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Forest restoration is an effective method for restoring degraded soil ecosystems (e.g., converting primary tropical forests into rubber monoculture plantations; RM). The effects of forest restoration on microbial community diversity and composition have been extensively studied. However, how rubber plantation-based forest restoration reshapes soil microbial communities, networks, and inner assembly mechanisms remains unclear. Here, we explored the effects of jungle rubber mixed (JRM; secondary succession and natural restoration of RM) plantation and introduction of rainforest species (AR; anthropogenic restoration established by mimicking the understory and overstory tree species of native rainforests) to RM stands on soil physico-chemical properties and microbial communities. We found that converting tropical rainforest (RF) to RM decreased soil fertility and simplified microbial composition and co-occurrence patterns, whereas the conversion of RM to JRM and AR exhibited opposite results. These changes were significantly correlated with pH, soil moisture content (SMC), and soil nutrients, suggesting that vegetation restoration can provide a favorable soil microenvironment that promotes the development of soil microorganisms. The complexity and stability of the bacterial-fungal cross-kingdom, bacterial, and fungal networks increased with JRM and AR. Bacterial community assembly was primarily governed by stochastic (78.79 %) and deterministic (59.09 %) processes in JRM and AR, respectively, whereas stochastic processes (limited dispersion) predominantly shaped fungal assembly across all forest stands. AR has more significant benefits than JRM, such as a relatively slower and natural vegetation succession with more nutritive soil conditions, microbial diversity, and complex and stable microbial networks. These results highlight the importance of sustainable forest management to restore soil biodiversity and ecosystem functions after extensive soil degradation and suggest that anthropogenic restoration can more effectively improve soil quality and microbial communities than natural restoration in degraded rubber plantations., 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 B.V.)

Parkinson's disease (PD) is a common and progressively worsening neurodegenerative disorder characterized by abnormal protein homeostasis and the degeneration of dopaminergic neurons, particularly in the substantia nigra pars compacta. The prevalence of PD has doubled in the past 25 years, now affecting over 8.5 million individuals worldwide, underscoring the need for effective management strategies. While current pharmacological therapies provide symptom relief, they face challenges in treating advanced PD stages. Recent research highlights the therapeutic benefits of retinoic acid (RA) in PD, demonstrating its potential to mitigate neuroinflammation and oxidative stress, regulate brain aging, promote neuronal plasticity, and influence circadian rhythm gene expression and retinoid X receptor heterodimerization. Additionally, RA helps maintain intestinal homeostasis and modulates the enteric nervous system, presenting significant therapeutic potential for managing PD. This review explores RA as a promising alternative to conventional therapies by summarizing the molecular mechanisms underlying its role in PD pathophysiology and presenting up-to-date insights into both preclinical and clinical studies of RA in PD treatment. It also delves into cutting-edge formulations incorporating RA, highlighting ongoing efforts to refine therapeutic strategies by integrating RA into novel treatments. This comprehensive overview aims to advance progress in the field, contribute to the development of effective, targeted treatments for PD, and enhance patient well-being. Further research is essential to fully explore RA's therapeutic potential and validate its efficacy in PD treatment., Competing Interests: Declaration of competing interest The authors affirm no known financial or personal conflicts that might have influenced the reported work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: The Blood and Marrow Transplant (BMT) Clinical Trials Network conducted a phase 3 randomized trial comparing gilteritinib with placebo after allogeneic hematopoietic cell transplantation (HCT) for FLT3-ITD+ acute myeloid leukemia (AML). The primary analysis demonstrated no statistically significant difference in relapse-free survival (RFS); however, patients with FLT3-ITD measurable residual disease (MRD) peri-HCT had significantly longer RFS with gilteritinib. This analysis investigates the effect of post-HCT gilteritinib vs placebo on health-related quality of life (HRQOL). HRQOL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (FACT-Leu), and EuroQOL-5 Dimensions (EQ-5D-5L) at post-HCT randomization; day 29; months 3, 6, 12, 18, 24; and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. HRQOL completion rate was acceptable (>70%) across all time points and measures. There were no differences in HRQOL scores at any time point between cohorts. Clinically meaningful and time to improvement in HRQOL were similar in both arms. Despite higher treatment-emergent adverse effects with gilteritinib, response to the question of being "bothered by side effects of treatment" did not differ between groups. Subgroup analysis of MRD-positive and negative patients demonstrated no differences in HRQOL between arms. For patients with FLT3-ITD+ AML undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. This trial was registered at www.ClinicalTrials.gov as #NCT02997202., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Klebsiella pneumoniae has emerged as a significant multidrug-resistant pathogen, classified as a critical priority by the World Health Organization. The rising rates of antibiotic resistance have led to increased therapeutic failures, diminishing the effectiveness of existing antibiotics. Consequently, there is an urgent need for alternative treatments to effectively inhibit the growth of K. pneumoniae and mitigate associated diseases. Phytochemicals have demonstrated potential advantages over traditional antibiotics, prompting their exploration as innovative therapeutic agents. This study aimed to identify phytochemicals that can inhibit dapB, a vital enzyme in the lysine biosynthesis pathway of K. pneumoniae, which is essential for protein synthesis and the cross-linking of the bacterial peptidoglycan cell wall. We screened 17,934 phytochemicals based on Lipinski's Rule of Five, along with their Absorption, Distribution, Metabolism, Excretion properties and toxicological parameters. Next, we conducted triplicate docking studies against dapB to evaluate the library further. The most promising molecules then underwent 100 ns Molecular Dynamics simulations in triplicate, followed by binding free energy calculations to identify potential dapB inhibitors. This in silico analysis highlighted limonin as a promising inhibitor of dapB in K. pneumoniae. Further experimental validation is crucial to enhance limonin's potential as a novel therapeutic agent against K. pneumoniae-associated diseases., (© 2024 Wiley‐VCH GmbH.)

