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Drought is one of the most detrimental natural calamities to the economy. Despite its significant consequences, the evolution from meteorological to agricultural and hydrological droughts still needs to be explored. A thorough investigation was carried out in India's eastern hills and plateau region to determine the extent of drought's impact through indices. Standardized Precipitation Index (SPI), Standardized Precipitation Evapotranspiration Index (SPEI), Standardized Soil Moisture Index (SSMI), and Standardized Streamflow Index (SSI) were analyzed to delineate meteorological, agricultural, and hydrological droughts across the region using precipitation, temperature, soil moisture, and streamflow data comprising of the 35 years (1987-2021) from 24 stations. Analytic Hierarchy Process (AHP) was employed with Geographic Information System (GIS) techniques for combined drought indicator. The findings show that compared to other indices, the maximum weightage is given to meteorological drought indices (SPI and SPEI). The combined drought index (CDI) resulted from 39.1% of SPI, 27.6% of SPEI, 19.5% of SSMI, and 13.8% of SSI. The AHP technique made it easier to generate maps. These maps categorize the area into five degrees of vulnerability, from severe drought to normal conditions. The propagation duration from the onset of meteorological drought to the emergence of agricultural and ultimately hydrological drought was explored. The propagation time of hydrological drought after meteorological drought is longer compared to agricultural drought. Additionally, wavelet coherence analysis investigated the interaction of meteorological drought with agricultural and hydrological drought in the region. Temporal assessments of the spatial extent of drought across the study area were also conducted, offering crucial details about the drought's regional and temporal pattern. This multidimensional method provides a thorough learning of the dynamics and sensitivity of drought in the eastern hills of India and the plateau region. This is helpful for the implementation of targeted mitigation and adaptation strategies to reduce the adverse impacts of drought., Competing Interests: Declarations. Ethical approval: • The manuscript has yet to be submitted to another journal for simultaneous consideration. • A single study has not been split into several parts to increase the quantity of submissions. • No data, text, or theories by others are presented. Consent to participate: All authors whose names appear on the submission made substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data. All the authors drafted the work or revised it critically for important intellectual content and approve the version to be published. We agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Consent for publication: We (both the authors) approve the publication of the manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Magnetic systems, wherein competing degree of freedoms arising from spin orbit coupling and crystal electric field lead to non-trivial magnetic ground states, remains in the forefront of research in condensed matter physics. Here, we present a comprehensive investigation on three-dimensional rare-earth based spin systems NdTaO4 and NdNbO4, where the Nd ions sit on a stretched diamond lattice. No signatures of long-range ordering and spin freezing are observed down to 1.8 K, in both cases. The low temperature Curie-Weiss analysis indicate towards the dominance of antiferromagnetic interactions between Nd3+ spins. A three-level crystal electric field model clearly explain the nature of susceptibility curve. At low temperatures, heat capacity data exhibit two-level Schottky anomaly associated with ground state Kramer's doublet. Additionally, the low temperature magnetic behaviour is found reliable to effective spin (Jeff) = ½ ground state, suggesting the presence of quantum fluctuations in both cases. First-principle calculations reveal a significant value of orbital moment with inclusion of spin orbit coupling and reinforce the Jeff = ½ nature of the ground state., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Self-assembly of amino acids and short-peptide derivatives attracted significant curiosity worldwide due to their unique self-assembly process and wide variety of applications. Amino acid is considered one of the important synthons in supramolecular chemistry. Self-assembly processes and applications of unfunctionalized native amino acids have been less reported in the literature. In this article, we are first-time reporting the self-assembly process of tyrosine (Tyr), an aromatic amino acid, in dimethyl sulfoxide (DMSO) solvent. Most of the studies related to Tyr self-assembly were reported in different aqueous solutions. In our work, we studied the self-assembly in several common organic solvents and found that Tyr could self-assemble into a supramolecular gel in dimethyl sulfoxide (DMSO) solvent. The self-assembly process was investigated by several techniques, such as UV-vis, fluorescence, FTIR, and NMR spectroscopy. Morphological features on the nanoscale were investigated through scanning electron microscopy (SEM). SEM images indicated the formation of nanofibrils with high aspect ratios. The supramolecular gel property was investigated by different rheological experiments. Computational study on the self-assembly process of Tyr in DMSO medium suggested that noncovalent interactions like hydrogen bonding and π-π stacking among the Tyr molecules played a prominent role. Finally, the charge-transfer complex formation ability of electron-rich Tyr with electron-deficient 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) was studied. In the presence of DDQ due to the charge-transfer complex formation, the supramolecular gel converted into a reddish color solution, and their fibrillar nanoscale morphologies collapsed.

Background: Judicious utilisation of tertiary care facilities through appropriate risk stratification assumes priority, in a raging pandemic, of the nature of delta variant-predominated second wave of COVID-19 pandemic in India. Prioritisation of tertiary care, through a scientifically validated risk score, would maximise recovery without compromising individual safety, but importantly without straining the health system., Methods: De-identified data of COVID-19 confirmed patients admitted to a tertiary care hospital in South India, between April 1, 2021 and July 31, 2021, corresponding to the peak of COVID-19 second wave, were analysed after segregating into 'survivors' or 'non-survivors' to evaluate the risk factors for COVID-19 mortality at admission and formulate a risk score with easily obtainable but clinically relevant parameters for accurate patient triaging. The predictive ability was ascertained by the area under the receiver operator characteristics (AUROC) and the goodness of fit by the Hosmer-Lemeshow test and validated using the bootstrap method., Results: Of 617 COVID-19 patients (325 survivors, 292 non-survivors), treated as per prevailing national guidelines, with a slight male predilection (358/617 [58.0%]), fatalities in the age group above and below 50 years were (217/380 [57.1%]) and (75/237 [31.6%]), p<0.001. The relative distribution of the various parameters among survivors and non-survivors including self-reported comorbidities helped to derive the individual risk scores from parameters significant in the multivariable logistic regression. The 'OUR-ARCad' risk score components were-Oxygen saturation SaO2<94%-23, Urea > 40mg/dL-15, Neutrophil/Lymphocytic ratio >3-23, Age > 50 years-8, Pulse Rate >100-8 and Coronary Artery disease-15. A summated score above 50, mandated tertiary care management (sensitivity-90%, specificity-75%; AUC-0.89), validated in 2000 bootstrap dataset., Conclusions: The OUR-ARCad risk score, could potentially maximize recovery in a raging COVID-19 pandemic, through prioritisation of tertiary care services, neither straining the health system nor compromising patient's safety, delivering and diverting care to those who needed the most., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Gopalan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Microbially Induced Calcium Carbonate Precipitation (MICP) plays a significant role in coastal soil stabilization and erosion prevention. In the present study, the biomineralizing potential of a newly isolated Bacillus sp. N₉ was investigated through MICP. The isolated Bacillus sp. N₉ induced calcium carbonate (CaCO 3 ) precipitation in broth, agar, and real beach rock was evaluated by X-ray Fluorescence, Scanning Electron Microscopy, and X-ray Diffraction. The visual appearance of calcites as white crystals on the rock and the sealing of cracks in the beach sand cubes confirmed the CaCO 3 precipitation by the isolated strain. The pH changes, soluble calcium (Ca 2+ ) concentration levels and urease activity during the growth of the isolated Bacillus sp. N₉ were studied. High urease activity was observed, resulting in an increased production of carbonate (CO 3 2- ) ions, which in turn promoted a higher rate of CaCO₃ precipitation. Further, the assembly of the 3.27 Mb genome of the isolated Bacillus sp. N₉ was evaluated using Nanopore sequencing technology, and various extracellular proteins, including urease, were identified. The gene annotation through PROKKA and RAST predicted 6700 and 7317 protein-coding sequences. The pathway annotation analysis through gene ontology, KEGG, and COG inferred the presence of genes in proteolytic characteristics, carbohydrate metabolism, and amino acid derivatives. The present study provides valuable insights into the isolated native Bacillus sp. N₉, demonstrating its potential to produce high urease activity and calcite precipitation through combined genomics and in vitro techniques., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vinod Kumar Nathan reports financial support was provided by University Grants Commission, India. If there are other authors, they 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 © 2025. Published by Elsevier B.V.)

Liver tissues, composed of hepatocytes, cholangiocytes, stellate cells, Kupffer cells, and sinusoidal endothelial cells, are differentiated from endodermal and mesodermal germ layers. By mimicking the developmental process of the liver, various differentiation protocols have been published to generate human liver organoids (HLOs) in vitro using induced pluripotent stem cells (iPSCs). However, HLOs derived solely from the endodermal germ layer often encounter technical hurdles such as insufficient maturity and functionality, limiting their utility for disease modeling and hepatotoxicity assays. To overcome this, we separately differentiated EpCAM + endodermal progenitor cells (EPCs) and mesoderm-derived vascular progenitor cells (VPCs) from the same human iPSC line. These cells were then mixed in a BME-2 matrix and concurrently differentiated into vascular human liver organoids (vHLOs). Remarkably, vHLOs exhibited a significantly higher maturity than vasculature-free HLOs, as demonstrated by increased coagulation factor secretion, albumin secretion, drug-metabolizing enzyme expression, and bile acid transportation. To enhance assay throughput and miniaturize vHLO culture, we 3D bioprinted expandable HLOs (eHLOs) in a BME-2 matrix on a pillar plate platform derived from EPCs and VPCs and compared them with HLOs derived from endoderm alone. Compared to HLOs cultured in a 50 μL BME-2 matrix dome in a 24-well plate, vHLOs cultured on the pillar plate exhibited superior maturity, likely due to enhanced nutrient and signaling molecule diffusion. The integration of physiologically relevant patterned liver organoids with the unique pillar plate platform enhanced the capabilities for high-throughput screening and disease modeling.

