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Manganese (Mn) is an essential element for plant growth but can be toxic at high levels. Pecan (Carya illinoensis), an important nut-producing species, has been observed to exhibit tolerance to high Mn levels. In this study, pecan seedlings were exposed to a nutrient solution containing either 2 μM (control) or 1000 μM (excess) MnSO 4 to investigate the physiological mechanisms. Despite substantial increases in Mn concentration in all pecan tissues, the presence of excess Mn did not induce visible symptoms of Mn toxicity on pecan leaves, nor did it result in any changes in malondialdehyde (MDA) levels. Photosynthetic rate and chlorophyll fluorescence parameters also remained unchanged. Subsequent examination revealed more cell layers and greater cell numbers in leaf palisade mesophyll tissue of Mn-treated plants compared with the control group. Cell length, and cell area decreased significantly in response to excess Mn, but total chloroplast area was unchanged and chloroplast structure remained intact. Subcellular fractionation analysis demonstrated that the cell walls, and to a lesser extent the soluble fraction, contained the majority of the Mn in leaves. The presence of excess Mn caused a marked increase in leaf concentrations of malic acid and citric acid, potential chelators of Mn. Our results suggest that the majority of Mn was sequestered in the leaf cell walls and may have been present as less-toxic chelated organic acids, thereby safeguarding the primary Mn target, the chloroplast, and ultimately conferring robust Mn tolerance in pecan., 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 Masson SAS. All rights reserved.)

Selective inhibition of histone deacetylase 8 (HDAC8) has emerged as a promising approach for treating various diseases, including cancer. However, finding key structural features for HDAC8 inhibition and developing effective and selective HDAC8 inhibitors (HDAC8 i s) pose significant challenges. In the past few years, the development of various scaffolds for inhibiting HDAC8 has significantly risen and the quest continues. In such cases, N -heterocyclic derivatives (such as thiazine, indole/pyrrole, pyrazole, triazole, indole, etc.) can play a crucial role in the discovery of novel selective HDAC8 inhibitors. In this current work, Bayesian and SARpy QSAR models were established on a structurally diverse set of 188 selective HDAC8 inhibitors after an extensive literature search. QSAR modelling suggests N -heterocyclic rings as important structural fingerprints for selective as well as promising HDAC8 inhibition. Further, molecular docking and molecular dynamics (MD) simulation studies were carried out on selected compounds ( 4 , 15 , 36 , 40 , and 188 ) containing N -heterocyclic rings to emphasize the significance of these scaffolds in HDAC8 potency. In addition to this, toxicity studies were carried out using density functional theory (DFT) to determine the toxicity profile of investigated compounds which indicated that the compounds are non-toxic. The outcomes of this research will aid in the exploration of certain key directions for the selective HDAC8 inhibitor design that could speed up the search for anticancer drugs.

To improve bioavailability, enhance the solubility and stability of the hydrophobic drug curcumin, nanoparticles such as carbon quantum dots (CQDs) are unique choices. In this study, we present a simple, cost-effective, and eco-friendly method for synthesizing nitrogen-doped carbon quantum dots (N-CQDs) and their application in the efficient delivery of hydrophobic drugs curcumin into live cancer cells. The N-CQDs produced in this study exhibit excellent water solubility, remarkable stability, and high biocompatibility. To synthesize the N-CQD, we use a carbon source found naturally (lemon juice) and for doping, we use N-rich doping agents such as ethylene diamine and urea by using eco-friendly chemical oxidation methods. The resulting N-CQDs, with particle sizes under 10 nm, exhibit a good quantum yield, reinforcing their utility for biomedical applications. N-CQDs and drug-loaded particles are evaluated using various techniques like UV-Vis, Fluorescence Spectroscopy, Dynamic Light Scattering (DLS), and Atomic Force Microscopy (AFM) as well. Additionally, we report a remarkable method to use N-CQDs as carriers for the anticancer drug curcumin, significantly enhancing the solubility in live cells. Our research also delved into the application of N-CQDs in in vivo bioimaging and drug release studies within live cancer cells, with a particular focus on their pH-dependence behavior., (© 2024 Wiley‐VCH GmbH.)

Hierarchical binder-free NiCo 2 O 4 @CuS composite electrodes have been successfully fabricated on a nickel foam surface using a facile hydrothermal method and directly used as a battery-type electrode material for supercapacitor applications. The surface morphological studies reveal that the composite electrode exhibited porous NiCo 2 O 4 nanograss-like structures with CuS nanostructures. The surface area of the composite is significantly enhanced (91.38 m 2 g -1 ) compared to NiCo 2 O 4 (52.16 m 2 g -1 ), with a predominant pore size of 3-6 nm. This synergistic combination enhanced the electrode's electrochemical properties. The NiCo 2 O 4 @CuS electrode delivered an impressive specific capacitance of 141.13 mA h g -1 at 1 A g -1 , surpassing the performance of the bare NiCo 2 O 4 electrode. The composite electrode also exhibited excellent rate capability and cycling stability, retaining 87.49% of its initial capacity at high current densities and 88.62% after 3000 cycles. A hybrid supercapacitor (HSC) device assembled using NiCo 2 O 4 @CuS and G-ink electrodes attained a peak energy density of 28.85 W h kg -1 at a power density of 238.2 W kg -1 , outperforming many reported HSCs. Additionally, the HSC device demonstrated exceptional cycling stability, retaining 87.59% of its initial capacitance after 4000 cycles. The superior performance of the NiCo 2 O 4 @CuS composite electrode is attributed to the synergistic combination of NiCo 2 O 4 and CuS, which promotes interfacial electron separation and facilitates rapid electron transfer., 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., (This journal is © The Royal Society of Chemistry.)

A highly efficient method has been developed for synthesizing 4-dienyl dihydropyridines through the nucleophilic dearomatization of activated pyridines using vinyl sulfoxonium ylides. This reaction follows the sequence involving ylide addition to activated pyridine, [2,3]-sigmatropic rearrangement, and subsequent sulfenic acid elimination. The resulting 4-dienyl dihydropyridines are then used in the synthesis of highly substituted bis -heterocyles. Control experiments and quantum chemical calculations were conducted to elucidate the selectivity and the mechanistic pathway.

