Search

The study area belongs to the Singhbhum metamorphic belt of Jharkhand, situated in the eastern part of India. The spatial distribution of the index minerals in the pelitic schists of the area shows Barrovian type of metamorphism. Three isograds, viz. garnet, staurolite and sillimanite, have been delineated and the textural study of the schists has revealed a time relation between crystallization and deformation. Series of folds with shifting values of plunges in the supracrustal rocks having axial-planar schistosity to the folds have been widely cited. Development of these folds could be attributed to the second phase of deformation. In total, two phases of deformation, D1 and D2, in association with two phases of metamorphism, M1 and M2, have been lined up in the study area. Chemographic plots of reactant and product assemblages corresponding to various metamorphic reactions suggest that the pattern of metamorphic zones mapped in space is in coherence with the temporal-sequential change during prograde metamorphism. The prograde P–T evolution of the study area has been obtained using conventional geothermobarometry, internally consistent winTWQ program and Perple_X software in the MnNCKFMASHTO model system. Our observations suggest that the progressive metamorphism in the area is not related to granitic intrusion or migmatization but that it was possibly the ascending plume that resulted in the M1 phase of metamorphism followed by D1 deformation. The second and prime metamorphic phase, M2, with its possible heat source generated by crustal overloading, was preceded by D1 and it lasted until late- to post-D2 deformation. [ABSTRACT FROM AUTHOR]

Nitrogen-containing heterocyclic cores are of immense importance due to their high abundance in naturally occurring or synthetic molecules having wide applications in different fields of basic and applied sciences. The functionalities introduced in an N-heterocyclic core play an important role in regulating the physiochemical behavior of the particular N-heterocycles to alter their chemical and biological reactivity. Suitably functionalized N-heterocycles demonstrate their widespread applications in pharmaceuticals, agronomy, materials sciences, synthetic chemistry, pigments, etc . During the last decade, electrochemistry has emerged as a sustainable alternative to conventional synthetic approaches by minimizing reagent uses and chemical waste. Synthetic chemists have extensively utilized the tool to functionalize N-heterocycles. This is evidenced by the appearance of more than a hundred methods on the topic over recent years, signifying the importance of the synthetic area. This review is focused on the accumulation of synthetic methods based on the electrochemical functionalization of N-heterocycles developed over the recent decade. Literature reports on the C-/N-H-functionalization and functional modifications of N-heterocycles that are accessible through the available search engines are included in the review. Relevant mechanistic details in support of the reported reactions are discussed to present a clear picture of the reaction pathways. The review aims to provide a clear picture of the possible pathways of electron transfer, the electrochemical behavior of different N-heterocyclic cores, functionalization reagents, and the chemical processes that occur during the electrochemical functionalization/modification of N-heterocycles.

Air pollution in households is a prime contributor to health issues in developing countries, as in the case of India. According to the latest National Family Health Survey Report 2022, more than half of India's rural population and 41 per cent overall still depend on solid or unclean fuel combustions, which may reflect in future health hazards. Thus, it is crucial to understand the issue empirically. To that end, the study traces the transitional pattern of unclean cooking fuel users towards clean fuel over the last 30 years using responses from all five National Family Health Survey rounds. Further, the study uses an adjusted probit model to analyse the determinants that lead to the choice of cooking fuel in a household and a logistic model to examine the association between the choice made and the respiratory health of children under five. The empirical results show that the number of households using unclean fuel has declined over the years, with a slightly higher decline in the last five years. Moreover, it also shows that poverty status and place of residence significantly influence cooking fuel choice. Additionally, children residing in households that use clean fuels are less likely to suffer respiratory infections. In conclusion, the present study provides strong evidence to ameliorate the existing policies in a way that exhorts clean energy use. The authors propose pro-poor, pro-rural policies to expedite the clean energy transition, benefitting the most vulnerable households.

Drug discovery is a complex and multifaceted process aimed at identifying new therapeutic compounds with the potential to treat various diseases. Traditional methods of drug discovery are often time-consuming, expensive, and characterized by low success rates. Because of this, there is an urgent need to improve the drug development process using new technologies. The integration of the current state-of-art of artificial intelligence (AI) and machine learning (ML) approaches with conventional methods will enhance the efficiency and effectiveness of pharmaceutical research. This review highlights the transformative impact of AI and ML in drug discovery, discussing current applications, challenges, and future directions in harnessing these technologies to accelerate the development of innovative therapeutics. We have discussed the latest developments in AI and ML technologies to streamline several stages of drug discovery, from target identification and validation to lead optimization and preclinical studies., 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.)