Sperm motility is the prime functional attribute for semen quality and fertility of the bull. However, the bull's age directly affects the semen quality, and the bull's fertility and productive life decline with age. Even though research on age has been conducted in the past, it is still unclear how old a bull should be maintained at artificial insemination centers. The minimum standard protocol (MSP) states that a bull has an 8-years productive lifespan, yet it has been shown that some bulls older than 8 years have produced freezable ejaculates. It has yet to be established what the bull's ideal productive life is under the tropical climate of India without affecting in-vitro sperm functions. For the validation of the maximum age of a bull up to that it could be utilized in the artificial insemination centers, cut-off values of oxidative stress in freezable semen ejaculates were used. The current study was done at the Artificial Breeding Research Centre, ICAR-NDRI, Karnal, Haryana, India. A total of eighteen Sahiwal breeding bulls were divided into three groups: Young (2-4 years), Adult (> 4-8 years), and Older (> 8-11 years). Three ejaculates were taken from each bull; thus, a total of 18 ejaculates were utilized in each group for semen examination. Semen quality of Young bulls was poor compared with adult and older bulls. Seminal parameters such as dead, moribund, apoptotic, reacted acrosome, and protamine deficient sperms were higher in older bulls than in adult bulls; however, the values were non-significant. Less difference was found in the semen parameters among adult and older bulls. This indicates that the semen quality of older Sahiwal bulls was optimum, freezable, and can be utilized for up to 11 years (Average 9.5 years)., Competing Interests: Declarations. Animal ethics and Consent to participate declarations: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To isolate and quantify cell-free DNA, analysis for p53 mutations, and correlation with tumor burden in women with epithelial ovarian cancer compared with benign and borderline epithelial ovarian tumors., Methods: In this case-control study, plasma samples of eligible women collected 1 hour before surgery and based on final histopathology, women with epithelial ovarian cancer recruited as cases and borderline, and benign ovarian tumors as controls. Cell-free DNA extracted from plasma serum and quantified using Nanodrop Spectrophotometer. Amplification refractory mutation system-based polymerase chain reaction was used to detect point mutation in exon 8, codon 239 of p53 using primer pairs. p53 immunostaining was performed on tissue samples., Results: A total of 40 women (20 cases of epithelial ovarian cancer and 10 each of benign and borderline ovarian tumors [controls]) were included in a 2:1:1 ratio. The mean cell-free DNA amount was 1330 ± 1705.4 ng/mL in women with epithelial ovarian cancer compared with 748.5 ± 444.8 and 448.5 ± 203.9 ng/mL in benign and borderline ovarian tumors, respectively (p = .023). In those with high-grade serous ovarian cancer, it was 2640 ± 2450.6 ng/mL compared with 600 ± 316.7 and 652.5 ± 158.9 ng/mL in low-grade serous and mucinous ovarian cancer, respectively (p = .006). In stage I and II ovarian cancer, these were 502.5 ± 134.4 and 330 ± 296.9 ng/mL, respectively, compared with 1655 ± 1924.8 ng/mL in stage III disease (p = .004). A total of 11 (55%) women with epithelial ovarian cancer harbored mutation in exon 8, codon 239 of p53 compared with 2 (20%) each in benign and borderline ovarian tumors (p = 0.07). Fair agreement was noted between cell-free DNA p53 mutation and abnormal tissue p53 staining on immunohistochemistry (κ = 0.41)., Conclusion: Cell-free DNA amount was higher in women with epithelial ovarian cancer than women with benign and borderline ovarian tumors, with higher levels in advanced stage and high-grade serous carcinoma sub-type. Cell-free DNA p53 mutational analysis yielded fair concordance with tumor tissue p53 immunohistochemical results., Competing Interests: Declaration of Competing Interests None declared., (Copyright © 2024 European Society of Gynaecological Oncology and the International Gynecologic Cancer Society. Published by Elsevier Inc. All rights reserved.)

In this study, water extract from Indian rosewood tree leaves was used to synthesize copper oxide nanoparticles (CuO NPs), further loaded on graphene oxide sheets to synthesize a novel nanocomposite (CuO@GO@IR). The maximum tetracycline removal was achieved at optimum conditions of pH 3, adsorbent dose 0.03g/50 mL, and 240 min contact time. The maximum adsorption capacity of the adsorbent was 769.23 mg/g. Experimental data was better fitted with the Freundlich isotherm and followed pseudo-second-order. The adsorption process was thermodynamically spontaneous and feasible. Nanocomposite has shown excellent regeneration efficiency with 0.1 M HCl as a desorbing agent. The overall performance of the nanocomposite suggests that it can be used as a promising adsorbent for treating antibiotics containing wastewater., Competing Interests: Declarations. Ethical approval: No prior ethical approval was necessary for the study. Consent to participate: No human subjects included in the study. Consent not required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Clostridium difficile ( Clostridioides difficile ) is a leading cause of nosocomial infections in hospitalized patients worldwide. Stool samples were collected from 112 inpatients admitted to different hospitals and were screened for C. difficile GDH + toxin A + B by immunoassay, and all positive samples by immunoassay were processed for molecular detection of C. difficile using the GeneXpert assay. C. difficile strains were detected in 12 (10.71%) out of 112 stool samples using the GDH + toxin A + B immunoassay method and toxigenic C. difficile was confirmed in 5 stool samples using the GeneXpert molecular assay. C. difficile strains were also detected in 7 (8.97%) out of 78 stool samples from intensive care unit patients, 3 (25%) out of 12 stool samples from internal medicine ward patients, 1 (11.11%) out of 9 stool samples from surgery ward patients, and 1 (10%) out of 10 stool samples from isolation ward patients using the GDH + toxin A + B immunoassay method and the toxigenic C. difficile strain was confirmed in 1, 2, 1, and 1 stool samples, respectively, using the GeneXpert molecular assay. Toxigenic C. difficile was confirmed in patients at 4 (51.14%) out of 7 hospitals. In the present study, we also analyzed the clinical information of patients with C. difficile -positive stool samples who were receiving one or more antibiotics during hospitalization. The binary toxin gene ( cdt ), the tcdC gene, and the C. difficile strain polymerase chain reaction (PCR) ribotype 027 were not detected using the GeneXpert molecular assay among 12 C. difficile- positive samples by immunoassay. This study should aid in the prevention of unnecessary empiric therapy and increase the understanding of the toxigenic C. difficile burden on the healthcare system in the southwestern province of Saudi Arabia.

The continuous exposure of chemical pesticides in agriculture, their contamination in soil and water pose serious threat to the environment. Current study used an approach to evaluate various pesticides like Hexaconazole, Mancozeb, Pretilachlor, Organophosphate and λ-cyhalothrin degradation capability of esterase. The enzyme was isolated from Salinicoccus roseus. Genome analysis unveiled the carboxylesterase genes underlying the degradation of pesticides, and was located between 2070Mbp to 2080Mbp region. Herein, partially purified esterase was immobilized into beads by mixing with an equal volume (1:1) of sodium alginate solution [2.5% (w/v)].Scanning electron microscopy (SEM) of the beads showed the microspheres for enhanced enzyme-substrate reaction, wide peak at 3316, 1635 and 696 cm - 1 in Fourier-transform infrared spectroscopy (FTIR) represented intermolecular hydrogen bonding, and thermogravimetric analysis (TGA) reaffirmed the binding of esterase entrapped into the beads. Maximum degradation rate (after 4 days) for free enzyme accounted 83.2% in Hexaconazole. Degradation rate moderately increased 4% in the presence of immobilized esterase. Degradation products were detected by liquid chromatography-mass spectrometry (LC-MS). Cytotoxicity test (root length and mitotic index) revealed differences in various treatments. Enzyme kinetics parameters, Michaëlis-Menten constant (K M ) 6.61 mM and maximum velocity (V max ) 1.89 µmol/min/mg increased after immobilization. Further, molecular docking results validated that esterase contributed to pesticide degradation by catalytic triad of Ser 93 -His 222 -Phe 24 , ligand interactions, and specific binding pockets. Additionally, molecular dynamics (MD) simulations confirmed the protein-ligand conformational stability. Hence, present study highlighted an effective method for improving the catalytic properties of esterase, and also potential candidate for bioremediation of pesticides., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent to publish: All authors agreed to manuscript publication., (© 2024. The Author(s).)