Groundwater (GW) contamination due to municipal solid waste (MSW) disposal in open dumpsites is a pressing global issue. Traditional GW assessment studies are limited to single-depth sampling from nearby wells/handpumps, providing limited insights into subsurface soil characteristics and are prone to cross-contamination. The present study introduces an innovative methodology integrating advanced techniques: Cone Penetration Testing (CPT), Hydraulic Profiling Tool (HPT), Continuous Soil Sampling, and Discrete GW Sampling. Conducted at an operational dumpsite in New Delhi, India, from January to February 2023, the site investigation program covered seven distinct locations to incorporate the entire dumpsite area. The investigation proceeded in stages, starting with subsurface soil characterisation using CPT and HPT, followed by extracting soil and GW samples using CPT and HPT data. Due to restrictions in the northeast direction, GW samples were directly extracted from borewells. The results revealed maximum and minimum concentrations of 171 items/l and 26 items/l of MPs, while ionic concentration reached 13,200 ppm for Cl - and 4437 ppm for SO 4 -2 . A maximum of 0.721 ppm, 0.663 ppm and 0.948 ppm concentration was observed for Ni, Cu and Mo in GW samples. Spearman correlation and principal component analysis underscore the influence of Ec, TDS, Na +1 and Cl -1 on GW quality. This integrated approach effectively identifies high-permeability layers, which are crucial for understanding contaminant dispersion, and ensures precise sampling at various depths with minimal cross-contamination. This research demonstrates the proposed methodology's effectiveness in providing more profound and precise insights into GW contamination dynamics and suggests its utility in forming the basis for more effective remediation and regulatory strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: COVID-19 has been linked to hyperglycemia and diabetes, with noteworthy variation in outcomes. This study aimed to compare the sociodemographic factors, clinical characteristics, and in-hospital and short-term post-discharge outcomes between COVID-19 patients with new onset hyperglycemia and pre-existing diabetes patients in tertiary care hospitals in Bangladesh., Methods: A prospective observational study was conducted among adult COVID-19 patients with new onset hyperglycemia or pre-existing diabetes admitted to the COVID-19 unit of Dhaka Medical College Hospital between April 2021 and October 2021. Patients were conveniently selected from indoors. Bivariate analysis was used to compare sociodemographic and clinical characteristics at admission and short-term outcomes. The Cox proportional hazard model was used to examine factors associated with time to death in the hospital. All statistical analyses were performed using Stata Version 17., Results: A total of 169 patients were included. Of these, 29 died in the hospital, and four left against medical advice. Out of the 136 survivors, 135 came for follow-up two weeks after discharge. At baseline, 30.18% of patients had new onset hyperglycemia, and 69.8% had pre-existing diabetes. The average age of patients was 56.38 ± 14.21 years, and 60.36% were male. A significantly higher proportion of COVID-19 patients with new onset hyperglycemia were smokers than those with pre-existing diabetes (p = 0.003). However, pre-existing diabetes was associated with higher lung involvement (p = 0.047) and comorbidities (p = 0.002). Age, income over 35,000 BDT (USD 335.5$), and a BMI over 25 kg/m2 emerged as significant predictors of prolonged hospital stay and mortality. Post-discharge follow-up indicated that new-onset hyperglycemia resolved in 8.89% of patients, whereas 19.26% continued to exhibit hyperglycemia, with smoking being a significant determinant of its persistence (p = 0.001)., Conclusion: In conclusion, our investigation illuminates the clinical trajectory of new-onset hyperglycemia in the context of COVID-19 and reinforces the necessity for diligent monitoring and management post-discharge. Therefore, close monitoring and follow-up of COVID-19 patients is recommended for the early detection and management of hyperglycemia and the prevention of diabetes development in the long run., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sultana Kakoly 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.)

Objective: Brain tumors are abnormal growths of brain cells that are typically diagnosed via magnetic resonance imaging (MRI), which helps to discriminate between malignant and benign tumors. Using MRI image analysis, tumor sites have been identified and classified into four distinct tumor categories: meningioma, glioma, not tumor, and pituitary. If a brain tumor is not detected in its early stages, it could progress to a severe level or cause death. Therefore, to address these issues, the proposed approach uses an efficient classifier based on deep learning for brain tumor detection., Methods: This article describes the classification and detection of brain tumor by an efficient two-channel convolutional neural network. The input image is initially rotated during the augmentation stage. Morphological operations, thresholding, and region filling are then used in the pre-processing stage. The output is then segmented using the Berkeley Wavelet Transform. A two-channel convolutional neural network is used to extract features from segmented objects. In the end, the most effective deep neural network is employed to determine the features of brain tumors. The classifier will utilize the Enhanced Serval Optimization Algorithm to determine the optimal gain parameters. MATLAB serves as the platform of choice for implementing the suggested model., Results: Several performance metrics are calculated to assess the proposed brain tumor detection method, such as accuracy, F measures, kappa, precision, sensitivity, and specificity. The proposed model has a 98.8% detection accuracy for brain tumors., Conclusion: The evaluation shows that the suggested strategy has produced the best results., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

A simple one-step deposition-precipitation method was used to synthesize highly active and well-defined CuNi alloy bimetallic nanoparticles supported on h-BN/g-C 3 N 4 . The nanocomposite was applied for hydrogen gas evolution via seawater splitting and photocatalytic chloramphenicol (CHP) removal. Through TEM and synchrotron studies, the formation of CuNi alloy and uniform distribution of CuNi bimetallic nanoparticles on the h-BN/g-C 3 N 4 surface was observed. The EXAFS analysis verified the successful formation of the alloy, while the XPS and XANES spectra showed that the bimetallic nanoparticles are in a metallic state. Additionally, XANES revealed nanoparticle distortion upon interaction with the support, confirming the effective formation of the nanocomposite. The nanocomposite achieved a maximum hydrogen evolution rate of 3658.9 μmol g -1 h -1 for 5 wt % CuNi(3:1)/h-BN/g-C 3 N 4 , outperforming CuNi(3:1) nanoparticles and pristine g-C 3 N 4 by 1.82 and 4.31 times, respectively. Additionally, it degraded chloramphenicol with a rate constant ( k app ) of 0.018 min -1 . Optical and electrochemical analysis revealed enhanced charge mobility, extended lifetime, improved photostability, and superior photoresponse. X-ray absorption spectroscopy (XAS) and density functional theory (DFT) calculations attributed the performance to the synergy between the bimetallic nanoparticles and the h-BN/g-C 3 N 4 sheet. DFT calculations demonstrated the effective breakdown of chloramphenicol and the promotion of hydrogen gas evolution, aligning with experimental observations. Cytotoxicity of CHP post-treatment was analyzed using Drosophila melanogaster (fruit fly) and the Oregon-R strain of D. melanogaster .

Aquaporins (AQPs) are integral membrane proteins responsible for facilitating the transmembrane transport of water and small solutes. Their involvement in diverse physiological functions extends to pathological conditions, including cancer, positioning them as promising targets for anticancer therapy. Tumor cells, particularly those with high metastatic potential, exhibit elevated AQP expression, reinforcing their critical role in tumor biology. Emerging evidence highlights AQPs' involvement in key oncogenic processes such as cell migration, proliferation, and tumor-associated edema, suggesting their potential as novel therapeutic targets. Despite this, the development of selective and potent AQP inhibitors has proven challenging. Efforts to produce small-molecule AQP inhibitors have largely been unsuccessful. However, recent advancements include monoclonal human IgG antibodies targeting extracellular domains of aquaporin-4, offering new therapeutic strategies, particularly in glioblastoma, where AQP-4 is overexpressed. However, recent advancements include monoclonal human IgG antibodies targeting extracellular domains of aquaporin-4, offering new therapeutic strategies, particularly in glioblastoma, where AQP-4 is over expressed. These antibodies hold promise for selectively targeting and eradicating AQP-4-expressing cells in malignant brain tumors. This review discusses the critical role AQPs play in cancer, including their contributions to tumor cell proliferation, migration, angiogenesis, and edema formation. Additionally, we explore innovative therapeutic approaches, such as antibody-based interventions, and outline potential future research directions in AQP-targeted cancer therapies., 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., (This journal is © The Royal Society of Chemistry.)

Lanthanide metal-organic frameworks (LMOFs) have established themselves as promising proton-conducting materials among all types of porous coordination polymers and covalent organic frameworks. The structural diversity of LMOFs and high oxophilicity with a high coordination number of lanthanide ions make LMOFs a standout material for proton conduction. In the last few years, ample research efforts have been devoted to designing and developing proton-conducting lanthanide metal-organic frameworks (PCLMOFs). Some of the PCLMOFs have shown great potential with proton conductivity comparable to that of commercially used perfluorosulfonic acid (PFSA) polymers for proton-exchange membranes (PEMs) in fuel cells. At present, it is apparent that PCLMOFs are becoming a potential platform to explore other functional properties ( e.g. fluorescence sensing, gas adsorption, molecular magnetism, impedance sensing, ferroelectricity, and nonlinear optics). The intrinsic structural features of PCLMOFs inevitably bring the opportunity to introduce the multifunctional character of such materials. Therefore, any scope for additional functional properties must be investigated for this class of material. In this article, we concisely discuss the design strategy and structural features of some multifunctional PCLMOFs. Furthermore, multifunctional properties of some excellent PCLMOFs are reviewed. In addition, the prospect of PCLMOFs is briefly discussed in the context of real-world material applications.

