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Influenza D virus (IDV), the cattle flu virus, is a novel multi-host RNA virus, circulating silently worldwide, with widespread seropositivity among US cattle, reaching up to 80% in some areas raising a potential threat of cattle-to-human transmission. Currently, five genetic lineages of IDV have been described, but their evolutionary dynamics have not been studied. Although IDV was first identified in 2011, our comprehensive analysis of all known IDV genomes suggests that the earliest ancestors of IDV likely to have evolved towards the end of the 20th century and D/OK lineage appears to have emerged in 2005. We confirmed a significantly higher substitution rate in IDV than in Influenza C virus, which is consistent with their global distribution and multi-host tropism. We identified multiple sub-populations within the D/OK lineage, highlighting extensive diversification and dissemination. Other findings are evidence for potential reassortment among IDV strains in the USA and transboundary circulation of IDV in Europe with introductions into Danish cattle, some of which potentially originated from France. IDV, an emerging virus with a higher rate of evolution and uncontrolled circulation, could facilitate its adaptation to humans. Our findings underscore the importance of targeted surveillance for IDV in humans and at-risk animal populations. Evolutionary dynamics and population stratification analysis of whole genomes of the cattle flu Influenza D virus reveal its high evolution rate, extensive diversification and global dissemination, stressing the need for targeted surveillance. [ABSTRACT FROM AUTHOR]

The aim of this study was to study the prevalence of obstructive sleep apnea syndrome in patients with nasal and nasopharyngeal pathologies. A total of 60 consenting patients between the age of 14 to 60 years with primary nasal and nasopharyngeal pathologies were taken up for the study. These patients underwent history taking, detailed clinical examination including BMI, diagnostic nasal endoscopy and overnight polysomnography. The polysomnography results of people with different pathologies were compared and analysed. Based on the analysis it was arrived that isolated pathologies like septal deviation, nasal polypi and adenoid hypertrophy provided a statistically significant association with occurrence and severity of OSA. Also, that patients with combined pathologies were more proportionately affected by OSA than those with isolated pathologies. Nasal and nasopharyngeal pathologies have significant association with obstructive sleep apnea syndrome and all patients with these pathologies need to undergo polysomnography along with other routine investigations. [ABSTRACT FROM AUTHOR]

While selenium is a cofactor of several antioxidant enzymes against cancer and is essential for human health, its excess intake may also be harmful. Though a safe intake of selenium has recently been recommended, it is not well understood in the Asian population. We aimed to determine the association between dietary intake of selenium and cancer risk in a case–control study of 3758 incident cancer cases (i.e., stomach, colon, rectum, lung cancers, and other sites) and 2929 control subjects in Vietnam. Daily intake of selenium was derived from a semiquantitative food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between selenium intake and cancer risk. We observed a U-shaped association between selenium intake and cancer risk. A safe intake ranged from 110.8 to 124.4 µg/day (mean 117.8 µg/day). Compared to individuals with the safe intake of selenium, individuals with the lowest intake (i.e., 27.8–77.2 µg/day) were associated with an increased risk of cancer (OR = 3.78, 95% CI 2.89–4.95) and those with the highest intake (169.1–331.7 µg/day) also had an increased cancer risk (OR = 1.86, 95% CI 1.45–2.39). A U-shaped pattern of association between selenium intake and cancer risk was stronger among participants with body mass index (BMI) < 23 kg/m2 and never smokers than BMI ≥ 23 kg/m2 and ever smokers (P’sheterogeneity = 0.003 and 0.021, respectively) but found in both never and ever-drinkers of alcohol (Pheterogeneity = 0.001). A U-shaped association between selenium intake and cancer risk was seen in cancer sites of the stomach, colon, rectum, and lung cancers. In summary, we found a U-shaped association between selenium intake and cancer risk and a safe selenium intake (mean: 117.8 µg/day) in the Vietnamese population. Further mechanistic investigation is warranted to understand better a U-shaped association between selenium intake and cancer risk. [ABSTRACT FROM AUTHOR]

Human P‐glycoprotein (P‐gp) utilizes energy from ATP hydrolysis for the efflux of chemically dissimilar amphipathic small molecules and plays an important role in the development of resistance to chemotherapeutic agents in most cancers. Efforts to overcome drug resistance have focused on inhibiting P‐gp‐mediated drug efflux. Understanding the features distinguishing P‐gp inhibitors from substrates is critical. Cryo‐electron microscopy has revealed distinct binding patterns, emphasizing the role of the L‐site or access tunnel in inhibition. We substituted 5–9 residues of the L‐site with alanine to investigate whether the binding of a second inhibitor molecule to the L‐site is required for inhibiting drug efflux. We reveal, for the first time, that mutations in the L‐site affect the drug efflux activity of P‐gp, despite their distance from the substrate‐binding pocket (SBP). Surprisingly, after the mutations were introduced, inhibitors such as tariquidar and zosuquidar still inhibited drug efflux by mutant P‐gps. Communication between the transmembrane helices (TMHs) and nucleotide‐binding domains (NBDs) was evaluated using the ATPase assay, revealing distinct modulation patterns by inhibitors for the mutants, with zosuquidar exhibiting substrate‐like stimulation of ATPase. Furthermore, L‐site mutations abolished ATP‐dependent thermal stabilization. In silico molecular docking studies corroborated the altered inhibitor binding due to mutations in the L‐site residues, shedding light on their critical role in substrate transport and inhibitor interactions with P‐gp. These findings suggest that inhibitors bind either to the SBP alone, and/or to alternate site(s) when the L‐site is disabled by mutagenesis. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV), a mosquito-borne flavivirus, is a significant global health concern due to its association with neurodevelopmental disorders such as congenital Zika syndrome (CZS). This study aimed to compare the replication kinetics, viral persistence, cytopathogenic effects, and immune gene expression in human microglia cells (CHME-3) infected with an Asian lineage ZIKV (PRVABC59, referred to as ZIKV-PRV) and an African lineage ZIKV (IBH30656, referred to as ZIKV-IBH). We found that ZIKV-PRV replicated more efficiently and persisted longer while inducing lower levels of cell death and inflammatory gene activation compared with ZIKV-IBH. These findings suggest that the enhanced replication and persistence of ZIKV-PRV, along with its ability to evade innate immune responses, may underlie its increased neuropathogenic potential, especially in the context of CZS. In contrast, ZIKV-IBH, with its stronger immune gene activation and higher cytopathogenicity, may lead to more acute infections with faster viral clearance, thereby reducing the likelihood of chronic central nervous system (CNS) infection. This study provides crucial insights into the molecular and cellular mechanisms driving the differential pathogenicity of ZIKV lineages and highlights the need for further research to pinpoint the viral factors responsible for these distinct clinical outcomes. [ABSTRACT FROM AUTHOR]

