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Conventional pre-genomics breeding methodologies have significantly improved crop yields since the mid-twentieth century. Genomics provides breeders with advanced tools for whole-genome study, enabling a direct genotype-phenotype analysis. This shift has led to precise and efficient crop development through genomics-based approaches, including molecular markers, genomic selection, and genome editing. Molecular markers, such as SNPs, are crucial for identifying genomic regions linked to important traits, enhancing breeding accuracy and efficiency. Genomic resources viz. genetic markers, reference genomes, sequence and protein databases, transcriptomes, and gene expression profiles, are vital in plant breeding and aid in the identification of key traits, understanding genetic diversity, assist in genomic mapping, support marker-assisted selection and speeding up breeding programs. Advanced techniques like CRISPR/Cas9 allow precise gene modification, accelerating breeding processes. Key techniques like Genome-Wide Association study (GWAS), Marker-Assisted Selection (MAS), and Genomic Selection (GS) enable precise trait selection and prediction of breeding outcomes, improving crop yield, disease resistance, and stress tolerance. These tools are handy for complex traits influenced by multiple genes and environmental factors. This paper explores new genomic technologies like molecular markers, genomic selection, and genome editing for plant breeding showcasing their impact on developing new plant varieties., (© 2024. The Author(s).)

Deep neural network-based deep potentials (DP), developed by Tuo et al., have been used to compute the thermodynamic properties of free aluminum clusters with accuracy close to that of density functional theory. Although Jarrold and collaborators have reported extensive experimental measurements on the melting temperatures and heat capacities of free aluminum clusters, no reports exist for finite-temperature ab initio simulations on larger clusters (N > 55 atoms). We report the heat capacities and melting temperatures for 32 clusters in the size range of 48-342 atoms, computed using the multiple histogram technique. Extensive molecular dynamics (MD) simulations at twenty four temperatures have been performed for all the clusters. Our results are in very good agreement with the experimental melting temperatures for 19 clusters. Except for a few sizes, the interesting features in the heat capacities have been reproduced. To gain insight into the striking features reported in the experiments, we used structural and dynamical descriptors such as temperature-dependent mean squared displacements and the Lindemann index. Bimodal features observed in Al116 and the weak shoulder seen in Al52 are attributed to solid-solid structural transitions. In confirmation of the earlier reports, we observe that the behavior of the heat capacities is significantly influenced by the nature of the ground state geometries. Our findings show that the sharp drop in the melting temperature of the 56-atom cluster is a consequence of the change in the geometry of Al55. Mulliken population analysis of Al55 reveals that the charge-induced local electric field is responsible for the strong bonding between core and surface atoms, leading to the higher melting temperature. Our calculations do not support the lower melting temperature observed in experimental studies of Al69. Our results indicate that Al48 is in a liquid state above 600 K and does not support the high melting temperature reported in the experiment. It turns out that the accuracy of the DP model by Tuo et al. is not reliable for MD simulations beyond 750 K. We also report low-lying equilibrium geometries and thermodynamics of 11 larger clusters (N = 147-342) that have not been previously reported, and the melting temperatures of these clusters are in good agreement with the experimental ones., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Hypertension, a key modifiable risk factor for cardiovascular diseases (CVD), significantly contributes to premature death and morbidity worldwide. Despite stabilization in age-adjusted global prevalence, the absolute number of hypertensive individuals doubled from 2000 to 2010, largely due to increases in low- and middle-income countries. In 2021, only 21% of hypertensive individuals globally had effective blood pressure (BP) control. In India, hypertension is the leading risk factor for death and disability, with prevalence rates of 24% in men and 21% in women, as reported by the 2019-2020 National Family Health Survey (NFHS-5). Alarmingly, just 25% of rural and 38% of urban hypertensive Indians are undergoing treatment, with only 10% and 20% achieving BP control, respectively. This highlights the hypertension paradox, where clinical inertia and hesitancy in intensifying BP-lowering therapy persist despite the availability of antihypertensive drugs. This expert opinion paper aims to provide a comprehensive evaluation of sacubitril/valsartan in hypertension management, leveraging insights from its approved use in heart failure and examining its benefits and challenges across diverse hypertensive populations. The formulation of this expert opinion involved employing evidence-based methodologies and utilizing all available data. The document underwent scrutiny by expert cardiologists, whose clinical experiences and examination of the evidence and guidelines informed the formation of the expert opinion. This expert opinion paper provides a thorough and informed evaluation of sacubitril/valsartan, highlighting its potential to address unmet needs in BP control, particularly in challenging cases such as resistant hypertension and chronic kidney disease., (© 2024. The Author(s).)

The current investigation was undertaken to elucidate the population-stratifying and ancestry-informative markers in Indian, Chinese, and wild yak populations using whole genome resequencing (WGS) analysis while employing various selection strategies (Delta, Pairwise Wright's Fixation Index-F ST , and Informativeness of Assignment) and marker densities (5-25 thousand). The study used WGS data on 105 individuals from three separate yak cohorts i.e., Indian yak (n = 29), Chinese yak (n = 61), and wild yak (n = 15). Variant calling in the GATK program with strict quality control resulted in 1,002,970 high-quality and independent (LD-pruned) SNP markers across the yak autosomes. Analysis was undertaken in toolbox for ranking and evaluation of SNPs (TRES) program wherein three different criteria i.e., Delta, Pairwise Wright's Fixation Index-F ST , and Informativeness of Assignment were employed to identify population-stratifying and ancestry-informative markers across various datasets. The top-ranked 5,000 (5K), 10,000 (10K), 15,000 (15K), 20,000 (20K), and 25,000 (25K) SNPs were identified from each dataset while their composition and performance was assessed using different criteria. The average genomic breed clustering of Indian, Chinese, and wild yak cohorts with full density dataset (105 individuals with 1,002,970 markers) was 81.74%, 80.02%, and 83.62%, respectively. Informativeness of Assignment criterion with 10K density emerged as the best combination for three yak cohorts with 86.94%, 96.46%, and 98.20% clustering for Indian, Chinese, and wild yak, respectively. There was an average increase of 7.56%, 22.72%, and 30.35% in genomic breed clustering scores of Indian, Chinese, and wild yak cohorts over the estimates of the original dataset. The selected markers showed overlap multiple protein-coding genes within a 10 kb window including ADGRB3, ANK1, CACNG7, CALN1, CHCHD2, CREBBP, GLI3, KHDRBS2, and OSBPL10. This is the first report ever on elucidating low-density SNP marker sets with population-stratifying and ancestry-informative properties in three yak groups using WGS data. The results gain significance for application of genomic selection using cost-effective low-density SNP panels in global yak species., (© 2024. The Author(s).)

The SERS spectra of six bacterial biomarkers, 2,3-DHBA, 2,5-DHBA, Pyocyanin, lipoteichoic acid (LTA), Enterobactin, and β-carotene, of various concentrations, were obtained from silver nanorod array substrates, and the spectral peaks and the corresponding vibrational modes were identified to classify different spectra. The spectral variations in three different concentration regions due to various reasons have imposed a challenge to use classic calibration curve methods to quantify the concentration of biomarkers. Depending on baseline removal strategy, i.e., local or global baseline removal, the calibration curve differed significantly. With the aid of convolutional neural network (CNN), a two-step process was established to classify and quantify biomarker solutions based on SERS spectra: using a specific CNN model, a remarkable differentiation and classification accuracy of 99.99 % for all six biomarkers regardless of the concentration can be achieved. After classification, six regression CNN models were established to predict the concentration of biomarkers, with coefficient of determination R 2  > 0.97 and mean absolute error (MAE) < 0.27. The feature of important calculations indicates the high classification and quantification accuracies were due to the intrinsic spectral features in SERS spectra. This study showcases the synergistic potential of SERS and advanced machine learning algorithms and holds significant promise for bacterial infection diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Human metabolomics has made significant strides in understanding metabolic changes and their implications for human health, with promising applications in diagnostics and treatment, particularly regarding the gut microbiome. However, progress is hampered by issues with data comparability and reproducibility across studies, limiting the translation of these discoveries into practical applications., Objectives: This study aims to evaluate the fit-for-purpose of a suite of human stool samples as potential candidate reference materials (RMs) and assess the state of the field regarding harmonizing gut metabolomics measurements., Methods: An interlaboratory study was conducted with 18 participating institutions. The study allowed for the use of preferred analytical techniques, including liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR)., Results: Different laboratories used various methods and analytical platforms to identify the metabolites present in human stool RM samples. The study found a 40% to 70% recurrence in the reported top 20 most abundant metabolites across the four materials. In the full annotation list, the percentage of metabolites reported multiple times after nomenclature standardization was 36% (LC-MS), 58% (GC-MS) and 76% (NMR). Out of 9,300 unique metabolites, only 37 were reported across all three measurement techniques., Conclusion: This collaborative exercise emphasized the broad chemical survey possible with multi-technique approaches. Community engagement is essential for the evaluation and characterization of common materials designed to facilitate comparability and ensure data quality underscoring the value of determining current practices, challenges, and progress of a field through interlaboratory studies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