The miniaturization of electrochemical supercapacitors (EC-SCs) requires electrode materials that are both durable and efficient. Boron-doped diamond (BDD) films are an ideal choice for EC-SC due to their durability and exceptional electrochemical performance. In this study, nanostructured boron-doped ultra-nanocrystalline diamonds (NBUNCD) are fabricated on Si micro-pyramids (Si P ) using a simple reactive ion etching (RIE) process. During the etching process, the high aspect ratio and the induction of sp 2 graphite in these nanorod electrodes achieved a maximum specific capacitance of 53.7 mF cm -2 at a current density of 2.54 mA cm -2 , with a 95.5% retention after 5000 cycles. Additionally, the energy density reached 54.06 µW h cm -2 at a power density of 0.25 µW cm -2 . A symmetric pouch cell using NBUNCD/Si P exhibited a specific capacitance of 0.23 mF cm -2 at 20 µA cm -2 , an energy density of 31.98 µW h cm -2 , and a power density of 0.91 µW cm -2 . These superior EC properties highlight NBUNCD/Si P 's potential for advancing miniaturized supercapacitors with high capacitance retention, cycle stability, and energy density., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Purpose: Postoperative nausea and vomiting (PONV) is a prevalent and distressing complication, especially in laparoscopic surgeries. This review compares the efficacy and safety of palonosetron and ondansetron in preventing PONV after laparoscopic surgery., Methods: A systematic review was conducted in PubMed, Google Scholar, Semantic Scholar, and Cochrane Library to identify comparative studies that reported the efficacy (nausea and vomiting) at three postoperative time points T1 (0-2 hours), T2 (2-6 hours), T3 (6-24 hours) and safety (incidence of adverse effects). Meta-analysis of relative risk was performed using a random effect model and subgroup analysis based on factors such as antiemetic dose and timing of administration, type of surgery, and anesthetic agents., Results: Twenty-one randomized controlled trials were published between 2011 and 2022, involving 2,043 participants. Nineteen trials were included in the meta-analysis (efficacy, 17; safety, 11). The pooled risk ratio revealed that patients receiving palonosetron demonstrated significantly less likelihood of developing nausea and vomiting at various postoperative time points. Subgroup analysis indicated significantly less PONV when palonosetron was administered before intubation and in combination with isoflurane anesthesia. Headache, dizziness, constipation, and drowsiness were the most commonly reported. The safety profiles of palonosetron and ondansetron were comparable., Conclusion: Palonosetron exhibits superior efficacy within the first 24 hours postoperatively and requires less rescue antiemetic intervention compared to ondansetron in laparoscopic surgery patients. Both demonstrate nearly comparable safety profiles. Future trials focusing on cardiac safety (QT interval) and cost consideration are needed.

Helicobacter pylori, a pathogenic bacterium residing in the human gut microbiome, is a forefront pillar of biological factors known to cause gastric cancer (GC) in human. At genetic levels, the emerging field of RNAomics has shed light on the need to investigate a significant biological macromolecule known as Noncoding RNA that plays pivotal role in diverse biological and functional facets of bacterial pathogenesis and survival. Notably, H. pylori harbour an array of coding and non-coding RNAs (ncRNAs). These ncRNAs exert pleiotropic effects, targeting numerous cellular pathways and thereby orchestrating transcriptomic-level regulation to adapt to various environmental conditions. Regrettably, the existing literature on H. pylori lacks a comprehensive and concise overview about these RNAs. Acknowledging this significant gap, our study systematically explores the regulation of biomarker ncRNA classes, associated molecules, and their therapeutic targets within the different cellular realm of bacterium. This elucidation of functional domains by computational and in vitro approach will provide essential insights for developing modern, synthetic, and personalized strategies to target these ncRNAs, ultimately eradicating the pathogenesis. Therefore, this research holds significant promise for advancing our potential understanding of H. pylori pathogenesis and paving the way for innovative therapeutic interventions., Competing Interests: Declaration of competing interest There are no competing interests to declare from authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the present study, pharmaceuticals and personal care products (PPCPs), endocrine disrupting compounds (EDCs), and heavy metals (HMs), were measured in water and sediment of the Ganga River during summer and winter seasons for two consecutive years. Additionally, this study estimated the ecological and human health risks associated with PPCPs, EDCs, and HMs. HMs detected in the range of not detected (n.d.) to 23.59 μg/L and 0.01-391.44 μg/g in water and sediment samples, respectively. All studied HMs were within the permissible limits, except for As in water, and Cr and Ni in sediment. The geo-accumulation index (I geo ) indicated that Cr (0.71-5.98) and Pb (0.90-3.90) had high I geo compared to other metals in sediment samples. Pb showed the highest ecological risk, followed by Cd, Co, Ni, Cu, Cr, As, and Zn. The maximum potential ecological risk index was observed at site G8. The hazard index (HI) value for water (0.08-0.89) and sediment (0.02-0.29) intake by adults remained within the acceptable limits, except at sites G8 (1.27) and G9 (1.34) for water intake. However, for children, the HI value was above the acceptable limit for water intake at sites G4 to G13 and for sediment at site G8. Among the studied compounds, metformin, triclosan, triclocarban, diclofenac, and methylparaben were the most abundant compounds present in the Ganga River. PPCPs and EDCs detected in the range of n.d. to 5850.04 ng/L and n.d. to 1080.41 ng/g in water and sediment samples, respectively. The environmental risk assessment identifies the maximum ecological risk in water exhibited by triclocarban followed by 17α-ethinylestradiol (EE2), diclofenac, and triclosan, while in sediment, the maximum ecological risk exhibited by triclocarban, followed by EE2, 17 β-estradiol (E2), triclosan, and diclofenac. However, none of the compounds showed human health risk, except for EE2, E2, and atenolol., 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.)

Traumatic brain injury (TBI) causes multiple cerebrovascular disruptions and oxidative stress. These pathological mechanisms are often accompanied by serious impairment of cerebral blood flow autoregulation and neuronal and glial degeneration., Background/objectives: Multiple biochemical cascades are triggered by brain damage, resulting in reactive oxygen species production alongside blood loss and hypoxia. However, most currently available early antioxidant therapies lack capacity and hence sufficient efficacy against TBI. The aim of this study was to test a novel catalytic antioxidant nanoparticle to alleviate the damage occurring in blast TBI., Methods: TBI was elicited in an open blast rat model, in which the rats were exposed to the effects of an explosive blast. Key events of the post-traumatic chain in the brain parenchyma were studied using immunohistochemistry. The application of a newly developed biologically compatible catalytic superoxide dismutase mimetic carbon-based nanocluster, a poly-ethylene-glycol-functionalized hydrophilic carbon cluster (PEG-HCC), was tested post-blast to modulate the components of the TBI process., Results: The PEG-HCC was shown to significantly ameliorate neuronal loss in the brain cortex, the dentate gyrus, and hippocampus when administered shortly after the blast. There was also a significant increase in endothelial activity to repair blood-brain barrier damage as well as the modulation of microglial and astrocyte activity and an increase in inducible NO synthase in the cortex., Conclusions: We have demonstrated qualitatively and quantitatively that the previously demonstrated antioxidant properties of PEG-HCCs have a neuroprotective effect after traumatic brain injury following an explosive blast, acting at multiple levels of the pathological chain of events elicited by TBI.

The secretory proteome of Plasmodium exhibits differential spatial and functional activity within host cells. Plasmodium secretes proteins that translocate into the human host cell nucleus. Liver-specific protein 2 of Plasmodium falciparum ( Pf- LISP2) shows nuclear accumulation in human hepatocytes during the late liver stage of malaria parasite development. However, the nuclear translocation mechanism for Pf- LISP2 remains largely uncharacterized. Here, we identified a classical bipartite nuclear localization signal (NLS) located in the C-terminal region of Pf- LISP2. Phylogenetic analysis revealed that this NLS is unique to Plasmodium falciparum and its close relative Plasmodium reichenowi , suggesting an evolutionary adaptation linked to their shared primate hosts. Functional assays confirmed the NLS's nuclear import activity, as fusion constructs of the Pf- LISP2 NLS with Pf- aldolase ( Pf- aldolase-NLS-EGFP) localized exclusively to the nucleus of HepG2 cells. Mutation analysis of key lysine and arginine residues in the bipartite NLS demonstrated that the basic amino acid clusters are essential for nuclear localization. Importin-α/β interaction was found to be crucial for Pf- LISP2 nuclear transport, as coexpression of the NLS constructs with the importin-α/β inhibitor mCherry-Bimax2 significantly blocked nuclear translocation. Specific interactions between the lysine and arginine residues of Pf- LISP2's NLS and the conserved tryptophan and asparagine residues of human importin-α1 facilitate the cytosol-to-nuclear translocation of Pf- LISP2. Additionally, LISP2 lacks any nuclear export signal. These results provide new insights into the mechanisms of nuclear transport in Plasmodium falciparum , potentially contributing to the understanding of its pathogenicity and host-cell interactions during liver-stage infection.

