Mitochondrial dysfunction and oxidative stress are thought to be relevant to the pathogenesis of age-related macular degeneration (AMD). Glutathione (GSH) homeostasis fulfills a number of important roles in mitochondria, such as maintenance of mitochondrial DNA and respiratory competency of cells. Although the transport of mitochondrial GSH (mGSH) is not fully understood, increasing evidence from non-ocular tissues suggests that OGC (2-oxoglutarate carrier, SLC25A11) and DIC (dicarboxylate carrier, SLC25A10) are involved in mGSH transport. However, whether OGC and DIC mediate the transfer of GSH into the mitochondria of retinal pigment epithelial cells (RPE) remains unknown. Thus, we investigated the expression, localization, and function of OGC and DIC in human RPE (hRPE) in relation to oxidative stress and GSH. Both OGC and DIC are expressed in hRPE and are localized in mitochondria. We also found a dose and time-dependent decrease of OGC and DIC expression under oxidative stress and increased expression in polarized RPE. Our data show that the downregulation of OGC and DIC resulted in increased apoptosis and mGSH depletion which can be overcome by co-treatment with GSH-MEE. These findings suggest that overexpression of OGC and DIC may be an effective strategy to decrease susceptibility to mitochondrial toxicants by elevation of mGSH.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

Drug repurposing is a valuable tool for combating the slowing rates of novel therapeutic discovery. The Computational Analysis of Novel Drug Opportunities (CANDO) platform performs shotgun repurposing of 2030 indications/diseases using 3733 drugs/compounds to predict interactions with 46,784 proteins and relating them via proteomic interaction signatures. An accuracy is calculated by comparing interaction similarities of drugs approved for the same indications. We performed a unique subset analysis by breaking down the full protein library into smaller subsets and then recombining the best performing subsets into larger supersets. Up to 14% improvement in accuracy is seen upon benchmarking the supersets, representing a 100–1000 fold reduction in the number of proteins considered relative to the full library. Further analysis revealed that libraries comprised of proteins with more equitably diverse ligand interactions are important for describing compound behavior. Using one of these libraries to generate putative drug candidates against malaria results in more drugs that could be validated in the biomedical literature than the list suggested by the full protein library. Our work elucidates the role of particular protein subsets and corresponding ligand interactions that play a role in drug repurposing, with implications for drug design and machine learning approaches to improve the CANDO platform.

Drug repurposing, the practice of utilizing existing drugs for novel clinical indications, has tremendous potential for improving human health outcomes and increasing therapeutic development efficiency. The goal of multidisease multitarget drug repurposing, also known as shotgun drug repurposing, is to develop platforms that assess the therapeutic potential of each existing drug for every clinical indication. Our Computational Analysis of Novel Drug Opportunities (CANDO) platform for shotgun multitarget repurposing implements several pipelines via large scale modelling and simulation of interactions between comprehensive libraries of drugs/compounds and protein structures. In these pipelines, each drug is described by an interaction signature that is then compared to all other signatures that are then sorted and ranked based on similarity. Pipelines within the platform are benchmarked based on their ability to recover known drugs for all indications in our library, and predictions are generated based on the hypothesis that (novel) drugs with similar signatures may be repurposed for the same indication(s). The drug-protein interactions in the platform used to create the drug-proteome signatures may be determined by any screening or docking method but the primary approach used thus far has been an in house similarity docking protocol. In this study, we calculated drug-proteome interaction signatures using the publicly available molecular docking method Autodock Vina and created hybrid decision tree pipelines that combined our original bio- and cheminformatic approach with the goal of assessing and benchmarking their drug repurposing capabilities and performance. The hybrid decision tree pipeline outperformed the corresponding two docking-based pipelines it was synthesized from, yielding an average indication accuracy of 13.3% at the top10 cutoff (the most stringent), relative to 10.9% and 7.1% for its constituent pipelines, and a random control accuracy of 2.2%. We demonstrate that docking based virtual screening pipelines have unique performance characteristics and that the CANDO shotgun repurposing paradigm is not dependent on a specific docking method. Our results also provide further evidence that multiple CANDO pipelines can be synthesized to enhance drug repurposing predictive capability relative to their constituent pipelines. Overall, this study indicates that pipelines consisting of varied docking based signature generation methods can capture unique and useful signal for accurate comparison of drug-proteome interaction signatures, leading to improvements in the benchmarking and predictive performance of the CANDO shotgun drug repurposing platform.

This paper aims to examine the potential for ecotourism development in the Pulicat Lake, a proposed Ramsar site situated in the Indian states of Andhra Pradesh and Tamil Nadu. Pulicat Lake has enormous potential for tourism and recreation; however, it is inevitable to ensure sustainable development in the region. The data for the study was collected using various methods, including case study techniques, qualitative interviews, observations, and information obtained from secondary sources. The study aimed to identify the sustainability dimensions of the location, including economic impact and income generation potentials through employment opportunities like field guides and travel companions. It is also examined the social impact on the local community and the development efforts made to reduce environmental pressures while conserving the flora and fauna. Additionally, the study discusses the possibilities and strategies for ornithological ecotourism at Pulicat Lake.

As gravitation and electromagnetism are closely analogous long-range interactions, and gravitation is formulated in terms of geometry in general relativity (GR), we expect the latter also to appear through the geometry. This unification has however remained an unfulfilled goal. The goal is achieved here in a new theory, which results from the principles of equivalence and Mach supplemented with a novel insight that the field tensors in a geometric theory of gravitation and electromagnetism must be traceless, since these long-range interactions are mediated by virtual exchange of massless particles whose mass is expected to be related to the trace of the field tensors. Hence the Riemann tensor, like the analogous electromagnetic field tensor, must be traceless. Thence emerges a scale- invariant, Machian theory of gravitation and electrodynamics unified, wherein the vanishing of the Ricci tensor appears as a boundary condition. While the field equations of the theory are given by the vanishing divergence of the respective field tensors and their duals, the matter and charge emerge from the spacetime. A quantitative formulation of the emergent fields embodied in ‘energymomentum super tensors’ follows from the respective Bianchi identities for the two fields. The resulting theory is valid at all scales and explains the observations without invoking the non-baryonic dark matter, dark energy or inflation. Moreover, it answers the questions that the GR-based standard paradigm could not address.

The worldwide outbreak of SARS-CoV-2 in early 2020 caused numer- ous deaths and unprecedented measures to control its spread. We employed our Computational Analysis of Novel Drug Opportunities (CANDO) multiscale therapeutic discovery, repurposing, and design platform to identify small molecule inhibitors of the virus to treat its resulting indication, COVID-19. Initially, few experimental studies existed on SARS-CoV-2, so we optimized our drug candidate prediction pipelines using results from two independent high-throughput screens against prevalent human coronaviruses. Ranked lists of candidate drugs were generated using our open source cando.py software based on viral protein inhibition and proteomic interaction similarity. For the former viral protein inhibition pipeline, we computed interaction scores between all compounds in the corresponding candidate library and eighteen SARS-CoV proteins using an interaction scoring protocol with extensive parameter optimization which was then applied to the SARS-CoV-2 proteome for prediction. For the latter similarity based pipeline, we computed interaction scores between all compounds and human protein structures in our libraries then used a consensus scoring approach to identify candidates with highly similar proteomic interaction signatures to multiple known anti-coronavirus actives. We published our ranked candidate lists at the very beginning of the COVID-19 pandemic. Since then, 51 of our 276 predictions have demonstrated anti-SARS-CoV-2 activity in published clinical and experimental studies. These results illustrate the ability our platform to rapidly respond to emergent pathogens and provide greater evidence that treating compounds in a multitarget context more accurately describes their behavior in biological systems.

Mushrooms have been an invaluable ingredient in terms of food and medicine to humanity since time immemorial. Mushrooms have been shown to be possessing properties such as anti-tumor, antiproliferative, antioxidant, immunomodulatory, anti-diabetic. Traditional Czech republic medicine involved using Piptoporus betulinus in curing colorectal cancer; similarly, fruiting bodies of Inonotus obliquus were employed in Folk medicine in eastern Europe since the 16^th century. The oriental practice of utilizing mushrooms has witnessed an overwhelming attentiveness from the global research fraternity in exploring its wonder substances. Cancer is one of the key problems faced by researchers in finding an efficient medicine without inducing severe health complications. Mushrooms contain a plethora of bioactive compounds involved in tumor inhibition, such as hispolon, lentinan, gannoderic acid, illudin-s, and many more. The current article briefly describes various edible mushrooms with anti-tumorigenic compounds and their effect on the cancer cells of various means.

Pharmaceutical packaging is very crucial in as much as it plays the role of enhancing the stability, efficacy as well as safety of the produced medicine through the material used in packaging. It is important to note that cGMP Chapters 661 and 671 are focused on explaining how one should assess the quality of container materials in the sphere of pharmaceuticals. These chapters encompass a number ofmatters among them being Plastic and glass containers and performance testing; they serve as a resource that aids in assuring all standards are met with profound proficiency. Following this, the performance of two core chapters of USP known as Chapter 661 on “Containers—Glass” and Chapter 671 on “Containers—Performance Testing” will be dealt with in a step-by-step manner in the following paper while providing a comprehensive review of both at the same time. Understanding and legal obedience to these rules, as stipulated in the above-mentioned chapter, are indispensable for almost all the parties involved in the production of the drugs, together with the policies and legislation on the same. Thus, the purpose of this paper is to describe and discuss the major aspects of the understanding, application, requirements and evaluation procedures depending on the USP Chapters 661 and 671 in the sphere of the pharmaceutical market.

An adaptive control technique has been implemented for DSTATCOM for power quality enhancement in three phase four wires(3P4W) distribution system. The reference source currents are extracted from active components of load current for each phase by using this technique. It has also been used for load balancing, harmonic suppression, power factor improvement and reactive power compensation in distribution system. The adaptive control technique has been tested at varying load in steady state and dynamic conditions. This technique is developed using MATLAB/Simulink and source side harmonics are mitigated under different load conditions which are acceptable in accordance with IEEE standard.

In statistics and probability theory, one of the most important statistics is the sums of random variables. After introducing a probability distribution, determining the sum of n independent and identically distributed random variables is one of the interesting topics for authors. This paper presents the probability density functions for the sum of n independent and identically distributed random variables such as Shanker, Akash, Ishita, Pranav, Rani, and Ram Awadh. In order to determine all aforementioned distributions, the problem-solving methods are applied which is based on the change-of-variables technique.

Bearing component damage contributes significantly to rotating machinery failures. It is vital for the rotor-bearing system to be in good condition to ensure proper functioning of the machine. Over recent decades, extensive research has been devoted to the condition monitoring of rotational machinery, with a particular focus on bearing health. This paper provides a comprehensive literature review of recent advancements in intelligent condition monitoring technologies for rolling element bearings. Fundamental monitoring strategies are introduced, covering various sensing, signal processing, and feature extraction techniques for detecting defects in rolling element bearings. While vibration-based monitoring remains prevalent, alternative sensor types are also explored, offering complementary diagnostic capabilities or detecting different defect types compared to accelerometers alone. Signal processing and feature extraction techniques, including time domain, frequency domain, and time-frequency domain analysis, are discussed for their ability to provide diverse perspectives for signal representation, revealing unique insights relevant to condition monitoring. Special attention is given to information fusion methodologies and the application of intelligent algorithms. Multisensor systems, whether homogeneous or heterogeneous, integrated with information fusion techniques, hold promise in enhancing accuracy and reliability by overcoming limitations associated with single sensor monitoring. Furthermore, the adoption of AI techniques, such as machine learning and metaheuristic optimisation, has led to significant advancements in condition monitoring, yielding successful outcomes in various studies. Finally, avenues for further advancements to improve monitoring accuracy and reliability are identified, offering insights into future research directions.

This research introduces Genus-Physiognomy-Ecosystem (GPE) mapping at a prefecture level through machine learning of multi-spectral and multi-temporal satellite images at 10m spatial resolution, and later integration of prefecture wise maps into country scale for dealing with 88 GPE types to be classified from a large size of training data involved in the research effectively. This research was made possible by harnessing entire archives of Level-2A product, Bottom of Atmosphere reflectance images collected by MultiSpectral Instruments onboard a constellation of two polar-orbiting Sentinel-2 mission satellites. The satellite images were pre-processed for cloud masking and monthly median composite images consisting of 10 multi-spectral bands and 7 spectral indexes were generated. The ground truth labels were extracted from extant vegetation survey maps by implementing systematic stratified sampling approach and noisy labels were dropped out for preparing a reliable ground truth database. Graphics Processing Unit (GPU) implementation of Gradient Boosting Decision Trees (GBDT) classifier was employed for classification of 88 GPE types from 204 satellite features. The classification accuracy computed with 25% test data varied from 65-81% in terms of F1-score across 48 prefectural regions. This research produced seamless maps of 88 GPE types first time at a country scale with an average 72% F1-score. In addition, mapping of solar panels and vegetation disturbance are added.