Dent disease type 1 is caused by changes in the chloride voltage-gated channel 5 (CLCN5) gene on chromosome X, resulting in the lack or dysfunction of chloride channel ClC-5. Individuals affected by Dent disease type 1 show proteinuria and hypercalciuria. Previously we found that lentiviral vector-mediated hCLCN5 cDNA supplementary therapy in ClC-5 null mice was effective only for three months following gene delivery, and the therapeutic effects disappeared four months after treatment, most likely due to immune responses to the ClC-5 proteins expressed in the treated cells. Here we tried two strategies to reduce possible immune responses: 1) confining the expression of ClC-5 expression to the tubular cells with tubule-specific Npt2a and Sglt2 promoters, and 2) performing gene therapy in newborn mutant mice whose immune system has not fully developed. We found that although Npt2a and Sglt2 promoters successfully drove ClC-5 expression in the kidneys of the mutant mice, the treatment did not ameliorate the phenotypes. However, gene delivery to the kidneys of newborn Clcn5 mutant mice enabled long-term transgene expression and phenotype improvement. Our data suggest that performing gene therapy on Dent disease affected subjects soon after birth could be a promising strategy to attenuate immune responses in Dent disease type 1 gene therapy., Competing Interests: Competing interests The authors declare no competing interests. Ethical approval The animal work was approved by the IACUC committee of Wake Forest Medical School (Animal protocol numbers A19-053 and A22-043)., (© 2024. The Author(s).)

Wound healing is an intricate multifactorial process that may alter the extent of scarring left by the wound. A substantial portion of the global population is impacted by non-healing wounds, imposing significant financial burdens on the healthcare system. The conventional dosage forms fail to improve the condition, especially in the presence of other morbidities. Thus, there is a pressing requirement for a type of wound dressing that can safeguard the wound site and facilitate skin regeneration, ultimately expediting the healing process. In this context, Chondroitin sulfate (CS), a sulfated glycosaminoglycan material, is capable of hydrating tissues and further promoting the healing. Thus, this comprehensive review article delves into the recent advancement of CS-based hydrogel/scaffolds for wound healing management. The article initially summarizes the various physicochemical characteristics and sources of CS, followed by a brief understanding of the importance of hydrogel and CS in tissue regeneration processes. This is the first instance of such a comprehensive summarization of CS-based hydrogel/scaffolds in wound healing, focusing more on the mechanistic wound healing process, furnishing the recent innovations and toxicity profile. This contemporary review provides a profound acquaintance of strategies for contemporary challenges and future direction in CS-based hydrogel/scaffolds for wound healing., 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.)

Aromatase inhibitors play a critical therapeutic role in treating ER+ breast cancer, especially in postmenopausal women. However, their efficacy is often limited by resistance and severe side effects. Identifying new compounds that can disrupt aromatase enzyme function is essential. In this study, structural anomalies in the aromatase enzyme were corrected through energy minimization, and the structure was validated via Ramachandran plot. We screened 170,269 natural compounds from the ASINEX Biodesign library using high-throughput screening algorithms to target the aromatase enzyme. Molecular docking identified three compounds: BDD30170158, BDE33872639, and BDE30177677, all showing stable binding interactions with the aromatase enzyme. Molecular dynamics simulations over 100 ns confirmed the conformational stability of these compounds. Although all three compounds exhibited the desired pharmacokinetic and drug metabolism properties, only one compound (BDE33872639) was identified as a non-blocker, demonstrating a reduced risk of adverse cardiac effects. This compound exhibits significant potential as a novel aromatase inhibitor, warranting further experimental research to develop it as a therapeutic option for ER+ breast cancer., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This study aimed to assess the nephrotoxicity associated with VRP-034 (novel formulation of polymyxin B [PMB]) compared to marketed PMB in a three-dimensional (3D) kidney-on-a-chip model. To model the human kidney proximal tubule for analysis, tubular structures were established using 23 triple-channel chips seeded with RPTEC/hTERT1 cells. These cells were exposed to VRP-034 or PMB at seven concentrations (1-200 µM) over 12, 24, and 48 h. A suite of novel kidney injury biomarkers, cell health, and inflammatory markers were quantitatively assessed in the effluent. Additionally, caspase and cytochrome C levels were measured, and cell viability was evaluated using calcein AM and ethidium homodimer-1 (EthD-1). Exposure to marketed PMB resulted in significantly elevated levels ( P < 0.05) of four key biomarkers (KIM-1, cystatin C, clusterin, and OPN) compared to VRP-034, particularly at clinically relevant concentrations of ≥10 µM. At 25 µM, all biomarkers demonstrated a significant increase ( P < 0.05) with marketed PMB exposure compared to VRP-034. Inflammatory markers (interleukin-6 and interleukin-8) increased significantly ( P < 0.05) with marketed PMB at concentrations of ≥5 µM, relative to VRP-034. VRP-034 displayed superior cell health outcomes, exhibiting lower lactate dehydrogenase release, while ATP levels remained comparable. Morphological analysis revealed that marketed PMB induced more severe damage, disrupting tubular integrity. Both treatments activated cytochrome C, caspase-3, caspase-8, caspase-9, and caspase-12 in a concentration-dependent manner; however, caspase activation was significantly reduced ( P < 0.05) with VRP-034. This study demonstrates that VRP-034 significantly reduces nephrotoxicity compared to marketed PMB within a 3D microphysiological system, suggesting its potential to enable the use of full therapeutic doses of PMB with an improved safety profile, addressing the need for less nephrotoxic polymyxin antibiotics., Competing Interests: The authors of this study are employees of Venus Medicine Research Centre, which is the developer of the drug being investigated. This study was funded by Venus Medicine Research Centre. The authors declare no additional competing interests.