The isoquinoline core is present in one of the largest subsets of bioactive natural products. The multifunctional isoquinoline core exerts diverse bioactivity, resulting in the development of numerous isoquinoline-based drugs and molecules that are currently under clinical trials. We developed a new approach for phosphite-mediated [1,2] alkyl migration for an overall ortho -C-H alkylation via N -alkylation of isoquinoline. Tuning the phosphite-mediated protocol to switch the site selectivity would expedite direct and diverse multi-C-H bond functionalization. We report a new approach starting with a simple N -alkylation of isoquinoline with sterically and electronically diverse alkyl bromides for their phosphite-mediated photochemical [1,3] N to C rearrangement followed by a rearomatization sequence that leads to meta -C-H (C4) alkylation. Combined experimental and computational studies unveiled the emergence of an unprecedented C-N bond cleavage pathway from the singlet excited state of the enamine-type intermediate. Our radical bond-cleavage pathway favors substituted alkyl group migration that complements the recently successful meta -alkylation methods with smaller and more reactive electrophiles. This switch in site selectivity via tuning the phosphite-mediated protocol resulted in sequential C-H difunctionalization of isoquinoline including regiodivergent ortho , meta -dialkylations of isoquinolines., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: Wound healing is a complex biological process involving numerous cellular and molecular events. Ixora coccinea and Rhododendron arboreum flowers have been traditionally used for their medicinal properties, prompting an investigation into their combined effects on wound healing using both in vitro and in silico approaches., Methods: Ixora and Rhododendron flowers were processed in a 1:1 ratio using an ethanolic solvent. Various concentrations of the extracts were applied to wounded mouse fibroblast cell monolayers (3T3-L1). Antioxidant potential was evaluated by DPPH and H 2 O 2 assays, while anti-inflammatory effects were assessed using BSA and EA assays. Wound closure kinetics were monitored with image analysis software. Molecular docking studies examined interactions between active compounds and essential wound-healing proteins., Results: The formulations inhibited ROS production at a low concentration (IC 50 ∼1.38 μg/mL), indicating suitability for managing oxidative stress. The extracts also showed protein denaturation inhibition with an IC 50 value of 14.5 μg/mL for BSA and 8.3 μg/mL for EA. In vitro , the combined extracts significantly enhanced wound closure compared to control groups, with higher concentrations (40 μg/mL) accelerating closure rates (99.66 %). Molecular docking revealed interactions between key compounds (Quercetin, Rutin) and essential wound healing proteins (MMP9, TGFβ1, IGFR), suggesting mechanisms underlying their therapeutic effects., Conclusion: In vitro and in silico findings suggest that Ixora and Rhododendron flower extracts promote wound closure and their interaction with key proteins in wound healing pathways, highlighting their potential therapeutic value., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: India, with the largest population and second-highest type 2 diabetes mellitus (T2DM) prevalence, presents a unique genetic landscape. This study explores the genetic profiling of T2DM, aiming to bridge gaps in existing research and provide insights for further explorations., Methods: We conducted a systematic review and meta-analysis of literature published up to September 2024 using databases like PubMed, Web of Science, Scopus, and Google Scholar to identify SNPs associated with T2DM in case-control studies within the Indian population. Data extraction followed a rigorously designed checklist independently verified by two reviewers. The quality of the studies assessed by utilizing Newcastle Ottawa scale, and heterogeneity through Cochran's Q, τ 2 , H 2 and I 2 statistics. Fixed effect and random effect model was employed for meta-analysis based on heterogeneity, and publication bias was assessed by funnel plot analysis, Egger's and Begg's statistical test. In SNPs with adequate studies meta-regression was used to assess source of heterogeneity. Statistical analyses were performed using Stata 18.0 software., Findings: Our search identified 1309 articles, with 67 included in the systematic review and 35 in the meta-analysis. These 67 case-control studies, involving 33,407 cases and 30,762 controls, analyzed 167 SNPs across 61 genes. Of these, 89 SNPs mapped to 46 genes showed significant associations with T2DM risk ( P  < 0.05), including 67 linked to increased risk and 16 with protective effects. Geographical analysis highlighted inter- and intra-regional variations. Meta-analysis of 25 SNPs revealed 12 SNPs with high T2DM risk compatibility. TCF7L2 gene exhibited a strong compatibility with an overall OR of 1.44 (95% CI 1.36-1.52) and S-value 112.41, while TCF7L2 variants rs7903146 and rs12255372, with OR 1.56 (95% CI 1.43-1.66) and S-value 89.036, OR of 1.36 (95% CI 1.17-1.35) with an S - value of 15.45 respectively., Interpretation: Our study highlights the importance of considering the diverse ethnic groups of India for development of targeted and effective T2DM management strategies., Funding: Department of Biotechnology (DBT) and Indian Council of Medical Research (ICMR), Government of India., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Triple-negative breast cancer (TNBC) stands as the most complex and daunting subtype of breast cancer affecting women globally. Regrettably, treatment options for TNBC remain limited due to its clinical complexity. However, immunotherapy has emerged as a promising avenue, showing success in developing effective therapies for advanced cases and improving patient outcomes. Improving TNBC treatments involves reducing side effects, minimizing systemic toxicity, and enhancing efficacy. Unlike traditional cancer immunotherapy, engineered nonmaterial's can precisely target TNBC, facilitating immune cell access, improving antigen presentation, and triggering lasting immune responses. Nanocarriers with enhanced sensitivity and specificity, specific cellular absorption, and low toxicity are gaining attention. Nanotechnology-driven immunoengineering strategies focus on targeted delivery systems using multifunctional molecules for precise tracking, diagnosis, and therapy in TNBC. This study delves into TNBC's tumour microenvironment (TME) remodeling, therapeutic resistance, and immunoengineering strategies using nanotechnology., 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 © 2024 Singh, Haque, Kim, Han and Yadav.)