This study presents a biosensor utilizing electrospun SnO 2 nanofiber films for real-time monitoring of C2C12 cells. The biosensor demonstrates sensitivity towards cellular behaviours, including adhesion, proliferation, and detachment. Alterations in semi-circle and dielectric properties are validated through Nyquist plot and an EEC model, highlighting the biosensor's potential for analyzing cellular dynamics.

The field of robotic surgery has grown exponentially over the past few decades. Surgical robots offer numerous benefits that enhance surgical precision, improve patient outcomes, and expand the capabilities of surgeons. Telesurgery, also known as a remote surgery, is a branch of telemedicine, which offers to perform surgical procedures requiring expertise of a surgeon located at a distance from a patient by using robotic systems and telecommunications technology. In a previous reported case, an animal experiment and clinical trial telesurgery using a dual console were performed. However, the mean latency time and data packet loss were considerably high. As a result, the performance of the telesurgery got severely impacted. This paper evaluates the feasibility, safety, and efficacy of remote telesurgery to precisely carryout predetermined surgical procedures using dual console SSI Mantra Surgical Robotic System. The trials were registered prospectively with trial registration number CTRI-2024-06-068361., (© 2024. The Author(s).)

Background and Objectives: With increasing life expectancy and prevalence of thalassaemia, it has led to a greater need for safe blood, yet the current supply from voluntary donors is insufficient to meet this demand. Thalassaemia recipients face a significant risk of alloimmunization because of repeated exposure to foreign red cell antigens. Study aims to determine high prevalent Rh antigen negative donors in western India donor population along with what percentage of these donors are willing to become dedicated voluntary donors for thalassaemia patients. Study also aims to examine factors influencing their willingness and challenges faced in mobilizing dedicated donors., Method: 700 whole blood donors from western India, following screening for inclusion & exclusion criteria as per Drugs and Cosmetic Act (DCA) 2020 amendment guidelines & were sero-negative for transfusion transmitted infections were enrolled for the study. Red cell phenotyping was performed using Conventional Tube Technique (CTT) for "D", "C", "E", "c", "e" and "K" antigen using known antisera. Donors that were "C" AND/OR "e" antigen negative were contacted telephonically and were counseled and motivated for becoming voluntary blood donors. Statistical analysis assessed correlation between donation frequency, donor's occupation and education., Result: Among 700 donors, 96.6% (n = 676) were males and 3.4% (n = 24) were females. The most predominant blood group was B > O > A > AB. Rh(D) antigen was present in 91.44% (n = 640) and absent in 8.6% (n = 60). Prevalence of other Rh antigens is as follows: "e" (99%) > "C" (85.4%) > "c" (59.1%) > "E" (18.0%). Only 1.15% had "K" antigen positive. The commonest Rh phenotype R 1 R 1 (DCe/DCe) was expressed by 40.57% (n = 283), and the least common r″r (cE/ce), r″r″ (cE/cE) and r'r' (Ce/Ce) was found in 0.14% (n = 1), respectively. 'C' negative, 'e' negative, 'C' and 'e' antigen negative donors constituted 14.8% (n = 104) with 93.2% (n = 97) C-antigen negative, 1.92% (n = 2) e-antigen negative and 4.8% (n = 5) both "C" and "e" antigen negative donors. The commonest phenotypes among C-antigen and e-antigen negative donors were rr (50%) and R z R 2 (1.94%) respectively. Likewise, the most common phenotype amongst both C- and e-antigens negative donors was R 2 R 2 (3.84%). 61.5% of the donors agreed to enroll for voluntary blood donation following telephonic invitation, while 6.8% of them refused permanently. Approximately, 3.9% of the blood donors were willing to donate blood only when needed and 27.8% of them could not be contacted., Conclusion: Creating a database of voluntary donors with known phenotype, especially who lack very common antigens like "C" and "e" and are willing to become dedicated, regular voluntary donors for thalassemic patients can ensure timely administration of safe blood. One of the major challenges for this noble initiative was lack of awareness which can be circumvent effectively with proper counseling efforts., (Copyright © 2024 Socit francophone de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Fibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral-fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza-induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral-mediated fibrotic remodelling., Experimental Approach: A retrospective analysis of TriNetX data sets was conducted. Serum from healthy controls and influenza A virus (IAV)-infected patients was analysed. An inhibitor of PDIA3, punicalagin, and a neutralizing antibody for SPP1 were administered in mice. Macrophage cells treated with macrophage colony-stimulating factor (M-CSF) were used as a cell culture model., Key Results: The TriNetX data set showed an increase in lung fibrosis and decline in lung function in flu-infected acute respiratory distress syndrome (ARDS) patients compared with non-ARDS patients. Serum samples revealed a significant increase in SPP1 and PDIA3 in influenza-infected patients. Lung PDIA3 and SPP1 expression increased following viral infection in mouse models. Punicalagin administration 2 weeks after IAV infection in mice caused a significant decrease in lung fibrosis and improved oxygen saturation. Administration of neutralizing SPP1 antibody decreased lung fibrosis. Inhibition of PDIA3 decreased SPP1secretion from macrophages, in association with diminished disulfide bonds in SPP1., Conclusion and Implications: The PDIA3-SPP1 axis promotes post-influenza lung fibrosis in mice and that pharmacological inhibition of PDIA3 or SPP1 can treat virus-induced lung fibrotic sequela., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background and Objectives: Hemolytic transfusion reactions (HTRs) pose significant risks in transfused patients, with anti-A and anti-B antibodies in donor plasma being potential contributing factors. Despite advancements in component preparation, HTRs remain a concern, particularly with apheresis-derived platelets. This study aimed to determine the prevalence of high anti-A and anti-B titers among A, B, and O blood group donors and to explore factors associated with high titers., Materials and Methods: A cross-sectional observational study was conducted over 18 months, enrolling 978 participants from a tertiary care teaching hospital in Western India. Anti-A and anti-B titers were determined using the Conventional Tube Technique (CTT). Statistical analysis assessed correlations between high titers and demographic factors., Results: The majority of participants were young males (98.8%). Prevalence of high titers for IgM anti-A was 12.2% and IgG anti-A was 2.5%. For anti-B, IgM titers were 2.3% and IgG titers were 0.2%. The prevalence of dangerous O was found to be 14.1%, while 3.52% and 10.5% of A and B blood group donors were found to have high titers, respectively. Factors associated with high titers included female gender, vegetarian diet, age <30 years, and O blood group., Conclusion: The study sheds additional light and provides supplementary information regarding the prevalence and correlation of high anti-A and anti-B titers among O, A and B blood donors. Understanding these factors is crucial for optimizing transfusion safety protocols, including selective screening of platelet units and tailored transfusion strategies based on donor characteristics., (Copyright © 2024 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Most pleural empyema cases are linked to pneumonia, a substantial fraction of patients present with empyema without any association to pneumonia. The occurrence of empyema caused by tuberculosis (TB) is increasing in regions where TB is prevalent. In May 2024, a bibliometric analysis was conducted involving the screening of 7,620 articles sourced from Google Scholar. Google Scholar was selected for its comprehensive nature, encompassing articles indexed in prominent databases like Web of Science, Scopus, and PubMed. This allowed access to significant studies that might be overlooked if they were not indexed by these databases. Articles were selected based on their citation count and specific inclusion criteria, focusing on early thoracotomy and decortication in pleural empyema. Two authors (VB and MK) independently conducted a thorough screening and data collection. The hundred top articles published from 1945 to 2015, garnered a total of 16,928 citations. These articles were written by 93 distinct first authors from 22 countries and 83 institutions, and were featured in 35 journals. The primary categories of literature included those describing the disease characteristics, features, causes, and types of pleural empyema, as well as various treatment modalities and management strategies, each constituting 37% of the literature. Additionally, pediatric empyema was a focus in 11% of the articles. The present analysis highlights publication trends, identifies gaps in the literature, and suggests areas for future research, serving as a valuable resource for guiding upcoming studies on early thoracotomy and decortication in pleural empyema., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bhende et al.)