Utilization of Bidirectional Reflectance Distribution Function (BRDF) model parameters obtained from the multi-angular remote sensing is one of the approaches for the retrieval of vegetation structural information. In this research, the potential of multi-angular vegetation indices, formulated by the combination of multi-spectral reflectance from different view angles, for the retrieval of forest above ground biomass was assessed. This research was implemented in the New England region with the availability of a high quality forest inventory database. The multi-angular vegetation indices were generated by the simulation of the Moderate Resolution Imaging Spectroradiometer (MODIS) BRDF/Albedo Model Parameters Product (MCD43A1 Version 6) based BRDF parameters. The effects of seasonal (spring, summer, autumn, and winter) composites of the multi-angular vegetation indices on above ground biomass, angular relationship of the spectral reflectance with above ground biomass, and the interrelationships between the multi-angular vegetation indices were analyzed. Among the existing multi-angular vegetation indices, only the Nadir BRDF-adjusted NDVI ( and Hot-spot incorporated NDVI ( showed significant relationship (more than 50%) with the above ground biomass. This research proposed two more sensitive vegetation structural indices, Fore-scattering Back-scattering NDVI and Vegetation Structure Index (VSI). The Fore-scattering Back-scattering NDVI showed higher sensitivity (R² = 0.62, RMSE = 52.46) towards the above ground biomass than existing multi-angular vegetation indices. Furthermore, the VSI performed in the most efficient way explaining 64% variation of the above ground biomass, suggesting that the right choice of the spectral channel and observation geometry should be considered for improving the estimates of the above ground biomass. In addition, the right choice of seasonal data (summer) was found to be important for estimating the forest biomass while other seasonal data were either insensitive or pointless. The promising results shown by the VSI suggest that it could be an appropriate candidate for monitoring vegetation structure from the multi-angular satellite remote sensing.

This paper presents ensemble learning of multi-source satellite sensors dataset to obtain better predictive performance of the forest biomass. Spectral, spectral-indices, and spectral-textural features were generated from two optical satellite sensors, Landsat 8 Operational Land Imager (OLI) and Sentinel-2 Multispectral Instrument (MSI). In addition, two radar satellite sensors, Sentinel-1 C-band Synthetic Aperture Radar (CSAR), and Advanced Land Observing Satellite (ALOS-2) Phased Array type L-band Synthetic Aperture Radar (PALSAR-2) were utilized to generate backscattering and backscattering-textural features. The plot-wise above ground biomass data available from five forests in New England region were utilized. Ensemble learning of multi-source satellite sensors dataset was carried out by employing four machine learning regressors namely, Support Vector Machines (SVM), Random Forests (RF), Gradient Boosting (GB), and Multilayer Perceptron (MLP). A five-fold cross-validation method was used to evaluate predictive performance of the multi-source satellite sensors. The integration of multi-source satellite features, comprising of spectral, spectral-indices, backscattering, spectral-textural, and backscattering-textural information, through ensemble learning and cross-validation approach implemented in the research showed promising results (R² = 0.81, RMSE = 46.2 Mg/ha) for the estimation of plots-level forest biomass in New England region.

Defect detection and identification from fruits and vegetables are particularly challenging for Indian agriculture. Defect Detection is a process to identify the defects or damages in vegetables and fruits, based on the shapes, colors and textures. The local market finds it difficult to cope with the defects and other infections in fruits and vegetables as quality evaluations and classification of vegetables and fruits have become tedious process. Recently, several approaches based on Image processing, Machine Learning and Artificial Intelligence methods have been proposed for the purpose of defect detection. On the basis of classifying the types of defects, related pathogens, and physical and morphological characteristics descriptors, we review the different approaches based on a corpus of 57 articles between 2016 and 2021. In the process of describing the defect analysis, steps from the target articles, algorithms, and methods including qualitative and quantitative evaluation are mainly summarized. The aim of this current review work is to present-day novel images and collects recent defective area calculation methods to detect surface defects of fruits and vegetables using RGB images and to classify whether the fruit is defected or fresh. A rigorous evaluation of many new algorithms provided for quality assurance by researcher’s probes of vegetables and fruits have been conducted in this work. This review work conveys that using the recent identification features will help to decrease the disadvantages in fruit storeroom owing to storage of the affected vegetables and fruits, ie. Preventing the spread of defects and other infections from the infected fruits and vegetables to the fresh ones.

In this paper, we discuss major issues of mathematics teaching and learning in Nepal. The issues coming from theories such as social and radical constructivism suggest that teachers are not trained to use such approach in teaching mathematics, and there is a lack of teaching aids and materials and technological tools. The issues related to social aspects are gender issues, language issues, social justice issues, and issues related to the achievement gap. The cultural issues are related to the diversity of language and ethnicity. The issues related to political aspects are equity and access, economic status, pedagogical choice, and professional organizations and unions. The issues related to technology include the technological skills, use of technology, and affordance. Finally, we suggest that all the stakeholders should pay attention to resolving these issues by improving the curriculum, training teachers, resourcing the classroom with locally made and new technological tools.

The impact of long-term soil and crop management practices on soil biological and chemical properties in oilseed brassica-based production systems were deliberated for holistic soil health improvement in the present study. Different tillage, crop residue re-cycling and cropping systems were studied for 5-years in 0-15 and 15-30 cm soil profiles. No-till permanent beds with crop residue (PB+R) noticeably improved soil organic carbon (SOC), microbial biomass carbon (MBC), enzymes [dehydrogenase (DHA) and alkaline phosphatase (AlP)], nitrogen fractions (available, nitrate and total), and available phosphorus and potassium content in both the soil layers compared to conventional tillage without crop residues. Though, the plow soil layer (0-15 cm) showed higher concentration of soil carbon, enzymes, N fractions and available P than in the sub soil (15-30 cm). The dynamic soil biological and chemical properties were also varied with the crop stage, and recorded higher MBC at 30 days, SOC and enzymatic activities at 60 days, and N fractions and available P and K at harvest of mustard crop. Green gram-mustard rotation showed higher values of biological and chemical parameters. Thus, the legume-based mustard crop rotation following no-till permanent beds and residue re-cycling found holistic in improving soil health, and nutrient cycling.

Broad-spectrum antifungal drug deployed for topical therapy, specific for onychomycosis, Itraconazole was used as the active pharmaceutical ingredient in a nail lacquer formulation¹. The objective of the study was to optimize an antifungal nail lacquer, which when applied topically onto the dorsal surface of the nail plate would facilitate the transungual penetration of the drug. Itraconazole hydrochloride was synthesized to aid the formulation of the lacquers. The optimization involved comparing four different formulations of 1%w/w Itraconazole nail lacquers containing combinations of penetration enhancers (Papain, Salicylic acid, Urea) based on their ability to facilitate diffusion of the drug through the nail plate over five days. The drug uptake was quantified by extracting the drug from the nail clippings and analyzing it. The tests conducted to account for the quality of the optimized formulation were drug content, spread ability, check for precipitation, and accelerated stability. The results demonstrated that the optimized 1%w/w Itraconazole nail lacquer contained 5%w/w Papain, 5 %w/w Salicylic Acid, and 2.8% w/w Urea. The drug uptake from nail clippings was higher than the literature derived reference MIC90 value for T. Rubrum strain, and the quality of the optimized lacquer was not compromised throughout three weeks [2]. The hypothesis stated that the inclusion of Salicylic acid, Papain, and Urea in an Itraconazole (1%w/w) nail lacquer would have the highest transungual penetration on application to the nail plate. In conclusion, the hypothesis was accepted, and the optimized lacquer passed the drug uptake evaluation and all quality control tests.

Nanowater (NW-water declusterized in the cold plasma generator) can potentially ameliorate ram semen quality after freezing. Eighteen ejaculates from six Olkuska rams were divided into six equal portions each, and then diluted (800 × 106 spermatozoa/ml) and frozen in the fructose-skimmed milk-egg yolk Kareta extender containing 3% or 7% of glycerol (C3% and C7%) and diluted in deionized water (DW) or NW declusterized for 15 min (NW15)’ or 30 min (NW30’). All frozen-thawed semen samples were subjected to standard evaluation. In addition, ex situ survival time of spermatozoa was measured, and the proportions of apoptotic, necrotic and live sperm were determined by flow cytometry. The percentage of spermatozoa with mid-piece defects was lower (p < 0.05) in NW15’-3% compared with C3%. The mean survival time of spermatozoa was greater (p < 0.05) in NW30’ extenders compared with their respective controls. The proportion of necrotic spermatozoa 1 h after thawing was greater (p < 0.05) in C7% compared with NW30’-7%, whereas the proportion of live cells detected immediately and 1 h after thawing were greater (p < 0.05) in NW30’-7% than in C7%. NW enhanced cryoprotective effects of glycerol-containing extenders with an overall increase in sperm survivability being greater with 7% than 3% of glycerol.

The guthi, an ancient institution deeply embedded in Nepal's social, cultural, and economic fabric, has long overseen the maintenance of temples, shrines, festivals, and heritage sites since the Lichchhavi era (400-750). Since 1960, however, this system has been challenged by government land reforms, which has impacted its influence on sustainable heritage conservation. Nevertheless, there's compelling evidence that land nationalization and the guthi's declining authority have harmed local heritage conservation. Nevertheless, the guthi system has endured, serving as an important informal means of heritage conservation and highlighting the adaptability of traditional institutions. These community-based trusts, originally established for social and religious purposes, have played a pivotal role in preserving cultural practices, monuments, and temples for future generations. This article aims to demonstrate the central role of the guthi as the cornerstone of Nepal's efforts to conserve and manage both tangible and intangible cultural treasures. Using observational techniques, case studies, and a qualitative approach, it explores the historical evolution of heritage conservation through the lens of the guthi, taking into account subjective, valued, and constructed realities. The paper concludes by urging policymakers to recognize the significant contribution of indigenous systems such as the guthi in achieving sustainable heritage conservation. Embracing such traditional strategies can mitigate multifaceted problems and effectively preserve Nepal's cultural heritage through the guthi.

The biological synthesis of nanoparticles has been emerging as an environmentally benign and eco-friendly method owing to its cost-effectiveness and high efficiency. Recently, the biological synthesis of semiconductor and metal-doped semiconductor nanoparticles with enhanced photocatalytic degradation efficiency and anticancer and antibacterial properties have gained tremendous attention. In pursuit of this purpose, for the first time, we biosynthesized zinc oxide (ZnO) and silver/ZnO nanocomposites (NCs) as semiconductor and metal-doped semiconductor nanoparticles, respectively, using the cell-free filtrate (CFF) of Lysinibacillus sphaericus bacterium. The biosynthesized ZnO and Ag/ZnO were characterized by various techniques such as ultraviolet-visible spectroscopy, X-ray diffraction, Fourier-transform Infrared spectroscopy, Field-emission scanning electron microscopy, transmission electron microscopy, and photoluminescence spectroscopy. The photocatalytic degradation potential of these semiconductor/metal-semiconductor nanoparticles was evaluated against the degradation of azo dye methylene blue (MB) under simulated solar irradiation. Ag/ZnO showed 90.7 ± 0.91% photocatalytic degradation of MB, compared to 50.7 ± 0.53% by ZnO in 120 min. The cytotoxicity of ZnO and Ag/ZnO on human cervical HeLa cancer cells was determined using an MTT assay. Both nanomaterials exhibited cytotoxicity in a concentration-dependent and time-dependent manner on HeLa cells. The antibacterial activity was also determined against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus). Compared to ZnO, Ag/ZnO NPs showed higher antibacterial activity. Hence, the biosynthesis of semiconductor nanoparticles could be a promising strategy for developing hybrid metal/semiconductor nanomaterials for different biomedical and environmental applications.

The main inhibitory neurotransmitter in the mammalian brain is 4-aminobutyric acid (GABA). Phthalimide acts as a sodium channel antagonist, one of the finest targets for treating epilepsy is the sodium channel and JNK kinase activity is inhibited to treat epilepsy. a novel compound with multiple targets of action for the treatment of epilepsy also anti-oxidant activity has been designed. The compounds are designed in two series aldehydes and aniline. Docking of all the designed compounds has been done with the suitable protein GABA-AT, sodium channel, JNK protein, and anti-oxidant from protein bank. QSAR was done for constructing many linear regression models. In combination with the developed Docking and QSAR outcomes, ADMET has been performed for the active compounds. The result shows that 11 of the compounds have excellent binding energy in docking with all the receptors and also have good QSAR results and follow the ADMET. The structural understanding of human GABA-AT inhibition was obtained from molecular dynamics simulation studies for compound no. 11 at 5 nanoseconds. Synthesis and pharmacological activity also suggest that the designed compound no.11 be considered the best Novel Compound.

Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated influenza virus vaccines (LAIVs) are thought to induce both humoral and cellular immune responses by mimicking a natural infection, but their effectiveness have recently come into question. Thus, the opportunity exists to find alternative approaches to improve overall influenza vaccine effectiveness. Two alternative IBV backbones were developed with re-arranged genomes, re-arranged M (FluB-RAM) and a re-arranged NS (FluB-RANS). Both re-arranged viruses showed temperature sensitivity in vitro compared to the WT type B/Bris strain, were genetically stable over multiple passages in embryonated chicken eggs and were attenuated in vivo in mice. In a prime-boost regime in naïve mice, both re-arranged viruses induced antibodies against HA with hemagglutination inhibition titers considered of protective value. In addition, antibodies against NA and NP were readily detected with potential protective value. Upon lethal IBV challenge, mice previously vaccinated with either FluB-RAM or FluB-RANS were completely protected against clinical disease and mortality. In conclusion, genome re-arrangement renders efficacious LAIV candidates to protect mice against IBV.

This paper explores the application of machine learning (ML) algorithms in predicting trends in the fixed bond market, where traditional analytical methods have proven inadequate. Focusing on various ML techniques such as supervised and unsupervised learning, neural networks, and deep learning, the study evaluates their effectiveness in forecasting market movements. It details a series of experiments in which different ML models are rigorously trained and tested against historical bond market data. The findings reveal that models employing time series analysis and advanced deep learning show marked potential in accurately predicting bond market trends. Additionally, the paper delves into the challenges and limitations inherent in these ML approaches, including data requirements and the risk of model overfitting. Finally, it proposes directions for future research, emphasizing the integration of ML into broader financial market analysis.