Health-seeking behavior represents the actions taken to prevent the disease and promote health. It emphasizes both the illness response and the healthcare utilization driven by perceived threat and effectiveness of the preventive behavior. This study aims to scrutinize the progression of research conducted on health-seeking behavior in high-risk period such as COVID-19 using bibliometric analysis. The bibliometric analysis is performed on Scopus and Web of Science databases. Research articles in the English language were extracted using keywords, such as health-seeking behavior and COVID. Eight hundred twenty-five research articles at the final and early publication stage in the English language were extracted from Scopus and 623 from WoS using the keywords Health Seeking Behavior and COVID. Of these, 259 in Scopus and 109 in WoS were selected for the final study following the authors' eligibility criteria. It analyses the research directions, countries of publications, core journals, leading authors and institutions and important publications followed by research trends in this field. It summarizes the academic interest of the researchers in health-seeking behavior in low- and middle-income countries. The paper informs and directs researchers and policymakers on the state of research in health-seeking behavior during high-health risk periods.

Platelets are essential component of circulation that plays a major role in hemostasis and thrombosis. During activation and its demise, platelets release platelet-derived microvesicles, with lysophosphatidylcholine (LPC) being a prominent component in their lipid composition. LPC, an oxidized low-density lipoprotein, is involved in cellular metabolism, but its higher level is implicated in pathologies like atherosclerosis, diabetes, and inflammatory disorders. Despite this, its impact on platelet function remains relatively unexplored. To address this, we studied LPC's effects on washed human platelets. A multimode plate reader was employed to measure reactive oxygen species and intracellular calcium using H 2 DCF-DA and Fluo-4-AM, respectively. Flow cytometry was utilized to measure phosphatidylserine expression, mitochondrial membrane potential (ΔΨm), and mitochondrial permeability transition pore (mPTP) formation using FITC-Annexin V, JC-1, and CoCl 2 /calcein-AM, respectively. Additionally, platelet morphology and its ultrastructure were observed via phase contrast and electron microscopy. Sonoclot and light transmission aggregometry were employed to examine fibrin formation and platelet aggregation, respectively. The findings demonstrate that LPC induced oxidative stress and increased intracellular calcium in platelets, resulting in increased phosphatidylserine expression and reduced ΔΨm. LPC triggered caspase-independent platelet death and mPTP opening via cytosolic and mitochondrial calcium, along with microvesiculation and reduced platelet counts. LPC increased the platelet's size, adopting a balloon-shaped morphology, causing membrane fragmentation and releasing its cellular contents, while inducing a pro-coagulant phenotype with increased fibrin formation and reduced integrin αIIbβ3 activation. Conclusively, this study reveals LPC-induced oxidative stress and calcium-mediated platelet death, necrotic in nature with pro-coagulant properties, potentially impacting inflammation and repair mechanisms during vascular injury., (© 2024 International Federation for Cell Biology.)

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder, predominantly affecting the posterior semicircular canal (PSC), and significantly impacts the quality of life (QoL) of patients. This study assesses the effectiveness of Epley's manoeuvre in improving QoL in patients with PSC-BPPV. This prospective analytical study, conducted at a tertiary care centre from January 2021 to December 2022, included 93 adult patients diagnosed with PSC-BPPV via the Dix-Hallpike test. Participants were evaluated using the dizziness handicap inventory (DHI) and visual vertigo analogue score (VAS) at baseline and on days 3, 10, and 30 post-treatments with Epley's manoeuvre. Data analysis focused on changes in DHI and VAS scores to assess the impact of treatment. The cohort comprised 58.1% males and 41.9% females, with a significant majority over 50 years of age. Notably, 90% of patients reported improvement by the first follow-up. Both DHI and VAS scores showed a statistically significant decrease over the follow-up period ( p  < 0.05), indicating a reduction in perceived dizziness and visual vertigo symptoms post-treatment. Epley's manoeuvre effectively improves the QoL in patients with PSC-BPPV, as evidenced by significant reductions in DHI and VAS scores. This study contributes to the evidence supporting Epley's manoeuvre as a key intervention in PSC-BPPV treatment, emphasizing its role in enhancing patient outcomes in clinical practice., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© Association of Otolaryngologists of India 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.)