Climate change poses a significant threat to the sustainability of livestock production systems in developing countries, particularly impacting small ruminants like goats, which are highly susceptible to heat stress. This stressor not only reduces productivity but also undermines economic viability. This study aimed to delve into the molecular mechanisms underlying heat stress tolerance in goats by conducting a comprehensive transcriptome analysis of heat-tolerant (HT, n = 4) and heat-susceptible (HS, n = 6) Jamunapari goats. Physiological metrics, such as rectal temperature, respiratory rate, and heart rate, were meticulously monitored under extreme environmental conditions (Temperature Humidity Index >92) to effectively classify goats based on their distinct heat stress responses. Samples of blood were obtained, and peripheral blood mononuclear cells (PBMCs) were extracted for subsequent RNA extraction. RNA-Seq analysis revealed a sum of 734 differentially expressed genes (DEGs), comprising 251 upregulated and 483 downregulated genes in HT goats compared to their HS counterparts. The WGCNA revealed three key modules, darkorange (tolerance), paleturquoise (respiration rate), and darkmagenta (heart rate). Moreover, functional enrichment analysis revealed that DEGs within these modules played intricate roles in crucial biological processes and pathways, including mitochondrial function, cardiac function, immune response, genomic stability, and metabolic regulation. This research notably enhances our comprehension of the genetic underpinnings of thermo-tolerance in goats and provides invaluable guidance for formulating breeding strategies aimed at bolstering livestock resilience against the challenges of climate change., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Microscopic observation data collected from approximately 1800 male and female Sprague Dawley (SD) control rats used on 104-week carcinogenicity studies performed at North American Labcorp Early Development, Inc, Madison, WI, were retrospectively evaluated for spontaneous nonneoplastic findings. This study provides incidence of the most common spontaneous nonneoplastic microscopic findings in each organ system of SD rats encountered during 104-week carcinogenicity studies. Some of the most common spontaneous background findings were cardiomyopathy; chronic progressive nephropathy; uterine cystic endometrial hyperplasia; prostate inflammation; pulmonary alveolar macrophage infiltrates; hepatocyte vacuolation, bile duct hyperplasia, and basophilic foci in the liver; pancreatic fibrosis; splenic extramedullary hematopoiesis and pigment; decreased lymphocytes and epithelial hyperplasia in the thymus; ventral brain compression; cystic degeneration and hyperplasia of the adrenal cortex; and mammary gland hyperplasia. The most common nonneoplastic findings in male SD rats were chronic progressive nephropathy (80.9%) and rodent progressive cardiomyopathy (73.2%). The most common nonnenoplastic findings in female SD rats were cystic degeneration of the adrenal cortex (64.7%) and ventral compression of the brain due to pituitary neoplasms (62.7%)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

G-quadruplexes (GQs) have been primarily studied in the context of cancer and neurodegenerative pathologies. However, recent research has shifted focus to their existence and functional roles in viral genomes, revealing GQ-regulated key pathways in various human pathogenic viruses. While GQ structures have been reported in the genomes of emerging and re-emerging viruses, RNA viruses have been understudied compared to DNA viruses, including notable examples such as human immunodeficiency virus-1, hepatitis C virus, Ebola virus, Nipah virus, Zika virus, and SARS-CoV-2. The flavivirus family, comprising the Japanese encephalitis virus (JEV), poses a significant global threat due to recurring outbreaks yet lacks approved antivirals. In this study, we identified and characterized eight putative G-quadruplex-forming motifs within essential genes involved in genome replication, assembly, and internalization in the host cell, conserved across different JEV isolates. The formation and stability of these motifs were validated through a multitude of biophysical and cell-based assays. The interaction and binding affinity of these motifs with the known GQ-binding ligand BRACO-19 were supported by biophysical assays, confirming the capability of these motifs to form GQ structures. Notably, BRACO-19 also exerted antiviral properties through reduction of viral replication and infectious virus titers as well as inhibition of viral protein expression, as evaluated by the cell-based assays. This comprehensive molecular characterization of G-quadruplex structures within the JEV genome highlights their potential as promising antiviral targets for intervention strategies against JEV infection through GQ-specific ligands.

Prolyl oligopeptidase, or S9 (MEROPS) family enzymes are crucial drug targets due to their association with various diseases, neurological disorders, cell growth, and survival. These implications render them an exceptionally fascinating field of research. Despite sharing similar structural features, they exhibit diverse enzyme activities, including endopeptidase, dipeptidyl peptidase, and acylaminoacyl peptidase. Additionally, a few members of the S9 family demonstrate carboxypeptidase activity. A recent study showed that the S9 peptidase of Bacillus subtilis (S9bs) possesses the conserved sequence feature necessary for carboxypeptidase activity despite being annotated as an acylaminoacyl peptidase in the UniProt database. However, the mechanism of action and identity of S9bs as carboxypeptidase remain unclear. Consequently, we focused our studies on thoroughly investigating S9bs for its carboxypeptidase activity. In the present study, we report biochemical and biophysical analyses of S9bs, confirming its identity as a carboxypeptidase. Further, structural analysis reveals the molecular basis of S9bs' carboxypeptidase activity, highlighting the crucial structural elements like the "cavity loop" and the "two-arginine" residues essential for this activity. Additionally, our studies confirmed that S9bs forms a stable tetrameric assembly and established its quaternary molecular arrangement, which reveals the presence of an oligomeric pore. Altogether, these structural features play a crucial role in substrate selection for S9 carboxypeptidases. Overall, our findings reveal a distinct carboxypeptidase within the S9 family and significantly enhance our understanding of these enzymes. Moreover, this study sheds light on the mechanisms underlying carboxypeptidase activity, offering valuable insights that could contribute to therapeutic and drug design., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The paper describes the construction of a new series of pyrimidinone-linked thiazole derivatives through bromination of the initial Biginelli reaction product followed by the Hantzsch thiazole synthesis route. Various analytical techniques, including FT-IR, 1 H NMR, 13 C NMR, and LCMS analysis, were employed to confirm the formation of the products. The synthesized compounds were primarily evaluated for their antibacterial activity, with a specific focus on their IC 50 values. Compound 4c demonstrated the most potent efficacy, displaying MIC and MBC values that varied from 0.23 to 0.71 mg/mL and 0.46-0.95 mg/mL, respectively. The anti-inflammatory potential was also observed in analogs 4a and 4c with marked activity in the 33.2-82.9 μM concentration range. Moreover, compounds 4a , and 4c demonstrated strong antioxidant effects, as reflected by their excellent IC 50 values of 38.6 - 43.5  μM respectively. DFT investigation showed that B. cereus was more susceptible, and E. coli was more resistant, with chloro-substituted compounds exhibiting potential reactivity. Some molecules with chloro-substituents showed promising results in density functional theory when compared to other substituents. In addition, the molecules underwent a corrosion study and demonstrated a high level of inhibition efficiency ( 4c ) in comparison to other molecules. Further in silico studies of the synthesized thiazoles confirmed the good interactions with the target., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Subrahmanya I Bhat is working as an Associate editor for Heliyon, Chemistry and followed the journal ethics and publishing policies., (© 2024 Published by Elsevier Ltd.)