Understanding the lattice thermal conductivity ( κ l ) of β-Ga 2 O 3 is very intriguing owing to its advantages in high-voltage and high-temperature applications. Despite several attempts, the underlying mechanism and causes of the notable discrepancies found in the κ l values of β-Ga 2 O 3 along [100] and [001] directions calculated using first principles remained unresolved. We demonstrate that the understanding of the nature of chemical bonding is crucial to overcome the inconsistency in theoretically reported κ l values. In low-symmetry structures such as β-Ga 2 O 3 , the nature of the interactions is primarily long-range; therefore, a sufficiently large supercell inclusive of various bonding characteristics is required to capture relevant phonon wavelengths. Bonding nature-aware structure modeling allows precise estimation of acoustic and optical mode contributions towards κ l . Additionally, phonon mean free path analysis confirms that considering only third-order interaction terms is adequate to determine the κ l of β-Ga 2 O 3 . The calculated κ l values are in excellent agreement with experimentally reported values in all three directions. Our results establish that the bonding nature and its influence on phonon scattering are essential to consider in calculating κ l accurately.

Traditionally, management of early-stage breast cancer has required adjuvant radiation therapy following breast conserving surgery, due to decreased local recurrence and breast cancer mortality. However, over the past decade, there has been an increasing emphasis on potential overtreatment of patients with early-stage breast cancer. This has given rise to questions of how to optimize deintensification of treatment in this cohort of patients while maintaining clinical outcomes. A multitude of studies have focused on identification of a subset of patients with invasive breast cancer who were at low risk of local recurrence based on clinicopathologic features and therefore suitable for RT omission. These studies have failed to identify a subset that does not from RT with respect to local control. Several ongoing trials are evaluating alternative approaches to deintensification while focusing on tumor biology. With regards to ductal carcinoma in situ (DCIS), the role of RT has been questioned since breast conservation was utilized. Paralleling invasive disease studies, studies have sought to use clinicopathologic features to identify low risk patients suitable for RT omission but have failed to identify a subset that does not from RT with respect to local control. Use of new assays in patients with DCIS may represent the ideal approach for risk stratification and appropriate deintensification. At this time, when considering deintensification, individualizing treatment decisions with a focus on shared decision making is paramount., Competing Interests: Disclosure The author Chirag Shah reported Consultant Impedimed, PreludeDX, and Videra Surgical as conflicts of interest. The remaining authors have stated that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cancer is characterized by genetic instability due to accumulation of somatic mutations in the genes which generate neoepitopes (mutated epitopes) for targeting by Cytotoxic T lymphocytes (CTL). Breast cancer has a high transformation rate with unique composition of mutational burden and neoepitopes load that open a platform to designing a neoepitopes-based vaccine. Neoepitopes-based therapeutic cancer vaccines designed by neoantigens have shown to be feasible, nontoxic, and immunogenic in cancer patients. Stimulation of CTL by neoepitope-based vaccine of self-antigenic proteins plays a key role in distinguishing cancer cells from normal cells and selectively targets only malignant cells. A neoepitopes-based vaccine to combat breast cancer was designed by combining immunology and bioinformatics approaches. The vaccine construct was assembled by the fusion of CTL neoepitopes, helper sequences (used for better separation of the epitopes), and adjuvant together with linkers. The neoepitopes were identified from somatic mutations in the MUC16, TP53, RYR2, F5, DNAH17, ASPM, and ABCA13 self-antigenic proteins. The vaccine construct was undertaken to study the immune simulations (IS), physiochemical characteristics (PP), molecular docking (MD) and simulations, and cloning in appropriate vector. Together, these parameters establish safety, stability, and a strong binding affinity against class I MHC molecules capable of inducing a complete immune response against breast cancer cells.Communicated by Ramaswamy H. Sarma.