This cross-sectional study aimed to investigate the role of peak inspiratory flow rate (PIFR) in the management of inhalation therapy for patients with chronic obstructive pulmonary disease (COPD). Conducted in the Department of Pulmonary Medicine at a tertiary care institute from July 2021 to January 2022, this study included a total of 351 patients who were clinically diagnosed with stable COPD and currently receiving inhaler therapy. Participants underwent comprehensive assessments that included demographic data collection, the use of the ABCD assessment tool to evaluate disease severity, the COPD Assessment Test (CAT) for quality of life measurement, and assessments for adherence to inhaler therapy and inhaler technique proficiency. The primary focus was on determining the prevalence of suboptimal PIFR and identifying associated demographic and clinical factors. The results indicated that 45% of the patients exhibited suboptimal PIFR, which is critical for effective medication delivery in COPD management. Analysis revealed several significant predictors of suboptimal PIFR: female gender, lower CAT scores, the type of inhaler device used, and a Modified Medical Research Council grade of ≥2, which indicates increased levels of breathlessness. These findings underscore the importance of assessing PIFR in COPD patients to ensure effective drug delivery. The study suggests that personalized inhaler device prescriptions tailored to individual PIFR can enhance treatment efficacy and improve overall management outcomes for COPD patients. By addressing factors contributing to suboptimal PIFR, healthcare providers can optimize inhalation therapy and ultimately improve patient quality of life.

Herein, we describe the design and synthesis of a series of C-5-substituted diazenyl derivatives of uracil, exhibiting selective and potent antileishmanial but not antibacterial or antifungal activity. The formation of the substituted derivatives was confirmed by using FTIR, 1 H, 13 C NMR, and HRMS analysis. Among all of the sets of tested compounds, only three [ 4a, 6b , and 8b ] showed the highest activity against Leishmania donovani (LD) promastigote and amastigote models of LD infections. Further, the cytotoxicity assays performed using three different cell lines, Vero cells, J774 cells, and THP1 cells, along with erythrocyte hemolysis assay showed the highest biocompatibility for the 4a , making it a lead compound for further biological assays. The LD cell death associated with 4a was not linked with ergosterol depletion, a common mechanism of action of antileishmanial drugs like amphotericin B (AmB). However, the LD cell death in the presence of 4a was reversed significantly through supplementation of uridine monophosphate (UMP), indicating the specific role of uridine biosynthesis pathway as the target of 4a . Furthermore, the in silico studies predicted orotidine monophosphate decarboxylase enzyme (OMPDCase) from LD as the plausible target for 4a . The proteomics analysis showed stronger downregulation of the aforementioned OMPDCase and also for a few other enzymes that are involved in the UMP biosynthesis pathway. This indicates that OMPDCase and other enzymes that regulate the UMP biosynthesis may be the target of 4a . Overall, the C-5-substituted diazenyl derivatives of uracil are presented here as novel and potent antileishmanial agents that can be used for treating visceral leishmaniasis (VL) wherein at present drug resistance and side effects of existing drugs demand a look for safer alternatives.

Acute myeloid leukemia (AML) is one of the leading leukemic malignancies in adults. The heterogeneity of the disease makes the diagnosis and treatment extremely difficult. With the advent of next-generation sequencing (NGS) technologies, exploration at the molecular level for the identification of biomarkers and drug targets has been the focus for the researchers to come up with novel therapies for better prognosis and survival outcomes of AML patients. However, the huge amount of data from NGS platforms requires a comprehensive AML platform to streamline literature mining efforts and save time. To facilitate this, we developed AMLdb, an interactive multi-omics platform that allows users to query, visualize, retrieve, and analyse AML related multi-omics data. AMLdb contains 86 datasets for gene expression profiles, 15 datasets for methylation profiles, CRISPR-Cas9 knockout screens of 26 AML cell lines, sensitivity of 26 AML cell lines to 288 drugs, mutations in 41 unique genes in 23 AML cell lines, and information on 41 experimentally validated biomarkers. In this study, we have reported five genes, i.e. CBFB, ENO1, IMPDH2, SEPHS2, and MYH9 identified via our analysis using AMLdb. ENO1 is uniquely identified gene which requires further investigation as a novel potential target while other reported genes have been previously confirmed as targets through experimental studies. Top of form we believe that these findings utilizing AMLdb can make it an invaluable resource to accelerate the development of effective therapies for AML and assisting the research community in advancing their understanding of AML pathogenesis. AMLdb is freely available at https://project.iith.ac.in/cgntlab/amldb., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: There has been an increase in the number of orphans around the world as a result of natural or man-made causes. Orphans are likely to face a number of challenges throughout their lives that go unrecognized. Considering these challenges, much focus needs to be given to manage their mental health issues., Purpose: The aim of the study is to examine the effectiveness of various psychosocial interventions in managing post-traumatic stress symptoms, emotional and behavioural problems, and depression among orphans., Method: Electronic searches on seven databases was done to identify studies investigating the effectiveness of interventions among orphans. The effectiveness of psychosocial interventions to reduce post-traumatic stress symptoms, emotional and behavioural problems, and depression was analyzed in seventeen studies. The risk of bias was assessed using the Cochrane risk of bias tool., Result: The overall intervention effect size of post-traumatic stress symptoms was found to be high with high heterogeneity, while low effect size for emotional and behavioural problems, and depression with substantial heterogeneity. Publication bias and exploratory moderating effects of study design and intervention type were also analyzed., Conclusion: Psychosocial interventions were more effective in reducing post-traumatic stress symptoms when compared to emotional and behavioural problems and depression., 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.

Despite significant advancement in the diagnostic and therapeutic aspects of breast carcinoma, the prognosis remains dismal. Recently, with advances in its understanding, various immune system-based management strategies have been developed. CTLA-4 suppresses lymphocyte reactivity, IL-2 secretion, and IL-2 receptor expression and triggers cell cycle arrest. PD-L1 inhibits the proliferation and cytotoxicity of T cells and inhibits release of cytokines. Hence, we planned to evaluate the immunoexpression of CTLA-4 and PD-L1 in invasive ductal carcinoma breast and seek correlation between their immunopositivity and the clinicopathological parameters. This was a retrospective study conducted on archival material of 50 cases of breast carcinoma tissue microarrays. Clinicopathological details were recorded. All cases were evaluated for immunohistochemical expression of CTLA-4 and PD-L1. Cytoplasmic expression of CTLA-4 and membranous expression of PD-L1 were considered positive and staining intensity was recorded as mild, moderate, and intense. Data was recorded and analyzed. Immunopositivity for CTLA-4 was seen in 92% of cases of breast carcinoma. CTLA-4 staining intensity showed significant association with TNM staging of breast carcinomas ( p  = 0.036). Age group of the breast carcinoma cases showed a statistically significant correlation with PD-L1 immunoexpression ( p  = 0.002). No significant correlation was found between all other clinicopathological characteristics and CTLA-4 or PD-L1 immunostaining. Our study shows that CTLA-4 is a more important immune checkpoint regulator in breast carcinomas in comparison to PD-L1. Thus, anti-CTLA-4 immunotherapy might prove to be of immense help in the treatment of invasive ductal carcinoma breast showing overexpression of CTLA-4., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12 min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment's impact on EDS was also evident on the other patients' and clinicians' perspectives scales. The AEs reported in ≥5 % patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings., Competing Interests: Declaration of competing interest Ramakrishna Nirogi, Anil Shinde, Vinod Kumar Goyal, Jyothsna Ravula, Vijay Benade, Satish Jetta, Veera Raghava Chowdary Palacharla, Dhanunjay Kumar Dogiparti, Ilayaraja Kalaikadhiban, Renny Abraham, Santosh Kumar Pandey, Ramkumar Subramanian, Abdul Rasheed Mohammed, Pradeep Jayarajan, and Venkat Jasti are full-time employees of Suven Life Sciences Ltd., India. Richard K. Bogan, MD, FCCP, FAASM disclosure includes: Shareholder WaterMark Medical, Healthy Humming, LLC; Board of Directors: WaterMark Medical; Consultant to Jazz Pharmaceuticals, Harmony Biosciences, Avadel Pharmaceuticals, Takeda, Oventus, Axsome; Industry funded research for Avadel, Axsome, Bresotec, Bayer, Idorsia, Suven, Jazz, Balance, NLS, Vanda, Merck, Eisai, Philips, Fresca, Takeda, Liva Nova, Roche, Sanofi, Sommetrics, Noctrix, Oura. Richard Bogan did not receive compensation for developing this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plants and their derived phytochemicals have a long history of treating a wide range of illnesses for several decades. They are believed to be the origin of a diverse array of medicinal compounds. One of the compounds found in kudzu root is puerarin, a isoflavone glycoside commonly used as an alternative medicine to treat various diseases. From a biological perspective, puerarin can be described as a white needle crystal with the chemical name of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one-8-D-glucopyranoside. Besides, puerarin is sparingly soluble in water and produces no color or light yellow solution. Multiple experimental and clinical studies have confirmed the significant therapeutic effects of puerarin. These effects span a wide range of pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, immunomodulation, anticancer properties, anti-diabetic properties, anti-osteoporosis properties, and more. Puerarin achieves these effects by interacting with various cellular and molecular pathways, such as MAPK, AMPK, NF-κB, mTOR, β-catenin, and PKB/Akt, as well as different receptors, enzymes, and growth factors. The current review highlights the molecular mechanism of puerarin as a neuroprotective agent in the treatment of various neurodegenerative and neurological diseases. Extensive cellular, animal, and clinical research has provided valuable insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, depression, and more., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The L-asparaginase (ASPN) enzyme has received recognition in various applications including acrylamide degradation in the food industry. The synthesis and application of thermostable ASPN enzymes is required for its use in the food sector, where thermostable enzymes can withstand high temperatures. To achieve this goal, the bacterium Bacillus subtilis was isolated from the hot springs of Tapovan for screening the production of thermostable ASPN enzyme. Thus, ASPN with a maximal specific enzymatic activity of 0.896 U/mg and a molecular weight of 66 kDa was produced from the isolated bacteria. The kinetic study of the enzyme yielded a Km value of 1.579 mM and a Vmax of 5.009 µM/min with thermostability up to 100 min at 75 °C. This may have had a positive indication for employing the enzyme to stop polyacrylamide from being produced. The current study has also been extended to investigate the interaction of native and mutated ASPN enzymes with acrylamide. This concluded that the M 10 (with 10 mutations) has the highest protein and thermal stability compared to the wild-type ASPN protein sequence. Therefore, in comparison to a normal ASPN and all other mutant ASPNs, M 10 is the most favorable mutation. This research has also demonstrated the usage of ASPN in food industrial applications., Competing Interests: Declarations. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Plastic polymers pose a significant challenge due to their resistance to degradation, resulting in their persistent accumulation in the environment and exacerbating a critical environmental concern. Urgent innovation and novel management technologies are essential to tackle this issue. Plastic biodegradation, distinguished by its environmentally friendly and safe attributes, has garnered substantial attention as a viable solution. Insects are pivotal in this process, utilizing their gut microbes to facilitate plastic degradation. The enzymatic action within the digestive tracts of diverse insect hosts and their microbial symbionts contributes to the breakdown of these polymers. This comprehensive review delves into the current landscape and strategies aimed at combating plastic pollution, with a specific focus on the involvement of insects such as mealworms (Tenebrio molitor Linnaeus), superworms (Zophobas atratus Blanchard), greater wax moths (Galleria mellonella Linnaeus), and various other insect species in the degradation of plastics. This review explores the different insects involved in plastic degradation, the mechanisms by which insects degrade plastics and delineates the characteristics of resultant degradable products. Furthermore, it investigates the future potential for plastic degradation by insects and examines the prospective developmental pathways for degradable plastics. Ultimately, this review provides an array of solutions by using various insects to pervasive the issue of plastic pollution., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential 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. If there are other authors, they 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.)