Arsenic (As) contamination of agricultural soil has become a major concern due to its adverse effects on plant growth and human health. Selenium nanoparticles (SeNPs), a novel selenium (Se) source, are characterised by their exceptional biocompatibility, degradability, and bioactivities. In the present study, SeNPs were biogenically synthesised and further characterised using UV-visible spectroscopy, XRD, FTIR, and TEM analysis. Different concentrations of the synthesised SeNPs were used to treat Spinacia oleracea L. (spinach) seeds to determine their impact on growth profile, gas exchange, photosynthetic pigments, oxidative stress, and antioxidant enzyme status upon arsenite (AsIII) treatment. The findings revealed that SeNP supplementation at a concentration of 100 µM (SeNPs100) led to a significant reduction in As accumulation by twofold in roots and 1.5-fold in leaves when compared to plants exposed to AsIII100 (µM) alone. Interestingly, the photosynthetic efficiency was also remarkably enhanced upon SeNPs100 treatment, associated with increased activities of the defence enzymes (ascorbate peroxidase, catalase, and glutathione peroxidase) in the AsIII + SeNP-exposed spinach plants as compared to AsIII treatment alone. Overall, the present study highlights the potential of biogenic SeNP supplementation in promoting plant growth and mitigating As toxicity in spinach under AsIII stress. This study could have significant implications for the use of SeNPs as a nanofertiliser in regions grappling with As-contaminated soils for sustainable agriculture and human health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The μ-opioid receptor (μOR), a prototypical G protein-coupled receptor (GPCR), is the target of opioid analgesics such as morphine and fentanyl. Due to the severe side effects of current opioid drugs, there is considerable interest in developing novel modulators of μOR function. Most GPCR ligands today are small molecules, however biologics, including antibodies and nanobodies, represent alternative therapeutics with clear advantages such as affinity and target selectivity. Here, we describe the nanobody NbE, which selectively binds to the μOR and acts as an antagonist. We functionally characterize NbE as an extracellular and genetically encoded μOR ligand and uncover the molecular basis for μOR antagonism by determining the cryo-EM structure of the NbE-μOR complex. NbE displays a unique ligand binding mode and achieves μOR selectivity by interactions with the orthosteric pocket and extracellular receptor loops. Based on a β-hairpin loop formed by NbE that deeply protrudes into the μOR, we design linear and cyclic peptide analogs that recapitulate NbE's antagonism. The work illustrates the potential of nanobodies to uniquely engage with GPCRs and describes lower molecular weight μOR ligands that can serve as a basis for therapeutic developments., (© 2024. The Author(s).)

Microbial byproducts and residues (hereafter 'necromass') potentially play the most critical role in soil organic carbon (SOC) sequestration. However, little is known about the influence of climate warming on necromass accumulation in the agroecosystem and the underlying mechanisms associated with microbial life strategies. In order to address these knowledge gaps, we used amino sugars as biomarkers of microbial necromass, and investigated their variation through an 8-year trial in an agroecosystem with two warming levels (+1.6 and + 3.2 °C) compared to ambient temperature. The results showed that the lower warming level had no impact on total microbial necromass carbon. Conversely, warming the soil 3.2 °C above ambient increased total microbial necromass by 17 % and its contribution to SOC by 21.3 %, mainly by increasing fungal necromass (+19.8 %), whereas +3.2 °C warming had no impact on bacterial necromass. At the phylum level, compared with the ambient control, +3.2 °C warming induced an increase in the abundance of Proteobacteria and a decrease in both Acidobacteria and Actinobacteria, whereas in the fungal community, Ascomycota increased and Mortierellomycota decreased. This indicates that r-strategists outcompete K-strategists in warmer climates, which led to increased microbial necromass production and accumulation, as supported by the positive correlation between r-strategists and microbial necromass. Stronger microbial competition for resources also resulted in a higher biomass turnover rate, greater cell death, and greater production of microbial necromass. This was supported by the lower bacterial and fungal network complexity and trophic links under warming conditions. In addition, the necromass generated from accelerated microbial turnover further offsets warming-induced deceases in microbial biomass. Consequently, bulk SOC did not change, despite microbial necromass having a much greater response to warming than the soil C pool. Therefore, future climate warming may influence the composition and persistence of SOC during microbial degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Our study focuses on Yakutian cattle, a Siberian native breed, examining its inbreeding and diversity through genome-wide analysis of runs of homozygosity (ROHs). Yakutian cattle are adapted to Siberia's harsh sub-arctic conditions, enduring temperatures below -70°C. However, the population genetics studies on this breed are scanty, to document the genetic uniqueness in these cattle., Results: We analyzed 40 Yakutian cattle with strict quality control for ROH detection yielding 683 homozygous segments, averaging 17 per individual with an average length of 9 Mb. ROH regions were found to be involved in important pathways pertaining to cold adaptation. Autozygosity ranged from 1% to 12% of the genome, with a relatively low average inbreeding coefficient (FROH) of 0.057, as compared to other breeds. Also, the different diversity indicators, namely, principal component analysis, heterozygosity, and effective population size analysis, revealed the prevalence of genetic diversity within the breed., Conclusion: Our findings on ROH are the first of its kind in Yakutian cattle that support their adaptability to colder environments, as evidenced by low inbreeding and high genetic diversity., (© 2024 S. Karger AG, Basel.)

Nanomedicine has the potential to transform healthcare by offering targeted therapies, precise diagnostics, and enhanced drug delivery systems. The National Institutes of Health has coined the term "nanomedicine" to describe the use of nanotechnology in biological system monitoring, control, diagnosis, and treatment. Nanomedicine continues to receive increasing interest for the rationalized delivery of therapeutics and pharmaceutical agents to achieve the required response while reducing its side effects. However, as nanotechnology continues to advance, concerns about its potential toxicological effects have also grown. This review explores the current state of nanomedicine, focusing on the types of nanoparticles used and their associated properties that contribute to nanotoxicity. It examines the mechanisms through which nanoparticles exert toxicity, encompassing various cellular and molecular interactions. Furthermore, it discusses the assessment methods employed to evaluate nanotoxicity, encompassing in-vitro and in-vivo models, as well as emerging techniques. The review also addresses the regulatory issues surrounding nanotoxicology, highlighting the challenges in developing standardized guidelines and ensuring the secure translation of nanomedicine into clinical settings. It also explores into the challenges and ethical issues associated with nanotoxicology, as understanding the safety profile of nanoparticles is essential for their effective translation into therapeutic applications., (© 2024. The Author(s).)

Background: This study aimed to evaluate and compare the efficacy of oral premedication with ibuprofen on the anesthetic efficacy of inferior alveolar nerve block (IANB) using 2% lignocaine and 1:100000 epinephrine in tobacco-chewing (TC) and non-tobacco-chewing (NTC) patients with symptomatic irreversible pulpitis (SIP) during nonsurgical endodontic intervention (NEI)., Methods: This multicenter, prospective, double-blind, two-arm parallel-group randomized controlled trial involving 160 patients was conducted for a period of 9 months. The patients were classified into the study (TC patients) and control (NTC patients) groups, which were subdivided into two subgroups 1 hour before the procedure based on oral premedication with tab ibuprofen 600 mg. Nicotine dependence was assessed using the Modified Fagerstrom Tolerance Nicotine Scale. Patients were administered an IANB injection of 2% lignocaine containing epinephrine 1:100000 after premedication. Pulpal anesthesia before NEI was confirmed using electric pulp testing and cold spraying. Patients rated their pain on the 10-point visual analog scale (VAS) during NEI thrice at the dentin, pulp, and instrumentation levels. No pain at each level indicated the success of anesthesia., Results: The success and failure rates did not differ between the premedication and non-premedication subgroups in the TC or NTC groups (P > 0.05). However, the success rate was higher in the premedication subgroup of the NTC group (52.5%) than in the TC group (45%). Most patients with premedication experienced failure at the instrumentation level, whereas patients in the non-premedication group experienced pain at the dentin level. Failure rates of IANB did not differ significantly at different levels between the groups (P > 0.05). The mean VAS scores differed significantly at the dentin level in both groups, with lower values in the premedication group (P < 0.05)., Conclusions: The efficacy of ibuprofen premedication with IANB during NEI did not differ significantly between the TC and NTC patients with SIP. The effect of premedication was more significant in the NTC group than in the TC group. A causal relationship between nicotine consumption and the success of premedication could not be established, and further studies are required to validate the results of the present study., Competing Interests: DECLARATION OF INTERESTS: The authors explicitly state that there are no conflicts of interest related to this article., (Copyright © 2024 Journal of Dental Anesthesia and Pain Medicine.)