Without the use of medicine drones, users are responsible for transporting goods at a high cost. The goal of this patient monitoring system is to identify people's health and, if necessary, administer medicine. The transportation drone is capable of finding healthcare information in a 360-degree rotation within the transportation infrastructure. IoT: Drone doctors are critical for the transportation of small gadgets such as drug treatments, blood leakages, and vaccines in the critical conditions of a heart patient, in the event of failure of traffic location infrastructure, highway roads, or hospitals due to intense climate or site visitor congestion, and for the transportation of small gadgets such as drug treatments, blood leakages, and vaccines. When transmission is difficult, the self-maintaining drone is the format for quickly transporting drug treatments to the appropriate locations. The shipping drone equipped with an Ardupilot can drive in autopilot mode, which guides the drone to its destination. It has a 7-minute flying period and can deliver up to 2 kg of medicine. When the detected heartbeat is 94bpm and the fever range is 101 degrees, a method has been presented in which an IoT Drone Doctor (IDD) System distributes the first AID box to vulnerable patients and heart patients.

: Belize is located within the Mesoamerican biodiversity hotspot and is an important link between critical biodiverse habitats in Central America. Despite considerable research on biodiversity in marine environments of Belize, research in freshwater environments is limited, with the most recent checklists having been published in obscure, mostly unavailable references more than 20 years ago.Belize is currently experiencing serious degradation of some of its major freshwater resources such as the New River in the northern part of the country. These unique habitats are increasingly threatened by agro-urban development, invasive species and erratic climatic events. The economically important barrier coral reef is also experiencing impacts from the degraded freshwater watersheds that empty into the sea near the reefs. This work addresses the paucity of documentation of the freshwater fishes of Belize, particularly for the Shipstern Peninsula area. The Shipstern Peninsula is a unique region in northern Belize, adjacent to the southern border of Mexico and the northeastern end of the Corozal Bay Wildlife Sanctuary. This paper reports on fish collected in 2015, with comparisons to historical data in surveys published in 1990, 1993, and 1997. We report on 12 genera/species collected in 2015 and provide molecular barcode data on several, which was not available in previous publications. Floridichthys polyommus, a new observation for the Shipstern Lagoon, and Dajaus monticola, a revised name and new observation for the Inland Blue Hole, were confirmed by barcodes. This update is vital to the continued management of freshwater environments in Belize, and especially for the Shipstern Peninsula and its important habitats held in trust for perpetuity for the Belizean people.

A review is here provided on the thermal effects on the optical chirality. To this goal, chiral objects dispersed in an embedding fluid are examined for their magnetoelectric coupling. Archetypal twisted-Omega particles are examined with respect to electron transport, phonon dynamics, and temperature effects. Continuum-mechanical aspect of thermo-elasticity is reviewed along with transverse deformations. A transition temperature delineating a sign flip in the chirality parameter is identified as well.

A review is here provided about the thermal effects on the optical chirality. To this goal, chiral objects dispersed in an embedding fluid are examined for their magnetoelectric coupling. Thermal effects on several chiral meta-atoms and their ensembles are examined. To this goal, DNA-like helical structures are examined in detail. Mechanical aspect of thermo-elasticity is reviewed along with transverse deformations, while drawing analogies from condensed-matter physics. In this respect, chirality-induced spin selection is reviewed along with the temperature-mediated elec-tron-phonon interactions. A wide range of materials such as polymers and biological cells are also examined for temperature effects. A transition temperature delineating a sign flip in the chirality parameter is identified as well. Chirality-associated functionalities such as ratchet motions, switching, and modulations are investigated for their respective thermal effects. Issues of fabri-cating chiral meta-atoms are also discussed.

Abandoned, lost, or otherwise discarded fishing gear (ALDFG) is a primary contributor to the entanglement of numerous marine species. Utilizing digital media platforms like Google, Facebook, and Instagram we conducted an assessment of the detrimental effects of ALDFG and plastic litter, on the biodiversity of Italy's marine ecosystem. Our investigation revealed that plastic litter has adverse consequences on various forms of marine life, including reptiles, mammals, birds, fish, crustaceans, and mollusks, along different Italian geographical sub-areas. Several records of interaction between plastic and endangered and vulnerable marine species have been described. Our reports even highlight the impact on marine turtles, mainly on Caretta caretta. This is the first report of entangled with fishing nets in Cetorhinus maximus, Oblada melanura, Serranus scriba, Homarus gammarus, Octopus vulgaris, and Phoenicopterus roseus. Furthermore, we identified that ghost nets have repercussions for endangered and vulnerable marine species. This update sheds light on the ongoing adverse effects of ghost nets on the Italian marine ecosystem, yet it is crucial to acknowledge that the true extent of the problem remains underestimated.

Japan Aerospace Exploration Agency (JAXA) is going to launch Advanced Land Observing Satellite 3 (ALOS-3) after 2022. ALOS-3 satellite is capable of observing global land areas with wide swath (4000 km along-track direction and 70 km cross-track direction) at high spatial resolution (panchromatic: 0.8m, multispectral: 3.2m). Maintenance and updating of land cover and vegetation information at national level is one of the major goals of the ALOS-3 mission. This paper presents the potential of simulated ALOS-3 images for the classification and mapping of land cover and vegetation types at Genus-Physiognomy-Ecosystem (GPE) level. We acquired and simulated WorldView-3 images according to the configuration of the ALOS-3 satellite sensor and the simulated ALOS-3 images were utilized for the classification and mapping of land cover and vegetation types in three sites (Hakkoda, Zao, and Shiranuka) in northern Japan. This research dealt with 17 land cover and vegetation types in Hakkoda site, 25 land cover and vegetation types in Zao site, and 12 land cover and vegetation types in Shiranuka site. Ground truth data were newly collected in three sites, and we employed eXtreme Gradient Boosting (XGBoost) classifier with the implementation of 10-fold cross-validation method for assessing the potential of ALOS-3S images. The classification accuracies obtained in Hakkoda, Zao, and Shiranuka sites in terms of f1-score were 0.810, 0.729, and 0.805 respectively. The fine scale (3.2m) land cover and vegetation maps produced in the study sites showed clear and detailed view of the distribution of plant communities. Regardless of the limited number of the temporal images, ALOS-3S images showed high potential (at least 0.729 F1-score) for the land cover and vegetation classification in all three sites. The availability of more cloud free temporal scenes is expected for improved classification and mapping in the future.

COVID-19 affects many organs in our body, including the heart and lungs. COVID-19 cases that require hospitalization often exhibit pulmonary hypertension (PH) due to changes in the lung microvasculature in which the blood vessels become stiff, damaged, or narrow, causing increased pulmonary arterial pressure. This review examines the hypothesis that PH can lead to right ventricular hypertrophy (RVH) as a long-lasting aftereffect of COVID-19. Recent studies have shown that significant percentages of hospitalized patients develop right ventricular hypertension and right ventricular dilatation (RVD), which may lead to right ventricular failure and death. Despite recommendations for echocardiogram reports to include right ventricular wall thickness to assess RVH, few published reports have reported this parameter. Relevant studies on animal models of PH in which the timing of PH can be precisely controlled suggest that one to three weeks of PH can cause RVH. Thus, according to the hypothesis proposed here COVID-19 patients who have long-lasting severe disease (e.g., needed to be on a ventilator for one or more weeks) accompanied by PH and RVD may develop RVH as a long-lasting sequela outlasting the infection itself. Echocardiogram studies of recovered COVID-19 patients may determine whether oft-reported cardiovascular sequelae include RVH.

This paper introduces an innovative Particle Swarm Optimization (PSO) Algorithm in-corporating Sobol and Halton Random number samplings. It evaluates the enhanced PSO's performance against conventional PSO employing Monte Carlo Random Number Samplings. The comparison involves assessing the algorithms across nine benchmark problems and the renowned Travelling Salesman Problem (TSP). The re-sults reveal consistent enhancements achieved by the enhanced PSO utilizing Sob-ol/Halton samplings across the benchmark problems. Particularly noteworthy are the substantial improvements demonstrated by the enhanced PSO in solving the Travel-ling Salesman Problem. These findings underscore the efficacy of employing Sobol and Halton random number generation methods in enhancing algorithm efficiency.

The specificity and potency of venom components gives them a unique advantage in development of various pharmaceutical drugs. Though venom is a cocktail of proteins rarely is the synergy and association between various venom components studied. Understanding the relationship between various components is critical in medical research. Using meta-analysis, we found underlying patterns and associations in the appearance of the toxin families. For Crotalus, Dis has the most associations with the following toxins: PDE; BPP; CRL; CRiSP; LAAO; SVMP P-I & LAAO; SVMP P-III and LAAO. In Sistrurus venom CTL and NGF had most associations. These associations can be used to predict presence of proteins in novel venom and to understand synergies between venom components for enhanced bioactivity. Using this approach, the need to revisit classification of proteins as major components or minor components is highlighted. The revised classification of venom components needs to be based on ubiquity, bioactivity, number of associations and synergies. The revised classification will help in increased research on venom components such as NGF which have high medical importance.

Clinical pathogens especially Gram-negative bacteria developing resistance to third-generation cephalosporins are making the clinical outcome more complicated and serious. This study was undertaken to evaluate the distribution of extended-spectrum beta-lactamases in Tamil Nadu regions in India. For this study, clinical samples were collected from five different hospitals located in Tamil Nadu and ESBL producing Gram-negative isolates were characterized. Minimal inhibitory concentration (MIC) was performed using cefotaxime and ceftazidime. The blaESBL producing genes were screened using multiplex PCR for the genes, CTX-M group-1,-2,-8,-9,-26. Conjugation studies were performed using E. coli AB1157 as a recipient for the isolates harbouring plasmid-borne resistance following broth-mating experiment. In total, 1500 samples were collected and 599 Gram-negative bacteria were isolated that included Escherichia coli (n=233), Klebsiella pneumoniae (n=182), Pseudomonas aeruginosa (n=79), Citrobacter spp. (n=30), Proteus mirabilis (n=28), Salmonella spp. (n=21), Acinetobacter baumannii (n=12), Serratia spp. (n=6), Shigella spp. (n=4), Morganella morganii (n=3) and Providencia spp. (n=1). MIC results showed that 358 isolates were resistant to cefotaxime and ceftazidime. Further, ESBL gene amplification results showed that 19 isolates had CTX-M group-1 gene including E. coli (n=16), K. pneumoniae (n=2) and P. aeruginosa (n=1) whereas one M. morganii isolate had CTX-M group-9 gene in their plasmid. Through conjugation studies, 12/20 isolates were found to be involved in the transformation of its plasmid-borne resistance gene. Our study highlighted the role of horizontal gene transfer in the dissemination of plasmid-borne blaCTX-M resistance genes among ESBL producing isolates.

Minerals play many important functions in plant and animal metabolism. Therefore, we investigated the concentration of Se and other minerals and their relationships in soils and fodder plants in Kosovo. Seventy-three samples of each soil and fodder plants (grass, maize, and wheat) from 30 farms were collected. Both soil and plant samples, after processing and digestion, were analyzed for mineral concentration by ICP-MS. Mineral concentrations in soil and fodder crops, and the best predicting/explanatory models for micro minerals concentration, achieved by stepwise linear regression, are presented. Results showed very low concentration of Se in most of the soil and all fodder samples. In addition, the concentration of Co, Zn and Fe was not sufficient to satisfy requirements for all categories of farm animals. Plant Se concentration showed a positive relationship with Se concentration in soils. Plant Zn, Mo, Mn, Fe and Pb, in general, showed no significant relationship with their concentration in soil, while plant Co and Cd showed positive relationship only in maize, and Cu in wheat grain. Among the soil properties, pH had the highest effect on the concentrations of Co, Mo, Mn, Cd and Pb in fodder crops.

Polylactic Acid (PLA) is an organic polymer commonly used in fused deposition (FDM) printing and biomedical scaffolding that is biocompatible and immunologically inert. However, variations in source material quality and chemistry make it necessary to characterize the filament and determine potential changes in chemistry occurring as a result of the FDM process. We used several spectroscopic techniques, including laser confocal microscopy, Fourier-Transform Infrared (FTIR) spectroscopy and photoacousitc FTIR spectroscopy, Raman spectroscopy, and X-ray photoelectron Spectroscopy (XPS) in order to characterize both the bulk and surface chemistry of the source material and printed samples. Scanning Electron Microscopy (SEM) and Differential Scanning Calorimetry (DSC) were used to characterize morphology, crystallinity, and the glass transition temperature following printing. Analysis revealed calcium carbonate-based additives which were reacted with organic ligands and potentially trace metal impurities, both before and following printing. These additives became concentrated in voids in the printed structure. This finding is important for biomedical applications as carbonate will impact subsequent cell growth on printed tissue scaffolds. Results of chemical analysis also provided evidence of the hygroscopic nature of the source material and oxidation of the printed surface, and SEM imaging revealed micro and sub-micron scale roughness that will also impact potential applications.