Maconellicoccus hirsutus is a highly polyphagous insect pest, posing a substantial threat to various crop sp., especially in the tropical and sub-tropical regions of the world. While extensive physiological and biological studies have been conducted on this pest, the lack of genetic information has hindered our understanding of the molecular mechanisms underlying its growth, development, and xenobiotic metabolism. The Cytochrome P450 gene, a member of the CYP gene superfamily ubiquitous in living organisms is associated with growth, development, and the metabolism of both endogenous and exogenous substances, contributing to the insect's adaptability in diverse environments. To elucidate the specific role of the CYP450 gene family in M. hirsutus which has remained largely unexplored, a de novo transcriptome assembly of the pink mealybug was constructed. A total of 120 proteins were annotated as CYP450 genes through homology search of the predicted protein sequences across different databases. Phylogenetic studies resulted in categorizing 120 CYP450 genes into four CYP clans. A total of 22 CYP450 families and 30 subfamilies were categorized, with CYP6 forming the dominant family. The study also revealed five genes (Halloween genes) associated with the insect hormone biosynthesis pathway. Further, the expression of ten selected CYP450 genes was studied using qRT-PCR across crawler, nymph, and adult stages, and identified genes that were expressed at specific stages of the insects. Thus, the findings of this study reveal the expression dynamics and possible function of the CYP450 gene family in the growth, development, and adaptive strategies of M. hirsutus which can be further functionally validated., 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 Inc. All rights reserved.)

The black gram is a traditional pulse crop and is a source of different nutritional components. Due to the scientific community's preference for yield and its components, the area of nutritional composition remains unexplored. Therefore, the evaluation of various quality traits such as proximate composition, cooking quality, texture profile, and association between them is keen important for the identification of the traits influencing the selection of the genotypes. This research aimed at the evaluation of the 25 black gram genotypes for their proximate composition, the effect of different cooking methods (conventional and microwave) on cooking quality parameters, and texture profile analysis. The genotypes were screened on 17 parameters, mean and replicated value of each variable were subjected to statistical analysis. The results for proximate composition showed the range from 11.2-11.7%, 24.24-28.22%, 1.25-1.85%, 3.10-4.45%, 5.35-6.60%, 60.23-64.86% and 368.35-372.75 Kcal/100 g for moisture, protein, fat, dietary fiber, ash, utilizable carbohydrate, and gross energy respectively. Cooking time ranged from 33 to 55.5 min (traditional) to 29.5-48.5 min (microwave), L: B ratio from 1.35 to 1.85, WUR from 1.85 to 2.60, and GSL from 0.25 to 11.30%. TPA's cohesiveness, gumminess, and chewiness ranged from 0.19 to 1.44 N, 0.14-1.30 N, 0.58-3.67 N, 1.14-10.81 N, and 0.58-5.29; 1.16-10.50 N in traditional and microwave cooking. Chewiness, gumminess, protein, ash, and cooking time were positively correlated. The first seven PCs have ≥ 1 eigenvalues, accounting for 23.30, 18.00, 13.50, 9.50, 7.40, 6.70%, and 6.40% of total variability. Mandi-2, Kinnour-1, Kirmour-1, Kangra-2, Bilaspur-1, Kangra-3, Kullu-1, Kullu-4, Chamba-3, and Chamba-7 to PCs 1-2 contributed the most to diversity, indicating good selection for subsequent upgrading initiatives., Competing Interests: Declarations Ethical Approval Not applicable. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The growing concerns regarding the depletion of fossil fuels, CO 2 emissions, and the effects of climate change prompt the usage of plug-in electric vehicles (PHEVs) all over the world in a big way. The increased electrical demand brought on by the charging of electric vehicles puts a burden on the distribution network parameters like energy loss, voltage profile and thermal limits. Recently, renewable energy-based distribution generation (RDGs) units are firmly integrated with the transmission and distribution system networks to lower the carbon footprint generated due to conventional thermal power plants. In addition, Battery Energy Storage Systems (BESS) are used to enhance grid operation and lessen the consequences of the high intermittency nature of RDGs power. In this work, two charging methods of PHEVs are considered: charging electric vehicles at home during night-time and charging electric vehicles at public fast charging stations (PFCS). The uncertain nature of arrival time and trip distance of PHEVs are addressed using probability density functions (PDFs). The 33-bus test system consists of commercial, industrial and residential buses is taken to implement the proposed methodology. In this work, 500 PHEVs are taken into consideration. The aforementioned charging methods produce a 24-h electric demand for PHEVs, which is then placed on the corresponding distribution system buses. The effect of PHEVs on technical distribution system metrics, including voltage profile and energy loss, is investigated. To improve the above metrics, optimal planning of inverter-based non-dispatchable PV units and dispatchable PV-BESS units in the distribution network by the inclusion of PHEVs electric load demand is addressed. The Pareto-based meta-heuristic multi-objective chaotic velocity-based butterfly optimization method (MOCVBOA) is chosen for optimization of desired objectives. The results of the MOCVBOA optimization algorithm are compared with those of the other optimization algorithms, NSGA-II & MOBOA, frequently described in the literature to assess its effectiveness., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background : Pyroptosis, an inflammatory cell death, is involved in the progression of atherosclerosis. Pyroptosis in endothelial cells (ECs) and its underlying mechanisms in atherosclerosis are poorly understood. Here, we investigated the role of a caspase-4/5-NF-κB pathway in pyroptosis in palmitic acid (PA)-stimulated ECs and EVs as players in pyroptosis. Methods : Human umbilical vein endothelial cells (HUVECs) were cultured in an endothelial cell medium, treated with Ox-LDL, PA, caspase-4/5 inhibitor, NF-κB inhibitor, and sEV release inhibitor for 24 h, respectively. The cytotoxicity of PA was determined using an MTT assay, cell migration using a scratch-wound-healing assay, cell morphology using bright field microscopy, and lipid deposition using oil red O staining. The mRNA and protein expression of GSDM-D, CASP4, CASP5, NF-κB, NLRP3, IL-1β, and IL-18 were determined with RT-PCR and Western blot. Immunofluorescence was used to determine NLRP3 and ICAM-1 expressions. Extracellular vesicles (EVs) were isolated using an exosome isolation kit and were characterized by Western blot and scanning electron microscopy. Results: PA stimulation significantly changed the morphology of the HUVECs characterized by cell swelling, plasma membrane rupture, and increased LDH release, which are features of pyroptosis. PA significantly increased lipid accumulation and reduced cell migration. PA also triggered inflammation and endothelial dysfunction, as evidenced by NLRP3 activation, upregulation of ICAM-1 (endothelial activation marker), and pyroptotic markers (NLRP3, GSDM-D, IL-1β, IL-18). Inhibition of caspase-4/5 (Ac-FLTD-CMK) and NF-κB (trifluoroacetate salt (TFA)) resulted in a significant reduction in LDH release and expression of caspase-4/5, NF-κB, and gasdermin D (GSDM-D) in PA-treated HUVECs. Furthermore, GW4869, an exosome release inhibitor, markedly reduced LDH release in PA-stimulated HUVECs. EVs derived from PA-treated HUVECs exacerbated pyroptosis, as indicated by significantly increased LDH release and augmented expression of GSDM-D, NF-κB. Conclusions: The present study revealed that inflammatory, non-canonical caspase-4/5-NF-κB signaling may be one of the crucial mechanistic pathways associated with pyroptosis in ECs, and pyroptotic EVs facilitated pyroptosis in normal ECs during atherosclerosis.