In the present era of "Diabetic Pandemic", peptide-based therapies have generated immense interest however, are facing odds due to inevitable limitations like stability, delivery complications and off-target effects. One such promising molecule is C-peptide (CPep, 31 amino acid polypeptide with t 1/2 30 min); it is a cleaved subunit of pro-insulin, well known to suppress microvascular complications in kidney but has not been able to undergo translation to the clinic till date. Herein, a polymeric CPep nano-complexes (NPX) was prepared by leveraging electrostatic interaction between in-house synthesized cationic, polyethylene carbonate (PEC) based copolymer (Mol. wt. 44,767 Da) and negatively charged CPep (Mol. wt. 3299 Da) at pH 7.4 and further evaluated in vitro and in vivo. NPX exhibited a spherical morphology with a particle size of 167 nm and zeta potential equivalent to +10.3, with 85.70 % of CPep complexation efficiency. The cellular uptake of FITC-tagged CPep NPX was 95.61 % in normal rat kidney cells, NRK-52E. Additionally, the hemocompatible NPX showed prominent cell-proliferative, anti-oxidative (1.8 folds increased GSH; 2.8 folds reduced nitrite concentration) and anti-inflammatory activity in metabolic stress induced NRK-52E cells as well. The observation was further confirmed by upregulation of anti-apoptotic protein BCl2 by 3.5 folds, and proliferative markers (β1-integrin and EGFR) by 3.5 and 2.3 folds, respectively, compared to the high glucose treated control group. Pharmacokinetic study of NPX in Wistar rats revealed a 6.34 folds greater half-life than free CPep. In in-vivo efficacy study in STZ-induced diabetic nephropathy animal model, NPX reduced blood glucose levels and IL-6 levels significantly by 1.3 and 2.5 folds, respectively, as compared to the disease control group. The above findings suggested that NPX has tremendous potential to impart sustained release of CPep, resulting in enhanced efficacy to treat diabetes-induced nephropathy and significantly improved renal pathology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The incidence of nerve tissue injuries, such as peripheral nerve injury, spinal cord injury, traumatic brain injury, and various neurodegenerative diseases (NDs), is continuously increasing because of stress, physical and chemical trauma, and the aging population worldwide. Restoration of the damaged nervous system is challenging because of its structural and functional complexity and limited regenerative ability. Additionally, there is no cure available for NDs except for medications that provide symptomatic relief. Stem cells offer an alternative approach for promoting damage repair, but their efficacy is limited by a compromised survival rate and neurogenesis process. To address these challenges, neural tissue engineering has emerged as a promising strategy in which stem cells are seeded or encapsulated within a suitable biomaterial construct, increasing cell survival and neurogenesis. Numerous biomaterials are utilized to create different types of constructs for this purpose. Researchers are trying to develop ideal scaffolds that combine biomaterials, cells, and molecules that exactly mimic the biological and mechanical properties of the tissue to achieve functional recovery associated with neurological dysfunction. This review focuses on exploring the development and applications of different biomaterials for their potential use in the diagnosis, therapy, nerve tissue regeneration, and treatment of neurological disorders., (© 2024 The Author(s). Macromolecular Bioscience published by Wiley‐VCH GmbH.)