A field experiment was conducted at farmer field of Sundarbazar, Lamjung during rainy season of 2020 with an objective to determine the dynamics of weed with respect different planting methods and varieties. The experiment was laid out in split plot design with three replications where five Varieties (KabreKodo 1, KabreKodo 2, Dalle 1, Okhale 1 and local) were used as the main plot factor and three planting methods (Direct sowing;10*10cm, Conventional transplanting;10*10 cm with 15 days old seedlings and System of Crop Intensification;25*25 cm with 30 days old seedlings) as sub plot factor. Result showed that among 5 genotypes of weeds based on Importance value index, Cyperusrotundus was the most dominant during the initial stage but after the first weeding, Aegeratumhaustinianum dominated the field. Weed biomass and density was recorded highest in directly sown field than that in transplanted field. Among the transplanted crop, weed infestation was seen higher in SCI than in conventionally transplanted finger millet due to wider spacing. But after the first hand weeding, due to profuse root growth and tillering in SCI, weeds were suppressed and thus weed biomass was observed higher in CT. After one hand weeding, SCI showed higher weed control index, crop resistance index and planting method efficiency index in terms of yield. Weed infestation was observed higher in Dalle 1 among varieties.

The effect of transition metal substitution for Fe and the structural and magnetic properties of Gd2Fe16Ga0.5TM0.5 (TM=Cr, Mn, Co, Ni, Cu, and Zn) compounds were investigated. Rietveld analysis of X-ray diffraction indicates that all the samples crystallize in the hexagonal Th2Ni17 structure. The lattice parameters: a, c and unit cell volume show TM ionic radii dependence. Both Ga and TM atoms show preferred site occupancy for 12j and 12k sites. The saturation magnetization at maximum room temperature was observed for Co, Ni, and Cu of 69, 73, and 77 emu/g, respectively while minimum value was observed for Zn (62emu/g) doping Gd2Fe16Ga0.5TM0.5. Highest Curie temperature of 590 K was observed for Cu doping which is 15% and 5% and thesehigher than Gd2Fe17 and Gd2Fe16Ga compounds, respectively. The hyperfine parameters viz. hyperfine field and isomer shift, show systematic dependence on the TM atomic number. The observed magnetic and Curie temperature behavior in Gd2Fe16Ga0.5TM0.5 is explained on the basis of Fe(3d)-TM(3d) hybridization. The superior Curie temperature and magnetization value of Co, Ni, and Cu doped Gd2Fe16Ga0.5TM0.5 compounds as compared to pure Gd2Fe17 or Gd2Fe16Ga makes Gd2Fe16Ga0.5TM0.5 a potential candidate for high-temperature industrial magnet applications.

Mitochondria are constantly subjected to stressful conditions due to their unique physiology and organization. The resulting damage leads to mitochondrial dysfunction, which underlies many pathophysiological conditions. Hence, constant surveillance is required to closely monitor mitochondrial health for sound maintenance of cellular metabolism and thus, for viability. In addition to internal mitochondrial chaperones and proteases, mitochondrial health is also governed by host cell protein quality control systems. The Ubiquitin-Proteasome System (UPS) and autophagy constitute the main pathways for removal of damaged or superfluous proteins in the cytosol, nucleus, and from certain organelles such as the ER and mitochondria. Although stress-induced ubiquitin-dependent degradation of mitochondrial outer membrane proteins has been widely studied, mechanisms of intramitochondrial protein ubiquitination have remained largely elusive due to the predominantly cytosolic nature of UPS components, separated from internal mitochondrial proteins by a double membrane. However, recent research has illuminated examples of intramitochondrial protein ubiquitination pathways and highlighted their importance under basal and stressful conditions. Owing to the dependence of mitochondria on the error-prone process of protein import from the cytosol, it is imperative that the cell eliminate any accumulated proteins in the event of mitochondrial import deficiency. Apparently, a significant portion of this activity involves ubiquitination in one way or another. In the present review article, following a brief introduction to mitochondrial protein quality control mechanisms, we discuss our recent understanding of intramitochondrial protein ubiquitination, its importance for the basal function of mitochondria, metabolic implications, and possible therapeutic applications.

This paper aimed to assess the technical efficiency of maize seed production and the major factors contributing on technical efficiency. Maize is the second most important staple crop in Nepal, but the average yield of maize is very low as compared to other countries having similar agro-climatic requirements. Inefficient use of resources had led to low yield in maize crop. The software Raosoft was used to determine the required sample size and total of 182 samples were selected using simple random technique in June, 2016. Stochastic production frontier model and Tobit model were used to derive the results. The average technical efficiency of maize seed production ranged from 0.25-0.92 with an average of 0.71which revealed the scope of increasing technical efficiency by 29 percent. The majority of the farmers (29.1%) were at higher technical efficiency level of 0.8-0.9 followed by 28.6 percent at 0.7-0.8 and 23.1 percent at 0.6-0.7. Age and schooling of household head, experience on maize seed production, area shared by maize crop and dummies variables such as livestock holding, source of seed and access to extension service had found significantly affecting on the technical efficiency level. For the least developed country like Nepal it would be better to use the available resources wisely and improvement of existing technologies would be more cost effective than that of discovering new technologies. The study recommended that the concerned organizations should focus on mixed agricultural farming system, access to better quality seed and provide technical knowledge which would help in improving technical efficiency.

This qualitative study explores the implementation and conformation process of digital devices in teaching and learning before, during, and after the COVID-19 pandemic in Nepal. Using Rogers' Diffusion of Innovation Theory as a framework, the study examines the adoption and adaptation of digital devices by in-service secondary mathematics teachers (n=62) and their perceptions and preferences towards instructional modality. The findings suggest that despite the increased reliance on digital devices during the pandemic, there is a less likelihood of using them in face-to-face classrooms in developing countries like Nepal. The adoption of online learning has not yet reached the confirmation stage, even after the onset of the COVID-19 pandemic. Prior to the pandemic, online learning was not widely implemented or confirmed by teachers in developing countries societies. The study also provides important insights into the challenges and opportunities of using digital devices in post-COVID-19 classrooms, and its implications for policymakers and educators in Nepal.

In this paper, Akbari-Ganji's and Taylor series methods are applied to find analytical solutions to nonlinear differential equations that arise in an immobilized-cell photobioreactor. Approximate analytical expressions for substrate and product concentrations and both liquid and gas phases for various parameter values are derived using both methods. Efficiency, accuracy, and convergence of the two methods relative to highly accurate numerical methods are investigated to establish reliable profiles of these two methods for solving general nonlinear equations that model various physical phenomena. Numerical simulations are presented to validate the theoretical investigations.

Classification and mapping of plant communities is an essential step for conservation and management of ecosystems and biodiversity. We adopt the Genus-Physiognomy-Ecosystem (GPE) system developed in previous study for satellite-based classification of plant communities. This paper assesses the potential of multi-spectral and multi-temporal images collected by Sentinel-2 satellites. This research was conducted in five representative study sites in a temperate region. It consists of 44 types of plant communities including a few land cover types as well. The plant community types were enumerated in the study sites and ground truth data were prepared with reference to extant vegetation surveys, visual interpretation of high-resolution images, and onsite field observations. We acquired all Sentinel-2 Level-1C product images available for the study sites between 2017-2019 and generated monthly median composite images consisting of ten spectral and twelve spectral-indices. Gradient Boosting Decision Trees (GBDT) classifier was employed as an efficient and distributed gradient boosting technique for the supervised classification of big datasets involved in the research. The cross-validation accuracy in terms of kappa coefficient varied from 87% in Oze site with 41 land cover and plant community types to 95% in Hakkoda site with 19 land cover and plant community types; with average performance of 91% across all sites. In addition, the resulting maps demonstrated a clear distribution of plant community types involved in all sites, highlighting the potential of Sentinel-2 multi-spectral and multi-temporal images with GPE classification system for operational and broad-scale mapping of land cover and plant communities.

Semiconductor materials have been shown to have better photocatalytic behavior and can be utilized for the photodegradation of organic pollutants. In this work, three-dimensional flower-like SnS₂ were synthesized by a facile hydrothermal method. Core-shell structured SiO₂@α-Fe₂O₃ nanocomposites were then deposited on the top of the SnS₂ flowers. The as-synthesized nanocomposites were characterized by X-ray diffraction (XRD), Raman spectroscopy, field emission scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET) and photoluminescence spectroscopy (PL). The photocatalytic behavior of the SnS₂-SiO₂@α-Fe₂O₃ nanocomposites was observed by observing the degradation of methylene blue (MB). The results show an effective enhancement of photocatalytic activity for the degradation of MB especially for the 15 wt. % SiO₂@α-Fe₂O₃ nanocomposites on SnS₂ flowers.

Epidemiological studies indicate that skipping breakfast as a universal behavior, may have adverse effects on cardiovascular diseases [CVDs}and metabolic diseases. However, eating breakfast regularly, may increase satiety, thereby reducing overeating later in the day which prevents weight gain. Recent studies indicate that skipping breakfast increases the risk of obesity, metabolic syndrome, hypertension, hypercholesterolemia, type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and cardiovascular mortality as well as all-cause mortality. However, many studies also reported that regular taking of breakfast decreases the risk of CVDs and T2DM and all-cause mortality. Previous studies reported that heavy breakfast, in particular eating western diet may increase circadian rhythm of CVDs and sudden cardiac death. It seems that those who do not eat breakfast, they tend to eat refined and sweetened products, possibly, more in the night resulting in to greater risk of CVDs and T2DM. Breakfast skipping and eating in the night, may be associated with circadian misalignment in the central and peripheral clocks, leading to oxidative stress and inflammation. Increased systemic inflammation damages the adipocytes, beta cells of pancreas, endothelial cells and smooth muscle cells as well as neurons, which may produce dysfunction in these cells resulting in to related diseases. The beneficial effects of breakfast, may also be, at least in part, due to nutrient dense foods rather than time of eating. Eating regular breakfast, in particular rich in Indo-Mediterranean foods; vegetables, whole grains, fruits, spices and nuts may be protective against circadian increase in oxidative stress in the morning, resulting in to significant decline in the risk of CVDs and T2DM.

We conducted this study to determine the potential cryopreservative effects of different hesperidin (vitamin P; HSP) doses on ram semen after freeze-thawing. Semen samples were obtained from Sönmez rams by an artificial vagina. The samples were divided into six groups: control, 10, 50, 100, 250, and 500 µg/mL HSP (C, HSP10, HSP50, HSP100, HSP250, and HSP500, respectively). At the end of the study, sperm motility and kinetic parameters, plasma membrane acrosome integrity (PMAI), high mitochondrial membrane potential (HMMP), viability, lipid peroxidation levels (LPL), chromatin damage, oxidant parameters, and antioxidant parameters were assayed. None of the doses of HSP added to the semen extender showed any enhancing effect on progressive motility compared to C (p>0.05). In fact, HSP500 had negative effects (p<0.05). Moreover, PMI activities were the highest at the HSP10 dose, while LPL values were the lowest (p<0.05). The doses of HSP10 and HSP50 added to the Tris extender medium showed positive effects on spermatozoon chromatin damage. Consequently, we can say that HSP doses used in this study are not effective on semen progressive motility, but the HSP10 dose is effective on PMAI and chromatin damage by reducing LPL.

Background: While several drugs are in the pipeline for treatment of various grades of COVID-19 disease, none of them have shown promise until now. Medicinal plants are crucial in developing and developed countries for their primary and basic health needs owing to better tolerability, superior compatibility with human body and having lesser side effects. AEV01 , a speciality extract of kutki (Picrorhiza kurroa), is one potential medicinal herb which can be effective for mild COVID19 in elderly patients at risk of complications and aging immunity. Purpose: The efficacy and safety of AEV01 for mild COVID-19 in elderly patients at risk of complications was investigated in this study. Study design: A prospective, phase 3, randomized, multicentric, placebo controlled double blinded parallel group interventional trial. Methods: This study was conducted in elderly patients diagnosed as COVID-19 with mild symptoms. 70 patients were randomized into two groups to receive AEV01 capsule (100mg) and placebo respectively thrice daily for 30 days along with standard care of treatment as per national WHO/ICMR guidelines. Clinical improvement timelines and corresponding scores using 8-point ordinal scale and NEWS were assessed for efficacy and safety of AEV01 in COVID-19 patients. Results: AEV01 group showed a significant improvement (P=0.0001) in the normalization of the SpO₂ rate and relief from cough. There was also significant difference in time to recovery, with patients in the AEV01 drugtreated group recovering in 4.5 days as compared to Placebo in 9.1 days. ESR, LDH, serum ferritin, Neutrophil-Lymphocyte ratio (NLR), TNF- alpha, IL-6 and CD4 cell counts, which are considered as prognostic markers in COVID19 infected patients, showed a significant improvement in patients treated with AEV01. The AEV01 drug treated group showed significant clinical improvement in the 8-point ordinal scale severity rating and NEW Score from day 3 onwards which continued up to end of study. Conclusion: AEV01 has shown a significant improvement in clinical and laboratory parameters. There was also reduction in the progression of the COVID-19 disease in unvaccinated elderly patients from mild to moderate when treated at an earlier stage.

The Seven Country study showed that traditional Japanese diet and Mediterranean diets are protective against cardiovascular diseases (CVDs). Japanese diet is considered the healthiest because it provides highest longevity and health to Japanese. DASH diet and Mediterranean style diets are also considered the healthy diets, although, it is possible that Indo-Mediterranean style diet may provide better protective effects among patients with CVDs, compared to other diets. The concept of Indo-Mediterranean type of diets was developed, after examining its role in the prevention of CVDs in India, the value of which was confirmed by a landmark study from France; The Lyon Heart Study. These workers found that eating alpha-linolenic acid rich Mediterranean style diet can cause significant decline in CVDs and all-cause mortality. Later on in 2018, PREDIMED Study from Spain also reported that a modified Mediterranean style diet can cause significant decline in CVDs, type 2 diabetes mellitus (T2DM) and cancer. The Indo-Mediterranean diet may be superior to DASH diet and Mediterranean diet because it contains millets, porridge, beans and spices; turmeric, cumin, fenugreek and coriander which may have better anti-inflammatory and cardio-protective effects. These foods are rich sources of nutrients; flavonoids, calcium and iron as well as proteins which are useful in the prevention of under as well as over-nutrition and related diseases. It is known that DASH diet and Mediterranean style diets have similar influence on CVDs. However, Indo-Mediterranean style diet, may be as good as Japanese diet, due to improved food diversity and high content of antioxidants in the diets.