Antimicrobial resistance (AMR) has become one of the most serious threats to One Health. Aquatic environments are an ideal non-clinical AMR reservoir and can act as a key battlefront for tackling the AMR. However, AMR data using the One Health approach remain scarce in aquatic environments worldwide. Here, we extensively assessed AMR in Escherichia coli isolated from urban and rural lake ecosystems using the One Health perspective. A total of 162 E. coli isolates obtained from lakes were tested against 25 antimicrobials using an in-vitro antimicrobial susceptibility testing method. A low (2%) to moderate (45%) drug resistance rate was found for all antimicrobials used in human/veterinary medicine or animal/plant agriculture. However, <80% E. coli isolates exhibited multidrug resistance (MDR) phenotype to highly important (amikacin, gentamicin, trimethoprim) or critically important (amoxicillin, ampicillin, colistin) drugs of both human and veterinary medicine. Of concern, >50% of E. coli isolates exhibited MDR to drugs used as last-resorts (chloramphenicol, colistin) or as frontline (nitrofurantoin, sulfamethoxazole, ampicillin, gentamicin) against E. coli infections. In conclusion, the presence of MDR E. coli strains in urban or rural lake ecosystems highlights their possible role as AMR reservoirs with potential One Health risks., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: Acromioclavicular joint (ACJ) disruptions are corrected by surgery either with an endobutton or a hook plate. The results in the long term were found to be similar in many randomized controlled trials. This study aims to conduct a meta-analysis to evaluate the functional outcome and complications of double endo button versus clavicular hook plate (CHP) for ACJ disruption (Rockwood types III-VI)., Materials and Methods: Two authors independently searched related articles from electronic databases (PubMed, Google Scholar, MEDLINE, SCOPUS, and Web of Science) till January 26, 2022. The data were extracted from the related articles and analyzed by Stata software. For bias calculation of each study, the Newcastle-Ottawa scale and the RevMan 5.4 software were used., Results: 14 cohort studies, 2 randomized control trial studies, and 1 case-control study including patients were selected in this meta-analysis. The results of our study showed a significantly higher Constant-Murley Score (WMD 5.79, 95% confidence interval [CI] 2.23-9.36), Visual Analog Scale (WMD- 0.63, 95% CI [-0.79, -0.46]) and University of California at Los Angeles shoulder score (UCLA) scale (WMD 3.32, 95% CI [2.87, 3.77]) for double endobutton group. At the same time, some complications like implant failure were more common in the double endobutton group., Conclusion: This meta-analysis shows better functional and clinical outcomes of shoulder joint for the treatment of acromioclavicular joint (ACJ) disruption cases (Rockwood types III-VI) with no need for secondary operation, unlike the CHP. Complications like subacromial erosion, ACJ arthrodesis, and infection rate are higher in the CHP group, whereas the chance of implant failure is higher in the double endobutton group., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Background: Poisoning is a significant health hazard and a leading cause of morbidity and mortality worldwide. India, being a predominantly agrarian country, routinely employs organophosphate (OP) pesticides in farming, and they are readily available "over the counter." OPs exert their toxicity by interfering with the normal function of acetylcholine, an essential neurotransmitter throughout the autonomic and central nervous systems. Due to the limited availability of facilities and resources in health-care systems, and economically restraining patients, it is necessary to rely more on clinical features to assess the severity of poisoning and manage the condition properly., Methodology: It was a hospital-based prospective observational study that included patients aged >13 years in a tertiary care hospital. All patients were clinically evaluated based on their history and examination. The diagnosis was made based on characteristic clinical manifestations or evidence of exposure to organophosphorus compounds (corroborative evidence such as empty containers and the odor of gastric aspirates). Clinical severity was assessed and categorized according to the Peradeniya Organophosphorus Poisoning Scale (POP scale). A score of 0-3 is considered mild poisoning, 4-7 as moderate poisoning, and 8-11 as severe poisoning., Results: Out of the 50 patients enrolled in the study, 17 (34.00%) were aged <20 years, 19 (38%) were in the 20-30 years age group, and 14 (28%) were aged >30 years. Ingestion is the only mode of exposure to poisoning. None of the patients had history of contact or inhalational exposure. Of the 50 cases, 12 (24.0%) were in the mild category, 26 (52.0%) in the moderate category, and 12 (24%) in the severe category on the POP grading. A comparison of the mean serum pseudocholinesterase, troponin-T, and pro-BNP levels with severity was performed. In mild OP poisoning, the mean serum PChE level was 2766.58 ± 1120.44; in moderate, it was 1969.35 ± 1330.07, and in severe, it was 701.83 ± 961.17. Pseudocholinesterase levels decreased progressively with increasing clinical severity from mild-to-severe cases, and this association was statistically significant (P < 0.001). Two-dimensional echocardiography screening done in all patients did not show any significant abnormalities., Conclusion: This study shows that serum PCE is reduced in OP poisoning and correlates with the clinical severity grading done by the POP scale and is also associated with an increase in the duration of intensive care unit stay. No significant evidence of direct cardiac injury was observed in this study. A low Glasgow Coma Scale score and an increased respiratory rate at presentation are associated with poor outcomes., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Abstract: Targeted immunotherapy became the most advanced approach for cancer treatment. Programmed death-1 (PD-1) expressed on activated T cells can reverse immune suppression and cause T-cell activation. Nivolumab, a PD-1 immune checkpoint inhibitor antibody that is a fully human immunoglobulin G4, blocks PD-1 and promotes antitumor immunity. Cabozantinib (tyrosine kinase inhibitor) inhibits the tyrosine kinase activity of vascular endothelial growth factor receptors 1, 2, and 3. As a result of enhancing immune response in normal tissues, immune-related adverse events can occur. Thyroid dysfunction is a common form of immune-related adverse event and seen on 18 F-FDG PET/CT scans post therapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We sought to describe national trends in hospitalization and post-acute care utilization rates in skilled nursing facilities (SNFs) and home health (HH) for both Medicare Advantage (MA) and Traditional Medicare (TM) beneficiaries, reaching up to the COVID-19 pandemic (2015-2019)., Design: Retrospective, observational using 100% sample of Medicare Provider Analysis and Review file (MedPAR), the Medicare Beneficiary Summary File, the Minimum Data Set (MDS), and the Outcome and Assessment Information Set (OASIS)., Setting and Participants: Medicare beneficiaries aged 66 and older enrolled in MA or TM who were hospitalized and discharged alive., Methods: We first calculated the proportions of MA and TM beneficiaries who were hospitalized and who used any post-acute care, as well as the total number of days of post-acute care used. We also calculated the size of the post-acute care network used by TM and MA beneficiaries within each hospital in our sample and the measured quality (star ratings) of the post-acute care providers used., Results: We found hospitalizations, SNF stays, and HH stays were all decreasing over time in both populations. Although similar proportions of MA and TM beneficiaries received SNF or HH care, MA beneficiaries received fewer days. The largest difference we found was in the number of post-acute care providers used in TM and MA, with MA using far fewer; however, quality ratings were similar among post-acute care providers used in each program., Conclusions and Implications: Together, these results suggest MA beneficiaries have fewer days in post-acute care, receive care from fewer providers of similar measured quality to TM, but have a similar number of days outside the hospital or SNF in the first 100 days after hospital discharge., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