Smoothing filters are widely used in EEG signal processing for noise removal while preserving signals' features. Inspired by our recent work on Upscale and Downscale Representation (UDR), this paper proposes a cascade arrangement of some effective image-processing techniques for signal filtering in the image domain. The UDR concept is to visualize EEG signals at an appropriate line width and convert it to a binary image. The smoothing process is then conducted by skeletonizing the signal object to a unit width and projecting it back to the time domain. Two successive UDRs could result in a better-smoothing performance, but their binary image conversion should be restricted. The process is computationally ineffective, especially at higher line width values. Cascaded Thinning UDR (CTUDR) is proposed, exploiting morphological operations to perform a two-stage upscale and downscale within one binary image representation. CTUDR is verified on a signal smoothing and classification task and compared with conventional techniques, such as the Moving Average, the Binomial, the Median, and the Savitzky Golay filters. Simulated EEG data with added white Gaussian noise is employed in the former, while cognitive conflict data obtained from a 3D object selection task is utilized in the latter. CTUDR outperforms its counterparts, scoring the best fitting error and correlation coefficient in signal smoothing while achieving the highest gain in Accuracy (0.7640%) and F-measure (0.7607%) when used as a smoothing filter for training data of EEGNet.

Epigenetic modifications play a pivotal role in the process of neurogenesis. Among these modifications, reversible acetylation fine-tunes gene expression for both embryonic and adult neurogenesis. The CBP/KAT3A and its paralogue p300/KAT3B are well-known lysine acetyltransferases with transcriptional coactivation ability that engage in neural plasticity and memory. The exclusive role of their KAT activity in neurogenesis and memory could not be addressed due to the absence of a p300/CBP modulator, which can cross the blood-brain barrier. Previous work from our laboratory has shown that a small molecule activator, TTK21, specific to CBP/p300, when conjugated to glucose-derived carbon nanospheres (CSP), is efficiently delivered to the mouse brain and could induce dendritic branching and extend long-term memory. However, the molecular mechanisms of p300 acetyltransferase activity-dependent enhanced dendritogenesis are yet to be understood. Here, we report that CSP-TTK21 treatment to primary neuronal culture derived from mouse embryo enhances the expression of five critical genes: Neurod1 (central nervous system development), Tubb3 (immature neural marker), Camk2a (synaptic plasticity and LTP), Snap25 (spine morphogenesis plasticity), and Scn2a (propagation of the action potential). Activation of these genes by inducing the p300/CBP KAT activity presumably promotes the maturation and differentiation of adult neuronal progenitors and thereby the formation of long and highly branched doublecortin-positive functional neurons in the subgranular zone of the dentate gyrus.

The growing challenge of food waste management presents a critical opportunity for advancing the circular bioeconomy, aiming to transform waste into valuable resources. This paper explores innovative strategies for converting food wastes into renewable food resources, emphasizing the integration of sustainable technologies and zero-waste principles. The main objective is to demonstrate how these approaches can contribute to a more sustainable food system by reducing environmental impacts and enhancing resource efficiency. Novel contributions of this study include the development of bioproducts from various food waste streams, highlighting the potential of underutilized resources like bread and jackfruit waste. Through case studies and experimental findings, the paper illustrates the successful application of green techniques, such as microbial fermentation and bioprocessing, in valorizing food wastes. The implications of this research extend to policy frameworks, encouraging the adoption of circular bioeconomy models that not only address waste management challenges but also foster economic growth and sustainability. These findings underscore the potential for food waste to serve as a cornerstone in the transition to a circular, regenerative economy.

Ischemic diseases are characterized by obstruction of blood flow to the respective organs, of which ischemia of the heart and brain are the most prominent manifestations with shared pathophysiological mechanisms and risk factors. While most revascularization therapies aim to restore blood flow, this can be challenging due to the limited therapeutic window available for treatment approaches. For a very long time, mesenchymal stromal cells have been used to treat cerebral and cardiac ischemia. However, their application is restricted either by inefficient mode of delivery or the low cell survival rates following implantation into the ischemic microenvironment. Nonetheless, several studies are currently focusing on using of mesenchymal stromal cells engineered to overexpress therapeutic genes as a cell-based gene therapy to restore angiogenesis. This review delves into the utilization of MSCs for angiogenesis and the applications of engineered MSCs for the treatment of cardiac and cerebral ischemia. Moreover, the safety issues related to the genetic modification of MSCs have also been discussed., (© 2024. The Author(s).)

