate the theory.

The utilization of vegetal fabric reinforced cementitious matrix (FRCM) represents an innovative approach to composite materials, offering distinct sustainable advantages when compared to traditional steel-reinforced concrete and conventional FRCM composites employing synthetic fibers. This article introduces a design for sandwich solutions based on a core of extruded polystyrene and composite skins combining mortar as a matrix and diverse vegetal fabrics as fabrics such as hemp and sisal. The structural behavior of the resulting sandwich panel is predominantly driven by the interaction between materials (mortar and polyurethane) and the influence of shear connectors penetrating the insulation layer. This study encompasses an experimental campaign involving double-shear tests, accompanied by heuristic bond-slip models for potential design of sandwich solutions. The analysis extends to the examination of various connector types, including hemp, sisal, and steel, and their impact on the shear performance of the sandwich specimens. The results obtained emphasize the competitiveness of vegetal fabrics in achieving effective composite strength comparable to other synthetic fabrics like glass fiber. Nevertheless, the study reveals that the stiffness of steel connectors outperforms vegetal connectors, contributing to an enhanced improvement in both stiffness and shear strength of the sandwich solutions

Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting of the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (&lt;-9.00 kcal/mol), surpassing that of RdRp-Ribavirin (&lt;-7.00 kcal/mol) along with promising ADMET score predictions (&lt;4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. This study highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.

Type IVc Pili (T4cP), also known as Tad or Flp pili, are long thin microbial filaments, which are made-up of small-sized pilins. These appendages serve different functions in bacteria including attachment, biofilm formation, surface sensing, motility, and host colonization. Despite their relevant role in diverse microbial lifestyles, knowledge about T4cP in bacteria that establish symbiosis with legumes, collectively referred to as rhizobia, is still limited. Sinorhizobium meliloti contains two clusters of T4cP-related genes: flp-1 and flp-2, which are located on the chromosome and pSymA megaplasmid, respectively. Bundle-forming pili associated to flp-1 have been involved in competitive nodulation of alfalfa plants but the role of flp-2 remains elusive. In this work, we have performed a comprehensive bioinformatic analyses of T4cP genes in the highly competitive S. meliloti strain GR4 and investigated the role of its flp clusters in pilus biogenesis, motility and in the interaction with alfalfa. Single and double flp cluster mutants were constructed in the wild-type genetic background as well as in a flagellaless derivative strain. Our data demonstrate that both chromosomal and pSymA flp clusters are functional in pili biogenesis, and contribute to surface translocation and nodule formation efficiency of GR4. In this strain, the presence of flp-1 in the absence of flp-2 reduces competitiveness for nodule occupation.

People with Down syndrome have more visual problems than general population. They experience a premature aging, and it would be expected they will also have an acceleration in worsening visual function. A prospective observational study which includes visual acuity, refractive error, accommodation, binocular and colour vision was performed to young adults with (n=69) and without (n=65) Down syndrome and to a senior group (n=55) without Down syndrome. Results showed significant differences in visual acuity between groups (p&lt;0.001) and it can be improved with a new prescription in 40% of the participants with Down syndrome. Regarding to accommodative state, no significant differences were found between groups of young people. Concerning binocular vision, 64.7% of strabismus was observed in the group with Down syndrome (p&lt;0.001). Visual abnormalities are significant in young adults with Down syndrome and are different from those of older people without Down syndrome, some of which can be improved by providing the optimal prescription as well as regular eye examinations.

Surface modification of polypropylene (PP) films is achieved using gamma-irradiation-induced grafting to proffer with antimicrobial activity. The copolymer was obtained through a versatile two-step route; pristine PP is exposed to gamma rays and grafted using methyl methacrylate (MMA), then N-vinylimidazole (NVI) is grafted onto the copolymer PP-g-MMA by simultaneous irradiation. The characterization included Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), Thermogravimetric Analysis (TGA), X-ray Photoelectron Spectroscopy (XPS), and physicochemical analysis of swelling and contact angle. The copolymer (PP-g-MMA)-g-NVI was loaded with vancomycin, and the drug released was quantified by UV-vis spectrophotometry at different pH. The surface of (PP-g-MMA)-g-NVI exhibited pH-responsiveness and moderate hydrophilicity, suitable properties for controlled drug release.

Mexico shows a high prevalence of obesity in children and adolescents. Geographical location and cultural environment could play a role in the promotion of healthy lifestyles in terms of physical activity (PA), sedentary behavior (SB) and nutrition. The purpose of this study was to assess rural and urban differences in body composition (BC), physical fitness (PF), PA and nutritional status of adolescents from the state of Jalisco (Mexico). The study involved 469 students aged 13-17 years (55.0% girls) from 8 high schools. BC was analyzed by bioimpedance, and PF by standardized field tests. Objective measurements of PA and SB were taken in a subsample (n=240). Energy intake (EI) was calculated from two 24h recalls. Rural residents presented a higher prevalence of overweight, waist circumference, trunk fat mass, regional fat free mass and muscle handgrip strength (all p&lt;0.05, ηp2&lt;0.06). Cardiorespiratory fitness was similar among participants, whereas urban adolescents showed higher muscle power, speed-agility and flexibility scores (all p&lt;0.05, ηp2&lt;0.07). Overall lifestyle behavior in urban adolescents was more sedentary (p&lt;0.05, ηp2= 0.11). EI was similar in both locations. In conclusion, urban Mexican adolescents presented a generally higher sedentary behavior and better fitness and fatness profile than their rural peers.

Embryonic and larval Danio rerio is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features as high genetic homology to mammals; robust phenotypes; and its value in high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN or Talen make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies; employing zebrafish as experimental model; comparing it with other in vivo and in vitro models; presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity to facilitate more extensive; easy and comprehensive knowledge of new generation drugs.