Introduction: This study evaluates the effectiveness of combining the Epley Maneuver with the Dizzy-Fix Training Device in treating Benign Paroxysmal Positional Vertigo (BPPV), aiming to enhance treatment outcomes and patient satisfaction., Methods: In this randomized controlled trial, 50 patients diagnosed with posterior canal BPPV were allocated into two groups: one receiving the traditional Epley Maneuver and the other undergoing the Epley Maneuver supplemented with the Dizzy-Fix Training Device. Key measures included the proportion of symptom-free patients at one month, changes in the Visual Analogue Scale (VAS) and Dizziness Handicap Inventory (DHI) scores, the recurrence rate within one month, and patient satisfaction., Results: The Dizzy-Fix group achieved a significantly higher symptom resolution rate by day 7 (90% vs. 60%) and reported greater patient satisfaction (4.5/5 vs. 3.8/5) compared to the Epley Maneuver alone group. Additionally, this group exhibited a more substantial decrease in DHI scores (from an average of 30 to 5) and a lower recurrence rate (10% vs. 40%) within the first month post-treatment., Conclusion: Incorporating the Dizzy-Fix Training Device with the Epley Maneuver significantly improves the management of BPPV, evidenced by faster symptom resolution, enhanced patient satisfaction, and reduced symptom recurrence. These findings underscore the value of integrating real-time visual feedback technologies in vestibular rehabilitation, promising better patient outcomes, and advancing the quality of care in BPPV treatment., Competing Interests: Conflict of InterestWe hereby declare that there are no conflicts of interest that could have influenced the outcome of this research. The study was conducted objectively, without any bias stemming from financial or personal relationships., (© Association of Otolaryngologists of India 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.)

In the world's flower trade, gladiolus (Gladiolus spp.) is ranked first among bulbous flowers and eighth among cut flowers, with more than 30,000 different cultivars being grown. Mass multiplication and commercialization are restricted by the traditional propagation methods. However, the large-scale proliferation and improvement of the gladiolus have been accomplished with the aid of plant tissue culture and other biotechnological techniques. The current review includes a thorough examination of the growth and development parameters required for successful in vitro gladiolus development as well as cormel formation. Moreover, focus is being given to various techniques and methods such as in vitro cytogenetic stability and modification of chromosome number, in vitro mutagenesis and selection of pest resistance, in vitro identification and selection to develop virus-free germplasm, cryopreservation, synthetic seed technology, identifying virus diseases by RT-PCR, somaclonal variation, and protoplast and somatic hybridization. Molecular markers and their applications for genetic diversity analysis, relationships between different genotypes, and clonal stability analysis in Gladiolus species have been conducted by several research groups worldwide and are also being discussed. The article also covers efforts to enhance the functionality of plant phenotypes through genetic transformation. Future prospects for further improvement of ornamental gladiolus are also explored. Overall, the current review provides insight into the applications of basic and advanced biotechnological tools for gladiolus improvement., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In order to prevent the growth of pathogens in food, bacteriocins produced by various probiotic lactic acid bacteria have been recognized as potential substitutes of chemical preservatives. In this study, enterocin LD3 was purified from the cell-free supernatant of a food isolate, Enterococcus hirae LD3 using multistep chromatography. In the fruit juice, lethal concentration (LC 50 ) of enterocin LD3 was found to be 260 µg/mL against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The cells treated with enterocin LD3 were red colour indicating dead cells after propidium iodide staining, while untreated cells were found blue after staining with 4', 6-diamidino-2-phenylindole. The mechanism of cell killing was analyzed using infrared spectrum of cells treated with enterocin LD3 which was found altered in the range of 1,094.30 and 1,451.82 cm -1 corresponding to nucleic acids and phospholipids, respectively. The morphology of target cells were severely ruptured and lysed as observed under electron microscopy. Thus, the present study suggested that enterocin LD3 showed bactericidal activity against Salm. enterica subsp. enterica serovar Typhimurium ATCC 13311 and may be applied as a bio-preservative for the safety of fruit juices., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The most prevalent form of dementia, Alzheimer's disease (AD) is a chronic illness that is on the rise among the geriatric population. Even though research into its biochemical, genetic, and cytogenetic pathways has advanced, its aetiology is still unclear and complex. In this study, we recruited sixty-eight participants diagnosed with AD where the cytogenetic, biochemical parameters and genetic mutations were analysed. Our results revealed chromosomal aberrations such as aneuploidies in the peripheral blood of Alzheimer's disease patients. Biochemical parameters revealed no statistical significance in the study though a pattern could be observed in the serum levels. Further few novel mutations at the c.21 C > T, c.56G > A were observed in the MCU gene of mitochondrial calcium uniporter. All these findings reveal the need for a larger cohort study to gain a better and more detailed understanding of the aetiology of Alzheimer's disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mental illness is a hidden epidemic in modern science that has gradually spread worldwide. According to estimates from the World Health Organization (WHO), approximately 10% of the world's population suffers from various mental diseases each year. Worldwide, financial and health burdens on society are increasing annually. Therefore, understanding the different factors that can influence mental illness is required to formulate novel and effective treatments and interventions to combat mental illness. Gut microbiota, consisting of diverse microbial communities residing in the gastrointestinal tract, exert profound effects on the central nervous system through the gut-brain axis. The gut-brain axis serves as a conduit for bidirectional communication between the two systems, enabling the gut microbiota to affect emotional and cognitive functions. Dysbiosis, or an imbalance in the gut microbiota, is associated with an increased susceptibility to mental health disorders and psychiatric illnesses. Gut microbiota is one of the most diverse and abundant groups of microbes that have been found to interact with the central nervous system and play important physiological functions in the human gut, thus greatly affecting the development of mental illnesses. The interaction between gut microbiota and mental health-related illnesses is a multifaceted and promising field of study. This review explores the mechanisms by which gut microbiota influences mental health, encompassing the modulation of neurotransmitter production, neuroinflammation, and integrity of the gut barrier. In addition, it emphasizes a thorough understanding of how the gut microbiome affects various psychiatric conditions., Competing Interests: Declaration of Competing Interest None to declare, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Proinflammatory T-lymphocytes recruited into the brain and spinal cord mediate multiple sclerosis (MS) and currently there is no cure for MS. IFN-γ-producing Th1 cells induce ascending paralysis in the spinal cord while IL-17-producing Th17 cells mediate cerebellar ataxia. STAT1 and STAT3 are required for Th1 and Th17 development, respectively, and the simultaneous targeting of STAT1 and STAT3 pathways is therefore a potential therapeutic strategy for suppressing disease in the spinal cord and brain. However, the pharmacological targeting of STAT1 and STAT3 presents significant challenges because of their intracellular localization. We have developed a STAT-specific single-domain nanobody (SBT-100) derived from camelids that targets conserved residues in Src homolog 2 (SH2) domains of STAT1 and STAT3. This study investigated whether SBT-100 could suppress experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We show that SBT-100 ameliorates encephalomyelitis through suppressing the expansion of Th17 and Th1 cells in the brain and spinal cord. Adoptive transfer experiments revealed that lymphocytes from SBT-100-treated EAE mice have reduced capacity to induce EAE, indicating that the immunosuppressive effects derived from the direct suppression of encephalitogenic T-cells. The small size of SBT-100 makes this STAT-specific nanobody a promising immunotherapy for CNS autoimmune diseases, including multiple sclerosis.