People living with HIV (PLHIV) are known to be at a higher risk of developing an array of aging-related diseases despite well-adhered combined antiretroviral therapy (cART). The present study aimed to investigate the impact of chronic HIV infection on neurocognitive function in virally suppressed PLHIV. We enrolled HIV-positive individuals randomly from an ART Center in Chennai, South India. A similar number of HIV-uninfected individuals matched for age and gender with the HIV-infected individuals served as controls. All individuals provided a detailed clinical history and underwent neuropsychological assessment using the International HIV Dementia Scale (IHDS). Plasma proteome analysis was performed using the Proximity extension assay (PEA) with the Olink® neuroexploratory panel, and untargeted metabolomics was performed using Ultra-High-Performance Liquid Chromatography/Mass Spectrometry/Mass Spectrometry. Despite a median duration of 9 years on first-line cART and suppressed viremia, a significant proportion of PLHIV registered significant levels of asymptomatic neurocognitive impairment, with 71% of these individuals scoring ≤ 10 in the IHDS test. We also observed significant alterations in a number of proteins and metabolites that are known to be associated with neuroinflammation, neurodegeneration, cognitive impairment, and gastrointestinal cancers, in the PLHIV group. Thus the study provides clinical as well as laboratory evidence to substantiate the presence of asymptomatic neurocognitive impairment in a large proportion of PLHIV, despite adequate cART and undetectable viremia, thereby supporting the view that HIV infection potentiates the risk for accelerated and accentuated neurological aging. This observation highlights the need to devise and implement appropriate intervention strategies for better long term management of HIV-infected persons., Competing Interests: Declarations. Ethics approval: The study was approved by the institutional ethics committees of ICMR-National Institute for Research in Tuberculosis and Government Hospital of Thoracic Medicine, Tambaram, Chennai. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Non-coding mutations in the TERT promoter (TERTp), typically at one of two bases -124 and -146 bp upstream of the start codon, are among the most prevalent driver mutations in human cancer. Several additional recurrent TERTp mutations have been reported but their functions and origins remain largely unexplained. Here, we show that atypical TERTp mutations arise secondary to canonical TERTp mutations in a two-step process. Canonical TERTp mutations create de novo binding sites for ETS family transcription factors that induce favourable conditions for DNA damage formation by UV light, thus creating a hotspot effect but only after a first mutational hit. In agreement, atypical TERTp mutations co-occur with canonical driver mutations in large cancer cohorts and arise subclonally specifically on the TERTp driver mutant chromosome homolog of melanoma cells treated with UV light in vitro. Our study gives an in-depth view of TERTp mutations in cancer and provides a mechanistic explanation for atypical TERTp mutations., Competing Interests: Competing interests A.S. is a co-inventor of the SiMSen-Seq technology that is patent protected (U.S. Serial No.:15/552,618). A.S. declares stock ownership in Tulebovaasta, Iscaff Pharma and SiMSen Diagnostics, and is a board member of Tulebovaasta. The other authors declare no competing interests., (© 2024. The Author(s).)

Cryopreservation in cryovials extends cell storage at low temperatures, and advances in organoid cryopreservation improve reproducibility and reduce generation time. However, cryopreserving human organoids presents challenges due to the limited diffusion of cryoprotective agents (CPAs) into the organoid core and the potential toxicity of these agents. To overcome these obstacles, we developed a cryopreservation technique using a pillar plate platform. To demonstrate cryopreservation application to human brain organoids (HBOs), early stage HBOs were produced by differentiating induced pluripotent stem cells (iPSCs) into neuroectoderm (NE) in an ultralow attachment (ULA) 384-well plate. The NE was transferred and encapsulated in Matrigel on the pillar plate. The NE on the pillar plate was exposed to four commercially available CPAs, including the PSC cryopreservation kit, CryoStor CS10, 3dGRO, and 10% DMSO, before being frozen overnight at -80 °C and subsequently stored in a liquid nitrogen dewar. We examined the impact of the CPA type, organoid size, and CPA exposure duration on cell viability post-thaw. Additionally, the differentiation of NE into HBOs on the pillar plate was assessed using RT-qPCR and immunofluorescence staining. The PSC cryopreservation kit proved to be the least toxic for preserving the early stage HBOs on the pillar plate. Notably, smaller HBOs showed higher cell viability postcryopreservation than larger ones. An incubation period of 80 min with the PSC kit was essential to ensure optimal CPA diffusion into HBOs with a diameter of 400-600 μm. These cryopreserved early stage HBOs successfully matured over 30 days, exhibiting gene expression patterns akin to noncryopreserved HBOs. The cryopreserved early stage HBOs on the pillar plate maintained high viability after thawing and successfully differentiated into mature HBOs. This on-chip cryopreservation method could extend to other small organoids, by integrating cryopreservation, thawing, culturing, staining, rinsing, and imaging processes within a single system, thereby preserving the 3D structure of the organoids.

Human liver organoids (HLOs) differentiated from embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells (ASCs) can recapitulate the structure and function of human fetal liver tissues, thus being considered as a promising tissue model for liver diseases and predictive compound screening. However, the adoption of HLOs in drug discovery faces several technical challenges, which include the lengthy differentiation process with multiple culture media leading to batch-to-batch variation, short-term maintenance of hepatic functions post-maturation, low assay throughput due to Matrigel dissociation and HLO transfer to a microtiter well plate, and insufficient maturity levels compared to primary hepatocytes. To address these issues, expandable HLOs (Exp-HLOs) derived from human iPSCs were generated by optimizing differentiation protocols, which were rapidly printed on a 144-pillar plate with sidewalls and slits (144PillarPlate) and dynamically cultured for up to 20 days into differentiated HLOs (Diff-HLOs) in a 144-perfusion plate with perfusion wells and reservoirs (144PerfusionPlate) for in situ organoid culture and analysis. The dynamically cultured Diff-HLOs exhibited greater maturity and reproducibility than those cultured statically, especially after a 10-day differentiation period. In addition, Diff-HLOs in the pillar/perfusion plate were tested with acetaminophen and troglitazone for 3 days to assess drug-induced liver injury (DILI) and then incubated in an expansion medium for 10 days to evaluate liver recovery from DILI. The assessment of liver regeneration post-injury is critical to understanding the mechanism of recovery and determining the threshold drug concentration beyond which there will be a sharp decrease in the liver's regenerative capacity. We envision that bioprinted Diff-HLOs in the pillar/perfusion plate could be used for high-throughput screening (HTS) of hepatotoxic compounds due to the short-term differentiation of passage-able Exp-HLOs, stable hepatic function post-maturation, high reproducibility, and high throughput with capability of in situ organoid culture, testing, staining, imaging, and analysis., Competing Interests: Conflict of interest M.Y.L. is the founder and C.E.O. of Bioprinting Laboratories Inc., the company manufacturing and commercializing the pillar/perfusion plate platform.