The key objective of the present paper is to propose a numerical scheme based on the homotopy analysis transform technique to analyze the time-fractional nonlinear predator-prey population model. The population model is coupled fractional order nonlinear partial differential equations often employed to narrate the dynamics of biological systems in which two species interact, first is a predator and the second is a prey. The proposed scheme provides the series solution with great freedom and flexibility by choosing appropriate parameters. The convergence of results is free from small or large parameters. Three examples are discussed to demonstrate the correctness and efficiency of the used computational approach.

Hepatitis C virus (HCV) represents a challenging global health threat in ~200 million infected individuals. Clinical data suggests that only ~10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts a myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence that includes, but not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here, we discussed a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.

Roller milling of sorghum and quinoa seeds into flour fractions (course, middle, and fine) was investigated, chemically analysed and applied in the baking of gluten-free sourdough bread. Gap settings were adjusted to 0, 5, 8 and 10 for quinoa and 3, 5, and 7 for sorghum. The fine fractions reached values of up to about 41% (gap 8) for quinoa and around 20% for sorghum (gap 5). SEM pictographs illustrated clear separation of each fraction with chemical analysis showing high contents of protein, TDF (total dietary fibre) and IDF (insoluble dietary fibre) in the course fraction. Up to 77% starch content was obtained in the fine fraction with significant amounts of SDF (soluble dietary fibre) which has good health benefits. Increasing the dough moisture up to 90% helped in decreasing the bread crumb firmness, while low Avrami parameters and RVA pasting behaviour indicated slow bread staling rate for both sourdough breads.

The upwelling phenomenon plays a vital role within marine ecosystems, transporting essential nutrients from the bottom to the surface and boosting biological productivity. However, the bacterial community structure in upwelling zones along Western coast of India (WCI) is under-studied. This research systematically examines bacterial diversity across three sea-sons—Pre-monsoon (PR), Monsoon (MN), and Post-monsoon (PM)—using next-generation se-quencing. Our findings show distinct spatial patterns of bacterial communities in the Arabian Sea and demonstrate that ecological variations influence bacterial distribution in this dynamic envi-ronment. During MN, the bacterial community was notably distinct and diverse than during PR and PM, despite their lower abundance in MN. Non-Metric MDS cluster analysis revealed a 78% similarity (at order level) between PR and PM, indicating MN supports unique bacterial diversi-ty. KEGG analysis showed significant seasonal variations in metabolic functions, with increased functional potential during MN. Additionally, Carbohydrate-Active enZymes (CAZymes) analy-sis revealed distinct seasonal profiles, among which the GH13 enzymes were the most prevalent glycoside hydrolases during MN; predominantly sucrose phosphorylase and glucosidase, known for breaking down glucan deposits derived from phytoplankton. The CAZymes profiles sup-ported taxonomic and KEGG pathway findings, reinforcing that microbial communities are sea-sonally distinct and functionally adapted to changing availability of nutrients.

As a new logistics system, Physical Internet (PI) provides a solution to cope with the continuous rise of urban logistics demand by exploring same-level and cross-level paths and flattening. This research suggests a PI-based urban logistics distribution cost minimization model based on the examination of the primary elements influencing PI distribution, intending to maintain the logistic transportation process' integrity. This proposed model enhances the flexibility of goods operation and reduces the global cost of logistics distribution using the interconnected and open PI logistics distribution mode. The experimental results show that the distribution cost of the PI logistics model is significantly better than that of a traditional logistics model. The elastic and cost advantages relatively grow as the infrastructure for distribution scales up and the interruptions from emergencies occur.

Background. COVID-19 efforts were often ineffective in controlling the spread of the pandemic. Identifying ineffective controls during a pandemic is thus vital. Method. Utilizing publicly available data on COVID deaths in the counties of US states, we create an index to capture and interpret ineffectiveness in the efforts to reduce the spread of the pandemic in US counties. This index is based on the Intervened Poisson Distribution (IPD) introduced originally by Shanmugam. Motivation for the research idea occurred while we noticed the data dispersion of the COVID deaths is smaller than the average only in some counties. Under-dispersed data is common in statistical modeling. A novel approach we adapted in this article includes the estimation of an intervention parameter estimated through iterative non-linear optimization. Results. Twenty-five counties in California, Idaho, Minnesota, Mississippi, Montana, Nebraska, North Carolina, North Dakota, Texas, and Utah were found to be ineffective in controlling for fatalities based on the expected probability distribution. A review of the policies enacted in these areas would provide insight into ineffective prevention efforts, and some of these issues are documented in current literature. Conclusion. The IPD index an innovate way to document efficacy of interventions during pandemics. The IPD may identify ineffective efforts prior to statistical models intended to evaluate efficacy of efforts.

The healthcare system is crucial to the development, standard of living, and sustainability of any country. Amid the pandemic, most developed countries are experiencing varying levels of difficulty managing their healthcare systems. Overloading of healthcare services is common, leading to prolonged waiting times for medical services; thus, the wastage of hospital resources must be addressed seriously. In this paper, we examine the problem of no-shows in outpatient clinics. Through a review of the literature and practical industrial experience, we identify the processes of these clinics. We then propose a robust optimisation approach for overbooking using a traditional overbooking model and a robust system. This model aims to mitigate the significant parameter uncertainties encountered during the pandemic. Considering risk aversion, the optimal policy for overbooking can be established while accounting for the costs associated with overbooking. The main contribution of this paper is the introduction of an alternative method to address the uncertainty of no-shows using an overbooking technique.

Quantum computing is an emerging field that have given a significant impact on optimization. Among the diverse quantum algorithm, the quantum gradient descent has become a prominent technique for solving unconstrained optimization problems. In this paper, we propose a quantum-spectral Polak-Ribi{\'e}re-Polyak (PRP) conjugate gradient approach. The technique is considered as a generalization of the spectral PRP method which employs a $q$-gradient that approximate the classical gradient with quadratically better dependence on the quantum variable $q$. Additionally, the proposed method reduces to the classical variant as quantum variable $q$ gets closer to $1$. The quantum search direction always satisfies the sufficient descent condition and does not depend on any line search. This approach is globally convergent with the standard Wolfe line search without any convexity assumption. Numerical experiments are conducted and compared with the existing approach to demonstrate the improvement of the proposed strategy.

The secretory pathway Ca2+-ATPase SPCA2 is a tumor suppressor in triple receptor negative breast cancer (TNBC), a highly aggressive molecular subtype that lacks tailored treatment options. Low expression of SPCA2 in TNBC confers poor survival prognosis in patients. Previous work has established that re-introducing SPCA2 to TNBC cells restores basal Ca2+ signaling, represses mesenchymal gene expression, mitigates tumor migration in vitro and metastasis in vivo. In this study, we examined the effect of histone deacetylase inhibitors (HDACi) in TNBC cell lines. We show that the pan-HDACi vorinostat and the class I HDACi romidepsin induce dose-dependent upregulation of SPCA2 transcript with concurrent downregulation of mesenchymal markers and tumor cell migration characteristic of epithelial phenotype. Silencing SPCA2 abolished the ability of HDACi to reverse epithelial to mesenchymal transition (EMT). Independent of ATPase activity, SPCA2 elevated resting Ca2+ levels to activate downstream components of non-canonical Wnt/Ca2+ signaling. HDACi treatment led to SPCA2-dependent phosphorylation of CAMKII and -catenin, turning Wnt signaling off. We conclude that SPCA2 mediates the efficacy of HDACi in reversing EMT in TNBC by a novel mode of non-canonical Wnt/Ca2+ signaling. Our findings provide incentive for screening epigenetic modulators that exploit Ca2+ signaling pathways to reverse EMT in breast tumors.

Depression and anxiety are the most common mental health disorders worldwide. Internet-Delivered Cogni-tive Behaviour Therapy (ICBT) can reduce barriers to care for broad cross sections of the population. How-ever, People of Diverse Ethnocultural Backgrounds (PDEGs) other than White/Caucasian underutilize mental health services and are underrepresented in clinical trials of psychological interventions. To address this research gap, we adapted an evidence-based ICBT program for PDEGs. The current pilot study explores the effectiveness, satisfaction, and engagement in the adapted ICBT by PDEGs (N=41) when benchmarked against a sample of PDEGs (N=134) drawn from a previous non-adapted version of the ICBT program. Inntent-to-treat analyses showed that the adapted ICBT program is effective in reducing anxiety and de-pression symptoms among PDEGs. Large within-group pre-to-post-treatment Cohen’s effect sizes of d = 1.23, 95% CI [0.68, 1.77] and d = 1.24, 95% CI [0.69, 1.79] were found for depression and anxiety, respectively. Further, 81.8% of the PDEGs who received the adapted ICBT program reported high overall satisfaction, 90.9 % reported increased confidence in managing symptoms, and 70.7% of participants completed the ma-jority of the psychoeducational lessons in the ICBT program. No statistically significant differences in clinical outcomes, engagement, and satisfaction were found between the pilot study and benchmark sample. Future directions for ICBT research with PDEGs are described.

We study a minimal model of the stress-driven p53 regulatory network that includes competition between active and mutant forms of the tumor-suppressor gene p53. Depending on the nature of the external stress signal, four distinct dynamical states are observed. These states can be distinguished by dierent dynamical properties and correspond to active, apoptotic, pre-malignant and cancer states. Transitions between any two of these states are found to be unidirectional and irreversible if the stress signal is either oscillatory or constant. When the signal decays exponentially, the apoptotic state vanishes, and for low stress the pre-malignant state is bounded by two critical points, allowing the system to transition reversibly from the active to the pre-malignant state. For signi cantly large stress, the range of the pre-malignant state expands and the system moves to the cancerous state which is a stable attractor. This suggests that identi fication of the pre-malignant state may be important both for therapeutic intervention as well as for drug discovery.

The sustainable development goals(SDG) of the UNO would be difficult to achieve without prevention of metabolic diseases and other non-communicable diseases (NCDs). Western diet and lifestyle, which are major risk factors of NCDs, are known to cause oxidative stress and decrease in production of molecular hydrogen in the intestines which leads to a decline in endogenous antioxidant status in the body, leading to increase in systemic inflammation. Many experts consider molecular hydrogen as a potential nutrient, which may be administered as gas in the body. There are gaps in the knowledge about the role molecular hydrogen plays, in the treatment of metabolic diseases and other NCDs This review aims to discuss the role of hydrogen in the pathogenesis and prevention of NCDs. Molecular hydrogen (H2) has been studied extensively as a therapeutic gas, with an estimated 2000 publications to date, exploring its potential therapeutic use in 170 disease models across every organ in the mammalian body. Hydrogen therapy can be administered through several methods, such as H2 inhalation, dissolving H2 gas in water to make hydrogen-rich water (HRW) for oral consumption or topical application, or hydrogen-rich saline. The exact mechanism of action of molecular hydrogen is not known but it is in itself a potential antioxidant that can also inhibit hydroxyl and nitrosyl radicals in the cells and tissues. Hydrogen is known to cause a marked decline in oxidative stress, and inflammation that are crucial in the pathogenesis of NCDs. Hydrogen therapy has been found protective against NCDs, including, metabolic diseases, cardiovascular diseases (CVDs), neurodegenerative diseases, chronic kidney disease, cancer and chronic lung diseases.

Hypertension (HTN) is the foremost contributor to cardiovascular diseases (CVD), which remain a leading cause of death. However, adherence to the properly prescribed dosage form is critical and challenging for patients with chronic diseases such as HTN to prevent illness progression and death. The study’s objective was to develop AMB-loaded subcutaneous implants to reduce the frequency of administration, thus improving patient compliance during HTN management. AMB subcutaneous implants were prepared using continuous hot melt extrusion technology using PCL and PLGA with dimensions of 7.5 cm (length) by 2 mm (diameter). The implants were characterized for thermal characteristics, drug-excipient incompatibilities, surface morphology, fracturability, in vitro release, and stability studies. DSC showed that the drug was in the crystalline state in the fabricated implants. Scanning Electron Microscopy (SEM) revealed a smooth surface. The lead formulation presented good drug content, showed an extended drug release profile over 30 days, and followed zero-order release kinetics with a mean dissolution time of 15 days. The formulation was stable over 30 days in accelerated stability conditions (the last time point was tested, 40℃/75% RH), and the release profile was similar to the initial drug release profile. The lead formulation showed good fracturability during textural analysis. Therefore, the hot melt extruded implants could be an alternative management strategy for conventional amlodipine besylate (AMB) formulation.