Anthropometry of the penis holds significant cultural and clinical importance, reflecting male genital development and aiding in the early identification of abnormalities., Objectives: To develop an age-related penile length nomogram for Indian children, to define a range of normalcy, and to develop age-matched controls for penile length assessment in managing conditions like hypospadias., Methods: This is a cross-sectional study (Design) initiated post-Institute Ethics Committee clearance (Ethics) based on 1276 volunteers (boys) aged 1-14 years (Participants) presenting to a pediatric surgery clinic (Setting) for conditions not affecting penile length. Participants were registered for the study and their age(years), weight(kg), and stretched penile length (SPL in cm) were recorded (Intervention). Generalized additive models for Location, Scale, and Shape (GAMLSS/extension of LMS method) were used. Outcome measures included weight (mean/range) and SPL (mean/range/standard deviation/median/centiles). The four distribution parameters were modeled as non-parametric smoothing cubic-spline functions of x with Box-Cox Power Exponential (BCPE) distribution and centiles (3, 5, 10, 25, 50, 75, 90, 95, 97) were calculated for the stretched penile length., Results: SPL increases with age (3.4 cm in a 1-year-old to 12.7 cm in a 14-year-old) of the child in a non-linear fashion (r = 0.67, p < 0.001). Centile curves showed two phases of steep SPL increase, at ages 2-4 years and 10-14 years, reflecting early childhood growth and pubertal spurt respectively., Conclusions: This is the largest cross-sectional study on the pediatric SPL in the Indian population. The data will serve as a useful resource for both parents and physicians in assessing penile development and guiding patient management., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Controlling the minimum gelation concentration (MGC) of low molecular weight (LMW) hydrogelators is a key for modulating gel properties, such as mechanical strength, viscoelasticity, and stability, which are crucial for applications ranging from drug delivery to tissue engineering. However, tweaking the MGC under specific conditions, such as pH and/or temperature, poses a considerable challenge. Herein, we varied the ionic strength of buffer solutions using NaCl for several LMW hydrogelators, including Fmoc-Phe, Fmoc-Tyr, Fmoc-Trp, Fmoc-Met, and Fmoc-Cha, and assessed their gelation efficiency at pH 7.4 and ambient temperature. Interestingly, Fmoc-Phe demonstrated a ∼67% (3-fold) MGC reduction, from 0.24 to 0.08 wt %, at 500 mM NaCl, transforming it a "super hydrogelator" (MGC < 0.1 wt %), while Fmoc-Trp showed 60% MGC reduction. Higher ionic strength effectively shields the electrostatic repulsion between negatively charged (-COO - ) groups on the Fmoc-Phe, promoting closer aggregation and more efficient self-assembly and allowing for gelation at lower concentrations. In contrast, Fmoc-Met, Fmoc-Cha, and Fmoc-Tyr precipitated in the presence of NaCl, suggesting that NaCl specifically modulates the MGC of Fmoc-amino acid gelators containing unsubstituted aromatic side chains. Furthermore, these results indicate that cation-π interactions likely play a role, alongside carboxylic acid neutralization. While Fmoc-Phe forms gels in the presence of other monovalent cations, it does not form a hydrogel in the presence of divalent (CaCl 2 ) and trivalent (AlCl 3 ), indicating that enhancement of hydrogelation is specific to monovalent cations. Although the fibrillar structure of Fmoc-Phe hydrogels remained consistent, addition of NaCl increased fibril stickiness, creating densely packed networks that modulate the mechanical strength. Unlike typical cases where increased ionic strength leads to precipitation, Fmoc-Phe gelation at high NaCl concentrations (150-500 mM) is significant, yielding a robust supramolecular hydrogel that remains stable in high ionic-strength environments. This outcome suggests that ionic strength could be a valuable factor to enhance the efficient gelation of LMW hydrogelators.

Deinococcus radiodurans , a natural transformation (NT)-enabled bacterium renowned for its exceptional radiation resistance, employs unique DNA repair and oxidative stress mitigation mechanisms as a strategic response to DNA damage. This study excavates into the intricate roles of NT machinery in the stressed D. radiodurans , focusing on the genes comEA , comEC , endA , pilT , and dprA , which are instrumental in the uptake and processing of extracellular DNA (eDNA). Our data reveal that NT not only supports the nutritional needs of D. radiodurans under stress but also has roles in DNA repair. The study findings establish that NT-specific proteins (ComEA, ComEC, and endonuclease A [EndA]) may contribute to support the nutritional requirements in unstressed and heavily DNA-damaged cells, while DprA contributes differently and in a context-dependent manner to navigating through the DNA damage storm. Thus, this dual functionality of NT-specific genes is proposed to be a contributing factor in the remarkable ability of D. radiodurans to survive and thrive in environments characterized by high levels of DNA-damaging agents.IMPORTANCE Deinococcus radiodurans is a bacterium known for its extraordinary radiation resistance. This study explores the roles of NT machinery in the radiation-resistant bacterium Deinococcus radiodurans , focusing on the genes comEA , comEC , endA , pilT , and dprA . These genes are crucial for the uptake and processing of eDNA and contribute to the bacterium nutritional needs and DNA repair under stress. The findings suggest that the NT-specific proteins ComEA, ComEC, and EndA may help meet the nutritional needs of unstressed and heavily DNA-damaged cells, whereas DprA plays a distinct role that varies, depending on the context in aiding cells to cope with DNA damage. The functionality of NT genes is proposed to enhance D. radiodurans survival in environments with high levels of DNA-damaging agents.

Adzuki bean, an underutilized grain legume, has a significant potential for enhancing food and nutritional security. The main obstacles to developing new cultivars and promoting the adzuki bean as a mainstream pulse crop are a lack of awareness about its potential and insufficient information on crop its genetic diversity. Here, we aimed to explore the untapped potential of adzuki bean germplasm by evaluating its agro-morphological traits and diversity at the molecular level and also to identify trait-specific germplasm by utilizing 100 adzuki bean accessions conserved in the Indian National Genebank. Significant variations was recorded for the morphological traits and identified promising accessions exhibiting desirable traits, such as early flowering (IC341945, EC340257 and EC340283), number of primary branches (IC341945 and IC469175), number of clusters per plant (EC000264, IC167611 and IC341939), number of pods per plant (IC469175, EC34264, EC000264), early maturity (EC340283; EC120460; IC341941) and number of seeds per pod (EC340240, IC455396 and IC341955). Molecular characterization of diverse accessions using 22 polymorphic SSR markers identified a total of 50 alleles, with a mean of 2.27 alleles per loci. The polymorphic information content (PIC) ranged from 0.03 to 0.46, indicating informativeness of markers in distinguishing diverse accessions. Further, the gene diversity among the accessions ranged from 0.03 to 0.57 with a mean of 0.19. Population structure analysis grouped the accessions into three genetic groups, supported by Principal Coordinate Analysis (PCoA) and a phylogenetic tree. Additionally, Analysis of Molecular Variance (AMOVA) confirmed a substantial genetic diversity among the adzuki bean accessions. Thus, the combined assessment of agro-morphological traits and molecular markers effectively distinguished adzuki bean accessions and provided valuable insights in understanding untapped variation at both morphological and molecular levels. The promising accessions identified in the study hold potential for integration into legume improvement programs through introgression breeding, contributing to the development of adzuki bean varieties with target trait., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Deshahalli Divakara 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.)

Chronic inhalation intake of radionuclides is possible for radiation workers in the nuclear industry. The International Commission on Radiological Protection (ICRP) provides organ retention fractions as well as daily urinary and fecal excretion for chronic intake of various radionuclides. In this study, organ retention fractions and daily urinary excretion for chronic intake were estimated for constant chronic intake (CCI) and realistic chronic intake (RCI) scenarios. CCI is a daily intake of 1 Bq, and RCI is an intake of 1.4 Bq for five working days followed by two days gap. Radiologically important radionuclides such as 239Pu, 60Co, 137Cs, 131I, and 3H having long, moderate, and short effective half-lives in the deposited organ or whole body were considered. The retention fractions and daily urinary excretion of all the radionuclides studied for RCI were found to converge with those for the CCI scenario at ~40 to 200 days except for daily urinary excretion of 131I., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Pulmonary venous developmental anomalies have historically been evaluated using echocardiography and catheter-based angiography. In recent years, however, multidetector CT angiography (MDCTA) and MR angiography have become increasingly important tools for detailed characterization of these anomalies. This case report provides an in-depth review of the radiologic findings in a 15-year-old patient diagnosed with the supracardiac type of Total Anomalous Pulmonary Venous Connection (TAPVC). The report emphasizes the imaging features that were instrumental in the diagnosis and underscores the crucial role of advanced imaging techniques in the management of this serious congenital heart defect., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Based on the research conducted so far, hydrogen sulphide (H 2 S) plays a crucial role in the development and stress resilience of plants. H 2 S, which acts as a signalling molecule, responds to different stresses such as heavy metals, drought, and salinity, and it regulates various aspects of plant growth and development including seed germination, root development, stomatal movement, flowering, and fruit ripening. Additionally, H 2 S is involved in mediating legume-Rhizobium symbiosis signalling. It modulates plant responses to external environmental stimuli by interacting with other signalling molecules like phytohormones, nitric oxide, and reactive oxygen species. Furthermore, H 2 S exerts these regulations since it can modify protein functions through a reversible thiol-based oxidative posttranslational modification called persulfidation, particularly in stress response and developmental processes. As a result, H 2 S is recognised as an important emerging signalling molecule with multiple roles in plants. Research in this field holds promise for engineering stress tolerance in crops and may lead to potential biotechnological applications in agriculture and environmental management., (© 2024 John Wiley & Sons Ltd.)