The global demographic and epidemiological transition have led to a rapidly increasing burden of cancer, particularly among older adults. There are scant data on the prevalence and demographic pattern of cancer in older Indian persons. This was a multicentric observational study conducted between January 2019 and December 2020. Data were retrieved from existing electronic databases to gather information on two key variables: the total number of patients registered with oncologists and the number of patients aged 60 years and above. The primary objective was to determine the percentage of older adults among patients with cancer served by these hospitals. Secondary objectives included understanding the prevalence of different types of cancer in the older population, and the sex- and geographic distribution of cancer in older Indian patients. We included 272,488 patients with cancer from 17 institutes across India. Among them, 97,962 individuals (36 %) were aged 60 years and above. The proportion of older adults varied between 20.6 % and 53.6 % across the participating institutes. The median age of the older patients with cancer was 67 (interquartile range, 63-72) years. Of the 54,281 patients for whom the details regarding sex were available, 32,243 (59.4 %) were male. Of the 56,903 older patients, head and neck malignancies were the most prevalent, accounting for 11,158 cases (19.6 %), followed by breast cancer (6260 cases, 11 %), genitourinary cancers (6242 cases, 10.9 %), lung cancers (6082 cases, 10.7 %), hepatopancreaticobiliary (6074, 10.7 %), and hematological malignancies (5226 cases, 9.2 %). Over one-third of Indian patients with cancer are aged 60 years and above, with a male predominance. Head and neck, breast, and genitourinary cancers are the most prevalent in this age group. Characterizing the burden of cancer in older adults is crucial to enable tailored interventions and additional research to improve the care and support for this vulnerable population., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest from any authors associated with this publication. No funding was required for this project., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The present research focused on the tail-approach synthesis of novel extended thiazolotriazoles (8a-8j) and triazolothiadiazines (11a-11j) including aminotriazole intermediate 10. After successful synthesis, all the compounds were evaluated for their inhibition potential against cytosolic isoforms of human carbonic anhydrase (hCA I, II), tumor-linked transmembrane isoforms (hCA IX, XII), and cathepsin B. As per the inhibition data, the newly synthesized compounds showed poor inhibition against hCA I. Many of the compounds showed effective inhibition toward hCA IX and/or XII in low nanomolar concentration. Despite the strong to moderate inhibition of hCA II by these compounds, more than half of them demonstrated better inhibition against hCA IX and/or XII, comparatively. Further, insights of CA inhibition data of these extended analogs and their comparison with earlier reported thiazolotriazole and triazolothiadiazine derivatives might help in the rational design of novel potent and selective hCA IX and XII inhibitors. The novel compounds were also found to possess anti-cathepsin B potential at a low concentration of 10 -7  M. Broadly, compounds of series 11a-11j presented more effective inhibition against cathepsin B than their counterparts in series 8a-8j. Moreover, these in vitro results with respect to cathepsin B inhibition were also supported by the in silico insights obtained via molecular modeling studies., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Multilevel inverters (MLIs) are commonly used in renewable energy systems for their high-quality output, low total harmonic distortion (THD), and reduced component count. This study presents a high-gain, single-source MLI designed for renewable applications like solar or wind power. It features a novel topology with twice the voltage-boosting factor, utilizing a single DC source. The inverter achieves thirteen voltage levels using just 10 power switches and three switched capacitors. The voltage gain is achieved without the need for bulky DC-DC converters or transformers. This is accomplished by configuring the switched capacitors in series and parallel arrangements to attain the desired voltage boost. Additionally, the self-balancing capacitors eliminate the need for extra sensors. Both symmetric and asymmetric variants of the extensible configuration are investigated. The suggested design lowers the total standing voltage (TSV) while achieving high gain. A selective harmonic removal technique using artificial neural networks (ANN) reduces THD by up to 6.07 %. An extensive review of recent literature reveals significant advancements and applications of ANNs in this field. The proposed system's benefits, such as gain factor, total standing voltage (TSV), and minimized device count, are assessed. Comparative analysis reveals that the proposed topology employs fewer components and features a more simplified design. Additionally, the inverter achieves an efficiency of 96.9 %. The design is validated through an experimental prototype after being confirmed with MATLAB/SIMULINK.© YEAR The Authors. Published by Elsevier Ltd. Peer-review under responsibility of the scientific committee of the Name of the Conference, Conference Organizer Name, Year or Edition of Conference., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction: In India, oral cavity cancer rates are the highest, largely due to tobacco and areca nut use. The primary goal of oncologic surgery is complete tumor resection with adequate margins, yet no accepted guidelines exist margin identification. NBI enhances mucosal lesion detection and may improve margin assessment in OSCC., Aims: This study aims to evaluate the proportion of negative superficial resection margins using NBI and to compare these results with margins assessed using white light (WL) examination., Materials and Methods: The study at AIIMS, Rishikesh, included 38 patients with T1-T3 biopsy-proven OSCC. Surgical margins were marked using WL and NBI. Histopathology classified margins as clear (>5mm), close (1-5 mm), or involved. Sensitivity, specificity, and predictive values of NBI were calculated., Results: The average NBI examination duration was 227 s. Negative margins were achieved in 68.42 % (>5mm) and 78.94 % (>3mm) of NBI cases, compared to 71.05 % and 84.21 % for WL. NBI had a sensitivity of 12.50 %, specificity of 96.67 %, and overall accuracy of 78.95 %., Discussion: NBI showed high specificity but low sensitivity. This could be due to the smaller number of patients in NBI positive group. In the present study, the single positive margin identified with NBI could also have been detected with the combined approach of white light and palpation, ensuring that no positive margins were missed., Conclusion: NBI can complement WL for margin assessment in oral SCC but requires a long learning curve and a dedicated team. Integrating NBI into standard protocols could improve surgical outcomes and reduce recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The energy response of gross gamma dose rate monitors needs to be flat in order to prevent overestimation of dose at low gamma energies. In this paper, a discriminator threshold modulation based electronic energy compensation algorithm has been proposed for SiPM-scintillator based gamma detectors. Theoretical simulation studies were carried out in order to optimize the parameters of the periodic ramp voltage used for modulation of the discriminator threshold of a SiPM-GGAG:Ce,B based gamma dose rate monitor. A customized threshold modulation circuit and signal processing electronics were developed for this gamma detector. For experimentally optimizing the parameters, the energy response studies of the detector, with and without the discriminator threshold modulation, were carried out. With the optimized parameters for a periodic ramp threshold, the count rates for 241Am (60 keV) and 60Co (1173 and 1332 keV) were observed to be within ±30% of the count rate obtained for 137Cs (662 keV). Using the electronic energy compensation techniques presented in this paper, a flat energy response of the SiPM-scintillator gamma detector for the energy range of 60 keV to 1.5 MeV could be achieved., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Interferon lambda (IFN-λ) plays diverse roles in bacterial infections. Previously we showed that IFN-λ is induced in the lungs of B. pertussis-infected adult mice and exacerbates inflammation. Here, we report that mice lacking the IFN-λ receptor (IFNLR1) specifically on neutrophils (MRP8creIFNLR1fl/fl mice) exhibit reduced lung bacterial load and inflammation compared to WT mice during B. pertussis infection. In B. pertussis-infected wild type (WT) mice, lung type I and III IFN responses were higher than in MRP8creIFNLR1fl/fl mice, correlating with increased lung inflammatory pathology. There was an increased proportion of IFN-γ-producing neutrophils in the lungs of MRP8creIFNLR1fl/fl mice compared to WT mice. IFNLR1-/- neutrophils incubated with B. pertussis exhibited higher killing compared to WT neutrophils. Treatment of WT neutrophils with IFN-λ further decreased their bacterial killing capacity and treatment of WT mice with IFN-λ increased lung bacterial loads. Contributing to the differential killing, we found that IFNLR1-/- neutrophils exhibit higher levels of reactive oxygen species, myeloperoxidase [1], matrix metalloproteinase-9 (MMP9) activity, neutrophil extracellular traps (NETs), and IFN-γ secretion than WT neutrophils, and inhibiting NADPH oxidase inhibited bacterial killing in IFNLR1-/- neutrophils. B. pertussis induced IFN-λ secretion and IFNLR1 gene expression in mouse and human neutrophils and this was dependent on the bacterial virulence protein pertussis toxin (PTX). PTX enhanced bacterial loads in WT but not in MRP8creIFNLR1fl/fl or IFNLR1-/- mice. Thus, PTX disrupts neutrophil function by enhancing type III IFN signaling, which prevents neutrophils from effectively clearing B. pertussis during infection, leading to higher bacterial loads and exacerbation of lung inflammation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Molecularly imprinted polymers (MIPs) are polymeric matrices that can mimic natural recognition entities, such as antibodies and biological receptors. Molecular imprinting of therapeutics is very appealing in the design of drug delivery systems since the specific and selective binding sites created within the polymeric matrix turn these complex structures into value-added carriers with tunable features, notably high drug-loading capacity and good control of payload release. MIPs possess considerable promise as synthetic recognition elements in 'theranostics'. Moreover, the high affinity and specificity of MIPs make them more advantageous than other polymer-based nanocomposites. This review summarizes the present state-of-the-art of MIP-based delivery systems for the targeted delivery of bioactives, with current challenges and future perspectives., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Thorium-232 (Th-232) is a promising fuel for advanced nuclear reactors. However, in case of internal human exposure to Th, there is currently no effective modality for its removal from liver and skeleton or for mitigating its effect. The FDA-approved agent, diethylenetriaminepentaacetate (DTPA), can remove Th and other actinides from blood circulation only. For the first time, a rationally-selected polyherbal hepatoprotective i.e. Liv52® (L52S), was evaluated in-combination with DTPA for its Th decorporation ability in Swiss mice. Inductively-coupled plasma mass spectroscopic analysis showed that oral administration of L52S in conjunction with DTPA significantly decreased Th burden from liver (20 %) and skeleton (33 %) as well as enhanced Th excretion (∼2.5 folds) through urine in comparison to DTPA or L52S alone. The combinatorial therapy was found to be complementary in-action, ameliorating Th-induced tissue damage in liver, spleen, and bone more effectively than monotherapy. Furthermore, markers of liver function (alanine transaminase) and liver inflammation and fibrosis (NF-κB & keratin) further validated the beneficial effect of L52S. The human consumption of L52S for various liver disorders further supports its clinical application for Th decorporation and mitigation of its health effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: BCOR-rearranged sarcomas (BRS) constitute relatively newly described sarcomas, which, within the musculoskeletal sites, usually occur in the bones, followed by soft tissues. Primary BRS involving the visceral organs is very rare, and only a single case is reported in the lung. These tumors share overlapping morphological and immunohistochemical (IHC) features with other neoplasms, such as synovial sarcoma, Ewing sarcoma, as well as carcinosarcoma, the latter especially when occurring in the visceral organs. BCOR immunostaining is useful in triaging a tumor for molecular diagnosis, which constitutes the "essential" diagnostic criterion for these tumors. To report an extremely rare case of a BRS, confirmed by BCOR-rearrangement by fluorescence in situ hybridization (FISH), primarily occurring in the lung, emphasizing the diagnostic approach and management, along with review of literature. An18-year-old boy presented with complaints of left-sided chest pain, along with cough, fever, loss of appetite, and weight. On radio imaging, there was a complete collapse of the left lower lobe of lung with moderate pleural effusion. The biopsy showed a biphasic tumor comprising primitive round cells admixed with spindle cells. Immunohistochemically, the tumor cells were positive for BCOR, TLE1, and p53. FISH showed BCOR gene rearrangement. A diagnosis of primary BRS of lung was offered. The patient had a favorable response to the chemotherapy regime. BRS is an ultra-rare tumor, which rarely involves visceral organs. The lung is an exceptionally rare site, with only single reported case previously. An exact confirmation by molecular testing has treatment-associated implications. A review of similar reported cases is presented herewith., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Skin cancer, which comprises both melanoma and non-melanoma forms, is frequently diagnosed as the predominant malignancy among today's population. Existing treatments are often prolonged and complex, have a low rate of success, and have side effects. This complexity leads to poor patient adherence and increases the risk of disease recurrence. Ethosomes, extensively studied for their applications in topical and transdermal therapies, are distinguished by their high ethanol content, which facilitates enhanced skin penetration and efficient drug delivery. Compared to traditional liposomes, ethosomes offer notable advantages due to their unique composition, demonstrating potential efficacy in treating various skin conditions, including basal cell carcinoma, squamous cell carcinoma, and melanoma. The present review provides a brief introduction to skin melanoma and its pathogenesis, signalling pathways, biomarkers, the need for ethogel-based drug delivery, applications of ethosomes against skin cancer, and clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Electrolysis of D 2 O may be used as a portable neutron source with numerous applications without the complexity of huge reactor operations. Herein, we report reproducible fast neutron generation by electrolysis of D 2 O using palladium cathode and platinum anode, which was detected with diamond detector, gas filled 3 He detectors after thermalisation with high density polythene, as well as novel epoxy resin and CR-39 detectors. Notably, a highly reproducible neutron generation at electrochemical surfaces of palladium electrode was observed and signature transmutation via Pd (d, n) Ag was corroborated. This was further explained using a theoretical model based on second order quantum perturbation theory., (© 2024. The Author(s).)