Global warming caused by climate change is a challenge for dairy farming, especially in sub-Saharan countries. Under high temperature and relative humidity dairy cows suffer from heat stress. The objective of this study was to investigate the effects and relationship of heat stress (HS) measured by temperature-humidity index (THI) on physiological parameters and milk yield and composition of lactating Holstein Friesian crosses reared in the humid coastal region of Tanzania. A total of 29 lactating Holstein Friesian x Zebu crossbred dairy cattle with 50% (HF50) and 75% (HF75) Holstein Friesian blood levels in their second and third month of lactation were used. Breed composition of Holstein Friesian was determined based on animal recording system used at the Tanzania Livestock Research Institute (TALIRI), Tanga. Data collected included daily temperature, relative humidity, daily milk yield, and physiological parameters (core-body temperature, rectal temperature, respiration rate, and panting score). The THI was calculated using the equation of National Research Council [39]. The THI values were categorized into three classes i.e. low THI (76-78), moderate THI (79-81) and high THI (82-84). The effects of THI on physiological parameters and milk yield and composition were assessed. Also, the effects of genotype, parity, lactation month, and interaction of these parameters with THI i on milk yield, milk composition, and physiological parameters were investigated. The results indicate that THI and its interaction with genotypes, parity, and lactation month had highly significant effect on all the parameters. THI affected (P ˂ 0.05) average daily milk yield and milk fat %, protein %, lactose %, and solids – not – fat %. When THI increased from moderate to high values, average daily milk yield declined from 3.49 ± 0.04 to 3.43 ± 0.05 liters/day while fat % increased from 2.66 ± 0.05% to 3.04 ± 0.06% and protein decreased from 3.15 ± 0.02% to 3.13 ± 0.03%. No decline was observed on lactose % whilst solids – not – fat % declined from 8.56 ± 0.08% to 8.55 ± 0.10%, when the THI values increased from moderate to high. Also, THI affected (P˂0.05) physiological parameters. Core-body temperature (CBT), rectal temperature (RT), respiration rate (RR) and panting score (PS) increased from 35.60 ± 0.01 to 36.00 ± 0.01oC, 38.03 ± 0.02 to 38.3.30 ± 0.02oC, 62.53 ± 0.29 to 72.35 ± 0.28 breaths/min and 1.35 ± 0.01 to 1.47 ± 0.09, respectively, when THI increased from low to high. THI showed a low positive correlation with average daily milk yield and fat percentage whilst protein, lactose, and solids – not - fat percentages showed negative relationships with THI (P ≤ 0.05). The CBT, RT, RR, and PS showed positive relationships (P ≤ 0.05) with THI. These negative relationships indicate that there is an antagonistic correlation between sensitivity to HS and degree of production. It is concluded that the THI, genotype, parity, and lactation month, and their interactions with THI significantly affected milk yield, milk composition, and physiological parameters of lactating Holstein Friesian dairy crosses at THI thresholds ranging from 77 to 84.

The purpose of this study was to evaluate the bioactivity and cell response of a well-characterized Nurse´s A-phase (7CaO•P2O5•2SiO2) ceramic and his effect compared to a control (tissue culture polystyrene-TCPS) on the adhesion, viability, proliferation and osteogenic differentiation of ahMSCs in vitro. Cell proliferation (Alamar Blue Assay), Alizarin Red-S (AR-s) staining, alkaline phosphatase (ALP) activity, osteocalcin (OCN) and collagen I (Col I) were evaluated. Also, field emission scanning electron microscopy (FESEM) images were acquired in order to visualise the cells and the topography of the material. The proliferation of cells growing in a direct contact with the material was slower at early stages of the study because of the new environmental conditions. However, the entire surface was colonized after 28 days of culture in growth medium (GM). Osteoblastic differentiation markers were significantly enhanced in cells growing on Nurse´s A phase ceramic and cultured with osteogenic medium (OM), probably due to the role of silica to stimulate the differentiation of ahMSCs. Moreover, calcium nodules were formed under the influence of ceramic material. Therefore, it is predicted that Nurse´s A-phase ceramic would present high biocompatibility and osteoinductive properties being a good candidate to be used as a biomaterial for bone tissue engineering.

Most authors have investigated the role of mannoproteins on wine quality but very few analyze the use of grape derived polysaccharides as they are not commercially available. Purified grape derived polysaccharides from red wine (WPP) and winemaking by-products (DWRP: Distilled Washing Residues Polysaccharides) were used as potential fining agents to modulate white wine flavour. Phenolics and volatile compounds were analyzed in control and wines treated with WPP, DWRP and commercial mannoproteins (CM) after one and twelve months of bottling, and a sensory analysis was conducted. WPP and DWRP, rich in rhamnogalacturonans-II, showed as good modulators of wine aroma and astringency. Improvement of wine aroma was related to an increase of all volatile families expect higher alcohols and volatile acids. The modulation of astringency and bitterness was related to a reduction in the proanthocyanidin content and its mean degree of polymerization. Extracts with polysaccharides with higher protein contents presented higher retention of volatile compounds, and DWRP extract showed more positive effects on the overall aroma. Our novel results open the possibility of obtaining valuable polysaccharides from distilled washing residues of wine-pomaces, which could promote its valorization as by-product. This is the first time to describe the potential use of this by-product.

Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function. Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) in the Saos-2 cell line (null p53) transfected as compared with p53WT transfected cells. The association between these miRNAs and the signaling pathways in which they might participate was performed through the miRPath Software. QRT-PCR was employed to validate the miRNAs profiles. In addition, we explored if the induction of cell migration and invasion by the p53R48Q mutant was dependent on the miR-182-5p. We observed that p53 mutants have an overall negative effect on miRNA expression. Likewise, we found miRNAs differentially expressed associated with regulating Oncogenic signaling pathways. We found overexpression of miR-182-5p, which is associated with processes such as cell migration and invasion. Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. Our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is also necessary to induce cell migration and invasion by the p53R248Q mutant in a cancer cell model.