Alzheimer's disease (AD) is a progressive decline in cognitive ability and behavior which eventually disrupts daily activities. AD has no cure and the progression rate varies unlikely. Among various causative factors, heavy metals are reported to be a significant hazard in AD pathogenesis. Metal-induced neurodegeneration has been focused globally with thorough research to unravel the mechanistic insights in AD. Recently, heavy metals suggested to play an important role in epigenetic alterations which might provide evidential results on AD pathology. Epigenetic modifications are known to play towards novel therapeutic approaches in treating AD. Though many studies focus on epigenetics and heavy metal implications in AD, there is a lack of research on heavy metal influence on epigenetic toxicity in neurological disorders. The current review aims to elucidate the plausible role of cadmium (Cd), iron (Fe), arsenic (As), copper (Cu), and lithium (Li) metals on epigenetic factors and the increase in amyloid beta and tau phosphorylation in AD. Also, the review discusses the common methods of heavy metal detection to implicate in AD pathogenesis. Hence, from this review, we can extend the need for future research on identifying the mechanistic behavior of heavy metals on epigenetic toxicity and to develop diagnostic and therapeutic markers in AD., (© 2024 Wiley Periodicals LLC.)

Bacterial endophytes are a crucial component of the phytomicrobiome, playing an essential role in agriculture and industries. Endophytes are a rich source of bioactive compounds, serving as natural antibiotics that can be effective in combating antibiotic resistance in pathogens. These bacteria interact with host plants through various processes such as quorum sensing, chemotaxis, antibiosis, and enzymatic activity. The current paper focuses on how plants benefit extensively from endophytic bacteria and their symbiotic relationship in which the microbes enhance plant growth, nitrogen fixation, increase nutrient uptake, improve defense mechanisms, and act as antimicrobial agents against pathogens. Moreover, it highlights some of the bioactive compounds produced by endophytes., Competing Interests: Authors declare no competing interest., (© 2024 The Author(s).)