Urea derivatives, polyureas, and poly(urea-urethanes) are materials of great interest. However, their current methods of synthesis involve toxic feedstocks - isocyanate and phosgene gas. There is significant interest in developing alternative methodologies for their synthesis from safer feedstocks. We report here new methods for the synthesis of urea derivatives, polyureas, and poly(urea-urethane) using a ruthenium pincer catalyst. In this approach, urea derivatives and polyureas are synthesized from the self-coupling of formamides and diformamides, respectively, whereas poly(urea-urethanes) are synthesized from the coupling of diformamides and diols. CO and H 2 gases are eliminated in all these processes. Decarbonylation of formamides using such organometallic catalysts has not been reported before and therefore mechanistic insights have been provided using experiments and DFT computation to shed light on pathways of these processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This study conducted a comprehensive analysis of trace element concentrations in the Upper Indus River Basin (UIRB), a glacier-fed region in the Western Himalayas (WH), aiming to discern their environmental and anthropogenic sources and implications. Despite limited prior data, 69 samples were collected in 2019 from diverse sources within the UIRB, including mainstream, tributaries, and groundwater, to assess trace element concentrations. Enrichment factor (EF) results and comparisons with regional and global averages suggest that rising levels of Zn, Cd, and As may pose safety concerns for drinking water quality. Advanced multivariate statistical techniques such as principal component analysis (PCA), absolute principal component scores (APCS-MLR), Monte Carlo simulation (MCS), etc were applied to estimate the associated human health hazards and also identified key sources of trace elements. The 95th percentile of the MCS results indicates that the estimated total cancer risk for children is significantly greater than (>1000 times) the USEPA's acceptable risk threshold of 1.0 × 10 -6 . The results classified most of the trace elements into two distinct groups: Group A (Li, Rb, Sr, U, Cs, V, Ni, TI, Sb, Mo, Ge), linked to geogenic sources, showed lower concentrations in the lower-middle river reaches, including tributaries and downstream regions. Group B (Pb, Nb, Cr, Zn, Be, Al, Th, Ga, Cu, Co), influenced by both geogenic and anthropogenic activities, exhibited higher concentrations near urban centers and midstream areas, aligning with increased municipal waste and agricultural activities. Furthermore, APCS-MLR source apportionment indicated that trace elements originated from natural geogenic processes, including rock-water interactions and mineral dissolution, as well as anthropogenic activities. These findings underscore the need for targeted measures to mitigate anthropogenic impacts and safeguard water resources for communities along the IRB and WH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Vascular Endothelial Growth Factor-C (VEGF-C) plays a critical role in tumor growth and invasion through lymphangiogenesis and helps to identify the variability of lymphatic potential of oral squamous cell carcinoma (OSCC) cases with or without lymph node metastasis., Materials and Methods: A total of 65 cases of OSCC were included. The clinical details were obtained from patient records. The cases were grouped as N0 versus any N categories. All the cases were immunohistochemically evaluated for VEGF-C within the primary tumor using a standard protocol. An average of 5 lymph nodes were dissected from all neck dissection specimens and were evaluated histopathologically. The data obtained were statistically evaluated at 95% confidence interval and P ≤ 0.05., Results: 100% cases in our study showed VEGF-C immunopositivity. The immunoreactivity increased linearly with advancing grades. A total of 31 out of 40 N0 OSCC revealed score 2 (26%-50%) of VEGF-C immunoreactivity. Eighteen cases were false negative clinically., Conclusion: Recognition of locoregional spread may empower clinicians for correct therapeutic decisions in N0 versus any N case., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Purpose: The Fukuda step test is a valuable tool for identifying vestibular dysfunction in humans. This study evaluated the intra-rater and test-retest reliabilities of videograph observations to determine the diversion time while performing the Fukuda test. This study aimed to determine the use of videographic observation as a beneficial tool for recording real-time assessment procedures in clinical settings., Methods: Fifty college students who were selected based on the inclusion criteria performed three consecutive sessions of the Fukuda step test. Intra-rater and test-retest reliabilities of the videograph observations were identified using the intraclass correlation coefficient (ICC)., Results: We noted both, good intra-rater (ICC= 0.78) and moderate-to-good test-retest reliabilities (ICC= 0.69) of the videograph observations., Conclusion: Videographic observation can be used in clinical settings to identify diversion times while performing the Fukuda step test.