Natural products have been pivotal in drug discovery, offering a wealth of bioactive compounds that significantly contribute to therapeutic developments. Despite the rise of synthetic chemistry, natural products continue to play a crucial role due to their unique chemical structures and diverse biological activities. This study reviews and evaluates the potential of natural products in drug discovery and development, emphasizing the integration of traditional knowledge with modern drug discovery methodologies and addressing the associated challenges. A comprehensive literature search was conducted across PubMed/MedLine, Scopus, Web of Science, Google Scholar, and Cochrane Library, covering publications from 2000 to 2023. Inclusion criteria focused on studies related to natural products, bioactive compounds, medicinal plants, phytochemistry, and AI applications in drug discovery. Data were categorized into source, extraction methods, bioactivity assays, and technological advances. The current review underscores the historical and ongoing importance of natural products in drug discovery. Technological advancements in chromatographic and spectroscopic techniques have improved the isolation and structural elucidation of bioactive compounds. AI and machine learning have streamlined the identification and optimization of natural product leads. Challenges such as biodiversity sustainability and development complexities are discussed, alongside innovative approaches like biosynthetic engineering and metagenomics. Natural products remain a vital source of novel therapeutic agents, providing unique chemical diversity and specific biological activities. Integrating traditional knowledge with modern scientific methods is essential for maximizing the potential of natural products in drug discovery. Despite existing challenges, ongoing research and technological advancements are expected to enhance the efficiency and success of natural product-based drug development., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. 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.)

Skin cancer remains one of the most common and deadly forms of cancer, necessitating accurate and early diagnosis to improve patient outcomes. In order to improve classification performance on unbalanced datasets, this study proposes a distinctive approach for classifying skin cancer that utilises both machine learning (ML) and deep learning (DL) methods. We extract features from three different DL models (DenseNet201, Xception, Mobilenet) and concatenate them to create an extensive feature set. Afterwards, several ML algorithms are given these features to be classified. We utilise ensemble techniques to aggregate the predictions from several classifiers, significantly improving the classification's resilience and accuracy. To address the problem of data imbalance, we employ class weight updates and data augmentation strategies to ensure that the model is thoroughly trained across all classes. Our method shows significant improvements over recent existing approaches in terms of classification accuracy and generalisation. The proposed model successfully received 98.7%, 94.4% accuracy, 99%, 95%, precision, 99%, 96% recall, 99%, and 96% f1-score for the HAM10000 and ISIC datasets, respectively. This study offers dermatologists and other medical practitioners' valuable insights into the classification of skin cancer., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Consumers are increasingly focused on food products' nutritional content and health aspects. Nutraceutical tablets containing nutritional supplements have seen remarkable progress and are well-known for their precise dosage, which can improve consumer health by increasing the intake of bioactive compounds and vital nutrients. Oral nutraceuticals are frequently used to enhance consumer well-being, with around 80% of products being in solid form. This manuscript aims to thoroughly analyze and summarize the gathered literature using various search engines to investigate key trends in the market, the components involved, and the functional impact of nutraceutical tablets. Furthermore, the manuscript explores various nutraceutical tablets such as chewable tablets, gelling capsules, vitamin tablets, spirulina tablets, and bran tablets. A perspective is provided on multiple production and manufacturing methods of nutraceutical tablets, along with comparing these processes. Following this, evaluating quality characteristics and enforcing quality assurance procedures have been emphasized. The manuscript discussed the physiological breakdown of ingestible nutraceutical tablets in the human body and the possible toxic effects of the components found in these tablets. Furthermore, the focus is on producing nutraceutical tablets in a more environmentally friendly manner, tackling sustainability issues, offering solutions, and delving into potential opportunities. This manuscript will create a significant platform for people from the research, scientific, and industrial fields seeking novel and inventive projects., 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.)

Visceral leishmaniasis derived from Leishmania donovani is transmitted by sand flies (Phlebotomus argentipes) throughout the Indian subcontinent. Although considered anthroponotic, L. donovani infects other mammals susceptible to sand fly bites, including dogs. Aggressive strategies to reduce sand fly populations in India have led to flies seeking nonhuman hosts, so understanding the role of dogs in L. donovani transmission has become critical. Our study investigated L. donovani infection in dogs and the potential for such infections to be transmitted back to sand flies. We performed xenodiagnosis by using P. argentipes on dogs (n = 73) with quantitative PCR-detectible parasitemia in both endemic and outbreak villages. We found that 12% (9/73) of dogs were infectious to sand flies during winter and rainy seasons. Patients with visceral leishmaniasis remain primary sources of L. donovani transmission, but our findings suggest a possible link between canine infection and human exposure.

Microplastics (MPs), plastic pieces smaller than 5 mm, are emerging as a critical ecological threat, potentially disrupting ecosystems and complicating waste management practices. Landfill-Mined Soil-Like Material (LMSLM), a byproduct of landfill reclamation, is gaining global traction for rehabilitating degraded land and repurposing it for geotechnical applications. While studies have examined contaminants like heavy metals and salts, MPs contamination has been largely overlooked, raising environmental concerns. The widespread use of LMSLM in earth-filling increases the risk of MP pollution. Additionally, significant gaps remain in understanding how MPs are distributed across different size fractions during sieving, which is critical for developing effective remediation strategies and informing future policies. This study aims to fill the existing knowledge gap by investigating the presence of microplastics in LMSLM collected from three aged waste dumpsites in New Delhi, India, and evaluating the ecological risks associated with its reuse. The results revealed the presence of MPs in all LMSLM samples with concentrations ranging from 25950 to 41110 items/kg. Fibers and fragments were the dominant shapes, with 60 % of particles measuring less than 425 µm. The color characteristics revealed the dominance of white, transparent, and black color. Polyethylene and polypropylene were the most common polymers, with smaller amounts of polyamide, polyethylene terephthalate, and polyester. SEM-EDX analysis revealed weathering effects and the presence of heavy metals, including Lead (Pb), Cadmium (Cd), and Arsenic (As), adsorbed on the MP surface. Ecological risk assessment using the Polymer Hazard Index and Pollution Load Index identified hazard levels of V and II, respectively, while the Potential Ecological Risk Index indicated a medium risk. Furthermore, the dimensional analysis demonstrates that MP width, particularly in fiber-shaped MPs, plays a crucial role in determining retention and migration during sieving, while MPs with uniform shapes, like spheres and fragments, exhibit limited movement. These findings underscore the need for protective measures when using LMSLM in geotechnical applications to prevent MP migration and contamination of surrounding environments. The study highlights the importance of further research on MP contamination in reclaimed landfill materials and its implications for sustainable land use and waste management., Competing Interests: Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report a rare case of multiple benign minor salivary gland tumors in a 60-year-old woman, presenting with progressive left nasal obstruction, intermittent anterior nasal discharge, and postnasal drip. Diagnostic nasal endoscopy and computed tomography (CT) scan revealed sessile, pale, non-pulsating masses in the left nasal cavity, septum, and nasopharynx. Histopathological examination confirmed ectopic minor salivary glands. The tumors were successfully removed via endoscopic excision, and the patient experienced resolution of symptoms with no evidence of recurrence during follow-up. This case highlights the importance of a systematic approach involving clinical assessment, imaging, and histopathological analysis for accurate diagnosis and management of nasal salivary masses., Competing Interests: Competing of InterestThe authors have no competing interests to declare that are relevant to the context of this article. The authors have no relevant financial or non-financial interests to disclose., (© 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.)