The processing of Mexican limes generates great amounts of peel as a byproduct. Lime peel is mainly rich in the flavonoid hesperidin, whose bioactivity is oriented mainly to cardiovascular diseases and cancer. The purpose of this work was to develop a green process for the extraction and purification of hesperidin from Mexican lime peel. The extraction of hesperidin was investigated on a laboratory scale by varying the solvent composition and the solid-to-solvent ratio. The best conditions (solid-to-solvent ratio of 0.33 g/mL and 60% ethanol) were used for the extraction of hesperidin in a pilot scale (Volume = 20 L). The kinetics of the extraction was studied to find the maximum hesperidin concentration at 100 min. The concentrated extract had a hesperidin content of 0.303 mg/mL. Next, a purification process using adsorption resins was assessed. Through static tests, it was determined that higher adsorption efficiencies were achieved with the EXA-118 resin and diluted extract (4:6 ratio with 10% DMSO). Finally, the adsorption of hesperidin from the diluted extract (hesperidin concentration of 0.109 mg/mL) was carried out at 25 °C in a column packed with 80 mL of EXA-118 resin. The mean recovery efficiency of hesperidin from the extract was almost 90%.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants of emerging concern, recognized for their toxicity and potential carcinogenic properties. PFAS chemicals are reported to act as endocrine disruptors through their interactions with various nuclear receptors (NRs). Despite their significant impact, comprehensive screenings and detailed analyses of PFAS binding strengths at both the orthosteric and allosteric sites of NRs are currently lacking in the literature. Our study addresses this gap by focusing on the binding interaction analysis of both common and uncommon PFAS with key nuclear receptors such as the vitamin D receptor (VDR), peroxisome proliferator-activated receptor gamma (PPARγ), pregnane X receptor (PXR), and estrogen receptor alpha (ERα). We used advanced docking simulations to screen 9,507 PFAS chemicals at the orthosteric and allosteric sites of the PPARγ, PXR, VDR, and ERα. We verified the accuracy of our docking protocol through multiple docking procedures and validations. The python code used for PFAS chemical screening is deposited in the supplementary file. Among the PFAS assessed at the orthosteric site of the VDR, 21 demonstrated similar binding affinities compared to the calcitriol, while 130 PFAS, exhibited stronger binding affinities than calcitriol. At the VDR allosteric site, where lithocholic acid (LCA) natively binds, 412 PFAS matched the binding energies of LCA, and 2,229 showed even greater binding energies. Similar testing on the PXR, PPARγ, and ERα revealed that the orthosteric site of PPARγ had 1,863 PFAS binding with a higher affinity than native ligand ET1 and 693 PFAS binding at the allosteric site with greater affinity than T35 native ligand. At the PXR orthosteric site, 650 PFAS bound with a greater affinity than native ligand 4WH, while at the allosteric site, 9,148 PFAS demonstrated a greater binding affinity than the known allosetric ligand glycerol. At the orthosteric site of ERα, 40 PFAS displayed binding with a greater affinity than the native ligand estradiol and at the allosteric site, only 8 PFAS exhibited greater binding affinity than coactivator ligand SRC-1. Further, our mixture modeling analysis indicates that PFAS can bind in various combinations with themselves and with endogenous or native ligands simultaneously, to disrupt the endocrine system and cause carcinogenic responses. These findings reveal that PFAS can interfere with nuclear receptor activity by displacing endogenous or native ligands by binding to the orthosteric and allosteric sites. This study elucidates the mechanisms through which PFAS exert their endocrine-disrupting effects, potentially leading to more targeted environmental regulations and therapeutic strategies. Importantly, this study is the first to explore the binding of PFAS at allosteric sites and to model PFAS mixtures at nuclear receptors. Given the high concentration and persistence of PFAS in humans, this study called for the urgent need for further research into the carcinogenic mechanisms of PFAS and the development of intervention strategies that target nuclear receptors. Our ongoing studies extend these findings by further investigating the interactions of PFAS and co-exposed chemicals with nuclear receptors. These investigations are supported by experimental verification, which will enhance our understanding of PFAS broad effects and aid in the design of effective mitigation strategies.

In this Case Report we analyze the possible causes of the poor health status of a professional Apis mellifera iberiensis apiary located in Gajanejos (Guadalajara, Spain). Several factors that potentially favor colony collapse were identified, including Nosema ceranae infection, alone or in combination with other factors (eg, BQCV and DWV infection), and the accumulation of acaricides commonly used to control Varroa destructor in the beebread (coumaphos and tau-fluvalinate). Based on the levels of residues, the average toxic unit estimated for the apiary, suggests a possible increase in vulnerability to infection by N. ceranae due to the presence of high levels of acaricides. These data highlight the importance of evaluating these factors in future monitoring programs, as well as the need to adopt adequate preventive measures as part of national and international welfare programs aimed at guaranteeing the health and fitness of bees.

Indoor environmental comfort is fundamental to human health as people spend 90% of their time indoors. This aspect is even more crucial in hospitals, where the concept of health is closely linked to well-being, ethics, and environmental aspects. Emerging methodologies and technologies such as Digital Twin, Building Information Modeling, the Internet of Things, sensing technologies, and data analytics offer new opportunities to ensure healthier environments and more efficient building management. This paper provides an assessment of how digitalization can support decision-making processes related to maintaining high levels of indoor environmental comfort in hospital settings, particularly by analyzing how real-time data processing and the application of machine learning can promote proactive interventions in these facilities. The methodological approach was based on four phases: defining the objectives of the digital twin, identifying the input data to build and feed the digital model, defining the KPIs to evaluate the system's correct functioning, and identifying the enabling technologies to be integrated into the system to achieve the set goal. The result is a digital twin for managing the operating room and its related services, with the aim of guiding decisions based on accurate data and improving operational efficiency, levels of environmental comfort, and safety regarding the diffusion of medical gases.

Insulin receptors are internalized by endothelial cells; however, the impact of hyperinsulinemia on this process is not known. Thus, the aim of this study is to determine the role of hyperinsulinemia on insulin receptor function and internalization, as well as the potential impact of protein tyrosine phosphatase 1B (PTP1B). To this end, hippocampal microvessels were isolated from male C57Bl/6J mice on either a control or high-fat diet and assessed for insulin receptor signaling. Cell surface insulin receptors in brain microvascular endothelial cells were labelled with biotin to assess the role hyperinsulinemia plays on receptor internalization in response to stimulation, with and without Claramine treatment, a potent PTP1B antagonist. Our results indicated that insulin receptor levels increased in tandem with insulin receptor dysfunction in the high-fat diet mouse hippocampal microvessels. Hyperinsulinemic cell-receptors demonstrate a shift in splice variation towards decreased IR-A/IR-B ratios and demonstrate a higher membrane-localized proportion. This corresponded with decreased autophosphorylation at sites critical for receptor internalization and signaling, however, Claramine restored signaling and receptor internalization in hyperinsulinemic cells. In conclusion, hyperinsulinemia negatively impacts brain microvascular endothelial cell insulin receptor function and internalization, likely through both alternative splicing and increased negative feedback from PTP1B.