Transcription factor MAFB regulates various homeostatic functions of macrophages. This study explores the role of MAFB in brown adipose tissue (BAT) thermogenesis using macrophage-specific Mafb-deficient (Mafb f/f ::LysM-Cre) mice. We find that Mafb deficiency in macrophages reduces thermogenesis, energy expenditure, and sympathetic neuron (SN) density in BAT under cold conditions. This phenotype features a proinflammatory environment that is characterized by macrophage/granulocyte accumulation, increases in interleukin-6 (IL-6) production, and IL-6 trans-signaling, which lead to decreases in nerve growth factor (NGF) expression and reduction in SN density in BAT. We confirm MAFB regulation of IL-6 expression using luciferase readout driven by IL-6 promoter in RAW-264.7 macrophage cell lines. Immunohistochemistry shows clustered organization of NGF-producing cells in BAT, which are primarily TRPV1 + vascular smooth muscle cells, as additionally shown using single-cell RNA sequencing and RT-qPCR of the stromal vascular fraction. Treating Mafb f/f ::LysM-Cre mice with anti-IL-6 receptor antibody rescues SN density, body temperature, and energy expenditure., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Heavy metals (HMs) enter waterbodies through various means, which, when exceeding a threshold limit, cause toxic effects both on the environment and in humans upon entering their systems. Recent times have seen an increase in such HM influx incident rates. This requires an instant response in this regard to review the challenges in the available classical methods for HM detection and removal. As well as provide an opportunity to explore the applications of artificial intelligence (AI) and machine learning (ML) for the identification and further redemption of water and wastewater from the HMs. This review of research focuses on such applications in conjunction with the available in-silico models producing worldwide data for HM levels. Furthermore, the effect of HMs on various disease progressions has been provided, along with a brief account of prediction models analysing the health impact of HM intoxication. Also discussing the ethical and other challenges associated with the use of AI and ML in this field is the futuristic approach intended to follow, opening a wide scope of possibilities for improvement in wastewater treatment methodologies., 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. Published by Elsevier Ltd.)

Background: Severe post-acne scarring has been implicated as a cause of considerable psychological distress, mainly among adolescents. Subcision and microneedling are cutting-edge treatment options available nowadays., Aim: In this study, we aimed to compare the efficacy of microneedling with platelet-rich plasma (PRP) against subcision with PRP in treating atrophic post-acne scars in a split-face study design., Materials and Methods: Fifty patients with atrophic post-acne facial scars were included in this prospective interventional study. Group A included the left side of the face managed by microneedling with PRP and group B included the right side of the face that was subjected to subcision with PRP. Results were assessed based on Goodman and Baron qualitative and quantitative grading., Results: In our study, at the end of the treatment, on the left side, 5 (10%) had 1 grade of improvement showing good response, 35 (70%) had 2 grades of improvement showing very good response, and 10 (20%) had 3 grades of improvement showing excellent response. On the right side, 1 (2%) patient had no improvement in acne grade showing poor response, 9 (18%) had 1 grade of improvement showing good response, 25 (50%) had 2 grades of improvement showing very good response, whereas 15 (30%) had 3 grades of improvement showing excellent response., Conclusion: Till date, apart from ours no other study has compared the two modalities head-to-head with adjuvant PRP in both groups. Although both modalities showed statistically significant results individually, there was no significant difference in qualitative improvement of acne scars between the two groups., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cutaneous and Aesthetic Surgery.)

Plantaricin LD1 was purified from a potential probiotic strain, Lactobacillus plantarum LD1 previously isolated from indigenous food, Dosa. In this study, we have performed a detailed mechanism of action of plantaricin LD1 against Escherichia coli ATCC 25922 considering Micrococcus luteus MTCC 106 as control. The plantaricin LD1 showed a minimum inhibitory concentration (MIC) of 34.57 µg/mL and a minimum bactericidal concentration (MBC) of 138.3 µg/mL against M. luteus MTCC 106, whereas MIC 69.15 µg/mL and MBC 276.6 µg/mL were found against E. coli ATCC 25922. The efflux of potassium ions, dissipation of membrane potential (∆ψ), and transmembrane pH gradient (∆pH) of plantaricin LD1-treated cells suggested the membrane-acting nature of plantaricin LD1. Plantaricin LD1 also caused degradation of the genomic DNA of the target strains tested. The cell killing was confirmed by staining with propidium iodide and visualized under light and electron microscopes. The bacteriocin-treated cells were found to be ruptured, swollen, and elongated. Thus, the findings indicate plantaricin LD1 kills E. coli ATCC 25922 by interacting with the cell membrane resulting in the efflux of intracellular contents and also causing degradation of nucleic acids leading to cell death., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin receptor or GPR109A, is a prototypical GPCR that plays a central role in the inhibition of lipolytic and atherogenic activities. Its activation also results in vasodilation that is linked to the side-effect of flushing associated with dyslipidemia drugs such as niacin. GPR109A continues to be a target for developing potential therapeutics in dyslipidemia with minimized flushing response. Here, we present cryo-EM structures of the GPR109A in complex with dyslipidemia drugs, niacin or acipimox, non-flushing agonists, MK6892 or GSK256073, and recently approved psoriasis drug, monomethyl fumarate (MMF). These structures elucidate the binding mechanism of agonists, molecular basis of receptor activation, and insights into biased signaling elicited by some of the agonists. The structural framework also allows us to engineer receptor mutants that exhibit G-protein signaling bias, and therefore, our study may help in structure-guided drug discovery efforts targeting this receptor., (© 2024. The Author(s).)