The microbiota-gut-brain axis involves complex bidirectional communication through neural, immune, and endocrine pathways. Microbial metabolites, such as short-chain fatty acids, influence gut motility and brain function by interacting with gut receptors and modulating hormone release. Additionally, microbial components such as lipopolysaccharides and cytokines can cross the gut epithelium and the blood-brain barrier, impacting immune responses and cognitive function. Ex vivo models, which preserve gut tissue and neural segments, offer insight into localized gut-brain communication by allowing for detailed study of nerve excitability in response to microbial signals, but they are limited in systemic complexity. Miniaturized in vitro models, including organ-on-chip platforms, enable precise control of the cellular environment and simulate complex microbiota-host interactions. These systems allow for the study of microbial metabolites, immune responses, and neuronal activity, providing valuable insights into gut-brain communication. Despite challenges such as replicating long-term biological processes and integrating immune and hormonal systems, advancements in bioengineered platforms are enhancing the physiological relevance of these models, offering new opportunities for understanding the mechanisms of the microbiota-gut-brain axis. This review aims to describe the ex vivo and miniaturized in vitro models which are used to mimic the in vivo conditions and facilitate more precise studies of gut brain communication., Competing Interests: Conflicts of interestThe author declare that he has no conflicts of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The study investigated production, characterisation, and biological properties of exopolysaccharide (EPS) from a thermophilic bacterium, Bacillus licheniformis using sucrose as a main carbon source at a temperature of 75 °C, resulting in a yield of 2.87 g/L. The surface topology of EPS was determined using FESEM indicating its porous nature. Subsequently, FTIR was employed to examine EPS and identified the presence of carboxyl and hydroxyl groups, which are believed to be associated with water-holding capacity (WHC). Comparing the FTIR spectrum of various exopolysaccharides, it was inferred that the exopolysaccharide derived from Ramkund closely resembles dextran. EDX and ICP-MS analysis revealed the presence of Sulphur and Selenium which might be involved in the anticancer properties of EPS. This is the first report on bacterial EPS from a hot spring (Ram kund) with antioxidant property, WHC, and high solubility. These properties offer beneficial resources for exploration in the pharmaceutical and agriculture industries.

This study focuses on developing novel antimicrobials to combat drug-resistant pathogens, addressing compounds failing clinical trials due to inadequate physicochemical properties. Sixteen imidazolidine-4-one derivatives were synthesized by extensive evaluation using molecular docking, absorption, distribution, metabolism, excretion (ADME) predictions, and antimicrobial testing. Molecular docking studies conducted with Schrödinger's Glide revealed that compounds S4 and G8 exhibited superior docking scores of -7.839 and -7.776, respectively. The G series outperformed the S series in scores. ADME analysis confirmed all compounds adhered to Lipinski's rule of five. In addition, IR and NMR provided details about the structure of the compounds. Antimicrobial activity was assessed against Escherichia coli, Staphylococcus aureus, and Candida albicans, with compounds G2 and S2 showing exceptional minimum inhibitory concentration (MIC) values of 6.25 μg/mL against E. coli. S2 also demonstrated impressive activity against S. aureus (MIC 3.12 μg/mL), and S4 exhibited potent activity against C. albicans (MIC 0.8 μg/mL) than fluconazole (1.6 μg/mL). Additionally, antihelmintic activity was evaluated, with G1, G3, G8, S2, S4, S7, and S8 showing effective paralysis and death time 20 min and below at 50 mg/mL concentration. These results underscore the potential of new imidazolidine-4-one derivatives as suitable sources to develop a drug candidate to treat resistant infections., (© 2024 John Wiley & Sons Ltd.)

An experiment was conducted to assess the response of chicks to in-ovo injection of Bacillus subtilis (probiotic), raffinose (prebiotic), and their combinations. The study used 1,500 embryonated eggs allotted to 10 groups/ 6 replicates (150 eggs/group). The experimental treatments were: 1) un-injected control (NC); 2) sham (sterile distilled water) (PC); 3) probiotic 4 × 10 5 CFU/egg (LBS); 4) probiotic 4 × 10 6 CFU/egg (HBS); 5) prebiotic 2 mg/egg (LR); (6 prebiotic 3 mg/egg (HR); 7) probiotic 4 × 10 5 CFU + prebiotic 2 mg/egg (LBS+LR); 8) probiotic 4 × 10 5 CFU + prebiotic 3 mg/egg (LBS+HR); 9) probiotic 4 × 10 6 CFU + prebiotic 2 mg/egg (HBS+LR); and 10) probiotic 4 × 10 6 CFU + prebiotic 3 mg/egg (HBS+HR). Results showed that in-ovo inclusion of Bacillus subtilis, prebiotic, and their combinations improved hatchability, yolk-free chick weight, and chick weight compared to the control group. Moreover, the in-ovo treatment reduced residual yolk weight on the day of hatch compared to the control group. Different levels of in-ovo B. subtilis alone or combined with raffinose significantly (P ≤ 0.001) reduced total bacterial count and total yeast and mold count compared to the negative control group. Total coliform and E. coli decreased significantly (P ≤ 0.001) in groups treated with probiotics, prebiotics, and synbiotics with different doses during incubation compared to those in the control. Clostridium spp. was not detected in the groups injected with B. subtilis alone or combined with raffinose. In-ovo probiotics and synbiotics (LBS+LR & LBS+HR) significantly (P ≤ 0.001) increased ileal villus length compared to other groups. In-ovo treatment increased mRNA expression of JAM-2 compared to the control group. The fold change significantly increased in group LBS+HR for genes MUC-2, OCLN, VEGF, SGLT-1, and EAAT-3 compared to the negative control. In conclusion, in-ovo injection of a low dose of B. subtilis plus a high or low dose of raffinose can positively affect hatching traits, cecal microbial populations, intestinal histomorphometry, nutrient transport- and intestinal function-related genes, and chick quality of newly hatched broiler chicks., Competing Interests: DISCLOSURES 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Microbially induced calcite precipitation (MICP) through urease enzyme has attained a lot of recognition in various fields of civil engineering and geotechnology for stabilizing the strength of soil and various concrete materials. The activity of urease has been found to be affected by various factors like temperature, substrate concentrations, pH of the medium, presence of inhibitors, etc. Through this study, the outcome of the interaction of pesticides (commonly found in Indian coastal regions) on Bacillus pasteurii urease, a major organism reported for MICP studies has been investigated in silico . The results from the study revealed that the enzyme has higher interactions of -4.1, -3.2, and -3.4 kJ/mol with common pesticides like dichloro diphenyl dichloro ethane(DDD), dichloro diphenyl trichloroe thane (DDT), and methyl parathion of organochlorides and organophosphates class. From the molecular dynamics simulation analysis, complex 1 (DDD -receptor) has been found to have the highest and more compact structure followed by methyl parathion -receptor. Prime MM-GBSA analysis also revealed the highest binding energy of -27.8 kcal/mol with the protein and DDD. Thus, it can be inferred from the current study that pesticides, particularly, DDD, DDT, and methyl parathion present in the coastal areas may have an impact on urease. This interaction can result in the inhibition of the urease activity of B. pasteurii, thus preventing the biomineralization process. This study would be the first report on the computational approach to understanding the interaction of prominent pesticides on the coastal region and B. pasteurii urease.Communicated by Ramaswamy H. Sarma.

Development of a rapid and sensitive detection method for hazardous dyes attracts considerable research interest. In this work, L-Tryptophan-based Carbon dots were developed as a fluorescence sensor for the detection of Malachite green (MG). Green fluorescent L-Trp-C-dots were synthesized by a simple pyrolysis technique using L-Trp as the starting precursor. L-Trp-C-dots exhibited different quenching responses to MG, and other interfering species, consequently offering a selective strategy to detect MG. The proposed sensor shows a limit of detection (LOD) of 0.06 μM and a limit of quantification (LOQ) of 0.22 μM with in the linearity range of 0 to 60 µM concentration. Additionally, the relative standard deviation (RSD) was found to be below 1.7 %. Furthermore, the recovery of MG from the real-time samples (green peas) was investigated., 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.)