Digital India is an initiative taken for the citizens to access the government services in a digital forum. The government is trying to confirm the vision and pillars of digital India program by investigating the citizen's perspective on digital services. This current study aims to investigate the citizen awareness, explore the citizen opinion on digital India services and to determine citizen opinion on features associated with digital India services. This research is based on descriptive research design and target populations are the Citizens of Tamil Nadu. The sampling method used in this research is non-probability convenience sampling with a sample size of 505 participants. Structured questionnaires using Likert 5-Point scale was used to collect data. The findings exposed that the awareness and perception of digital India services towards digital India initiative at Tamilnadu was highly valued and they recognized that the Citizens are aware about digital India service features and advantages having the optimistic view on digital India initiative. This research study suggests that keeping citizens involved with the digital India services is the most significant aspect and it leads them to feel self-confident and self-reliant towards better results. The future study would be to pre-determine categories like usage, adoption, loyalty and satisfaction and citizen empowerment through digital India services. [ABSTRACT FROM AUTHOR]

The growing urban population, increasing income per capita, and significant rise in the number of people living in cities are all placing a strain on the nation's water supply and calling for innovative methods of urban water management. Water stress, excessive resource consumption, nutrient discharge into aquatic ecosystems, and financially unstable utilities are all consequences of the traditional linear "take, make, waste" approach to water management. Many strategies are required to achieve economic, environmental, and social sustainability. More closed‐loop urban wastewater and resource management systems can be developed and implemented with the help of a toolkit that includes stormwater management/rainwater harvesting, water conservation, water reclamation and reuse, energy management, nutrient recovery, and source separation. Water conservation, water reclamation, and wastewater reuse are becoming the norm in many water‐poor regions. This shift is hastened by decentralization, made possible by dispersed stormwater management/rainwater collection and innovative high‐performance treatment technologies. Similar changes are occurring in conventional methods of residual management due to the need for more energy recovery and nutrient recovery and reuse. Finding the most outstanding long‐term solutions requires an economic study done well. The practice of stove‐piping must be eradicated from urban wastewater and resource management. These novel techniques for managing urban wastewater and resources can produce more long‐term, financially stable, resource‐efficient, environmentally friendly, nutrient‐sensitive, and sanitary outcomes. [ABSTRACT FROM AUTHOR]

Groundwater is essential to human well‐being and sustains a variety of aquatic ecosystems in both urban and rural settings. Yet, it is commonly overlooked in these contexts. As a result, groundwater may be very important to the development and well‐being of many nations if it is properly evaluated and utilized. Although the possibility for sustainable groundwater resource development is still debated in the literature, these issues still lack quantitative understanding. In order to assess groundwater potential in two different urbanized regions of "Northern Kerala, Southern India," this research uses the "Enhanced Fuzzy Analytic Hierarchy Process (E‐Fuzzy AHP) based Multi‐Criteria Decision Making (MCDM)‐Geospatial Framework employing Improved Particle Swarm Optimization (IPSO)". The study area is a coastal region that is quickly becoming urbanized and relies on groundwater resources to meet its basic needs. By incorporating both spatial and non‐spatial data into the Geographic Information System (GIS) platform, a groundwater potential zone map with an accurate integer value was created, known as the "groundwater potential index (GWPI)". The very excellent potential zone occupies 35% and 11%, respectively, of the "urban and peri‐urban zones," according to the final groundwater potential map, which employed the quantile technique to split the research territory into four zones. The statistical effectiveness and dependability of results in the overall decision‐making phase were examined in the validation study using the data on mean water depth level, and it was found that the reliability was well within the tolerance threshold. [ABSTRACT FROM AUTHOR]

MTX-211 is a first-in-class dual inhibitor of epidermal growth factor receptor (EGFR) and phosphoinositide-3 kinase (PI3K) signaling pathways with a compelling pharmaceutical profile and could enhance the effectiveness of mitogen-activated protein kinase kinase (MEK) inhibitor therapy in colorectal tumors with KRAS mutations. However, the specific mechanisms contributing to the acquired resistance to MTX-211 in human cancers remain elusive. Here, we discovered that the overexpression of the ATP-binding cassette (ABC) drug transporter ABCG2, a prevalent mechanism associated with multidrug resistance (MDR), could diminish the effectiveness of MTX-211 in human cancer cells. We showed that the drug efflux activity of ABCG2 substantially decreased the intracellular accumulation of MTX-211 in cancer cells. As a result, the cytotoxicity and effectiveness of MTX-211 in suppressing the activation of the EGFR and PI3K pathways were significantly attenuated in cancer cells overexpressing ABCG2. Moreover, the enhancement of the MTX-211-stimulated ATPase activity of ABCG2 and the computational molecular docking analysis illustrating the binding of MTX-211 to the substrate-binding sites of ABCG2 offered a further indication for the interaction between MTX-211 and ABCG2. In summary, our findings indicate that MTX-211 acts as a substrate for ABCG2, underscoring the involvement of ABCG2 in the emergence of resistance to MTX-211. This finding carries clinical implications and merits further exploration. [ABSTRACT FROM AUTHOR]