Parkinson's Disease (PD) is becoming a growing global concern by being the second most prevalent disease next to Alzheimer's Disease (AD). Henceforth new exploration is needed in search of new aspects towards the disease mechanism and origin. Evidence from recent studies has clearly stated the role of Gut Microbiota (GM) in the maintenance of the brain and as a root cause of various diseases and disorders including other neurological conditions. In the case of PD, with an unknown etiology, the GM is said to have a larger impact on the disease pathophysiology. Although GM and its metabolites are crucial for maintaining the normal physiology of the host, it is an undeniable fact that there is an influence of GM in the pathophysiology of PD. As such the Enteroendocrine Cells (EECs) in the epithelium of the intestine are one of the significant regulators of the gut-brain axis and act as a communication mediator between the gut and the brain. The communication is established via the molecules of neuroendocrine which are said to have a crucial part in neurological diseases such as AD, PD, and other psychiatry-related disorders. This review is focused on understanding the proper role of GM and EECs in PD. Here, we also focus on some of the metabolites and compounds that can interact with the PD genes causing various dysfunctions in the cell and facilitating the disease conditions using bioinformatical tools. Various mechanisms concerning EECs and PD, their identification, the latest studies, and available current therapies have also been discussed., 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.)

β-arrestins (βarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), and their interaction is driven primarily by agonist-induced receptor activation and phosphorylation. Here, we present seven cryo-electron microscopy structures of βarrs either in the basal state, activated by the muscarinic receptor subtype 2 (M2R) through its third intracellular loop, or activated by the βarr-biased decoy D6 receptor (D6R). Combined with biochemical, cellular, and biophysical experiments, these structural snapshots allow the visualization of atypical engagement of βarrs with 7TMRs and also reveal a structural transition in the carboxyl terminus of βarr2 from a β strand to an α helix upon activation by D6R. Our study provides previously unanticipated molecular insights into the structural and functional diversity encoded in 7TMR-βarr complexes with direct implications for exploring novel therapeutic avenues.

Discovering a therapeutic that can counteract the aggressiveness of this disease's mechanism is crucial for improving survival rates for cancer patients and for better understanding the most different types of cancer. In recent years, using these viruses as an anticancer therapy has been thought to be successful. They mostly work by directly destroying cancer cells, activating the immune system to fight cancer, and expressing exogenous effector genes. For the treatment of tumors, oncolytic viruses (OVs), which can be modified to reproduce only in tumor tissues and lyse them while preserving the healthy non-neoplastic host cells and reinstating antitumor immunity which present a novel immunotherapeutic strategy. OVs can exist naturally or be created in a lab by altering existing viruses. These changes heralded the beginning of a new era of less harmful virus-based cancer therapy. We discuss three different types of oncolytic viruses that have already received regulatory approval to treat cancer as well as clinical research using oncolytic adenoviruses. The primary therapeutic applications, mechanism of action of oncolytic virus updates, future views of this therapy will be covered in this chapter., (Copyright © 2024. Published by Elsevier Inc.)