Background: Females undergoing laparoscopic gynaecological surgeries have a high incidence of postoperative nausea and vomiting. Apart from the established risk factors, hormonal, psychological, genetic and ethnic factors may also contribute to postoperative nausea and vomiting. This study aimed to evaluate the relationship between preoperative anxiety and serum oestrogen level with postoperative nausea and vomiting in patients undergoing diagnostic laparoscopy - hysteroscopy for infertility., Methods: In total, 100 female patients, between the ages of 20-40 years, undergoing diagnostic laparoscopy - hysteroscopy for infertility were recruited for this study. Preoperative anxiety level was assessed using Depression, Anxiety and Stress Scale-21 (DASS-21) Questionnaire. Serum oestrogen samples were taken before anaesthesia. Postoperative nausea and vomiting grading was rated with 0-3 Likert-type scale. An association of anxiety and oestrogen levels to postoperative nausea and vomiting was done., Results: The analysis between median DASS 21 scores to postoperative nausea and vomiting grading showed no association between DASS 21 scores and postoperative nausea and vomiting grades. Comparing the mean oestrogen levels in patients among each grade of postoperative nausea and vomiting showed no significant difference in the mean oestrogen levels., Conclusion: Our study did not find evidence of a significant association between serum oestrogen levels, preoperative anxiety, and postoperative nausea and vomiting., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The management of oral leukoplakia (OL) is challenging because of a high risk for recurrence and malignant transformation (MT), and recurrent OL is associated with a higher risk of MT than nonrecurrent OL. The present meta-analysis aimed to examine the association between OL recurrence and surgical techniques used for their management as well as their clinicopathological factors. Electronic searches were conducted in EMBASE, PubMed, Scopus, and Web of Science to retrieve studies reporting OL recurrence after surgery. The pooled proportion of OL recurrence after surgical excision was estimated. Subgroup analyses were conducted based on the surgical technique, data type, grades of epithelial dysplasia, anatomical subsites, clinical type and size of the lesion, surgical margin, and risk habits. Meta-regression analyses were conducted to identify the association between age, sex, and follow-up duration and OL recurrence. The risk of MT based on the recurrence status was also estimated. A network meta-analysis was performed to determine the surgical modality associated with the least OL recurrence. Eighty studies with a total of 7,614 samples and various surgical modalities (laser-based techniques, conventional scalpel surgery, cryosurgery, and photodynamic therapy) were included in the meta-analysis. A pooled proportion of recurrence of 22% was observed. Laser-based surgeries resulted in fewer OL recurrences than other surgical modalities, and the combination of laser excision and vaporization was identified to be the best treatment approach. OL in the retromolar area and multiple sites, nonhomogeneous OL, advanced age, female sex, inadequate surgical margin, retrospective data, and betel quid chewing habit were significantly associated with higher OL recurrence. Recurrent OL showed a 7.39 times higher risk of MT than nonrecurrent OL. These results suggest that the combination of laser excision and vaporization might reduce OL recurrence. Furthermore, OL in older patients, females, and nonhomogeneous OL need close monitoring after any surgical therapy., 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.

Background: Dietary knowledge, perception and practices may have a role in determining the nutritional status of patients with inflammatory bowel disease (IBD). However, the assessment of these patterns has infrequently been done in developing countries. We aimed to evaluate patients with ulcerative colitis (UC) about their dietary beliefs, practices and changes after the diagnosis., Methods: We conducted a cross-sectional survey among patients with UC at a tertiary care centre in North India. Apart from clinical details, we collected information about dietary beliefs, sources of information, dietary practices and changes after the diagnosis of UC. The information was collected using a designed and pretested survey questionnaire., Results: We included 93 patients with a mean age of 40.6 ± 13.3 years and 49 (52.7%) were men. A majority of patients felt that diet had an important role in the causation of IBD (86%, n  = 80) and triggering relapses (86%, n  = 80). A total of 94.6% of patients ( n  = 88) felt that certain foods (especially spicy and fatty food and milk) items increased the symptoms of IBD. Patients felt that some food items (yogurt and buttermilk) improved the symptoms. A total of 96.8% of patients ( n  = 90) changed their diet in some form (commonly, restriction of milk products and outside food), 64% of patients ( n  = 60) deprived themselves of their favourite food after diagnosis, 80.6% of patients ( n  = 75) felt a need for additional dietary advice. Regular milk intake was seen more often by patients in remission than those with active disease in IBD (36/47 (76.6%) vs 7/15(46.6%), p  = 0.03)., Conclusion: Most patients believe that diet has an important role in the causation, relapses and treatment of UC. Patients also felt the need for more information regarding diet in IBD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