Targeted Protein Silencing (TPS) is an elegant approach to investigate protein function and its role in the cellular landscape, overcoming limitations of genetic perturbation strategies. In contrast to CRISPR/Cas9 and RNA interference, these systems act in a reversible manner and reduce off-target effects. Several TPS have been developed and wisely improved, including compartment delocalization tools and protein degradation systems. In this review, we focus on Anchor-Away, deGradFP, auxin inducible degron (AID) and dTAG technologies, and discuss their recent applications and advances. Finally, we propose Nano-Grad, a novel nanobody-based protein degradation tool to specifically proteolyze endogenous tag-free target protein.

A synoptic compendium of the legumes of the Mimosoideae clade in northeastern Mexico is presented for the first time, including changes in their botanical nomenclature and retypification of genera. Furthermore, based on new information recently published, the taxonomic limits of several new genera segregated from Acacia (Acaciella, Mariosousa, Senegalia and Vachellia) and Prosopis (Neltuma and Strombocarpa) are clarified and included. Based on field work, collecting botanical samples during the last 30 years, a review of botanical materials and database in national and international, we have completed the diversity of legumes of the Mimosoideae clade of northeastern Mexico. Three tribes (Acacieae, Ingeae and Mimosaeae), 22 genera and 92 species, and 19 infraspecif categories were recorded. Only the genus Painteria is endemic to Mexico. Eighty-eight species are native to Mexico, and four are exotic, Acacia salicina, Neptunia prostrata, Neltuma chilensis and Albizia lebbeck. Twenty-eight species are endemic to Mexico, nine species are endemic of northeastern Mexico, and four species endemic to only one state in Mexico. The 22 registered genera represent 44% and 65% of the generic flora of the Mimosoideae clade for Mexico and the planet respectively while the 92 species registered represent 3% and 18% of the species of the Clade Mimosoideae for the planet and Mexico respectively. According to the new nomenclature of legumes, the number of genera in the Mimosoideae clade in northern Mexico has been increased from 19 to 24.

Cobalt, like other critical elements, is gaining in importance today. The great technological advances and the deep knowledge of the physical and chemical properties of this element have allowed to enhance its applications in various fields, such as: catalysts, paints, alloys for the mechanical and aerospace industries, as well as the medical sector and in recent times, its use within the rechargeable battery industry. The main exploitable deposits are in the Democratic Republic of the Congo, which have economic potential due to a strong influence on their mineralization processes. However, the growing demand for cobalt and the search for less dependence on African deposits leads to targeting other regions, so it is necessary to carry out exhaustive exploration to find out the potential of its reserves for a subsequent benefit of the mineral. Generally, cobalt comes as a by-product of the extraction of other metallic minerals, mainly from Cu-Co, Ni-Co, Ni-Cu-Co deposits. From the above, a first review is carried out on the differences that exist in the geochemical, mineralogical and forecast properties that exist within the different deposits that harbor cobalt. As a second review topic, it delves into efficient processing for cobalt recovery, which is generally carried out by flotation, acid leaching, in addition to its recovery from secondary sources, such as batteries and metallurgical waste. However, generally speaking there is still a vast lack of fundamental knowledge about the processability of cobalt. Said processing has been affected from the point of view of mineralogy, that is, understanding and knowing the cobalt-bearing minerals, as well as gangue mineralogy, these aspects exercise significant control during their processing and selection of the most appropriate route. suitable for cobalt extraction (leaching and/or flotation). In this context, the document concludes with a vision of the challenges that the mining industry must implement to enter circular economy models, mainly in the creation of sustainable processes from secondary sources.

Metabolic Syndrome (MetS) is a serious condition that significantly increases the risk of cardiovascular diseases and the severity of type 2 diabetes, also impacting on the development and evolution of other chronic diseases. Predicting metabolic syndrome is a complex task due to the multifactorial nature of this condition, which involves a combination of various risk factors such as abdominal obesity, insulin resistance, dyslipidemia, and hypertension. The complex interplay of these factors makes it challenging to predict the syndrome. Both genetic predisposition and environmental factors also contribute to the development of metabolic syndrome. Metabolic syndrome affects diverse populations with different ethnicities, lifestyles, and socioeconomic backgrounds. Prediction models, in addition, need to account for population heterogeneity and consider variations in risk factors across different groups. The present study analyzed data from participants in a cohort from Mexico City to identify key risk factors in men and women, addressing the presence of unbalanced data. In order to tackle the issues posed by data imbalance data, SMOTE and ADASYN were applied to assess significant differences in the selection of risk factors for MetS prediction. Random Forest and RPART models using ADASYN and SMOTE demonstrated better performance, achieving a balanced accuracy of approximately 87%. In women, they highlighted sleep quality, anxiety factors, tobacco consumption, and nutritional components. In the case of men, stronger associations were identified with the social development index and factors related to gout in parents.

Recent advances in DNA sequencing technology have shown that the human milk microbiota of healthy women varies substantially. The gDNA extraction method may influence the observed variation, biasing the microbiological reconstruction after all. In this study, a genomic DNA extraction method for DNA isolation from human milk samples was standardized and compared with commercial and standard hose make methods. Spectrophotometric measurements, gel electrophoresis, and PCR amplifications were used as criteria for evaluating the quantity, quality, and functionality of the extracted DNA. Furthermore, the standardized method of extracting gDNA from human milk was evaluated for its ability to isolate functional DNA from gram-positive, and gram-negative bacteria and fungi, to improve the reconstruction of microbiological profiles. The novel DNA extraction method increased the quantity and quality of the gDNA extracted compared with commercial and standard house-make protocols. This method even allowed PCR amplification of the V3-V4 regions of the 16S ribosomal gene in all samples, and the ITS-1 region of the fungal 18S ribosomal gene in 95 % of the samples as well. It is concluded that the proposed method provides better performance for the extraction of gDNA from complex samples such as human milk.