Background: Paraquat, a widely used herbicide known for its efficacy in weed control, has gained notoriety for its potential toxicity to humans. The current study examines the manifestations, consequences, and course of paraquat intoxication. Methodology: At our tertiary care center, 10 cases of paraquat poisoning were recorded during the course of the study, which lasted a full year. In our study, all cases included purposeful ingestion, meaning the patient attempted suicide. Out of ten patients, only one patient survived. This suggests that patients who present early (4 hours) and with less ingestion have a higher chance of surviving. Conclusion: Among the various systemic effects associated with paraquat poisoning, lung involvement stands out as a critical and often fatal manifestation. According to our study, pulmonary fibrosis, Respiratory failure and ultimately multi-organ failure are the most frequent consequences that result in mortality. This article explores the intricacies of lung complications arising from paraquat exposure, shedding light on the underlying mechanisms, clinical presentation, diagnostic challenges, and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) remains a public health concern, with epidemics in endemic regions and sporadic outbreaks in new areas posing significant threats. Several mosquito-borne flaviviruses that can cause human illness, including West Nile, Usutu, and St. Louis encephalitis, have associations with birds. However, the susceptibility of chickens to ZIKV and their role in viral epidemiology is not currently known. We investigated the susceptibility of chickens to experimental ZIKV infection using chickens ranging from 1-day-old chicks to 6-week-old birds. ZIKV caused no clinical signs in chickens of all age groups tested. Viral RNA was detected in the blood and tissues during the first 5 days post-inoculation in 1-day and 4-day-old chicks inoculated with a high viral dose, but ZIKV was undetectable in 6-week-old birds at all timepoints. Minimal antibody responses were observed in 6-week-old birds, and while present in younger chicks, they waned by 28 days post-infection. Innate immune responses varied significantly between age groups. Robust type I interferon and inflammasome responses were measured in older chickens, while limited innate immune activation was observed in younger chicks. Signal transducer and activator of transcription 2 (STAT2) is a major driver of host restriction to ZIKV, and chicken STAT2 is distinct from human STAT2, potentially contributing to the observed resistance to ZIKV infection. The rapid clearance of the virus in older chickens coincided with an effective innate immune response, highlighting age-dependent susceptibility. Our study indicates that chickens are not susceptible to productive ZIKV infection and are unlikely to play a role in the ZIKV epidemiology. [ABSTRACT FROM AUTHOR]

Background: A principal protective component of the mammalian blood–brain barrier (BBB) is the high expression of the multidrug efflux transporters P-glycoprotein (P-gp, encoded by ABCB1) and ABCG2 (encoded by ABCG2) on the lumenal surface of endothelial cells. The zebrafish P-gp homolog Abcb4 is expressed at the BBB and phenocopies human P-gp. Comparatively little is known about the four zebrafish homologs of the human ABCG2 gene: abcg2a, abcg2b, abcg2c, and abcg2d. Here we report the functional characterization and brain tissue distribution of zebrafish ABCG2 homologs. Methods: To determine substrates of the transporters, we stably expressed each in HEK-293 cells and performed cytotoxicity and fluorescent efflux assays with known ABCG2 substrates. To assess the expression of transporter homologs, we used a combination of RNAscope in situ hybridization probes and immunohistochemistry to stain paraffin-embedded sections of adult and larval zebrafish. Results: We found Abcg2a had the greatest substrate overlap with ABCG2, and Abcg2d appeared to be the least functionally similar. We identified abcg2a as the only homolog expressed at the adult and larval zebrafish BBB, based on its localization to claudin-5 positive brain vasculature. Conclusions: These results demonstrate the conserved function of zebrafish Abcg2a and suggest that zebrafish may be an appropriate model organism for studying the role of ABCG2 at the BBB. [ABSTRACT FROM AUTHOR]

The Serratia marcescens is a Gram-negative bacterium from the Enterobacteriaceae family. Recently, S. marcescens have evolved to become a versatile and opportunistic pathogen. Furthermore, this bacterium is also a multi-drug resistant pathogen exhibiting Extended-Spectrum Beta-Lactamases (ESBL) activity. This bacterium is highly associated with infections in healthcare settings and even leads to death. Hence, an advanced approach based on non-protein coding RNA (npcRNA) of S. marcescens was considered in this study to understand its regulatory roles in virulence, pathogenesis, and the differential expression of these transcripts in various growth phases of the bacterium. BLASTn search of known npcRNAs from Salmonella typhi, Escherichia coli, and Yersinia pestis against S. marcescens was performed to discover putative conserved homologous transcripts. The novelty of these putative homologous npcRNAs was verified by screening through the Rfam web tool. The target mRNA for the homologs was predicted via the TargetRNA2 webtool to understand the possible regulatory roles of these transcripts. The npcRNA homologs, which were predicted to regulate virulence target mRNA were assessed for their expression profile at different growth stages via reverse transcription PCR and the band intensity was quantitatively analysed using the Image J tool. The known npcRNA ssrS, from S. typhi showed expression in S. marcescens during three growth stages (lag, log, and stationary). Expression was observed to be high during the lag phase followed by a similarly low-level expression during the log and no expression during stationary phase. This ssrS homolog was predicted to regulate mRNA that encodes for protein FliR, which is associated with virulence. This is a preliminary study that lay the foundation for further elucidation of more virulence-associated npcRNAs that are yet to be discovered from S. marcescens, which can be useful for diagnostics and therapeutic applications. [ABSTRACT FROM AUTHOR]

Influenza D virus (IDV) is the most recent addition to the Orthomyxoviridae family and cattle serve as the primary reservoir. IDV has been implicated in Bovine Respiratory Disease Complex (BRDC), and there is serological evidence of human infection of IDV. Evolutionary changes in the IDV genome have resulted in the expansion of genetic diversity and the emergence of multiple lineages that might expand the host tropism and potentially increase the pathogenicity to animals and humans. Therefore, there is an urgent need for automated, accurate and rapid typing tools for IDV lineage typing. Currently, IDV lineage typing is carried out using BLAST-based searches and alignment-based molecular phylogeny of the hemagglutinin-esterase fusion (HEF) gene sequences, and lineage is assigned to query sequences based on sequence similarity (BLAST search) and proximity to the reference lineages in the tree topology, respectively. To minimize human intervention and lineage typing time, we developed IDV Typer server, implementing alignment-free method based on return time distribution (RTD) of k-mers. Lineages are assigned using HEF gene sequences. The server performs with 100% sensitivity and specificity. The IDV Typer server is the first application of an RTD-based alignment-free method for typing animal viruses. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a clear threat to humanity. It has infected over 200 million and killed 4 million people worldwide, and infections continue with no end in sight. To control the pandemic, multiple effective vaccines have been developed, and global vaccinations are in progress. However, the virus continues to mutate. Even when full vaccine coverage is achieved, vaccine-resistant mutants will likely emerge, thus requiring new annual vaccines against drifted variants analogous to influenza. A complimentary solution to this problem could be developing antiviral drugs that inhibit SARS CoV-2 and its drifted variants. Host defense peptides represent a potential source for such an antiviral as they possess broad antimicrobial activity and significant diversity across species. We screened the cathelicidin family of peptides from 16 different species for antiviral activity and identified a wild boar peptide derivative that inhibits SARS CoV-2. This peptide, which we named Yongshi and means warrior in Mandarin, acts as a viral entry inhibitor. Following the binding of SARS-CoV-2 to its receptor, the spike protein is cleaved, and heptad repeats 1 and 2 multimerize to form the fusion complex that enables the virion to enter the cell. A deep learning-based protein sequence comparison algorithm and molecular modeling suggest that Yongshi acts as a mimetic to the heptad repeats of the virus, thereby disrupting the fusion process. Experimental data confirm the binding of Yongshi to the heptad repeat 1 with a fourfold higher affinity than heptad repeat 2 of SARS-CoV-2. Yongshi also binds to the heptad repeat 1 of SARS-CoV-1 and MERS-CoV. Interestingly, it inhibits all drifted variants of SARS CoV-2 that we tested, including the alpha, beta, gamma, delta, kappa and omicron variants. [ABSTRACT FROM AUTHOR]