The present study conducts the phase analysis, microstructural characteristics, and mechanical property evaluation on the as-cast and quenched Ti-15Mo-xFe alloys with high iron content ranging from 4 to 12 weight percent. All the four alloys were produced in a button-arc melting furnace. Heat treatment in the form of solution treatment was performed in a muffle furnace at a temperature of 1100°C, with a 1-hour holding time. The samples were rapidly quenched in ice-brine. Various characterization techniques were used to analyze samples both in the as cast and quenched conditions. X-ray diffractometer (XRD) was used to analyses the phases present in each alloy whereas the optical microscope (OM) was employed to track the microstructural evolution. The mechanical properties of the alloys were evaluated using a tensile test method while the micro-Vickers hardness measurements were conducted to evaluate hardness of the alloys. OM micrographs revealed equiaxed β grains and substructures in as-cast TMF0, dendritic structure, and equiaxed β grains with pores forming around the grain boundaries in TMF1, and micrograph full of dendrites and pores was observed in the as-cast TMF2 and TMF3 alloys. The quenched TMF0 showed only β equiaxed grains whereas TMF1, TMF2, and TMF3 revealed micrographs full of equiaxed grains of β phase with pores throughout the grain boundaries. The XRD patterns of cast TMF0 showed peaks belonging to the β and orthorhombic α″ martensitic phases and the quenched sample showed the bcc β phase only. The TMF1, TMF2, and TMF3 alloys in as-cast condition indicated peaks belonging to β , α″ and intermetallic B2 TiFe phases, however, their quenched samples showed the presence of β and Fe·Ti·O2 phases in TMF2 and TMF3 alloys. The tensile properties such as ultimate tensile strength (UTS) and elastic modulus (E) of as-cast TMF0 were 264 MPa and 79 GPa and these properties changed upon quenching to 411 MPa and 66 GPa respectively. The elastic modulus of TMF1 in as-cast condition was 74 GPa. The UTS and E of TMF1, TMF2, and TMF3 in as cast and quenched conditions were not recorded due to the fragility of the samples that failed prior to yielding any useful data. The micro-Vickers hardness in as cast and quenched conditions showed a similar trend with hardness increasing slightly upon quenching for TMF0, TMF1, and TMF3 alloys but slightly decreased in the case of TMF2. 6). The fracture surfaces of TMF0 exhibited both ductile and brittle fracture in as cast and quenched conditions whereas the only brittle fracture mode was observed in the TMF1, TMF2 and TMF3 alloys in both conditions.

The Coronavirus disease 2019 (COVID-19) rapidly spread to over 180 countries and abruptly disrupted the production rates and supply chains worldwide. Since then, 3D printing also recognized as additive manufacturing (AM) and known to be a novel technique that uses layer-by-layer deposition of material to produce the intricate 3D geometry, has been engaged in reducing the distress caused by the outbreak. During the early stages of this pandemic, shortages of Personal Protection Equipment (PPE), including facemasks, shields, respirators, and other medical gears, were significantly answered by remotely 3D printing them. Amidst the growing testing requirements, the 3D printing emerged as a potential and fast solution manufacturing process to meet the production needs due to its flexibility, reliability, and rapid response capabilities. In the recent past, some of the other medical applications that have gained prominence in the scientific community include 3D printed ventilator splitters, device components, and patient-specific products. Regarding the non-medical applications, researchers have successfully developed contact-free devices to address the sanitary crisis in public places. This work aims to systematically review the applications of 3D printing or AM techniques that have been involved in producing various critical products essential to limit this deadly pandemic's progression.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The KEGG pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, a combinational effect of the mixture of three herbs was found. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFAs-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

Newcastle disease (ND) is a highly contagious and usually causes severe illness that affects Aves all over the world, including domestic poultry. Depending on the virus's virulence, it can impact the nervous, respiratory, and digestive systems and causes up to 100% mortality. The chIFITM genes are activated in response to viral infection. The current study was conducted to quantify the mRNA of chIFITM genes in vitro in response to ND viral infection. It also examined its ability to inhibit ND virus replication in Chicken Embryo Fibroblast (CEF) cells of Aseel and Kadaknath breeds. Results from the study showed that the expression of all chIFITM genes was significantly upregulated throughout the period in the infected CEF cells of both breeds compared to uninfected CEF cells. In CEF cells of the Kadaknath breed, elevated levels of expression of the chIFITM3 gene dramatically reduced the ND viral growth and the viral load was 60% lower than in CEF cells of the Aseel breed. The expression level of the chIFITMs in Kadaknath ranged from 2.39 to 11.68 log2 folds higher than that of control CEFs, and was consistently (p<0.01) higher than Aseel CEFs. Similar to this, IFN-γ gene expresses strongly quickly and peaks at 13.9 log2 fold at 48 hpi. The result suggests that the Kadaknath chicken breed may have a higher level of disease tolerance compared to the Aseel chicken.

Yeast, crucial in beer production, holds promise as a valuable by-product resource, known as brewer's spent yeast (BSY), with potentially beneficial physiological effects. This study aimed to compare the composition and soluble polysaccharide content of Brewer's spent yeast with those of pure cultured yeast strains, namely Saccharomyces cerevisiae (SC) and S. boulardii (SB), to facilitate the utilization of BSY as an alternative source of functional polysaccharides. BSY exhibited significantly higher carbohydrate content and lower crude protein content than SC and SB cells. The residues recovered through autolysis were 53.11%, 43.83%, and 44.99% for BSY, SC, and SB, respectively. Notably, the polysaccharide content of BSY residue (641.90 μg/mg) was higher than that of SC (553.52 μg/mg) and SB (591.56 μg/mg). The yields of alkali-extracted water-soluble polysaccharides were 40%, 30%, and 35% for BSY, SC, and SB, respectively, with BSY comprising a higher proportion of water-soluble saccharides than SC and SB, including 49.3% mannan and 20.1% β-glucan. Furthermore, BSY demonstrated antioxidant activities, including superoxide dismutase (SOD), ABTS, and DPPH scavenging potential, suggesting its ability to mitigate oxidative stress. BSY also exhibited a significantly higher total phenolic compound content, indicating its potential as an effective functional food material.

The increasing popularity of Robo-Advisors highlights the need for sophisticated systems combining big data analytics and deep learning for portfolio optimization. Despite their potential, these AI-driven platforms face notable challenges such as financial data inaccuracies and the risk of overfitting in deep learning models. Overcoming these hurdles requires a concerted effort to enhance reliability and performance. To tackle these challenges effectively, it is imperative to prioritize real-time data integration while minimizing reliance on historical data. By adopting this approach, Robo-Advisors can better adapt to dynamic market conditions, enabling them to provide informed and timely investment recommendations. This proactive stance not only ensures computational efficiency but also fosters investor confidence in the platform's ability to navigate evolving market dynamics. In conclusion, by continually refining data integration methods and reducing dependencies on historical data, Robo-Advisors can offer more accurate and timely recommendations. This not only enhances the overall investor experience but also upholds ethical standards in automated investment platforms.

In this paper, we present a novel approach for managing the file system in Linux using a voice assistant. Our system allows users to perform file system operations such as creating directories, renaming files, and deleting files by issuing voice commands. We develop a voice assistant using Python libraries and integrate it with the file system in Linux. The voice assistant is capable of understanding natural language and executing commands based on the user's voice inputs. We conduct experiments to evaluate the performance of the system and demonstrate that our approach is effective and efficient in managing the file system using voice commands. Our system can enhance the accessibility and usability of the file system in Linux for individuals with disabilities or those who prefer a hands-free approach to file management.

Gastrodia pubilabiata is a nonphotosynthetic and mycoheterotrophic orchid belonging to subfamily Epidendroideae. Compared to other typical angiosperm species, the plastome of G. pubilabiata is dramatically reduced in size to be only 30,698 base pairs (bp). This reduction has led to the loss of most photosynthesis-related genes and some housekeeping genes in the plastome, which now only contains 19 protein coding genes, three tRNAs, and three rRNAs. This study decoded the entire mitogenome of G. pubilabiata, which consisted of 44 contigs with a total length of 867,349 bp. Its mitogenome contained 38 protein coding genes, nine tRNAs, and three rRNAs. To determine possible gene transfer events between the plastome and the mitogenome, individual BLASTN searches were conducted, using all available orchid plastome sequences and flowering plant mitogenome sequences. Plastid rRNA fragments were found at a high frequency in the mitogenome. Seven plastid protein coding gene frangments (ndhC, ndhJ, ndhK, psaA, psbF, rpoB, and rps4) were also identified in the mitogenome of G. pubilabiata. Phylogenetic trees using these seven plastid protein coding gene fragments suggested that horizontal gene transfer (HGT) from plastome to mitogenome occurred before losses of photosynthesis related genes, leading to the lineage of G. pubilabiata. Compared to species phylogeny of the lineage of orchid, it was estimated that HGT might have occurred approximately 30 million years ago.

The disease COVID-19 is brought on by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) First appeared in China in December 2019 and quickly spread around the world after being declared a worldwide pandemic by the World Health Organization in March 2020. COVID-19, Medical Laboratory Professionals, SARS-COV-2, Diagnostic, Importance and difficulties for testing were the selected terms to search the databases of PubMed and Google Scholar for previously published material. Many diagnostic tests are applied in corona virus detection like Droplet Digital PCR (ddPCR), Multiplex PCR, Loop-mediated Isothermal Amplification (LAMP) and more. There is a lack of availability of molecular and serologic tests that have been clinically validated or authorized by national or international regulatory bodies. Clinical laboratory experts are tackling threats to our global defense and wellness, including infectious diseases. The opportunity to express gratitude to the unsung medical laboratory heroes and COVID0-19 pandemic allies is now greater than ever. Each year, Medical Laboratory Professionals Week should honors those who contribute key diagnostic data that help save lives. This review article explore overall summary on testing methods including Important and Difficult Tasks for Medical Laboratories which will provide good message for better public health matter.

Human activities (e.g., exploitation, utilization, and conservation) exert substantial impact on forest ecological functions (FEF). The human influence on FEF significantly varies across developmental stages, which are attributed to the temporal and spatial in nature. This study evaluates some notable FEF indices (FEFI) in the 448 counties within the Yellow River basin (YRB) using panel data from the Seventh to Ninth National Forest Inventory. Data analysis involves employing the residual trends, geographical and temporal weighted regression. Results indicate that, firstly, the overall forest ecological function in the YRB is moderate to inferior, with superior FEF in counties endowed with more natural forest resources. Afforestation demonstrates a short-term improvement, but its effectiveness diminishes over time. Secondly, the positive spatial correlation is stronger among counties, characterized by both high-high and low-low agglomeration effects. Scattered planting, simple stand structure, and concentrated harvesting of forests at the identical stand ages hinder the formation of complex and large-scale FEF agglomerations. Thirdly, significant spatial-temporal differences exist in the impact of human activities on FEF. In the upper reaches of the basin, increased vegetation coverage through agricultural and forestry production benefited FEF, however, some over-exploitation of forests and grasslands is observed there. In the middle reaches, the economic development, expanding population and the greening activities help to improve FEF effectively, but excessive water using in agricultural production brought more difficulties to FEF improvement. In the lower reaches of the basin, improved wastelands and forest protection positively influence FEF. This study recommends that county governments should prioritize forest management with multi-species and multi-layered complex forests. Each county should define its position in regional development and ecological protection, considering the potential impacts on neighboring regions. This holistic approach promotes more effective integrated regional management.

BA.2, a sublineage of Omicron BA.1, is now prominent in many parts of the world. Early reports indicate that BA.2 is more infectious than BA.1. To gain insight into BA.2 mutation profile and the resulting impact of mutations on interaction with receptor and/or monoclonal antibodies, we analyzed available se-quences, structures of Spike/receptor, and Spike/antibody complexes, and conducted molecular dynamics simulations. The results showed that BA.2 has 50 high-prevalent mutations compared to 48 in BA.1. Seventeen BA.1 mutations are not present in BA.2. Instead, BA.2 has 19 unique mutations and a signature Delta variant mutation (G142D). Intriguingly, the BA.2 has 28 signature mutations in Spike, compared to 30 in BA.1. This is due to two revertant mutations S446G and S496G in the receptor-binding domain (RBD), making BA.2 somewhat similar to Wuhan-Hu-1 (WT), which has G446 and G496. The molecular dynamics simulations showed that the RBD consisting of G446/G496 is more stable than S446/S496 containing RBD. Thus, our analyses suggest that BA.2 has evolved with novel mutations (i) to maintain receptor binding similar to WT, (ii) evade the antibody binding greater than BA.1, and (iii) acquire mutation of the Delta variant that may be associated with the high infectivity.

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

The proliferation of Internet of Things (IoT) devices on Linux platforms has heightened concerns regarding vulnerability to malware attacks. This paper introduces a novel approach to investigating the behavior of Linux IoT malware by examining syscalls and library syscall wrappers extracted through static analysis of binaries, as opposed to the conventional method of using dynamic analysis for syscall extraction. We rank and categorize Linux system calls based on their security significance, focusing on understanding malware intent without execution.Feature analysis of the assigned syscall categories and risk ranking is conducted with statistical tests to validate their effectiveness and reliability in differentiating between malware and benign binaries. Our findings demonstrate that potential threats can be reliably identified with an F1 score of 96.86%, solely by analyzing syscalls and library syscall wrappers. This method can augment traditional static analysis, providing an effective preemptive measure to enhance Linux malware analysis. This research highlights the importance of static analysis in strengthening IoT systems against emerging malware threats.