Despite the potential toxicity of commercial chemicals to the development of the nervous system (known as developmental neurotoxicity or DNT), conventional in vitro cell models have primarily been employed for the assessment of acute neuronal toxicity. On the other hand, animal models used for the assessment of DNT are not physiologically relevant due to the heterogenic difference between humans and animals. In addition, animal models are low-throughput, time-consuming, expensive, and ethically questionable. Recently, human brain organoids have emerged as a promising alternative to assess the detrimental effects of chemicals on the developing brain. However, conventional organoid culture systems have several technical limitations including low throughput, lack of reproducibility, insufficient maturity of organoids, and the formation of the necrotic core due to limited diffusion of nutrients and oxygen. To address these issues and establish predictive DNT models, cerebral organoids were differentiated in a dynamic condition in a unique pillar/perfusion plate, which were exposed to test compounds to evaluate DNT potential. The pillar/perfusion plate facilitated uniform, dynamic culture of cerebral organoids with improved proliferation and maturity by rapid, bidirectional flow generated on a digital rocker. Day 9 cerebral organoids in the pillar/perfusion plate were exposed to ascorbic acid (DNT negative) and methylmercury (DNT positive) in a dynamic condition for 1 and 3 weeks, and changes in organoid morphology and neural gene expression were measured to determine DNT potential. As expected, ascorbic acid did not induce any changes in organoid morphology and neural gene expression. However, exposure of day 9 cerebral organoids to methylmercury resulted in significant changes in organoid morphology and neural gene expression. Interestingly, methylmercury did not induce adverse changes in cerebral organoids in a static condition, thus highlighting the importance of dynamic organoid culture in DNT assessment., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Sorghum hybrids demonstrated increased productivity and helped offset the decreasing cultivated areas, particularly in Asia. The diversity in cytoplasmic male sterility systems, stability of restorers and high yield of sorghum is an important factor for achieving food security and sustainability. In sorghum, hybrid production has been limited to A1 cytoplasmic source to date, primarily due to limited number of restorers on other cytoplasmic sources. This work aimed at filling this gap through diversifying and assessing the producibility and stability of cytoplasmic backgrounds across environments, evaluating the stability of restorers across cytoplasms and environments, and evaluating the performance of the hybrid F1 products under different water regimes across cropping seasons. The effects of genotypes and interactions between the genotypes and the tested environments were shown visually using GGE biplot, which also categorized the genotypes based on performance per se and stability. Analysis of variance revealed significant (P < 0.001) differences between genotypes, environments and their interaction components for all the plant characteristics studied. The various GGE biplot patterns revealed that the restorers G4 (IS 33844-5), G5 (M 35-1-19), G8 (ICSV 15014), and G10 (ICSR 13009) were stable across environments and cytoplasms. We observed the following order of superiority in cytoplasmic restoration and seed producibility, A 2 >A 1 >A 3 >A 4 . The A 2 cytoplasm can therefore reliably offer seed producibility advantage to commercial seed producers. Furthermore, the which-won-where model for hybrid grain yield revealed specific adaptations of hybrid genotypes G143, G195 and G215 to first mega environment (E1 and E3), whereas G167, G110, and G112 were adapted to the second mega-environment (E2 and E4). With a GGE biplot goodness of fit of 70 % the best possible yield- and stability-based ranking of hybrid genotypes was G143, G215, G189, G200, G69, G162, G119, G54, and G81. The newly uncovered hybrid products should therefore be considered for downstream testing stages and candidates for release and commercial cultivation. Clearly, this work resulted in novel findings particularly in terms of seed producibility, universal restorers across the 4 cytoplasms and environments, and superior and stable hybrid products, all of which are expected to add value to conventional and heterosis breeding in the process of sorghum cultivar development., Competing Interests: All the authors declare that they have no conflict that may have influenced the research presented in this paper., (© 2024 The Authors.)

Host-defense peptides (HDPs) and their analogs hold significant potential for combating multidrug-resistant (MDR) bacterial infections. However, their clinical use has been hindered by susceptibility to proteases, high production costs, and cytotoxicity towards mammalian cells. Synthetic polymers with diverse topologies and compositions, designed to mimic HDPs, show promise for treating bacterial infections. In this study, we explored the antibacterial activity and biocompatibility of synthetic amphiphilic linear (LPs) and cyclic terpolymers (CPs) containing hydrophobic groups 2-ethylhexyl (E) and 2-phenylethyl (P) at 20% and 30% content. LPs were synthesized via RAFT polymerization and then cyclized into CPs through a hetero-Diels-Alder click reaction. The bioactivity of these terpolymers was correlated with their topology (LPs vs. CPs) and hydrophobic composition. LPs demonstrated superior antibacterial efficacy compared to CPs against four Gram-negative bacterial strains, with terpolymers containing (P) outperforming those with (E). Increasing the hydrophobicity from 20% to 30% in the terpolymers increased toxicity to both bacterial and mammalian cells. Notably, our terpolymers inhibited the MDR Gram-negative bacterial strain PA37 more effectively than gentamicin and ciprofloxacin. Furthermore, our terpolymers were able to disrupt cell membranes and rapidly eliminate Gram-negative bacteria (99.99% within 15 minutes). Interestingly, CPs exhibited higher hemocompatibility and biocompatibility with mammalian macrophage cells compared to LPs, showcasing a better safety profile (CPs > LPs). These findings underscore the importance of tailoring polymer architectures and optimizing the hydrophilic/hydrophobic balance to address challenges related to toxicity and selectivity in developing antimicrobial polymers., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Non-identification of serious bacterial infection (SBI) in febrile infants is a common occurrence in clinical practice, culminating in catastrophic presentations. Six infants who initially presented to the clinician with fever without a focus, and were lately diagnosed with bacterial meningitis were analyzed for clinician-related factors contributing to the non-identification of meningitis. In a febrile neonate and a febrile young infant, lack of comprehensive evaluation was contributing to the non-identification of SBI; in four infants above the age of 3 months, meningitis was missed in spite of clinicians practicing treatment guidelines. Inadequate symptom characterization in two febrile infants and inappropriate interpretation of hemogram in three febrile infants also contributed to the non-identification of meningitis. Except for one, all infants developed complications. We conclude that the characterization of clinical features of SBI-like meningitis, interpretation of lab data, and adherence to the treatment guidelines are crucial in the management of an infant presenting as fever without a focus., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Hiatal hernia (HH) is commonly detected during endoscopic examinations and is associated with gastroesophageal reflux disease. In recent years, there have been significant advancements in diagnosing and treating HH. Surgical techniques for HH repair include open surgery, various laparoscopic procedures, transoral incisionless fundoplication, and magnetic sphincter augmentation (MSA). Laparoscopic Nissen fundoplication is often considered the standard for treating gastroesophageal reflux disease-related HH due to its effectiveness. Other procedures, such as Toupet and Dor fundoplications, may be suited for patients with specific conditions, such as impaired esophageal motility. Newer approaches, including the MSA system and mesh repair, focus on patient-specific treatments to achieve the best outcomes. This review synthesizes the literature from 2014 to 2024 to provide an overview of current trends in HH management., 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, Singhal et al.)

Polyhalite-based POLY4, a multi-nutrient source containing potassium, calcium, magnesium, and sulphur, is increasingly recognised for its potential to improve crop yields and soil health in agricultural systems. It is also been considered as a feasible approach for addressing the deficiency in potassium, calcium, and sulphur within a single application source. The present study aimed to investigate the impact of polyhalite-based POLY4 application, either as a complete or partial substitute for traditional potassium fertiliser and gypsum supplement, on the improvement of peanut ( Arachis hypogaea ) growth and soil quality. An extensive field study was conducted from 2021 and 2022, employing ten distinct nutrient management treatments with three replications in a randomised complete block design. The findings of the study indicated that the application of polyhalite (POLY4) in conjunction with only NP fertilisers resulted in a higher yield advantage (approximately 150-200 kg ha -1 ) than in plots treated with NPK + gypsum (at 500 kg ha -1 ) and control plots. The application of polyhalite-based fertiliser (POLY4) at a rate that was 100% equivalent to K along with NP fertilisers resulted in a significant increase in pod yield (5.3-12.8%) over NPK + gypsum and control plots. Thus, the increased crop yield led to an increase in gross returns of 4.88% and in net returns of 4.28% with the application of POLY4 (100%) + NP fertilisers over other treatments. Likewise, variable rates of conventional fertilisers along with POLY4 (100% recommended) + NP + gypsum at 310 kg/ha significantly increased the linoleic acid content (38.5%), oleic acid content, and oil content (48.1%) by reducing palmitic acid (11.96%) content in the groundnut seed. Interestingly, POLY4 use at the 50% recommended rate also resulted in yields that were comparable with those obtained with 100% NPK. Therefore, applying POLY4, a polyhalite fertiliser, in either a 100% or 50% equivalent of essential K can be an effective way of increasing the production of peanut crops and promoting agricultural sustainability., Competing Interests: Authors NA and VM were employed by the company AngloAmerican Crop Nutrients Pvt. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gopinath, Rajanna, Visha Kumari, Singh, Ajay, Awasthi, Mishra, Sukumaran, Venkatesh and Rajkumar.)

Microbially induced calcium carbonate precipitation (MICP) is a soil remediation method that has emerged as a viable and long-term solution for enhancing soil mechanical qualities. The technique of MICP that has been extensively researched is urea hydrolysis, which occurs naturally in the environment by urease-producing bacteria as part of their fundamental metabolic processes. The objectives of the current study include screening and identifying native ureolytic bacteria from soil in Uttarakhand, optimizing growth factors for increased urease activity, and calcite precipitation by the bacteria using response surface methodology. Additionally, it was assessed how well the isolated bacteria in the medium biomineralized when using synthetic media and cheaper alternatives such as cow urine and eggshell as sources of urea and Ca 2+ , respectively. The isolated strain identified as Lysinibacillus sp. was found to be the very active strain after soil samples were screened for ureolytic bacteria. It was discovered that optimization studies with values of pH 8, urea concentration (0.8 M), inoculum concentration (3%), and incubation time (48 h) yielded a higher activity of 33.7 U/mL (threefold increase), and a higher calcium carbonate precipitation (enzyme activity: 10.96 U/mL, pH: 8.92, soluble Ca 2 ⁺: 25.53 mM and insoluble Ca 2 ⁺: 0.856 g). The calcite precipitation in broth media supplemented with ready-made substrates and alternative sources demonstrated a similar result of increased pH and ammonia release. Thus, the current study successfully paves the way for several possibilities to stabilize the slopy soils prone to landslides and erosion in Uttarakhand and pinpoint an economic approach through biomineralization., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polymorphism plays a pivotal role in generating a range of crystalline materials with diverse photophysical and mechanical attributes, all originating from the same molecule. Here, we showcase two distinct polymorphs: green (GY) emissive and orange (OR) emissive crystals of 5'-(4-(diphenylamino)phenyl)-[2,2'-bithiophene]-5-carbaldehyde (TPA-CHO). These polymorphs display differing optical characteristics, with GY exhibiting thermally activated delayed fluorescence (TADF) and OR showing room temperature phosphorescence (RTP). Additionally, both polymorphic crystals display mechanical flexibility and optical waveguiding capabilities. Leveraging the AFM-tip-based mechanophotonics technique, we position the GY optical waveguide at varying lengths perpendicular to the OR waveguide. This approach facilitates the exploration of the interplay between TADF and RTP phenomena by judiciously controlling the optical path length of crystal waveguides. Essentially, our approach provides a clear pathway for understanding and controlling the photophysical processes in organic molecular crystals, paving the way for advancements in polymorphic crystal-based photonic circuit technologies., (© 2024 Wiley-VCH GmbH.)