The high expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the emergence of multidrug resistance (MDR) in individuals afflicted with either solid tumors or blood cancers. MDR poses a major impediment in the realm of clinical cancer chemotherapy. Recently, substantial endeavors have been dedicated to identifying bioactive compounds isolated from nature capable of counteracting ABCG2-mediated MDR in cancer cells. Imperatorin, a natural coumarin derivative renowned for its diverse pharmacological properties, has not previously been explored for its impact on cancer drug resistance. This study investigates the chemosensitizing potential of imperatorin in ABCG2-overexpressing cancer cells. Experimental results reveal that at sub-toxic concentrations, imperatorin significantly antagonizes the activity of ABCG2 and reverses ABCG2-mediated MDR in a concentration-dependent manner. Furthermore, biochemical data and in silico analysis of imperatorin docking to the inward-open conformation of human ABCG2 indicate that imperatorin directly interacts with multiple residues situated within the transmembrane substrate-binding pocket of ABCG2. Taken together, these results furnish substantiation that imperatorin holds promise for further evaluation as a potent inhibitor of ABCG2, warranting exploration in combination drug therapy to enhance the effectiveness of therapeutic agents for patients afflicted with tumors that exhibit high levels of ABCG2. [ABSTRACT FROM AUTHOR]

Production of industrial solvents and chemicals from a renewable resource is quite appealing due to the dwindling fossil fuel reserves. It is essential to replace the utilization of plastic materials with biodegradable plastic materials like poly-lactic acid (PLA). In the current work, Pediococcus pentosaceus HLV1, a newly identified acetogenic strain, was used to produce LA from sugarcane field residue (SFR). One of the several lignocellulosic potential substrates that are readily available in tropical regions is SFR. SFR has a cellulose content of 40.3 3.5%, a hemicellulose content of 28.5 3.0%, and lignin content of 20.3 2.6%. Around 69% of the lignin and 73% of the hemicellulose were solubilized after the sequential dilute alkali and acid treatments. Cellulase was used to perform enzymatic saccharification of the pretreated substrate at a concentration of 10% (w/v), and produced 0.681of glucose per gram of pretreated biomass. 5 g/l of residual sugar and 61.5 g/l of LA were produced during the batch fermentation procedure. The actual fermentation procedure yielded a 1.12 g LA/g substrate used with a productivity of 0.86 g/L/h. HMF and furfural were reduced to 0.65 g/L and 0.15 g/L from 1.83 g/l to 0.91 g/l, respectively, after fermentation. In the polyphenols, the most inhibitory compounds vanillin and syringaldehyde were reduced to very low concentrations to 0.087 and 0.09 g/l from 0.284 to 1.536 g/l respectively. These compounds have not shown any inhibitory action on microbial growth and lactic acid production. The current study describes how SFR was sequentially acid pretreated and then enzymatically hydrolyzed to acquire the greatest amount of fermentable sugars, as well as how freshly isolated Pediococcus pentosaceus HLV1 was used it to produce lactic acid. [ABSTRACT FROM AUTHOR]

The present study was carried out with an aim to report incidence of canine babesiosis based on rapid antibody diagnostic test in and around Navsari, Gujarat, over a period from October 2022 to June 2023. Out of 1040 cases of dogs registered at Veterinary Clinical Complex (VCC), Navsari, 52 cases were suspected for canine babesiosis based on clinical symptoms, blood smear examination and haematological findings. Blood samples from these suspected cases were subjected to rapid antibody diagnostic test. The overall incidence of canine babesiosis was 2.79 % (29/1040). Among 52 suspected cases, the incidence was 55.77 % (29/52). Comparatively, higher incidence was observed in dogs aged between 3-6 years (34.48 %) followed by 1-3 years (20.70 %), ≤1 year (17.24 %), 6-9 years (17.24 %) and >9 years (10.34 %). The incidence was higher in males (58.62%) than females (41.38%). Season-wise, the incidence was higher in summer (62.07%) followed by winter (34.48%) and monsoon (3.45%). The incidence was the highest in Labrador retriever (34.48%) followed by German shepherd (17.24%), Non-descript (17.24%) and Lhasa Apso & others (3.45% each). [ABSTRACT FROM AUTHOR]

Background: Equine piroplasmosis (EP) is a tick-borne disease of horses caused by the intraerytrocytic protozoan parasites. The infected animals remain carriers of these blood parasites for long periods and spread the disease. The introduction of carrier animals into areas where competent tick vectors are prevalent can lead to an epizootic spread of the disease. Methods: Total 295 blood smears from diseased and healthy horses were examined and 295 serum samples were analyses by cELISA for the presence of antibodies against T. equi and B. caballi whereas 90 DNA samples from seropositive horses were screened by PCR for presence of parasite's DNA. Result: In present study, 1.35% horses were found positive for T. equi by means of blood smear examination. Using c-ELISA, it was found that 03 (1.02%) horses had antibodies against B. caballi and 182 (61.69%) against T. equi, while none of the sample showed mixed reactions. Ninety (90) seropositivehorses screened for T. equi and B. caballi by PCR method, out of which, only Nine (09) horses werefound positive indicating an overall prevalence rate of T. equi was 10.00% by PCR. None of the horses found positive for B. caballi through blood smear examination and PCR method. [ABSTRACT FROM AUTHOR]

Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties. Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats. Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ's neuroprotective effects, the locomotor activity, nonspatial memory, and learning were assessed. Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (-7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties. Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSGinduced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders. [ABSTRACT FROM AUTHOR]