Background: Parents and families have a role to play in helping children develop healthy behaviours that will carry over into adulthood. The sugary drink and fruit juice consumption is significantly related to unhealthy weight gain in childhood. Hence, this study was planned to assess parental knowledge, attitudes, and practices about juice and sugar-sweetened beverages (SSBs) among parents of children (2-24 months) and identify factors that contribute to their early introduction., Methods and Material: A cross-sectional study was conducted on 400 children-parent dyads (2-24 months). A questionnaire regarding the knowledge and attitudes about initiating fruit juice and SSB among children was prepared with 6 statements that were validated for contents by two subject experts. Each of the questions was designed to be answered on a Five-point Likert-type scale. STATA 14.2 version was used to analyse data., Results: Out of 400, 14 (26.9%) and 125 (68%) parents planned to introduce SSBs and juices respectively in the first year life of their child. None of the parents had an excellent knowledge score. There was no significant difference reported between parents with less than high school and those with high school/graduation educated in their intention to introduce juice and SSBs ( P = 0.68) to their babies in the first year of life and about its knowledge ( P = 0.82). Most parents with lower socio-economic status (58.6%) showed less likeliness to introduce juices and SSBs to their child's diet as reflected by a statistically significant ( P = 0.01) knowledge score., Conclusion: There was a knowledge gap among parent's of children irrespective of their education level and socio-economic status., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Artemisinin-based combinational therapies (ACTs) constitute the first line of malaria treatment. However, due to its trichome-specific biosynthesis, low concentration, and poor understanding of regulatory mechanisms involved in artemisinin biosynthesis and trichome development, it becomes very difficult to meet the increased demand for ACTs. Here, we have reported that a bHLH transcription factor, AaMYC2-type, plays an important role in regulating GST development and artemisinin biosynthesis in Artemisia annua. AaMYC2-type encodes a protein that is transcriptionally active and localised to the nucleus. It is prominently expressed in aerial parts like leaves, stems, inflorescence and least expressed in roots. AaMYC2-type expression is significantly increased under different hormonal treatments. In transgenic overexpression lines, AaMYC2-type OE, a significant increase in the expression of trichome development and artemisinin biosynthesis genes was observed. While in knockdown lines, Aamyc2-type, expression of trichome development and artemisinin biosynthesis genes were significantly reduced. Yeast one-hybrid assay clearly shows that the AaMYC2-type directly binds to the E-boxes in the promoter regions of ADS and CYP71AVI. The SEM microscopy depicted the number of trichomes elevated from 11 mm -2 in AaMYC2-type OE lines to 6.1 mm -2 in Aamyc2-type. The final effect of the alteration in biosynthetic and trichome developmental genes was observed in the accumulation of artemisinin. In the AaMYC2-type OE, the artemisinin content was 12 mg g -1 DW, which was reduced to 3.2 mg g -1 DW in the Aamyc2-type. Altogether, the above findings suggest that the AaMYC2-type play a dual regulating role in controlling both trichome developmental and artemisinin biosynthetic genes., (© 2024 Scandinavian Plant Physiology Society. Published by John Wiley & Sons Ltd.)

Introduction: Wilson's disease is an autosomal recessive condition where excessive amount of copper accumulates in the body, especially in the liver, brain, and eyes. It is caused by a mutation in the ATP7B gene on chromosome 13. In 25-30% of patients, joint involvement occurs at the later course of disease; osteoarthritis being the commonest manifestation. Synovial chondromatosis (SC) is a benign metaplasia which occurs in the synovial membrane and it results in the formation of intra-articular loose bodies (LB), but its occurrence in a patient of Wilson's disease has not yet been reported in medical literature., Case Report: A young male in his 30s, a diagnosed case of Wilson's disease on maintenance therapy of d-penicillamine, zinc, trientine, and lithium presented to the hospital with restriction of movement at the knee joints and a valgus deformity. Examination showed firm to hard globular swellings which were partly mobile around the knee joint. The Magnetic Resonance Imaging (MRI) findings were suggestive of a SC after which the patient underwent corrective surgery and debridement and removal of the LB and a histopathology report confirmed the diagnosis. The patient was followed up at 12 weeks and was found to have pain-free movements with minimal support. His 24-h urinary copper excretion was found to be within normal limits and his maintenance therapy was optimized. The patient was initiated on speech therapy for his persistent slurring of speech and psychiatric counseling for rehabilitation in social and personal life. The patient was advised for 6 monthly follow-up., Conclusion: This case summarizes the unique presentation of SC with genu valgum in a patient of Wilson's disease and hence warrants a keen eye for the physician and orthopedician alongside osteoarthritis; which has been widely reported in Wilson's disease, thus providing an opportunity for early correction of valgus deformity of the subject., Competing Interests: Conflicts of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Desulphurization of fossil fuels is a critical process in reducing the sulphur content from environment, which is a major contributor to atmospheric pollution. Traditional desulphurization techniques, while effective, often involve high energy consumption and the use of harsh chemicals. Recently, photocatalytic desulphurization has emerged as a promising, eco-friendly alternative, leveraging the potential of photocatalysts especially semiconductor heterojunctions to enhance photocatalytic efficiency. This review comprehensively discusses the significance and mechanism of photocatalytic desulphurization reactions, designing of various heterojunctions such as conventional, p-n, Z-scheme and S-scheme, their charge transfer mechanism and properties and their contribution to the photocatalytic desulphurization activity. Heterojunctions, formed by combining different semiconductor materials, facilitate efficient charge separation and broaden the light absorption range, thereby improving the photocatalytic performance under visible light. Furthermore, the recent advancements in the heterojunction systems in the field of photocatalytic desulphurization activity have been discussed in detail and summarized. The current limitations and challenges in this particular field are also explored. The paper concludes with an outlook on future research directions and the potential industrial applications of heterojunction-powered photocatalytic desulphurization, emphasizing its role in achieving cleaner energy production and environmental sustainability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The Potentilla genus has long been used traditionally as food and a folklore medicine. In the present study, aerial parts of two Potentilla species, Potentilla fulgens and Potentilla atrosanguinea, of western Himalayan origin, were studied for their anti-breast cancer activity. Ethyl acetate (PAA-EA, PFA-EA), methanolic (PAA-ME, PFA-ME) and hydro-methanolic extract (PAA-HM, PFA-HM) of the plants were tested for their antiproliferative activities against MCF-7 and T-47D breast cancer cell lines. The extracts showed good antiproliferative activity against ER-α dominant breast cancer cell line T-47D, having IC 50 values 6.19 ± 0.01 to 33.23 ± 0.04 μg/ml. Eight compounds were isolated, characterized, and quantified from ethyl acetate and methanolic extracts by column chromatography, 1D, 2D-NMR, HRMS and TLC densitometric analysis. Two compounds (4 and 6) have shown better antiproliferative activity than standard bazedoxifene and were further evaluated for their ER-α binding affinity via-fluorescence polarization-based competitive binding assay. The antiestrogenic properties of both compounds were assessed using western blotting. Compounds 4 and 6 were found to have significant affinity for the ER-α and managed to decrease its expression by 38 and 54% respectively. Compounds 4 and 6 also had good stability and reactivity as measured by minimal fluctuations in molecular dynamic simulation analysis, a good dock score in molecular docking, and a respectable HOMO-LUMO energy gap in DFT calculations. Compounds 4 and 6 have shown reliable results and can be used in the development of natural product-based anti-breast cancer agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)