What do you want to do ?New mailCopyBackground: to analyze the changes that a therapeutic physical exercise program is capable of causing in the functionality of patients suffering from ALS and in addition, to analyze the respiratory capacity. Methods: a systematic review of the PubMed, SCOPUS, Cochrane, SciELO, PEDro, CINAHL and MEDline databases is carried out. The information was filtered using the following MeSH terms: "Amyotrophic lateral sclerosis", "Physical Therapy", "Physical and Rehabilitation Medicine". Clinical trials published in the last 5 years were included in which one of the interventions was therapeutic physical exercise in patients with ALS, which included the ALSFRS-R as a result variable. Results: 10 clinical trials with a total of 421 patients were analyzed, of which 183 underwent rehabilitation with physical exercise and were part of the case group; the rest belong to the control group and their treatment was mostly passive. The observed trend is of a decrease of approximately 6 points in the ALSFRS-R scale at 6 months in the case groups; however, no behavior pattern was met in the controls. Conclusions: Therapeutic physical exercise could contribute to slow down the deterioration of the musculature of people with ALS, thus facilitating the performance of their daily activities.

Background: to analyze the changes that a therapeutic physical exercise program is capable of causing in the functionality of patients suffering from ALS and in addition, to analyze the respiratory capacity. Methods: a systematic review of the PubMed, SCOPUS, Cochrane, SciELO, PEDro, CINAHL and MEDline databases is carried out. The information was filtered using the following MeSH terms: "Amyotrophic lateral sclerosis", "Physical Therapy", "Physical and Rehabilitation Medicine". Clinical trials published in the last 5 years were included in which one of the interventions was therapeutic physical exercise in patients with ALS, which included the ALSFRS-R as a result variable. Results: 10 clinical trials with a total of 421 patients were analyzed, of which 183 underwent rehabilitation with physical exercise and were part of the case group; the rest belong to the control group and their treatment was mostly passive. The observed trend is of a decrease of approximately 6 points in the ALSFRS-R scale at 6 months in the case groups; however, no behavior pattern was met in the controls. Conclusions: Therapeutic physical exercise could contribute to slow down the deterioration of the musculature of people with ALS, thus facilitating the performance of their daily activities.What do you want to do ?New mailCopy

High rates of resistance to antibiotics are associated with healthcare-related infections, thus appealing for the urgent need for effective antimicrobials against these maladies. The present study aims to determine the chemical composition of essential oil (EO) from Clausena anisata leaves, and evaluate their antibacterial activity against selected nosocomial bacteria. Fresh leaves of Clausena anisata were subjected to a steam distillation using a Clevenger apparatus to afford the essential oil. The phytochemical composition of this oil was analyzed using gas chromatography-mass spectrometry (GC-MS). The essential oil was further tested against selected nosocomial bacteria, including Staphylococcus and Klebsiella species, among others, using a microdilution method. As a result, 0.77% of essential oil was extracted from fresh leaves of Clausena anisata. The GC-MS analysis revealed that the as-prepared essential oil contain E-anethole (70.77%), methyl isoeugenol (13.85%), estragole (4.10%), γ-terpinene (3.33%), myrcene (2.82%) and sabinene (0.77%), with E-anethole being the major constituent. Meanwhile, twenty two compounds were identified in the EO of Clausena anisata leaves through gas chromatography. Upon antibacterial test against selected nosocomial pathogens, the E-anethole-rich essential oil exhibited minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 3.91 to 125 µg/mL and 7.81 to 125 µg/mL, respectively, indicative of a bactericidal orientation of the plant’s essential oil (MIC/MBC ratio: 4). This novel contribution highlights the scientific validation of the use of Clausena anisata leaves in the traditional treatment of various infectious diseases. However, toxicity and pharmacokinetic studies, mechanistic basis of the antibacterial action, and in vivo antibacterial experiments of the E-anethole-rich essential oil of Clausena anisata should be investigated to successfully use this plant in the treatment of infectious diseases.

Microplastics (MPs) quantification in benthic marine sediments is typically performed by time-consuming and moderately accurate mechanical separation and microscopy detection. In this paper we describe the results of our innovative Polymer Identification and Specific Analysis (PISA) of microplastic total mass, previously tested on either less complex sandy beach sediment or less demanding (because of the high MPs content) wastewater treatment plant sludges, applied to the analysis of benthic sediments from a sublittoral area north-west of Leghorn (Tuscany, Italy). Samples were collected from two shallow sites characterized by coarse debris in a mixed seabed of Posidonia oceanica, and by a very fine silty-organogenic sediment, respectively. After sieving at &lt;2 mm the sediment was sequentially extracted with selective organic solvents and the two polymer classes polystyrene (PS) and polyolefins (PE and PP) were quantified by pyrolysis-GC/MS. A contamination in the 8-65 ppm range by PS could be accurately detected. Acid hydrolysis on the extracted residue to achieve total depolymerization of all natural and synthetic polyamides, tagging of all aminated species in the hydrolyzate with a fluorophore, and reversed-phase HPLC (RP-HPLC) analysis, allowed to quantify within the 137-1523 ppm range the individual mass of contaminating Nylon 6 and Nylon 6,6, based on the detected amounts of the respective monomeric amines 6-aminohexanoic acid (AHA) and hexanediamine (HMDA). Finally, alkaline hydrolysis of the residue from acid hydrolysis followed by RP-HPLC analysis of the purified hydrolysate showed contamination by polyethylene terephthalate (PET) in the 12.1-2.7 ppm range, based on the content of its comonomer, terephthalic acid.