ATP-binding cassette transporters, including ABCB1 (P-glycoprotein) and ABCG2 (BCRP/MXR/ABCP), are pivotal in multidrug resistance (MDR) development in cancer patients undergoing conventional chemotherapy. The absence of approved therapeutic agents for multidrug-resistant cancers presents a significant challenge in effectively treating cancer. Researchers propose repurposing existing drugs to sensitize multidrug-resistant cancer cells, which overexpress ABCB1 or ABCG2, to conventional anticancer drugs. The goal of this study is to assess whether furmonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor overcomes drug resistance mediated by ABCB1 and ABCG2 transporters. Furmonertinib stands out due to its ability to inhibit drug transport without affecting protein expression. The discovery of this characteristic was validated through ATPase assays, which revealed interactions between furmonertinib and ABCB1/ABCG2. Additionally, in silico docking of furmonertinib offered insights into potential interaction sites within the drug-binding pockets of ABCB1 and ABCG2, providing a better understanding of the underlying mechanisms responsible for the reversal of MDR by this repurposed drug. Given the encouraging results, we propose that furmonertinib should be explored as a potential candidate for combination therapy in patients with tumors that have high levels of ABCB1 and/or ABCG2. This combination therapy holds the potential to enhance the effectiveness of conventional anticancer drugs and presents a promising strategy for overcoming MDR in cancer treatment. [ABSTRACT FROM AUTHOR]

Rice tends to accumulate heavy metals present in soil that have been introduced by human activities and pass them up the food chain. The present study aimed to evaluate the accumulation of selected trace elements (Cu, Zn, and Pb) in paddy and soil and the transfer of these metals from soil to rice by analysing the bioconcentration factor (BCF), bioaccumulation factor (BAF), and translocation factor (TF) of heavy metals in paddy (Oryza sativa L.) and soil. Samples of matured paddy and the substrates were collected from three different areas located near a rural point (RP), a transportation point (TP), and an industrial point (IP). Heavy metal concentrations present in the soil and various parts of the plants were ascertained using an atomic absorption spectrophotometer (AAS). Cu, Zn, and Pb accumulation in the soil were detected in increasing orders of RP > TP > IP, IP > TP > RP, and IP > RP > TP, respectively. The BCFshoot, BAF, and transfer factor of both Zn and Pb from soil to rice were detected in the order of TP > IP > RP, which was different from Cu, where BCFshoot and TF showed the order of RP > IP > TP but the BAF indicated IP > RP > TP. TF > 1 was discovered for Zn and Pb at the TP, and for Cu at the RP, which could be attributed to the TP's strongly acidic soil and Cu's abundance in the RP's soil. Paddy height and yield traits were the most significant at the IP site, showing the highest number of fertile spikelets, the average weight of a 1000-paddy spikelet, and the harvest index (0.56). These findings can be related to the normal range of Zn and Pb found in rice plants that support growth. Thus, the findings of this study demonstrated that soil properties and metal abundance in soil from certain land use practices can partially influence the mobility and transfer of metals through soil–plant pathways. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a clear threat to humanity. It has infected over 200 million and killed 4 million people worldwide, and infections continue with no end in sight. To control the pandemic, multiple effective vaccines have been developed, and global vaccinations are in progress. However, the virus continues to mutate. Even when full vaccine coverage is achieved, vaccine-resistant mutants will likely emerge, thus requiring new annual vaccines against drifted variants analogous to influenza. A complimentary solution to this problem could be developing antiviral drugs that inhibit SARS CoV-2 and its drifted variants. Host defense peptides represent a potential source for such an antiviral as they possess broad antimicrobial activity and significant diversity across species. We screened the cathelicidin family of peptides from 16 different species for antiviral activity and identified a wild boar peptide derivative that inhibits SARS CoV-2. This peptide, which we named Yongshi and means warrior in Mandarin, acts as a viral entry inhibitor. Following the binding of SARS-CoV-2 to its receptor, the spike protein is cleaved, and heptad repeats 1 and 2 multimerize to form the fusion complex that enables the virion to enter the cell. A deep learning-based protein sequence comparison algorithm and molecular modeling suggest that Yongshi acts as a mimetic to the heptad repeats of the virus, thereby disrupting the fusion process. Experimental data confirm the binding of Yongshi to the heptad repeat 1 with a fourfold higher affinity than heptad repeat 2 of SARS-CoV-2. Yongshi also binds to the heptad repeat 1 of SARS-CoV-1 and MERS-CoV. Interestingly, it inhibits all drifted variants of SARS CoV-2 that we tested, including the alpha, beta, gamma, delta, kappa and omicron variants. [ABSTRACT FROM AUTHOR]

Ethnopharmacological evidence has demonstrated that Terminalia chebula Retz is traditionally employed for the management of hepatic ailments. Presently, a significant number of prevalent diseases and nutritional disorders are managed through the utilization of natural remedies. The efficacy of herbal medications relies on the administration of a sufficient dosage of the therapeutically active component. However, there is a significant constraint in terms of their bioavailability when taken via oral or topical routes. Phytosomes are a novel class of herbal formulations that have been recently introduced. These formulations exhibit enhanced absorption properties, leading to improved bioavailability and efficacy compared to traditional phyto compounds or botanical extracts. The objective of the current investigation was to assess the qualitative and quantitative phytochemical analysis, high-performance liquid chromatography, optical microscopic research, and in vitro antioxidant properties of Terminalia chebula Retz leaves obtained from the Bhopal region of Madhya Pradesh. The hydroalcoholic extract of phytosome was prepared using a mixture of phospholipids and cholesterol. The characterization of phytosome was conducted using various analytical techniques, including Fourier-transform infrared spectroscopy, determination of entrapment efficiency, measurement of particle size and size distribution, examination under an optical microscope, high-performance liquid chromatography analysis. The concurrent utilization of phospholipids and Terminalia chebula Retz has the potential to produce a synergistic outcome. This synergistic effect can be assessed by evaluating the free radical scavenging activity using the DPPH model. [ABSTRACT FROM AUTHOR]