Black soldier fly larvae (BSFL) are considered important organisms, utilized as tools to transform waste including manure into valuable products. The growth and cultivation of BSFL are influenced by various factors, such as the presence of toxic substances in the feed and parasites. These factors play a crucial role in hormesis, and contributing to regulate these contaminants hermetic doses to get sustainable byproducts. This review aims to understand the effects on BSFL growth and activities in the presence of compounds like organic and inorganic pollutants. It also assesses the impact of microbes on BSFL growth and explores the bioaccumulation of pharmaceutical compounds, specifically focusing on heavy metals, pesticides, pharmaceuticals, indigenous bacteria, insects, and nematodes. The review concludes by addressing knowledge gaps, proposing future biorefineries, and offering recommendations for further research., 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.)

Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Female urethral stricture (FUS) accounts for about 4%-13% of cases of female bladder outlet obstruction. FUS was and is still managed by repeated dilatations and/or direct visual internal urethrotomy. There are many alternative options for reconstruction like buccal or vaginal mucosal graft urethroplasty. Our aim was to describe the technique of dorsal onlay buccal mucosal graft (BMG) urethroplasty for FUS and present the outcomes., Methods: Between January 2014 and December 2021, 37 patients who underwent dorsal onlay BMG urethroplasty were included in the study. Their pre-operative diagnosis was confirmed with uroflowmetry, micturating cystourethrogram, urethral calibration, and on table cystoscopy. Bladder catheter was removed after 2 weeks. Patients were followed up at 3 months, 6 months, 1 year, and then annually with urine analysis, uroflowmetry, and post-void residual assessment. We defined success as a maximum flow rate (Q max ) above 15 mL/s without the need for an additional instrumentation., Results: The mean age of patients was 47.8 (standard deviation [SD] 11.3) years. Twenty patients had previously undergone urethral dilatations. The mean pre-operative Q max was 7.79 (SD 3.73) mL/s. However, the mean Q max improved to 23.20 (SD 8.25) mL/s after surgery. The mean post-void residual urine after surgery was 30.50 (SD 10.70) mL. This reduced from a mean value of 139.00 (SD 147.24) mL before surgery. The mean follow-up was 30.2 (SD 18.3, range 18-44) months. There was no post-operative incontinence. There were Clavien-Dindo Grade 1 complications in 6 out of 37 (16.2 %) patients during hospital stay. The only long-term complication was recurrence of stricture in 4 (10.8%) patients., Conclusion: Dorsal onlay BMG urethroplasty in females is a safe, effective technique which can avoid repeated painful dilatations and multiple urethrotomies. One should always consider reconstruction in FUS without any fear of incontinence., Competing Interests: The authors declare no conflict of interest., (© 2024 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Millettia pinnata is an important medicinal plant that has been used as a treatment of various diseases due to presence of wide range of pharmacological properties. The plant contains quercetin, kaempferol, karanjin, pongaglabrone, kanjone, kanugin, gammatin, pongaglabol, and other bioflavonoids. Kaempferol is a natural flavonol that shows many pharmacological properties including anti-inflammatory, antioxidant, anticancer, and antidiabetic activities etc. The enzyme flavonol synthase (FLS, EC 1.14.20.6) catalyses the conversion of dihydroflavonols to flavonols, i.e. biosynthesis of kaempferol from dihydrokaempferol. The current work examined the binding affinity-based approach to improve the enzyme catalytic activity using computational methods. Sequential site-directed mutagenesis was used to create four mutants with the goal to increase hydrogen bonds and further improving the ligand (dihydrokaempferol) binding efficiency. Simulations were done to monitor the stability of the mutants followed by molecular docking to confirm interactions with ligand. For structure validation, various dynamic analysis like RMSD, RMSF, ROG, SASA, H-bond, PCA, DCCM, and FEL were performed, which predicts the stability of wild-type (WT) proteins and mutants. The Mutant&#95;2 and Mutant&#95;3 showed maximum H-bonding and better stability than other mutants and WT that proved higher affinity suggesting improved catalysis. Mutant&#95;2 and Mutant&#95;3 exhibited binding affinities of -7.6 and -8.2 kcal/mol, respectively for the ligand. The outcome of present study will provide significant improvement in synthesis of kaempferol and other plant-based flavonoids.Communicated by Ramaswamy H. Sarma.

Background: Long-intergenic non-protein coding gene 01140 (LINC01140) a long non-coding RNA is highly expressed in various cancers. However, its biological functions in gastric cancer progression is still unknown., Method: To elucidate LINC01140 function, 70 GC tumor samples and 30 normal gastric tissues were collected. LINC01140 expression level were determined by qRT-PCR analysis and correlated with different clinico-pathological parameters. Then we tried to see the impact of LINC01140 on gastric cell line aggressiveness by knocking down the target gene and performing cell viability assay, migration assay and invasive capacity of the cell lines along with immunoblotting to check several protein levels., Result: LINC01140 RNA is found to be positively correlated with FGF9 and significantly up regulated in GC tissues. LINC01140 knockdown inhibited the viability, migratory capacity and invasive capacity of AGS cells. LINC01140 targets miR-140-5p, while miR-140-5p targeted FGF9 to form lncRNA-miRNA-mRNA axis. The affect of miR-140-5p inhibition on gastric cancer cell aggressiveness were opposite to those of LINC01140 or FGF9 knockdown. Additionally, inhibition partially reversed the effects of LINC01140 knockdown on FGF9 protein levels, gastric cancer cell phenotypes., Conclusion: LINC01140, miR-140-5p and FGF9 form a lncRNA-miRNA-mRNA axis that modulates the gastric cancer phenotypes and in turn affects gastric cancer cell aggressiveness., Competing Interests: Conflict of interest The authors state that there are no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Microbial interactions within diverse ecosystems are intricately governed by the dynamic interplay of exopolysaccharides (EPSs) produced by microorganisms. This review delves into the multifaceted roles of EPS in microbial signalling, quorum sensing (QS), and community dynamics, highlighting their significance in orchestrating cooperative behaviours and shaping community structures. EPSs serve as pivotal signalling molecules, influencing chemical communication and promoting intricate interactions among microorganisms. The integration of EPS into QS mechanisms adds an additional layer of complexity, allowing microorganisms to assess population density and synchronise communal responses. Furthermore, EPSs actively contribute to community dynamics by influencing spatial organisation, adhesion, and resistance to environmental stressors. By providing comprehensive knowledge of EPS dynamics, this review offers valuable insights into microbial ecology, serving as a foundational resource for future research. It will benefit the research community by advancing our understanding of microbial ecosystems, with broad applications in biotechnology, environmental science, and beyond.

Multilevel thresholding image segmentation will subdivide an image into several meaningful regions or objects, which makes the image more informative and easier to analyze. Optimal multilevel thresholding approaches are extensively used for segmentation because they are easy to implement and offer low computational cost. Multilevel thresholding image segmentation is frequently performed using popular methods such as Otsu's between-class variance and Kapur's entropy. Numerous researchers have used evolutionary algorithms to identify the best multilevel thresholds based on the above approaches using histogram. This paper uses the Energy Curve (EC) based thresholding method instead of the histogram. Chaotic Bidirectional Smell Agent Optimization with Adaptive Control Strategy (ChBSAOACS), a powerful evolutionary algorithm, is developed and employed in this paper to create and execute an effective method for multilevel thresholding segmentation of breast thermogram images based on energy curves. The proposed algorithm was tested for viability on standard breast thermogram images. All experimental data are examined quantitatively and qualitatively to verify the suggested method's efficacy., (© 2024. The Author(s).)

Ion phase-space holes are solitary kinetic structures found in the ion phase-space of collision-less plasmas, and are nonlinear solutions to the Vlasov-Poisson equations, identified as Bernstein-Greene-Kruskal (BGK) modes. In this study, interactions between an ion phase-space hole and a travelling ion KdV soliton is presented. This interaction, which is simulated in a fully ionised highly magnetised plasma within a cylindrical wave-guide, exhibits acceleration and deacceleration of the ion hole, depending on its mode of collision with the travelling ion soliton. We present these interactions and discuss the mechanism of this interaction between the two solitary waves., (© 2024. The Author(s).)