The flexitarian diet, which emphasizes a reduction in meat consumption, has been identified as a crucial factor in transitioning to sustainable food systems that can help combat climate change and improve food and nutritional security, particularly in areas where food choices are abundant. Despite Brazil being a major meat producer, meat consumption among Brazilians has been decreasing in recent years, with a growing portion of the population adopting meat-free and meat-reduced dietary models. In this study, we conducted the first non-industry funded scientific investigation of Brazilian flexitarians, with the goal of characterizing their socio-economic and demographic characteristics, motivations for adopting flexitarianism, frequency of animal-based meat consumption, and main substitutes consumed. Data was collected from 1029 self-identified flexitarians in Brazil. Our findings indicate that the flexitarian food model is primarily adopted by women and is motivated by concerns about the environmental impact of meat consumption, personal health, and animal welfare. Flexitarians were found to have a consumption profile that can be divided into three groups: low (consuming meat 36 times a week), medium (consuming meat 7 times a week), and high (consuming meat 4 times a week). The flexitarian meals pattern is characterized by lower consumption of beef (less than 2 times per week) and higher consumption of chicken (3 times per week) and is supplemented by plant-based protein sources and eggs as the main meat substitutes.

Previously we demonstrated, in rats, that the treatment with growth hormone (GH) and rehabilitation, carried out immediately after a motor cortical ablation, significantly improved the motor affectation produced by the lesion and induced the re-expression of nestin in the contralateral motor cortex. Here we analyze cortical proliferation after ablation of the frontal motor cortex and investigate the re-expression of nestin in the contralateral motor cortex and the role of the striatum and thalamus in motor recovery. The rats were subjected to ablation of the frontal motor cortex in the dominant hemisphere or sham-operated and immediately treated with GH or vehicle (V), for five days. At 1 dpi (days after injury), 5 rats received daily injections (4 days) of bromodeoxyuridine and were sacrificed. The other 15 rats (n = 5 / group) underwent treatment and rehabilitation and were sacrificed at 25 dpi. GH induced the greatest number of proliferating cells in the perilesional cortex. GH and rehabilitation produced the functional recovery of the motor lesion and increased the expression of nestin in the striatum. In the thalamic ventral nucleus ipsilateral to the lesion, cells positive for nestin and actin were detected, but this was independent of GH. Our data suggest that GH-induced striatal nestin is involved in motor recovery.

Medicinal plants are being tested as options to prevent infectious diseases in many countries. Baccharis crispa Spreng. (Asteraceae), is a native medicinal species widely used throughout South America. Our objective was to evaluate the antiviral activity of four wild populations of B. crispa from the province of Córdoba (Argentina) and determine if there is variability between them. The cytotoxicity of the extracts (chlorofom, ethanol and aquose) was evaluated by the neutral red uptake method. Using the plaque-forming unit reduction assay, virucidal and antiviral activity against Herpes Simplex type 1 and Chikungunya viruses were tested. Phytochemical screening of each extract was also performed. Puesto Pedernera (PP) population showed the best antiviral and virucidal effect, standing out the ethanolic extract as the least toxic and with the best inhibitory activity against both viral models. Villa del Parque (VP) population was inactive, regardless of the extract and the virus tested. The results revealed that extracts bioactivities vary significantly depending on the geographic area of collection, with PP and VP populations showing the most significant variability, not only in activity but also in chemical composition. These findings support the potential use of extracts as a source of therapeutic agents against different viruses.

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in-silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physiological conditions. Dynamic light scattering and size exclusion chromatography coupled with tetra detection were utilized to characterize the protein complexes, measure their concentrations, and calculate the equilibrium free binding energy, ΔGbind. In addition, PRODIGY, a QSAR-like model with excellent predictive ability, was employed to obtain in-silico ΔGbind estimations. The results obtained indicate that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. The difference in binding affinity was explained based on the contribution of the different interfacial contact (IC) descriptors to the ΔGbind value estimated by the PRODIGY model. Furthermore, experiments revealed that the pertuzumab IgG antibody binds preferentially to two HER2 proteins, one per Fab fragment, while trastuzumab mainly forms a monovalent complex. This finding was interpreted based on a geometrical model that identified steric crowding in the trastuzumab-HER2 complex as compared to the pertuzumab-HER2 complex.

Traumatic Brain Injury represents a significant public health concern due to its role in traumatic death and disability, often caused by head impacts or rapid accelerations. Despite advancements in Finite Element Head Models, existing models primarily represent adult males, neglecting anatomical and physiological differences between genders and age groups. Additionally, the mechanistic roles of specific intracranial tissues, such as the dura mater, have conventionally been overlooked. To better understand the mechanical behavior of the brain and its injured regions in the context of TBI, including the dura mater, this study proposes the development of a Female Finite Element Head Model. This model, representative of a middle-aged female subject, was developed using medical image-derived geometry and finite element modeling techniques. The validation results demonstrate a similarity between the numerical displacement curves and those obtained experimentally. In the model with dura mater, the numerical results show analogous behavior to the experimental results, despite minimal variations in the amplitude of the curves. These advancements highlight the significance of including the dura mater in biomechanical brain modeling. Incorporating the dura mater in Finite Element Head Models produces more realistic results than models without it. This emphasizes the importance of enhancing biomechanical models to better represent anatomical complexity.

The main commercial variety of coffee is the Coffea arabica specie, however, it is very susceptible to damage caused by nematodes, for this reason scions of the C. arabica specie are used on ro-busta (Coffea canephora) rootstocks to improve tolerance to these microorganisms, because they modify the organoleptic, nutraceutical and nutritional characteristics. The objective of this work was to assess the effect of five roasting degrees on commercial beans (light, medium light, medi-um, medium, medium dark and dark) in two varieties of Coffea arabica species (Colombia and Costa Rica) and their respective scions on C. canephora of the Romex variety. The scion of the Co-lombia variety with the medium dark roast had the highest concentration of caffeine, while the coffee beans of the Costa Rica variety with the light roast grade had the highest concentration of chlorogenic acid (5-CQA), while the highest acrylamide content was found in the scion of the Co-lombia variety with the medium light roast beans and nutritional content differs considerably between varieties, however, there is similarity between roasting degrees. The degree of roasting, variety and scion of coffee influences the organoleptic, nutraceutical and nutritional content of the coffee infusion.