A nanometer is one billionth of a metre, hence nanotechnology is an intersection of science, engineering, and technology that works with structures and materials at the nanoscale scale, often in the range of 1 to 100 nanometers. Materials frequently display distinctive and innovative features at this scale that are distinct from those at the macroscopic or even microscopic levels. Nanotechnology is the manipulation, design, and control of materials and devices at the nanoscale to produce new products, technologies, and applications. Nanotechnology is essential to the development of tailored medication delivery systems, imaging agents, and diagnostic instruments in medicine. It offers the promise for more targeted treatments that are also less likely to cause negative effects. Since ancient times, turmeric (Curcuma longa L.) has been widely used as a spice and a remedy. Curcumin, a polyphenol that aids in the prevention and management of neurological, pulmonary, cardiovascular, metabolic, inflammatory, and autoimmune illnesses as well as some malignancies, is the primary active component of turmeric. Curcumin does have certain disadvantages, though, including limited water solubility, poor absorption, rapid metabolism, rapid systemic elimination, inadequate bioavailability subpar pharmacokinetics, low stability, and subpar penetration targeting effectiveness. A typical approach is to encapsulate curcumin in nanocarriers for targeted distribution to get over these disadvantages. Concerns have been raised about the degradation of nanocarrier products. In this study, curcumin nanoparticles and nanocurcumin were created without the aid of nanocarriers. To do this, raw turmeric rhizome was soxhlet extracted to obtain curcumin. The stock solutions of various curcumin concentrations made in dichloromethane were sonicated for varying lengths of time and included in boiling water at various flow rates. With 5.00 mg/mL of stock solution concentration, 0.10 mL/min flow rate, and 30 minutes of sonication, an average particle size of 82 04 nm was produced. Particle size seems to decline with sonication time but tends to increase with flow rate and curcumin content in the stock solution. Although nanocurcumins are amorphous, X-ray diffraction reveals crisp and powerful diffraction peaks for curcumin, suggesting its integrity and high crystallinity. The presence of all the functional groups of curcumin in nanocurcumin is confirmed by Fourier-transform infrared spectroscopy spectra. Images obtained using transmission and scanning electron microscopy display the morphology of completely spherical objects. [ABSTRACT FROM AUTHOR]

The present study discloses a composition for regulating blood sugar levels, comprising a synergistic blend of Momordica Charantia extract, Fenugreek seed extract, and additional natural extracts. The composition offers a natural and holistic approach to blood sugar regulation, harnessing the potential benefits of these extracts to support glycemic control. Momordica Charantia extract, derived from the fruits of the Momordica Charantia plant, contains bioactive compounds such as charantin, polypeptide-p, and vicine. Fenugreek seed extract, obtained from Trigonella foenum graecum seeds, comprises soluble dietary fibers, saponins, and alkaloids, known for their potential in blood sugar regulation. [ABSTRACT FROM AUTHOR]

Background: Impaired wound healing is the most common and significant complication of Diabetes. While most other complications of Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain and suffering in patients. Wound closure and repair are orchestrated by a sequence of events aided by the release of pro-inflammatory cytokines, which are dysregulated in cases of Diabetes, making the wound environment unfavorable for healing and delaying the wound healing processes. This concise review provides an overview of the dysregulation of pro-inflammatory cytokines and offers insights into better therapeutic outcomes. Purpose of review: Although many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review. Recent findings: Although complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value. Summary: The adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals’ patients. The target-specific proinflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy. [ABSTRACT FROM AUTHOR]

Natural polymers have attracted significant attention in drug delivery applications due to their biocompatibility, biodegradability, and versatility. However, their surface properties often limit their use as drug delivery vehicles, as they may exhibit poor wettability, weak adhesion, and inadequate drug loading and release. Plasma treatment is a promising surface modification technique that can overcome these limitations by introducing various functional groups onto the natural polymer surface, thus enhancing its physicochemical and biological properties. This review provides a critical overview of recent advances in the plasma modification of natural polymer-based drug delivery systems, with a focus on controllable plasma treatment techniques. The review covers the fundamental principles of plasma generation, process control, and characterization of plasma-treated natural polymer surfaces. It discusses the various applications of plasma-modified natural polymer-based drug delivery systems, including improved biocompatibility, controlled drug release, and targeted drug delivery. The challenges and emerging trends in the field of plasma modification of natural polymer-based drug delivery systems are also highlighted. The review concludes with a discussion of the potential of controllable plasma treatment as a versatile and effective tool for the surface functionalization of natural polymer-based drug delivery systems. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of psychiatric disturbances, cognitive and motor dysfunction. The daily performances and life quality of HD patients have been severely interfered by these clinical signs and symptoms until the last stage of neuronal cell death. To the best of our knowledge, no treatment is available to completely mitigate the progression of HD. Mangiferin, a naturally occurring potent glucoxilxanthone, is mainly isolated from the Mangifera indica plant. Considerable studies have confirmed the medicinal benefits of mangiferin against memory and cognitive impairment in neurodegenerative experimental models such as Alzheimer's and Parkinson's diseases. Therefore, this study aims to evaluate the neuroprotective effect of mangiferin against 3-nitropropionic acid (3-NP) induced HD in rat models. Adult Wistar rats (n = 32) were randomly allocated equally into four groups of eight rats each: normal control (Group I), disease control (Group II) and two treatment groups (Group III and Group IV). Treatment with mangiferin (10 and 20 mg/kg, p. o.) was given for 14 days, whereas 3-NP (15 mg/kg, i. p.) was given for 7 days to induce HD-like symptoms in rats. Rats were assessed for cognitive functions and motor coordination using open field test (OFT), novel object recognition (NOR) test, neurological assessment, rotarod and grip strength tests. Biochemical parameters such as oxidative stress markers and pro-inflammatory markers in brain hippocampus, striatum and cortex regions were evaluated. Histopathological study on brain tissue was also conducted using hematoxylin and eosin (H&E) staining. 3-NP triggered anxiety, decreased recognition memory, reduced locomotor activity, lower neurological scoring, declined rotarod performance and grip strength were alleviated by mangiferin treatment. Further, a significant depletion in brain malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) level, succinate dehydrogenase (SDH), superoxide dismutase (SOD) and catalase (CAT) activities, and a decrease in tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels were observed in mangiferin treated groups. Mangiferin also mitigated 3-NP induced histopathological alteration in the brain hippocampus, striatum and cortex sections. It could be inferred that mangiferin protects the brain against oxidative damage and neuroinflammation, notably via antioxidant and antiinflammatory activities. Mangiferin, which has a good safety profile, may be an alternate treatment option for treating HD and other neurodegenerative disorders. The results of the current research of mangiferin will open up new avenues for the development of safe and effective therapeutic agents in diminishing HD. [ABSTRACT FROM AUTHOR]

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affnities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus. [ABSTRACT FROM AUTHOR]