Thoracic tracheal tumors are relatively rare in routine clinical practice. Though surgery is the preferred management choice, acute presentation is challenging for the surgeon and the anesthetist. In this study, we discuss the role of the percutaneous trans-tracheal endoscopic approach (PTTEA) in the modern era of minimally invasive surgery. Its indications, advantages, complications, and anesthetic options are enumerated. A retrospective review was performed of patients with thoracic tracheal lesions treated in our department between 2015 and 2022. A total of 16 patients underwent PTTEA in an emergency after a failed fiberoptic or transoral approach and were included in the review. Twelve patients were ventilated by intermittent apnea, and four had a Cardiopulmonary bypass. Amongst the 16 patients, nine had benign, and seven had malignant pathologies. All the benign lesions were excised completely, and patients were de-cannulated, except for one case with disseminated respiratory papillomatosis. Malignant lesions underwent debulking of the lesions for acute respiratory distress, followed by initiation of adjuvant therapy. PTTEA is an effective alternative to traditional fiberoptic or rigid bronchoscopy techniques for selected patients for whom minimally invasive techniques fail. The advantages of the approach include better surgical access, hemostasis, and airway control, resulting in reduced operative time and minimal complications., Competing Interests: Conflict of InterestThere are no conflicts of interest among the authors., (© 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.)

CSF rhinorrhea secondary to anterior skull base defect may be spontaneous or traumatic (accidental or iatrogenic), spontaneous being common in middle aged, obese females. Nowadays endoscopic technique is gold standard for anterior skull base defect repair. The graft materials available may be autologous (fat, temporalis fascia, fascia lata, septal mucosa, cartilage, middle turbinate), homologous e.g., cadaveric pericardium or allograft e.g. dural substitute. Leukocyte-platelet rich fibrin (L-PRF) is a newer graft material that contain concentrated platelets and doesn't require any exogenous material or chemical in blood. A prospective study including 31 patients was carried out at tertiary care centre in eastern India, over the period of 2 years. All the surgeries targeted for closure of the anterior skull base defect were performed endoscopically under general anaesthesia. 30 out of 31 (96.77%) patients successfully improved after repair and one patient required revision surgery due to recurrence of disease and was cured after revision surgery. Autologous Leokocyte-plasma rich fibrin (L-PRF) is a newer and cost-effective graft material for the CSF leak repair with good healing property and with a success rate of more than 95%., Competing Interests: Conflict of InterestNone., (© 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 current scenario, Alzheimer's disease is a complex, challenging, and arduous health issue, and its prevalence, together with comorbidities, is accelerating around the universe. Alzheimer's disease is becoming a primary concern that significantly impacts an individual's status in life. The traditional treatment of Alzheimer's disease includes some synthetic drugs, which have numerous dangerous side effects, a high risk of recurrence, lower bioavailability, and limited treatment. Hence, the current article is a detailed study and review of all known information on plant-derived compounds as natural anti-Alzheimer's agents, including their biological sources, active phytochemical ingredients, and a possible mode of action. With the help of a scientific data search engine, including the National Center for Biotechnology Information (NCBI/PubMed), Science Direct, and Google Scholar, analysis from 2001 to 2024 has been completed. This article also described clinical studies on phytoconstituents used to treat Alzheimer's disease. Plant-derived compounds offer promising alternatives to synthetic drugs in treating Alzheimer's disease, with the potential for improving cognitive function and slowing down the progression of the disease. Further research and clinical trials are needed to fully explore their therapeutic potential and develop effective strategies for managing this complex condition., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study investigates sonophotocatalysis for the oxidation of Rhodamine B (RhB) dye using Zr doped ZnO nanoparticles. The synthesized nanoparticles were characterized by scanning electron microscope, Fourier-transform infrared, X-ray diffraction, Brunauer Emmett-Teller, thermogravimetric analysis, and photoluminescence. The hybrid sonophotocatalysis system achieved 98.73 ± 1.25% degradation of RhB under the conditions: RhB dye concentration = 10 ppm, 4 wt% of Zr doped ZnO = 0.1 g, reaction temperature = 30 °C, time = 60 min, pH = 7. A kinetic model was developed to predict the efficiency of RhB degradation through intrinsic elementary chemical reactions. The high coefficient of determination (R 2  = 0.96) indicates the model's prediction accuracy in describing the degradation kinetics of RhB within sonophotocatalysis system. The electrical energy per order (E EO ) analysis demonstrated that US + UVC + 4 wt% of Zr doped ZnO significantly reduced E EO (1055 kWh m -3 order -1 ). The synergy index for this combination was approximately 1.60, demonstrating a significant synergistic effect. Density Functional Theory (DFT) studies were utilized to propose the most probable degradation pathway, identifying reactive sites and potential byproducts. The simulations revealed the central carbon atom (1C site) as highly susceptible to radical attacks, indicating potential decolorization pathways such as N-de-ethylation, chromophore cleavage, and ring opening. Toxicity assessments of both the parent dye and its intermediates were conducted using ECOSAR (Ecological Structure Activity Relationship) to evaluate their ecological impacts. The combination of experimental results and kinetic modeling and simulations offers a deep understanding of RhB degradation complexities, driving advancements in sustainable water treatment technologies., 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.)

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.)

Introduction: Preeclampsia (PE) is a pregnancy complication marked by high blood pressure, posing risk to maternal and fetal health. "Genomic imprinting", an epigenetic phenomenon regulated by DNA methylation at Differently Methylated Regions (DMR's), influences placental development. Research on circulating extracellular vesicles (EVs) in PE suggests them as potential source for early biomarkers, but methylation status of EV-DNA in Preeclampsia is not reported yet., Methods: This study examines the methylation and expression profile of imprinted genes - PEG10, PEG3, MEST, and DLK1 in circulating EVs of 1 st and 3 rd trimester control and early onset preeclampsia (EOPE) pregnant women (n = 15) using pyrosequencing and qRT-PCR respectively., Results: In 1 st trimester, PEG3 was significantly hypermethylated, whereas no significant methylation changes were noted in PEG10 and MEST in EOPE. In 3 rd trimester, significant hypomethylation in PEG10, PEG3 and IGDMR was observed whereas significant hypermethyaltion noted in MEST. mRNA expression of PEG10, PEG3 and DLK1 was not affected in circulating EVs of 1 st trimester EOPE. However, in 3 rd trimester significant increased expression in PEG10, PEG3 and DLK1 noted. MEST expression was reduced in 3 rd trimester EOPE. No correlation was observed between average DNA methylation and gene expression in PEG10 and PEG3 in 1 st trimester. However, in 3 rd trimester, significant negative correlation was noted in PEG10 (r = -0.426, p = 0.04), PEG3 (r = -0.496, p = 0.01), MEST (r = -0.398, p = 0.03) and DLK1 (r = -0.403, p = 0.03)., Discussion: The results of our study strengthen the potential of circulating EVs from maternal serum as non-invasive indicators of placental pathophysiology, including preeclampsia., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In recent days, in tropical and subtropical regions, secondary vectors of Anopheles mosquitoes are becoming more important in transmitting diseases to humans as primary vectors. Various molecular techniques have separated closely related Anopheles subpictus and Anopheles vagus mosquitoes based on their diversity with other mosquito species. Despite their widespread distribution, the An. subpictus and An. vagus mosquitoes, which carry Plasmodium in their salivary glands, were not considered primary malaria vectors in India. An. vagus mosquitoes are zoophilic and physically similar to An. subpictus. We intend to identify An. subpictus and An. vagus mosquito's sister species based on their Interspaced Transcribed Region-2 (ITS2). We isolated the midgut gDNA from each mosquito and used ITS2-PCR and Sanger sequencing to characterize the mosquito species. BioEdit software aligned the sequences, and MEGA7 built a phylogenetic tree from them. According to this study, the information gathered from these mosquito samples fits the An. subpictus species A form and the An. vagus Indian form. Furthermore, gut microbiome plays an important role in providing nutrients, immunity, and food processing, whereas mosquitoes' midgut microbiota changes their hosts and spreads illnesses. So, we used the Illumina sequencer to look at the gut microbiome diversity of An. subpictus and An. vagus mosquitoes using 16S rRNA-based metagenomic sequencing. Both mosquito species had an abundant phylum of Pseudomonadota (Proteobacteria), Bacillota, Bacteroidota, and Actinomycetota in their gut microbiomes. Notably, both mosquito species had the genus Serratia in their gut. In the subpictus midgut, the genus of Haematosprillum bacteria was dominant, whereas in the vagus mosquito, the genus of Salmonella was dominant. Notably, current research has observed the Sodalis spp. Bacterial genus for the first time., 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.)