Male infertility (MI) involves various endogenous and exogenous facts. These include oxidative stress (OS), which is known to alter several physiological pathways and it is estimated to be present at high levels in up to 80 % of infertile men. That is why since the late 20th Century, the relationship between OS and MI has been widely studied. New terms have emerged, such as Male Oxidative Stress Infertility (MOSI), which is proposed as a new category to define infertile men with high OS levels. Another important term is MOXI: Male, Antioxidants, and Infertility. Such term refers to the hypothesis that antioxidants could improve male fertility without the use of assisted reproductive technology. However, there is no evidence-based antioxidant treatments that directly improve seminal parameters or birth ratio. In this regard, there is controversy about their use. While certain scientists argue against their use due to the lack of results, others support this use because of their safety profile and low price. Some uncertainties related to the use of antioxidants for treating MI are their questionable efficacy or the difficulties to know their correct dosage. In addition, the lack of quality methods for OS detection can lead to an excessive antioxidant supplementation, resulting in “reductive stress”. Another important problem is that, although the inflammatory process is interdependent and closely linked to OS, it is usually ignored. To solve these uncertainties, new trends have recently emerged. These include the use of molecules with anti-inflammatory and antioxidant potential, and which are also able to specifically target the reproductive tissue; as well as the use of new methods that allow for reliable quantification of OS and a quality diagnosis. This review aims to elucidate the main uncertainties about MOXI and to outline the latest trends in research to achieve effective therapies with clinically relevant outcomes.

This research aims to explore the integration method of deep learning and large language models in speech recognition to improve the system’s recognition accuracy and ability to handle complex contexts. Deep neural network (DNN), convolutional neural network (CNN), long short-term memory network (LSTM) and Transformer-based large language model are used to build an integrated acoustic and language model framework. Experiments on TIMIT, LibriSpeech and Common Voice datasets show that the ensemble model shows significant improvements in both word error rate (WER) and real-time factor (RTF) compared to traditional models. Especially in terms of adaptability to multiple languages and accent changes, the model shows superior performance. The conclusion shows that through technology integration, the performance of the speech recognition system in complex environments can be effectively improved, providing a new direction for the future development of speech recognition technology.

SARS-CoV-2 attachment and entry inside mammalian cells is mainly mediated by human angiotensin-converting enzyme 2 (ACE2) and its interaction with spike protein. However, it is well known that spike protein also interacts with other molecules like glycosaminoglycans (GAG), e.g., heparan sulfate (HS) or Enoxaparin (EX), which are linear, anionically charged polysaccharides known for their biological activities. The mode of action of these two polysaccharides is to bind spike protein to block the interaction with ACE2 receptors. This study aimed to assess a model capable of confirming the activity of these GAGs in both the wild-type strain of SARS-CoV-2 and its variants, such as the highly variable BA.2.86. This was achieved by combining in silico modeling with in vitro determination using BacMam technology. The results showed the antiviral activity of HS and EX both in vitro and through the in-silico analysis, reconciling conflicting findings from recent studies on the cellular entry of SARS-CoV-2. In conclusion, it is possible to highlight the ability of these molecules to circumvent the high variability of SARS-CoV-2, providing valuable insights into intervention strategies targeting cell entry mechanisms and establishing a safe in vitro model.

Large language models (LLMs) excel in providing natural language responses that sound authoritative, reflect knowledge of the context area, and can present from a range of varied perspectives. Agent Based Models and Simulation consist of simulated agents that interact within a simulated environment to explore societal, social, and ethical, among other, problems. Agents generate large volumes of data over time and discerning useful and relevant content is an onerous task. LLMs can help in communicating agents’ perspectives on key events by providing natural language narratives. However, these narratives need to be factual, transparent, and reproducible. To this end, we present a structured narrative prompt for sending queries to LLMs. Chi-square tests and Fisher’s Exact tests are applied to assess statistically significant difference in sentiment scores of the narrative messages between simulation generated narratives, ChatGPT-generated narratives, and real tweets. The narrative prompt structure effectively yields narratives with the desired components from ChatGPT. This structure is expected to be extensible across LLMs. In 14 out of 44 categories, ChatGPT generated narratives which has sentiment scores that were not discernibly different, in terms of statistical significance (alpha level of 0.05), from the sentiment expressed in real tweets. Three outcomes are provided: (1) a list of benefits and challenges for LLMs in narrative generation; (2) a structured prompt for requesting narratives of a LLM based on simulated agents’ information; and (3) an assessment of statistical significance in the sentiment prevalence of the generated narratives compared to real tweets. This indicates significant promise in the utilization of LLMs for helping to connect simulated agent’s experiences with real people.

Ecosystem physical structure, defined by the quantity and spatial distribution of biomass, influences a range of ecosystem functions. Remote sensing tools permit the non-destructive characterization of canopy and root features, potentially providing opportunities to link above- and belowground structure at fine spatial resolution in functionally meaningful ways. To test this possibility, we employed ground-based portable canopy lidar (PCL) and ground penetrating radar (GPR) along co-located transects in forested sites spanning multiple stages of ecosystem development and, consequently, of structural complexity. We examined canopy and root structural data for coherence at multiple spatial scales ≤ 10 m within each site using wavelet analysis. Forest sites varied substantially in vertical canopy and root structure, with leaf area index and root mass more evenly distributed by height and depth, respectively, as forests aged. In all sites, above- and belowground structure, characterized as mean maximum canopy height and root mass, exhibited significant coherence at a scale of 3.5-4 meters, and results suggest that the scale of coherence may increase with stand age. Our findings demonstrate that canopy and root structure are linked at characteristic spatial scales, which provides the basis to optimize scales of observation. Our study highlights the potential, and limitations, for fusing lidar and radar technologies to quantitatively couple above- and belowground ecosystem structure.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder of the white matter. Pathophysiology is thought to be immune mediated as in most cases the condition follows an infection or triggering incident. More recent literature has demonstrated that there may be a link between autoimmune conditions and ADEM. Here we present a case of ADEM in a middle-aged woman with systemic lupus erythematosus that recovered well after treatment with corticosteroids and Rituximab.