Objective: To compare the levels of microRNA (miRNA) 24 levels in diabetic patients with acute coronary syndrome (ACS)with non-diabetics suffering from ACS. Methodology: A prospective case-control study was carried out among 40 patients with ACS residing in Belagavi, Karnataka, South India. Patient characteristics based on demographics, ACS related information and treatment, biochemical parameters, and miRNA-24 levels were compared between diabetics and non-diabetics. Finally, miRNA-24 was evaluated for effectiveness as a clinical biomarker for CAD severity in ACS pateints in both the groups. Results: The majority of patients were males between the age group of 18 and 77 years living in urban areas with physical activities restricted to NHYA class 2. A significant level of differences was found between the cases and controls inpatient characteristics such as duration of diabetes diagnosis, treatment of diabetes, family history of diabetes, comorbidities, random blood sugar and HbA1c. Within the levels of miR-24 also, significant variation was observed between the diabetics and non-diabetics. The ROC analysis for evaluating the efficiency of miR-24 as a clinical biomarker for diabetic patients with ACS was established. Conclusions: The control (non-diabetic) group showed significant CT values of miRNA-24 compared to diabetics, suggesting an up-regulation of mi-RNA and thereby may play a protective role of miRNA-24 in these patients. Moreover, the ROC analysis for fold change in miRNA-24 level in diabetic patients with ACS was found to be significant, suggestive of a possible link between expression of miRNA-24 and glucose levels. Therefore, the current study supports the use of miRNA-24 as a prognostic marker inACS outcome. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects many mammals, and SARS-CoV-2 circulation in nonhuman animals may increase the risk of novel variant emergence. Cats are highly susceptible to SARS-CoV-2 infection, and there were cases of virus transmission between cats and humans. The objective of this study was to assess the prevalence of SARS-CoV-2 variant infection of cats in an urban setting. We investigated the prevalence of SARS-CoV-2 variant infections in domestic and community cats in the city of Pittsburgh (n = 272). While no cats tested positive for SARS-CoV-2 viral RNA, 35 cats (12.86%) tested SARS-CoV-2-antibody-positive. Further, we compared a cat-specific experimental lateral flow assay (eLFA) and species-agnostic surrogate virus neutralization assay (sVNT) for SARS-CoV-2 antibody detection in cats (n = 71). The eLFA demonstrated 100% specificity compared to sVNT. The eLFA also showed 100% sensitivity for sera with >90% inhibition and 63.63% sensitivity for sera with 40–89% inhibition in sVNT. Using a variant-specific pseudovirus neutralization assay (pVNT) and antigen cartography, we found the presence of antibodies to pre-Omicron and Omicron SARS-CoV-2 variants. Hence, this approach proves valuable in identifying cat exposure to different SARS-CoV-2 variants. Our results highlight the continued exposure of cats to SARS-CoV-2 and warrant coordinated surveillance efforts. [ABSTRACT FROM AUTHOR]

Simple Summary: P-glycoprotein (P-gp, ABCB1) is an ATP-binding cassette (ABC) transporter that contributes to the development of multidrug resistance (MDR) in cancer cells. P-gp pumps various amphipathic agents including anticancer drugs out of cells. The elucidation of the P-gp mechanism of drug transport is critical to develop strategies to overcome MDR. We used interdisciplinary approaches including cell biological, biochemical, mutational analysis, and molecular dynamics simulations to understand the conformational changes that occur in the homologous transmembrane helices (TMHs) 4 and 10 from the inward-open to the ATP-bound inward-closed states of P-gp during the transport cycle. We found that after substituting seven residues in either TMH4 or TMH10 with alanine, there was no significant effect on the transport function. However, the TMH4,10-14A mutant with 14 substitutions lost the ability to transport most of the substrates tested, revealing that conformational changes in both TMHs 4 and 10 are critical for P-gp's transport function. P-glycoprotein (P-gp, ABCB1) transports structurally dissimilar hydrophobic and amphipathic compounds, including anticancer drugs, thus contributing to multidrug-resistant cancer. Cryo-EM structures of human P-gp revealed that TMHs 4 and 10 contribute to the formation of the drug-binding cavity and undergo conformational changes during drug transport. To assess the role of the conformational changes in TMH4 and TMH10 during drug transport, we generated two mutants (TMH4-7A and TMH10-7A), each containing seven alanine substitutions. Analysis of the drug efflux function of these mutants using 15 fluorescent substrates revealed that most of the substrates were transported, indicating that even seven mutations in an individual helix have no significant effect on transport function. We then designed the TMH4,10-14A mutant combining seven mutations in both TMHs 4 and 10. Interestingly, when the TMH4,10-14A mutant was tested with 15 substrates, there was no efflux observed for fourteen. The basal ATPase activity of the TMH4,10-14A mutant, similar to that of the WT protein, was inhibited by zosuquidar but was not stimulated by verapamil or rhodamine 6G. Molecular dynamics simulations indicated that the mutations cause TMHs 4 and 10 to pack tighter to their proximal helices, reducing their independent mobility. In aggregate, our findings demonstrate the critical role of the residues of homologous TMHs 4 and 10 for substrate transport, consistent with conformational changes observed in the structure of P-gp. [ABSTRACT FROM AUTHOR]

The propensity of manufacturers to produce goods at affordable cost, with more accuracy, and at a faster rate force them to search for novel solutions, such as deploying robots in place of people in a sector that can accommodate their needs. Welding is one of the most crucial processes in the automotive industry. This process is time-consuming, subject to error, and demands skilled professionals. The robotic application can improve this area of production and quality. Other industries, such as painting and material handling, can also profit from the use of robots. This work describes the fuzzy DC linear servo controller, which functions as a robotic arm actuator. Robots have been widely employed in most productive sectors in recent years, including assembly plates, welding, tasks at higher temperatures, etc. Controlling a robot accurately is a difficult undertaking as a robot is very nonlinear with many joints that are often organized and unstructured. To carry out the effective task, an effective PID control based on fuzzy logic has been employed together with the method of Particle Swarm Optimization (PSO) approach for the estimate of the parameter. This offline technique determines the lowest number of optimal robotic arm control parameters. To verify the controller design with computer simulation, a comparative assessment of controllers is given by means of a fuzzy surveillance controller with PSO which improves the parameter gain to provide a rapid climb, a smaller overflow, no steady condition error signal, and effective torque control of the robot arm. [ABSTRACT FROM AUTHOR]