Soil is a crucial component for plant growth, as it provides water, nutrients, and mechanical support. Various factors, such as crop cultivation, microflora, nutrient addition, and water availability, significantly affect soil properties. Maintaining soil health is important, and one approach is the introduction of native organisms with multifaceted activities. In this study, the effects of four native microbes (Trichoderma asperellum strain TAIK 1, Bacillus cabrialesii strain BIK3, Pseudomonas putida strain PIK1, and Pseudomonas otitidis strain POPS1) and their consortia on soil health, plant growth, and the incidence of stem rot disease caused by Sclerotium oryzae in rice are evaluated. Upon bioagent treatment of soil through seed treatment or soil application, variations in chemical properties of the soil were observed, viz., pH, Electrical Conductivity (EC), Organic Carbon (OC), available Soil Nitrogen (SN), Soil Phosphorus (SP), Soil Potassium (SK), and soil enzymes (urease, acid and alkaline phosphatase, dehydrogenase), compared to untreated soils. The treated seeds with the consortia of four native bioagents resulted in a significant increase in plant height (39.16%), number of panicles (30.29%), and average grain yield (41.36%) over control plants. Under controlled conditions, the bioagents-treated plants showed a 69.37% reduction in stem rot disease. The findings of this study indicate a positive correlation between soil properties and plant growth as well as a highly negative association with stem rot disease severity. The results suggest that using native bioagents as a management strategy can control stem rot disease and enhance crop productivity while reducing reliance on chemical interventions. These findings provide valuable insights for the development of sustainable agricultural practices that promote soil health, plant growth, and disease management.

RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found in silico evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway through interaction with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51 binding sites in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-binding sites in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway were significantly occupied by RAD51 in all four cell lines. Taken together, these results predicted a novel role of RAD51 that had not been addressed previously, and provided evidence that RAD51 could possibly be involved in regulating genes associated with the autophagy pathway, through interaction with E-box binding proteins.

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

Heavy load carrying of water, firewood, and sand/stones is a ubiquitous activity for women living in developing countries. Although the intra-abdominal pressure associated with heavy load carrying is hypothesized to increase the risk of pelvic organ prolapse (POP) among women, relevant epidemiologic data are lacking. We conducted a comparative study involving two exploratory cross-sectional studies among convenience samples of women carrying heavy loads, with different characteristics: (1) as part of their activities for daily living, in Shinyanga region, Tanzania; and (2) working as sand miners in Pokhara, Nepal. Women were categorized has having “low” or “high” load-carrying exposures based on the measured weights of the loads being carried at the time of the survey, as well as on self-reported duration and frequency of load carrying. A summary score for lower abdominal discomfort suggestive of POP was generated using questions from the Pelvic Organ Prolapse Distress Inventory (POPDI-6). Women with higher load carrying exposures had on average higher discomfort scores in both Tanzania (adjusted prevalence difference (PDa)=3.7; 95% CI: -3.8-11.3; p=0.33) and Nepal (PDa=9.3; 95% CI: -4.9-23.6; p=0.18). We identified trends suggestive of an association between increasing heavy load carrying exposures and symptoms of lower abdominal discomfort. Our findings underscore the need for larger epidemiologic studies of the potential adverse reproductive health effects of heavy load carrying activities on women in developing countries.

Ovarian cancer is a deadly disease attributed to late-stage detection as well as recurrence and development of chemoresistance. Ovarian cancer stem cells (OCSCs) are hypothesized to be largely responsible for emergence of chemoresistant tumors. Although chemotherapy may initially succeed at decreasing the size and number of tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that Aldehyde dehydrogenase 1A1 (ALDH1A1) is essential for the survival of OCSCs. We identified a novel ALDH1A1 inhibitor, compound 974, and used 974 as a tool to decipher the mechanism of stemness regulation by ALDH1A1. Treatment of OCSCs with 974 significantly inhibited ALDH activity, expression of stemness genes, spheroid, and colony formation. In vivo limiting dilution assay demonstrated that 974 significantly inhibited CSC frequency. Transcriptomic sequencing of cells treated with 974 revealed significant downregulation of genes related to stemness and chemoresistance as well as senescence and senescence associated secretory phenotype (SASP). We confirmed that 974 inhibited senescence and stemness induced by platinum-based chemotherapy in functional assays. Overall, these data establish that ALDH1A1 is essential for OCSCs survival and ALDH1A1 inhibition sup-presses chemotherapy induced senescence and stemness. Targeting ALDH1A1 using small molecule inhibitors in combination with chemotherapy therefore presents a promising strategy to pre-vent ovarian cancer recurrence and has potential for clinical translation.

Background DaVinci Single-Port (SP) robotic surgery offers several benefits compared to traditional multiport laparoscopic or robotic surgeries. One of the main advantages is that it allows for a minimally invasive approach, resulting in a single, smaller incision and reduced trauma to the patient’s body leading to less postoperative pain, faster recovery, and reduced risk of complications. The cosmesis of a single port with minimal visible scarring is also an attractive aspect to the patients; however, many surgeons use an additional port for energy device, stapler use, and drain insertion. Pure single port surgery with one incision is still rare. Here we share our experience of first 10 cases using SP robotic platform in colorectal surgery. Methods From May 2023 to December 2023, colorectal patients who underwent SP-robotic surgery were analyzed. Placement of the incision was umbilicus for 8 patients, and right lower quadrant for 2 patients through which ileostomy maturation was performed. Data including perioperative parameters and postoperative outcomes were analyzed with a median follow-up of 4.6months (range 0.6-7.4months). Results A total number of 10 colorectal patients underwent DaVinci Single-Port robotic colorectal surgery at our institution during this period. Demographics of the patients showed 4 males (40%) and 6 females (60%) with a median age of 63.5years (range 50-75years). Median body mass index (BMI) was 22.89kg/m2 (range 19.92-26.84kg/m2), and 9 patients were diagnosed with colorectal cancer and 1 patient was diagnosed with rectal gastrointestinal tumor. One patient underwent anterior resection and cholecystectomy simultaneously. Mean operation time was 222min (range 142-316min), and mean wound size was 3.25cm (range 2.5-4.5cm). Nine patients underwent surgery with single incision through which single port trocar was inserted, and one patient had one additional port for drain insertion. Mean hospital stay was 6 days (range 4-8 days) with 1 postoperative complication of bleeding requiring transfusion, but there was no re-admission within 30 days. Conclusion Overall, our experience with single-port robotic colorectal surgery has been promising. With only one patient with additional port for drain insertion, all nine patients underwent SP-robotic surgery with single incision for colon as well as rectal surgeries. Compared to an average postoperative length of stay of 6.5-8 days in laparoscopic colorectal surgeries reported in literature, SP-robotic surgery showed faster recovery of 6 days highlighting its benefits in patient recovery and satisfaction.

Acid lime [Citrus aurantifolia (Christm.) Swingle] is a fruit crop, enriched with high commercial value and is cultivated in 60 out of 75 districts representing all geographical landscapes of Nepal. Lack of high yielding cultivars is probably one of the main reason for its extremely reduced productivity which warrants a deep understanding of genetic diversity in existing germplasm. Hereby, we aim to access the genetic diversity of acid lime germplasm cultivated at 3-different ecological gradients of eastern Nepal employing PCR-based Inter-Simple Sequence Repeats markers (ISSR). Altogether, 21 polymorphic ISSR markers were used to assess the genetic diversity in 60 acid lime cultivars sampled from different geographical locations. Analysis of binary data matrix was performed on the basis of bands obtained, scoring of the data was done accordingly, and principal coordinate analysis and phenogram were constructed using different computer algorithms. ISSR profiling yielded 234 amplicons, of which 87.18% were found to be polymorphic. The number of amplified fragments ranged from 7-18 with amplicon size ranging from 250-3200 bp. The NTSYS based Cluster analysis using UPGMA algorithm taking Dice Similarity coefficient separated 60 accessions into 2-major and 3-minor clusters. The genetic diversity analysis revealed the highest for Terai and the lowest for High-hill zone. Cluster I comprised of accessions from High-hill and Mid-hill regions revealing the close genetic relationship, whereas cluster II comprised of accessions from all three agro-ecological zones and the exotic varieties. Furthermore, our results revealed the accessions harvested from different geographical gradients were not genetically distinct, but highest diversity was observed in Terai accessions in comparison to the regions belonging to the High and Mid-hills. Thus, our data indicate that the ISSR provides a better option for evaluating the genetic diversity of Nepalese Acid Lime cultivars and furnished significant information, assisting parental selection in current and future breeding programs and germplasm conservation which ultimately may help to provide a technological breakthrough for the farmers of the developing country like Nepal.

Bone marrow mononuclear cells (BMMNCs) have emerged as a potential therapeutic strategy for various incurable conditions including autism spectrum disorder (ASD). To study its safety and efficacy, we analyzed 1011 patients who underwent intrathecal administration of autologous BMMNCs along with neurorehabilitation. At mean follow-up of 19.3 months after intervention, 90.6% patients showed overall improvement. Improvements were observed in attention concentration, command following, eye contact, sitting tolerance, social interaction, hyperactivity, communication, speech, aggressiveness, stereotypical and self-injurious behavior. Statistically significant changes were observed in scores of Indian Scale of Autism Assessment and Childhood Autism Rating Scale (p<0.05). On subgroup analysis, improvements were recorded irrespective of age and disease severity and better outcome was observed in patients who took multiple doses of cell therapy compared to single dose. Comparative Brain PET-CT scan of 401 patients showed improved brain metabolism after the intervention. No major adverse events were reported. Only 9 out of 1011 patients experienced seizures which were managed using medications. 4 out of 9 had history of seizures while 5 had normal EEG with no history. However, improvements were still observed in these 9 patients. Thus, intrathecal transplantation of autologous BMMNCs along with neurorehabilitation is safe and efficacious in patients with ASD.

Kluyveromyces marxianus (K. marxianus) is a newly emerging industrially relevant yeast. It is known to possess a highly efficient Non-Homologous End Joining (NHEJ) pathway that promotes random integration of non-homologous DNA fragments into its genome. The nature of the integration events was traditionally analyzed by Southern blot hybridization. However, the precise DNA sequence at the insertion sites were not fully explored. We transformed a PCR product of the Saccharomyces cerevisiae URA3 gene (ScURA3) into an uracil auxotroph K. marxianus wildtype strain and picked 24 stable Ura+ transformants for sequencing analysis. We took advantage of rapid advances in DNA sequencing technologies and developed a method using a combination of Illumina MiSeq and Oxford Nanopore sequencing. This approach enables us to uncover the Gross Chromosomal Rearrangements (GCRs) that are associated with the ScURA3 random integration. Moreover, it will shine a light on understanding DNA repair mechanisms in Eukaryotes, which could potentially provide insights for cancer research.

Hydrogenated water has emerged as a novel approach in the field of health and wellness. It is be-lieved to have potent antioxidant properties that can neutralize harmful free radicals in the hu-man body. It has also been shown to be beneficial in mitigating oxidative stress-induced damage through its anti-inflammatory and anti-apoptotic pathways. We aim to conduct a systematic re-view to evaluate the potential benefits of hydrogenated water. The review protocol was uploaded on PROSPERO. After the initial search criteria, the articles were reviewed by two blinded inves-tigators, and a total of 25 articles were included in the systematic review. The potential benefits of hydrogenated water on various aspects of health, including exercise capacity, physical endurance, liver function, cardiovascular disease, mental health, COVID-19, oxidative stress, and anti-aging research, are a subject of growing interest and ongoing research. Although preliminary results in clinical trials and studies are encouraging, further research with larger sample sizes and rigor-ous methodologies is needed to substantiate these findings. Current research needs to fully ex-plain the mechanisms behind the potential benefits of hydrogenated water. Continued scientific exploration will provide valuable insights into the potential of hydrogenated water as an adjunc-tive therapeutic approach in the future.

DNA polymerases replicate cell genomes and/or participate in the maintenance of genome integrity. DNA polymerases sharing high sequence homology with E. coli DNA polymerase I (pol I), have been grouped in Family A. Pol I participates in Okazaki fragment maturation and in bacterial genome repair. Since its discovery in 1956, pol I has been extensively studied, primarily to get deeper insights into the mechanism of DNA replication. As research on DNA polymerases advances, many novel functions of this group of polymerases are uncovered. For example, human DNA polymerase θ (a Family A DNA pol) has been shown to synthesize DNA using RNA as a template, a function typically attributed to retroviral reverse transcriptase. A heightened interest in drug discovery against pol θ has emerged due to its roles in cancer. Likewise, Pol I family enzymes also appear attractive drug-development targets against microbial infections. Development of antimalarial compounds targeting apicoplast apPOL, an ortholog of Pol I, further extends the druggability of this family of enzymes. Here, we summarize reported drug-development efforts against Family A polymerases, and future perspective regarding these enzymes as antibiotic targets. Current techniques such artificial intelligence can be used to facilitate the goal of new drugs.

Healthcare leaders are faced with many financial challenges in the contemporary environment, leading to many bankruptcies in recent years. What is not well understood are the specific conditions that lead to organizational economic failure. Ideally, hospital leaders could examine the literature for guidance to predict bankruptcy before it occurs. However, existing regression methods have proven inadequate, especially when the finance variables follow a nonnormal frequency pattern. Furthermore, the regression approach encounters difficulties due to multicollinearity and nonnormality issues. Therefore, an alternate stochastic approach for predicting the probability of hospital bankruptcy is warranted. This new method includes computing and interpreting the correlations between the hospital’s revenue and expenses for bivariate lognormal data, calculating the risk of bankruptcy due to the mismatch between revenues and expenses, determining the likelihood of a hospital’s expense exceeding the state’s median expense level, and evaluating a hospital’s financial memory level. Ultimately in our research, we demonstrate a novel approach to anticipate hospital bankruptcy, which can be particularly useful for health policy analysts and hospital leaders in making informed financial decisions and proactively managing risks to ensure the sustainability and stability of their institutions.