The Vitamin D Receptor (VDR) mediates the actions of vitamin D, which has important roles in bone homeostasis, growth/differentiation of cells, immune functions and reduction of inflammation. Emerging evidences suggest that epigenetic modifications of the VDR gene, particularly DNA methylation, may contribute to the onset and progression of many human disorders. This review aims to summarize the available information on the role of VDR methylation signatures in different pathological contexts, including autoimmune diseases, infectious diseases, cancer and others. The reversible nature of DNA methylation could enable the development of therapeutic strategies, offering new avenues for the management of these worldwide diseases.

This review analyzes the preparation and characterization of metal organic frameworks (MOFs) and their application as photocatalysts for water purification. The study begins by highlighting the problem of water scarcity and the different solutions for purification, including photocatalysis with semiconductors such as MOFs. It also describes the different methodologies that can be used for the synthesis of MOFs, paying attention to the purification and activation steps. The characterization of MOFs and the different approaches that can be followed to learn on the photocatalytic processes are also detailed. Finally, the work reviews literature focused on the degradation of contaminants from water using MOF-based photocatalysts under light irradiation.

Traumatic brain injury represents one of the main health problems in developed countries. Growth Hormone (GH) and rehabilitation have been claimed to significantly contribute to the recovery of lost motor function after acquired brain injury, but the mechanisms by which this occurs are not well understood. In this work, we have investigated cell proliferation in the piriform cortex (PC) of adult rats with ablation of the frontal motor cortex treated with GH and rehabilitation, in order to evaluate if this region of the brain, related to the sense of smell, could be involved in benefits of GH treatment. Male rats were either ablated the frontal motor cortex in the dominant hemisphere or sham-operated and treated with GH or vehicle at 35 days post-injury (dpi) for five days. At 36 dpi, all rats received daily injections of bromodeoxyuridine (BrdU) for 4 days. We assessed motor function through the paw-reaching-for-food task. GH treatment and rehabilitation at 35 dpi significantly improved the motor deficit caused by the injury and promoted an increase of cell proliferation in the PC ipsilateral to the injury, which could be involved in the improvement observed. Cortical ablation promoted greater number of BrdU+ cells in the piriform cortex that was maintained long-term, which could be involved in the compensatory mechanisms of the brain after injury.

The fungal order Entomophthorales in the Zoopagomycotina includes many fungal pathogens of arthropods. This review explores five genera in the Erynioideae subfamily, namely Erynia, Furia, Pandora, Strongwellsea, and Zoophthora. This is the largest subfamily in the Entomophthorales including 125 described species. The species diversity, global distribution, and host range of this subfamily are summarized, revealing that relatively few taxa are geographically widespread, and few have broad host ranges, contrasting with a large number of species with single reports, from one location and one host species. The insect orders infected by the greatest numbers of species are the Diptera and Hemiptera. Across the subfamily relatively few species have been cultivated in vitro and those that have require more specialized media than any fungi. Given their potential to attack arthropods and in the fungal evolutionary tree, which species might be adopted for biological control purposes or biotechnological innovations are highlighted. Current challenges in the implementation of these species in biotechnology include the limited ability or difficulty in culturing many in vitro, a correlated paucity in genomic resources, and considerations regarding the host ranges of different species.

We tested the bioactivity of a dalbavancin + heparin (DH) vs. dalbavancin (D) against biofilms of Staphylococcus aureus ATCC43300 (MRSA) and Staphylococcus epidermidis ATCC35984 (MRSE) comparing DH median value of cfu counts and metabolic activity with that obtained for D before and during storage under freezing up to 6 months. The addition of heparin to a dalbavancin lock solution did not affect its bioactivity against staphylococcal biofilms irrespective of its preservation time under freezing.

Chlorogenic acid or 5-Caffeoylquinic acid is a polyphenolic component present in coffee and its by-products. Chlorogenic acid has been shown to exert biological properties, particularly in relation to glucose and lipid metabolism, including antibacterial, antioxidant, anti-inflammatory activities, among others. Due to its importance, it is necessary to evaluate the reliability of the analytical method for its determination in complex matrices such as food. In this work, different methods of chlorogenic acid extraction in coffee Silverskin were studied, as well as its quantification by HPLC. The results showed that the method of extraction with a mixture of methanol:water (3:1 v/v) in an ultrasonic bath, favored the recovery of chlorogenic acid with a recovery of 77.44%. The instrument detection limit for chlorogenic acid was 3.311 µg/mL and the quantification limit was 11.037 µg/mL. For coffee Silverskin, the concentration obtained of chlorogenic acid by the three extraction methods evaluated was in the range of 57 to 224 mg/kg of coffee silverskin (dry basis).

In the pursuit of functional foods that promote health, nanoliposomal carriers have been used to enhance the stability and functionality of dairy products such as yogurt, promising therapeutic benefits. This study aimed to evaluate the impact of fucoxanthin-loaded nanoliposomes in yogurt on its antioxidant, physico-chemical, and rheological properties under cold storage (21 days). Fucoxanthin-loaded nanoliposomes were prepared using the ultrasonic film dispersion technique and added at concentrations of 0%, 5% and 10% at the yogurt (Y-C, Y-FXN-5, Y-FXN-10). Homogeneous and uniform nanoliposomes (98.28 nm) were ob-tained, preserving their integrity and functionality, and ensuring prolonged release and bioavailability of fucoxanthin. Y-FXN-10 maintained the highest antioxidant activity according to the DPPH (52.96%), ABTS (97.97%), and FRAP (3.16 mmol ET/g) methods. This formulation exhibited enhanced erythroprotective potential, inhibiting hemolysis, photohemolysis, and heat-induced hemolysis, thereby preventing lipid pe-roxidation. However, viscosity and firmness decreased, affecting the texture and appearance. Sensory properties such as color, flavor, aftertaste, texture, and overall acceptance improved with the 10% fuco-xanthin-enriched yogurt formulation. These results suggest that nanoliposomal are suitable for carries fuco-xanthin, their incorporation into food matrices is key to developing functional foods. Regulatory approvals and consumer perceptions regarding nanotechnology-based products must be addressed, emphasizing their safety and health benefits.