Throughout its history, marketing has relied on the ingestion of new types of customer data and the translation of this data into ever-more-effective methods for engaging and targeting customers. Different marketing approaches have been used to the focus on customer digital segmentation: relationship marketing, experience marketing, and more recently, attempts at "collaborative" marketing. The goal of customer segmentation is to more successfully encourage specific segments to make repeat purchases. The transition to social networking marketing including social customer relations management, problems of social CRM, however, has not been without major drawbacks, much like previous approaches. While social media's advent and the way it has been used for marketing purposes have created the potential for more ways to track and categorise consumer behaviour, this paper emphasises how all but a few specific marketing strategies have limitations when it comes to "making up" successful markets. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), believed to have originated from a bat species, can infect a wide range of non-human hosts. Bats are known to harbor hundreds of coronaviruses capable of spillover into human populations. Recent studies have shown a significant variation in the susceptibility among bat species to SARS-CoV-2 infection. We show that little brown bats (LBB) express angiotensin-converting enzyme 2 receptor and the transmembrane serine protease 2, which are accessible to and support SARS-CoV-2 binding. All-atom molecular dynamics (MD) simulations revealed that LBB ACE2 formed strong electrostatic interactions with the RBD similar to human and cat ACE2 proteins. In summary, LBBs, a widely distributed North American bat species, could be at risk of SARS-CoV-2 infection and potentially serve as a natural reservoir. Finally, our framework, combining in vitro and in silico methods, is a useful tool to assess the SARS-CoV-2 susceptibility of bats and other animal species. [ABSTRACT FROM AUTHOR]

Inhibition of ABC transporters is a promising approach to overcome multidrug resistance in cancer. Herein, we report the characterization of a potent ABCG2 inhibitor, namely, chromone 4a (C4a). Molecular docking and in vitro assays using ABCG2 and P-glycoprotein (P-gp) expressing membrane vesicles of insect cells revealed that C4a interacts with both transporters, while showing selectivity toward ABCG2 using cell-based transport assays. C4a inhibited the ABCG2-mediated efflux of different substrates and molecular dynamic simulations demonstrated that C4a binds in the Ko143-binding pocket. Liposomes and extracellular vesicles (EVs) of Giardia intestinalis and human blood were used to successfully bypass the poor water solubility and delivery of C4a as assessed by inhibition of the ABCG2 function. Human blood EVs also promoted delivery of the well-known P-gp inhibitor, elacridar. Here, for the first time, we demonstrated the potential use of plasma circulating EVs for drug delivery of hydrophobic drugs targeting membrane proteins. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) has killed millions of people since first reported in Wuhan, China, in December 2019. Intriguingly, Withania somnifera (WS) has shown promising antiviral effects against numerous viral infections, including SARS-CoV and SARS-CoV-2, which are contributed by its phytochemicals. This review focused on the updated testing of therapeutic efficacy and associated molecular mechanisms of WS extracts and their phytochemicals against SARS-CoV-2 infection in preclinical and clinical studies with the aim to develop a long-term solution against COVID-19. It also deciphered the current use of the in silico molecular docking approach in developing potential inhibitors from WS targeting SARS-CoV-2 and host cell receptors that may aid the development of targeted therapy against SARS-CoV-2 ranging from prior to viral entry until acute respiratory distress syndrome (ARDS). This review also discussed nanoformulations or nanocarriers in achieving effective WS delivery to enhance its bioavailability and therapeutic efficacy, consequently preventing the emergence of drug resistance, and eventually therapeutic failure. [ABSTRACT FROM AUTHOR]

Constitutive activation of the phosphoinositide-3-kinase (PI3K)/Akt signaling pathway is crucial for tumor growth and progression. As such, this pathway has been an enticing target for drug discovery. Although HS-173 is a potent PI3K inhibitor that halts cancer cell proliferation via G2/M cell cycle arrest, the resistance mechanisms to HS-173 have not been investigated. In this study, we investigated the susceptibility of HS-173 to efflux mediated by the multidrug efflux transporters ABCB1 and ABCG2, which are two of the most well-known ATP-binding cassette (ABC) transporters associated with the development of cancer multidrug resistance (MDR). We found that the overexpression of ABCB1 or ABCG2 significantly reduced the efficacy of HS-173 in human cancer cells. Our data show that the intracellular accumulation of HS-173 was substantially reduced by ABCB1 and ABCG2, affecting G2/M arrest and apoptosis induced by HS-173. More importantly, the efficacy of HS-173 in multidrug-resistant cancer cells could be recovered by inhibiting the drug-efflux function of ABCB1 and ABCG2. Taken together, our study has demonstrated that HS-173 is a substrate for both ABCB1 and ABCG2, resulting in decreased intracellular concentration of this drug, which may have implications for its clinical use. [ABSTRACT FROM AUTHOR]

Biological macromolecules like polysaccharides/proteins/glycoproteins have been widely used in the field of tissue engineering due to their ability to mimic the extracellular matrix of tissue. In addition to this, these macromolecules are found to have higher biocompatibility and no/lesser toxicity when compared to synthetic polymers. In recent years, scaffolds made up of proteins, polysaccharides, or glycoproteins have been highly used due to their tensile strength, biodegradability, and flexibility. This review is about the fabrication methods and applications of scaffolds made using various biological macromolecules, including polysaccharides like chitosan, agarose, cellulose, and dextran and proteins like soy proteins, zein proteins, etc. Biopolymer-based nanocomposite production and its application and limitations are also discussed in this review. This review also emphasizes the importance of using natural polymers rather than synthetic ones for developing scaffolds, as natural polymers have unique properties, like high biocompatibility, biodegradability, accessibility, stability, absence of toxicity, and low cost. [ABSTRACT FROM AUTHOR]

Polyaniline films modified by carboxylic acid dopents have been formed by in situ chemical oxidative polymerization using ammonium persulfate as an oxidizing agent and investigated for NH3 gas sensor. We demonstrate that butyric acid-doped polyaniline (BPANI) film is highly selective to NH3 with high selectivity (513% at 100 ppm), fast response time (8.94 s). Furthermore, good reproducibility was also observed at 100 ppm. The room-temperature functioning of the sensor is critical, which facilitate low-power operation and also enhances the life time of the sensor. The results indicate that the carboxylic acid-doped polyaniline films are promising for NH3 gas detection. [ABSTRACT FROM AUTHOR]