Background: Epidermal growth factor receptor (EGFR/HER-1) and its role in tumor development and progression through the mechanism of tumor angiogenesis is prevalent in non-small lung cancer, head and neck cancer, cholangiocarcinoma & glioblastoma. Previous treatments targeting the oncogenic activity of EGFR's kinase domain have been hindered by acquired mutational resistance and side effects from existing drugs like erlotinib, highlighting the need for new EGFR inhibitors through structure- based drug designing., Objective: The research aims to develop novel quinazoline derivatives through structure-based virtual screening, molecular docking, and molecular dynamics simulation to potentially interact with EGFR's kinase domain and impede tumor angiogenic phenomenon., Methods: Quinazoline derivatives were retrieved and filtered from the PubChem database using structure- based virtual screening and the Lipinski rule of five drug-likeness studies. Molecular docking-based virtual screening methods and molecular dynamics simulation were then carried out to identify top leads., Results: A total of 1000 quinazoline derivatives were retrieved, with 671 compounds possessing druglike properties after applying Lipinski filters. Further filtration using ADME and toxicity filters yielded 28 compounds with good pharmacokinetic profiles. Docking-based virtual screening identified seven compounds with better binding scores than the control drug, dacomitinib. After cross-checking binding scores, three top compounds QU524, QU571, and QU297 were selected for molecular dynamics simulation study of 100 ns interval using Desmond module of Schrodinger maestro to understand their conformational stability., Conclusion: The research results showed that the selected quinazoline leads exhibited better binding affinity and conformational stability than the control drug, erlotinib. These compounds also had good pharmacokinetic and pharmacodynamic profiles and did not violate Lipinski's rule of five limits. The findings suggest that these leads have the potential to target EGFR's kinase domain and inhibit the EGFR-associated phenomenon of tumor angiogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Xanthelasma palpebrarum (XP) is a benign cosmetic condition. Although the role of CO 2 laser is well described, there are only a few studies on Erbium: YAG in XP. Similarly, trichloroacetic acid (TCA) is commonly used in XP. However, there are only a few studies comparing these modalities in the treatment of XP., Aim: To evaluate the effectiveness and safety of Erbium: YAG laser and 50% TCA in the treatment of XP with the role of dermoscope in the evaluation of lesions., Materials and Methods: A total of 20 subjects were randomly allocated into two groups: group A (TCA) and group B (laser). All patients were subcategorized into three grades viz. I (mild), II (moderate), and III (severe) using a self-devised scoring system., Results: About 25% and 70% of patients achieved complete clearance in groups A and B, respectively ( P = 0.017). The rate of recurrence was 40% and 15% in groups A and B. Dyspigmentation and erythema were the most common side effects. Pretreatment dermoscopic evaluation of the lesion showed a network of brown streaks on a background of a yellowish structureless area and was used to assess the area and margins of the lesion where the adipose tissue was found during the procedure and serial assessment of the lesion., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Cutaneous and Aesthetic Surgery.)

Climate change and increasing population pressure have put the agriculture sector in an arduous situation. With increasing demand for agricultural production overuse of inputs have accentuated the negative impact on environment. Hence, sustainable agriculture is gaining prominence in recent times with an emphasis on judicious and optimum use of resources. The field of nanotechnology can immensely help in achieving sustainability in agriculture at various levels. Use of nutrients and plant protection chemicals in nano-form can increase their efficacy even at reduced doses thus decreasing their pernicious impact. Seed priming is one of the important agronomic practices with widely reported positive impacts on germination, seedling growth and pathogen resistance. In the current study, the effect and efficacy of selenium nanoparticles synthesized using phyto-extracts as a seed priming agent is studied. This nanopriming enhanced the germination, hastened the seedling emergence and growth with an increase in seedling vigour and nutrient status. This eco-friendly and economical method of synthesizing nanoparticles of various nutrient minerals can optimize the resource use thus helping in sustainable agriculture by reducing environment damage without compromising on efficacy., (© 2023. The Author(s).)

Background: Curcuminoids are the phenolic compounds found exclusively in turmeric. Their presence is known to increase immunity and resistance against certain cancers and neurological disorders in humans also, protecting the plant itself against salinity stress., Methods: In this experiment, we studied the expression levels of MAPK1 and DCS genes, their curcuminoid biosynthesis under salinity stress conditions so that the impact of individual genes can be understood using semi- quantitative PCR., Results: The expressions of the genes with respect to curcuminoid biosynthesis showed fluctuations in their band intensity values due to the production of curcuminoids, which is initiated first in the leaves followed by the rhizomes. Not all the genes responsible for the curcuminoid biosynthesis show positive regulation under salt stress conditions which is observed in response to the severity of the stress imposed on the cultivars., Conclusions: In our findings, both the genes MAPK1 and DCS were down-regulated for curcuminoid biosynthesis compared to their controls in both the cultivars Vallabh Sharad and Selection 1., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Respiratory tract infections remain the leading cause of morbidity and mortality worldwide. The burden is further increased by polymicrobial infection or viral and bacterial co-infection, often exacerbating the existing condition. Way back in 1918, high morbidity due to secondary pneumonia caused by bacterial infection was known, and a similar phenomenon was observed during the recent COVID-19 pandemic in which secondary bacterial infection worsens the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) condition. It has been observed that viruses paved the way for subsequent bacterial infection; similarly, bacteria have also been found to aid in viral infection. Viruses elevate bacterial infection by impairing the host's immune response, disrupting epithelial barrier integrity, expression of surface receptors and adhesion proteins, direct binding of virus to bacteria, altering nutritional immunity, and effecting the bacterial biofilm. Similarly, the bacteria enhance viral infection by altering the host's immune response, up-regulation of adhesion proteins, and activation of viral proteins. During co-infection, respiratory bacterial and viral pathogens were found to adapt and co-exist in the airways of their survival and to benefit from each other, i.e., there is a cooperative existence between the two. This review comprehensively reviews the mechanisms involved in the synergistic/cooperativity relationship between viruses and bacteria and their interaction in clinically relevant respiratory infections., Competing Interests: The 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 © 2023 Lalbiaktluangi, Yadav, Singh, Singh, Iyer, Vellingiri, Zomuansangi, Zothanpuia and Ram.)