Bioactive compounds are the food constituents, providing beneficial health effects to functional foods and nutraceuticals. These compounds have antioxidants activity including anti-inflammatory, antifungal, and have additional preventative actions. Since these compounds are important constituents enhancing function of the foods, therefore, these constituents are necessary to be incorporated under the umbrella of functional foods. Functional foods provides health benefits though bioactive compounds, as these compounds target mechanisms that manage, prevent, and/or treat chronic or acute diseases. The bioactive compounds are quite essential for functional foods that are crucial for optimal health, thereby leading to the inclusion of these compounds in the most recent definition of functional foods. Some experts have defined that bioactive compounds are the chemical components that contributes and regulates in biological mechanisms. These bioactive compounds are more accurately defined by Dr. Martirosyan and Pisarski as the “primary and secondary metabolites of nutritive and non-nutritive natural components generating health benefits by preventing or managing chronic disease or its symptoms”. These compounds have potential antioxidant and anti-inflammatory activity, which provide benefits to health. Although they are a small proportion of a food source, these compounds can also trigger the mechanisms that will alter and can improve human health. Certain bioactive compounds present in foods are extremely beneficial, but if consumed in excess, they can cause toxicity. Therefore, each bioactive compound must be fully evaluated in order to establish a beneficial and a toxic threshold amount.

There has been limited research on improving Internet-delivered Cognitive Behavioural Therapy (ICBT) in routine online therapy clinics that serve people from diverse ethnocultural groups (PDEGs). This article describes a patient-oriented adaptation approach used to address this gap in research. A working group consisting of people with lived experience, community stakeholders, ICBT clinicians, managers, and researchers, was formed. The working group examined archival feedback on ICBT from past clients who self-identified as being from diverse ethnocultural back-grounds (N=278) and results of interviews with current patients (N=16), community stakeholders (N=6), and clinicians (N=3). The archival data and interviews revealed the majority of the pa-tients reported being satisfied with and benefitting from ICBT. Suggestions for improvement were not related to the cognitive-behavioural model and techniques, but rather to making treatment materials more inclusive. Consequently, the ICBT adaptation focused on adding content related to cultural influences on mental health, addressing stigma, diversifying case stories, examples and imagery, adding audiovisual introductions, and replacing English idioms with more descriptive language. Moreover, further training was offered to clinicians and efforts were made to improve community outreach. This study demonstrates a process for using patient-oriented research to improve ICBT within routine care serving patients of diverse backgrounds.

Previously, we demonstrated that IR triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–STAT3/CREB-1–EMT pathway. Here, we have demonstrated the involvement of a novel intracellular signaling mechanism in γ-ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration. Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2, MMP-9, and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB. Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression followed by a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

Organic light-emitting diodes (OLEDs) have ushered in a technological revolution with their remarkable impact on diverse sectors of our daily lives. These versatile devices known for their outstanding display and lighting capabilities, have become indispensable components in various industries including smartphones, tablets, televisions, and automotive applications. This paper delves into the development of a group of twisted donor-acceptor-donor (D-A-D) derivatives incorporating bicarbazole and benzophenone structures for potential use as blue emitters in OLEDs. The synthesized compounds, namely DB14, DB23 and DB29, were designed with various alkyl side chains to enhance their film forming properties as for blue emitters. Characterization and evaluation of these derivatives included photophysical, electrochemical, thermal, and electroluminescent analysis. Some of the OLED devices incorporating these emitters demonstrated promising performance with maximum current efficiency (CEmax) of 2.6 cd/A and external quantum efficiency (EQEmax) of 5.3%. Notably, the DB23 emitter exhibited the highest EQE among all devices. The study also emphasizes the influence of host-guest energy transfer, optimal doping concentrations, and molecular structures on device performance. This research not only contributes to the understanding of advanced OLED materials but also provides insights into designing efficient blue emitters for future display and lighting applications, thereby advancing the field of organic electronics.

There is evidence that behavioral risk factors such as western type diet, and life style can predispose to oxidative stress, deficiency in antioxidant status, hyperglycemia, dyslipidemia and increase in inflammation in tissues of various organs: beta cells of the pancreas, LDL receptors in the hepatocytes, endothelium, neurons, osteocytes and gut. Further studies indicate that diets rich in antioxidant flavonoids, omega-3 fatty acids and fiber in foods were inversely associated whereas western-type foods were positively associated with risk of mortality due to cardiovascular diseases (CVDs). One important cause for beneficial effects of diet may be certain foods and nutrients such as vegetables, fruits and whole grains that are rich in fiber and flavonoids, known to produce liters og molecular hydrogen in the gut. It seems that, high-fiber diets, prebiotic and probiotics can produce greater hydrogen, which acts as an antioxidant and may inhibit free radical generation. Recent studies indicate that molecular hydrogen can inhibit hydroxyl and nitrosyl radicals and can directly act as antioxidant in the cells and tissues, which can cause marked decline in oxidative stress and inflammation leading to significant decline in CVDs and metabolic diseases. Clinical and experimental studies indicate that hydrogen therapy such as hydrogen rich water can provide benefits in the management of CVDs and metabolic diseases. Larger studies are necessary to verify the role of hydrogen administration in CVDs.

Medicinal plants have been a cornerstone of traditional medicine systems for centuries, offering a vast array of bioactive compounds with therapeutic potential. However, the identification, characterization, and elucidation of the pharmacological properties of these plants have often been challenging due to their complex chemical composition and diverse biological activities. Bioinformatics, with its interdisciplinary approach combining biology, computer science, and information technology, presents a powerful toolkit for the systematic study of medicinal plants. This review provides an overview of bioinformatics methodologies and resources that can facilitate the identification, phytochemical analysis, pharmacological investigation, and conservation of medicinal plants. It highlights the integration of omics technologies, computational algorithms, database resources, and molecular modeling techniques in advancing our understanding of medicinal plants' therapeutic potential and their applications in drug discovery and development.

The utilization of wild genera in sugarcane has been recognized as an important strategy to enhance the genetic base to impart biotic and abiotic stress tolerance in hybrid cultivars. A set of 15 Erianthus procerus derived hybrids along with five popular check varieties were evaluated for two years (2018–19 and 2019–20) for agro-morphological, quality, physiological traits and three years (2018–19, 2019–2020, and 2020–21 for winter sprouting potential. The E. procerus hybrid GU 12-19 recorded the highest winter sprouting potential with a winter sprouting index (WSI) of 10.6 and a percent superiority of 279 over best check (Co 0238) followed by GU 12-22 with WSI: 8.5 and % superiority over best check was 204. The other top-performing hybrids, GU 12-21 and GU 12-29, recorded the excellent winter sprouting potential with WSI of 7.2 and 6.9 respectively. The four E. procerus hybrids identified with higher WSI were also resistant to the prevalent races of red rot in both tropical and subtropical conditions. The association analysis revealed significant correlations between various traits, particularly fibre content with a maximum number of associations, which indicates its multifaceted impact on sugarcane characteristics. Principal component analysis (PCA) summarized the data, explaining 57.6% of the total variation for measured traits and genotypes, providing valuable insights into the performance and characteristics of the E. procerus-derived hybrids under subtropical climate. The anthocyanin content of E. procerus hybrids was better than the check varieties with a mean of 0.147 (2018–19) and 0.144 (2019–20) and range of 0.123–0.179 (2018–19) and 0.111–0.172 (2019–20), anthocyanin plays a vital role in mitigating the cold injury, acting as an antioxidant in cool weather conditions, particularly in sugarcane. Further, seven hybrids recorded more than 22% fibre threshold, indicating their industrial potential. These hybrids would be potential donors for cold tolerance and high ratooning ability along with red rot resistance under subtropical climate.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

Alzheimer’s disease(AD) progression correlates with the propagation of hyperphosphorylated Tau (pTau) from the entorhinal cortex to the hippocampus and neocortex. Neutral sphingomyelinase2(nSMase2) is critical in the biosynthesis of extracellular vesicles (EVs), which play a role in pTau propagation. We recently conjugated DPTIP, a potent nSMase2 inhibitor, to hydroxyl-PAMAM-dendrimer nanoparticles which can improve brain delivery. We showed that dendrimer-conjugated-DPTIP (D-DPTIP) robustly inhibited pTau spread in an AAV-pTau propagation model. To further evaluate its efficacy, we tested D-DPTIP in the PS19 transgenic mouse model. Unexpectantly, D-DPTIP showed no beneficial effect. To understand this discrepancy, we assessed D-DPTIP’s brain localization. Using immunofluorescence and fluorescence-activated cell-sorting, D-DPTIP was found to be primarily internalized by microglia where it selectively inhibited microglial nSMase2 activity with no effect on other cell types. Furthermore, D-DPTIP inhibited microglia-derived EV release into plasma without affecting other brain-derived EVs. We hypothesize that microglial targeting allowed D-DPTIP to inhibit tau propagation in the AAV-hTau model, where microglial EVs play a central role in propagation. However, in PS19 mice, where tau propagation is independent of microglial EVs, it had a limited effect. Our findings confirm microglial targeting with hydroxyl-PAMAM dendrimers and highlight the importance of understanding cell-specific mechanisms when designing targeted AD therapies.

The recent outbreak of the novel Coronavirus Disease (COVID-19) has given rise to diverse health issues due to its high transmission rate and limited treatment options. Almost the whole world, at some point of time, was placed in lock-down in an attempt to stop the spread of the virus, with resulting psychological and economic sequela. As countries start to ease lock-down measures and reopen industries, ensuring a healthy workplace for employees has become imperative. Thus, this paper presents a mobile app-based intelligent portable healthcare (pHealth) tool, called iWorkSafe, to assist industries in detecting possible suspects for COVID-19 infection among their employees who may need primary care. Developed mainly for low-end Android devices, the iWorkSafe app hosts a fuzzy neural network model that integrates data of employees' health status from the industry's database, proximity and contact tracing data from the mobile devices, and user-reported COVID-19 self-test data. Using the built-in Bluetooth low energy sensing technology and K Nearest Neighbor and K-means techniques, the app is capable of tracking users’ proximity and trace contact with other employees. Additionally, it uses a logistic regression model to calculate the COVID-19 self-test score and a Bayesian Decision Tree model for checking real-time health condition from intelligent e-health platform for further clinical attention of the employees. Rolled out in an apparel factory on 12 employees as a test case, the pHealth tool generates an alert to maintain social distancing among employees inside the industry. In addition, the app helps employee to estimate risk with possible COVID-19 infection based on the collected data and found that the score is effective in estimating personal health condition of the app user.

There is evidence that optimal nutrition is fundamental to human health and in the prevention of non-communicable diseases (NCDs) later in adult life. The identification, production and consumption of functional foods worldwide can increase health benefits for all who can access and afford such foods subject to advice from nutritionists. Recent meetings organized by the health agencies, give a crucial opportunity to make nutrition, a central part of the post-2015 sustainable human and agricultural development agenda. The aim of discussions in these meetings was to provide functional crops and foods to achieve optimal health by prevention of NCDs. It is possible that these efforts might ensure that the goals and targets set in the agenda are adequate to address the many challenges of global undernutrition as well as obesity which are major risk factors of NCDs. In many developing and middle income countries, food security provided by the governments, in one sense understandably, gave least consideration to functional foods supply and the prevention of obesity and metabolic syndrome, resulting in to emergence of NCDs. The Thailand Declaration reiterates that commitments to eradicate hunger and undernutrition as well as over-nutrition, and to increase investments in effective interventions; designers foods and designers crops. However, in planning coherent policies, our past experience on rapidly absorbed, energy-rich processed foods should be taken in to account while developing sustainable food systems. The food industry should be educated to exploit the expertise of food scientists and health professionals in designing functional foods taking cognizance of manufacturing and processing. Similarly, agriculture scientists may be actively involved in educating farmers so as to grow cash crops providing functional foods. The aim should be to achieve an increase in the availability of functional foods to an extent, or by a policy, by which such foods are available to poors, at affordable cost to prevent hunger and undernutrition and related diseases as well as NCDs. In addition our efforts might help in developing an international consensus on how to approach the development of new designer foods by farmers and food industry to produce low glycemic index foods. Such efforts may establish an international framework for the prevention of NCDs, so that human susceptibility to these diseases is substantially diminished.

Study Objective: This study examined office workstation types’ impact on objective health-related metrics including stress, physical activity (PA), and sleep quality. We propose a sensor-based sleep quality index (SB-SQI) to fill a needed gap for objective sleep quality measurement over short timescales. Methods: We monitored 231 office workers using chest-worn sensors for 72 hours, yielding 11,736 hours of usable data from 163 participants (mean age 43.4, 56% women). SB-SQI was based on a validated algorithm estimating sleep-onset latency, total sleep time, and sleep efficiency, using the scoring method from the Pittsburg Sleep Quality Index (PSQI). We examined the relationships between SB-SQI, office workstation type (open-bench seating, cubicle, and private office), work-hours stress (standard deviation of heart rate variability), and after-work PA (relative duration of moderate-to-vigorous activity). Results: The sensor-derived poor-sleep ratio of the private office workers was higher than with other office workstation types (81% vs. 66.1%, p = 0.023). PSQI revealed a similar but insignificant trend with a lower effect-size. Among good-sleepers, open-bench seating workers had 22% (p = 0.018) less stress during work hours than others. A significant association between work-hours stress and after-work hours PA (r = 0.331, p = 0.000) was observed irrespective of office workstation type, with the highest PA level observed for open-bench seating workers. Conclusions: Office workstation type had a significant impact on work-hours stress, affecting PA after work hours, which influenced sleep quality. SB-SQI could be more sensitive than PSQI in determining the impact of office workstation types on sleep quality.