Pulmonary infections have a profound influence on global mortality rates. Medicinal plants offer a promising approach to address this challenge, providing nontoxic alternatives with higher levels of public acceptance and compliance, particularly in regions where access to conventional medications or diagnostic resources may be limited. Understanding the pathophysiology of viruses and bacteria enables researchers to identify biomarkers essential for triggering diseases. This knowledge allows the discovery of biological molecules capable of either preventing or alleviating symptoms associated with these infections. In this review, medicinal plants that have an effect on COVID-19, influenza A, bacterial and viral pneumonia, and tuberculosis are discussed. Drug delivery has been briefly discussed as well. It examines the effect of bioactive constituents of these plants and synthesizes findings from in vitro, in vivo, and clinical studies conducted over the past decade. In conclusion, many medicinal plants can be used to treat pulmonary infections, but further in-depth studies are needed as most of the current studies are only at preliminary stages. Extensive investigation and clinical studies are warranted to fully elucidate their mechanisms of action and optimize their use in clinical practice., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Nanoparticles (NPs) have garnered increasing attention for their applications in agriculture and plant science, particularly for their interactions with reactive oxygen species (ROS) and nitric oxide ( • NO). NPs, owing to their novel physicochemical properties, can be used to uniquely modulate ROS levels, enabling great control over redox homeostasis and signaling cascades. In addition, NPs may act as carriers for • NO donors, thus facilitating controlled and synchronized release and targeted delivery of • NO within plant systems. This opinion article provides insights into the current state of knowledge regarding NP interactions with ROS and • NO homeostasis in plants, highlighting key findings and knowledge gaps, as well as outlining future research directions in this rapidly expanding and potentially transformative field of research., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Inhalation of particulate matter (PM), one of the many components of air pollution, is associated with the development and exacerbation of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD). COPD is one of the leading causes of global mortality and morbidity, with a paucity of therapeutic options and a significant contributor to global health expenditure. This review aims to provide a mechanistic understanding of the cellular and molecular pathways that lead to the development of COPD following chronic PM exposure. Our review describes how the inhalation of PM can lead to lung parenchymal destruction and cellular senescence due to chronic pulmonary inflammation and oxidative stress. Following inhalation of PM, significant increases in a range of pro-inflammatory cytokines, mediated by the nuclear factor kappa B pathway are reported. This review also highlights how the inhalation of PM can lead to deleterious chronic oxidative stress persisting in the lung post-exposure. Furthermore, our work summarises how PM inhalation can lead to airway remodelling, with increases in pro-fibrotic cytokines and collagen deposition, typical of COPD. This paper also accentuates the interconnection and possible synergism between the pathophysiological mechanisms leading to COPD. Our work emphasises the serious health consequences of PM exposure on respiratory health. Elucidation of the cellular and molecular mechanisms can provide insight into possible therapeutic options. Finally, this review should serve as a stark reminder of the need for genuine action on air pollution to decrease the associated health burden on our growing global population., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Pelvi-Ureteric Junction Obstruction (PUJO) is a common cause of hydronephrosis (HDN) in children. While ultrasonography (USG) is useful for initial assessment and grading of hydronephrosis, it cannot differentiate obstructive from non-obstructive cases. Renal Dynamic Scintigraphy (RDS) confirms the diagnosis but involves ionizing radiation exposure. Ureteric jets using colour Doppler USG have been proposed for diagnosing obstructive HDN., Objective: Our study aimed to evaluate Ureteric Jet Frequency (UJF) and Relative Jet Frequency (RJF) in unilateral PUJO before and after furosemide (Lasix) administration, assessing their diagnostic and post-operative utility., Materials and Methods: Children (<14 years) with unilateral HDN underwent USG and RDS for PUJO diagnosis. Pyeloplasty was performed based on standard criteria. UJF and RJF were assessed before and after furosemide administration (0.5 mg/kg) by colour Doppler USG. The non-obstructed side was taken as the control. Follow-up included repeat RDS and ureteric jet assessment., Results: Fifty-two cases were included. UJF (pre- and post-Lasix) was significantly lower in the obstructed side compared to the non-obstructed side at baseline and post-pyeloplasty (p < 0.0001). However, the baseline UJF difference between cases and controls was not significant (p > 0.05). UJF and RJF (pre- and post-Lasix) increased postoperatively. The UJF difference decreased postoperatively (p < 0.05). (attached Table) CONCLUSION: UJF and RJF are useful for diagnosing and monitoring unilateral PUJO. The effect of furosemide on UJF needs to be assessed using additional studies with larger sample sizes to understand if it can affect UJF in a way similar to that noted in diuretic scintigraphy., Competing Interests: Conflict of interest None to declare., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Bladder cancer disproportionately affects men and often presents as nonmuscle-invasive bladder cancer (NMIBC). Despite initial treatments, the recurrence and progression of NMIBC are linked to autophagy. This study investigates the expression of autophagy genes (mTOR, ULK1, Beclin1, and LC3) in low and high-grade NMIBC, providing insights into potential prognostic markers and therapeutic targets., Material and Methods: A total of 115 tissue samples (n = 85 NMIBC (pTa, pT1, and CIS) and n = 30 control from BPH patients) were collected. The expression level of autophagy genes (mTOR, ULK1, Beclin1, and LC3) and their proteins were assessed in low and high-grade NMIBC, along with control tissue samples using quantitative real-time polymerase chain reaction and western blotting. Association with clinicopathological characteristics and autophagy gene expression was analyzed by multivariate and univariate survival analysis using SPSS., Result: In high-grade NMIBC, ULK1, P = 0.0150, Beclin1, P = 0.0041, and LC3, P = 0.0014, were substantially downregulated, whereas mTOR, P = 0.0006, was significantly upregulated. The KM plots show significant survival outcomes with autophagy genes. The clinicopathological characters, high grade (P = 0.019), tumor stage (CIS P = 0.039, pT1 P = 0.018, P = 0.045), male (P = 0.010), lymphovascular invasion (P = 0.028) and autophagy genes (ULK1 P = 0.002, beclin1 (P = 0.010, P = 0.022) were associated as risk factors for survival outcome in NMIBC patients., Conclusion: The upregulated mTOR, downregulated ULK1, and beclin1 expression is linked to a high-grade, CIS and pT1 stage, resulting in poor recurrence-free survival and progression-free survival and highlights the prognostic significance of autophagy gene in nonmuscle-invasive bladder cancer., 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 nucleolar localization of proteins is regulated by specific signals directing their trafficking to nucleus and nucleolus. Here, we elucidate the mechanism underlying the nuclear and nucleolar localization of the nucleomethylin (NML) protein, focusing on its nuclear localization signals (NLSs) and nucleolar localization signal (NoLS). Using a combination of bioinformatic analysis and experimental validation, we identified two monopartite and one bipartite NLS motifs within NML. The combined presence of both monopartite NLSs significantly enhances nuclear localization of the protein, while specific basic amino acid clusters within the bipartite NLS are crucial for their functionality. We also reveal the functional role of the NLS-coupled NoLS motif in driving nucleolar localization of NML, which contains an arginine-rich motif essential for its function. The basic residues of the arginine-rich motif of NoLS of NML interacts with nucleophosmin 1 (NPM1), allowing the possible liquid-liquid phase separation and retention of NML in the nucleolus. Remarkably, the strong NoLS of NML can direct the nucleolar localization of a cytosolic protein, aldolase, emphasizing its potency. Overall, our findings provide insights into the combinatorial functioning of NLSs and NoLS in regulating the subcellular localization of NML, highlighting the intricate regulatory mechanisms governing its localization within the nucleus and nucleolus., (© 2024 Wiley Periodicals LLC.)