The peroxidase family of enzymes is a ubiquitous cluster of enzymes primarily responsible for the oxidation of organic and inorganic substrates. The mammalian heme peroxidase subfamily is characterized by a covalently linked heme prosthetic group which pays a key role in the oxidation of halides and psuedohalides in their respective hypohalous acid and hypothiocyanous acid under the influence of H 2 O 2 as substrate. The members of the heme peroxidase family include Lactoperoxidase (LPO), Eosinophil peroxidase (EPO), Myeloperoxidase (MPO), Thyroid peroxidase (TPO) and Peroxidasin (PXDN). The biological activity of LPO, MPO and EPO pertains to antibacterial, antifungal and antiviral while TPO is involved in the biosynthesis of the thyroid hormone and PXDN helps maintain the ECM. While these enzymes play several immunomodulatory roles, aberrations in their activity have been implicated in diseases such as myocardial infarction, asthma and Alzheimer's amongst others. The sequence and structural similarities amongst the members of the family are strikingly high while the substrate specificities and subcellular locations vary. Hence, it becomes important to provide a consortium of information regarding the members to study their function, pathological and clinical function., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: BRAFV600E-mutated colorectal cancer (CRC) exhibits a strong correlation with DNA hypermethylation suggesting this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits DNA methyltransferase activity, is not efficacious in BRAFV600E CRC in vivo., Experimental Design: We randomized and treated mice implanted with patient-derived tumor xenografts harboring BRAFV600E mutation with control, 5-azacitidine, vemurafenib (BRAF inhibitor), or the combination. Comprehensive epigenomic profiling was conducted on control and 5-azacitidine-treated tumor samples, including DNA methylation, histone modifications, chromatin accessibility, and gene expression. Combinations of epigenetic agents were explored in preclinical BRAFV600E CRC models., Results: A profound reduction of DNA methylation levels upon 5-azacitidine treatment was confirmed, however, transcriptional repression was not relieved. This study unbiasedly explored the adaptive engagement of other epigenomic modifications upon 5-azacitidine treatment. A loss of histone acetylation and a gain of histone methylations, including H3K27 and H3K4 trimethylation, were observed around these hypomethylated regions suggesting the involvement of polycomb repressive complex (PRC) activity around the genome with loss of DNA methylation, therefore maintaining the repression of key tumor suppressor genes. Combined inhibition of PRC activity through EZH2 inhibitor with 5-azacitidine treatment additively improved efficacies in BRAFV600E CRC cells., Conclusions: In conclusion, DNA hypomethylation by 5-azacitidine exhibits a close association with H3K27me3 and PRC activity in BRAFV600E CRC, and simultaneous blockade of DNMT and EZH2 holds promise as a potential therapeutic strategy for patients with BRAFV600E-mutated CRC.

This study aims to investigate the physical stability, droplet size, zeta potential, and antimicrobial properties of nanoemulsions formulated with betel leaf extract using β-cyclodextrin (CD) and sodium alginate (SA) biopolymers. Nanoemulsions with β-cyclodextrin exhibit superior stability at lower temperatures, with limited droplet size, and strong electrostatic repulsion. Morphological images demonstrate the successful encapsulation of betel leaf extract within both biopolymers, highlighting their potential for antimicrobial applications. Both CD and SA nanoemulsions display inhibitory effects on bacterial strains (E. coli, P. aeruginosa, L. monocytogenes, S. aureus, and B. cereus) and fungal growth (A. brasiliensis, R. stolonifer, F. oxysporum, and C. albicans). SA nanoemulsions show higher antimicrobial activity due to H + ion release, particularly against A. brasiliensis and C. albicans. These findings underscore the potential of betel leaf extract nanoemulsions, especially those with SA, for various antimicrobial applications for sustainable food packaging, highlighting their significance in addressing microbial challenges., 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.)

Central nervous system tuberculosis (CNS-TB) is a severe form of extra-pulmonary tuberculosis with high mortality and morbidity rates. The standard treatment regimen for CNS-TB parallels that of pulmonary TB, despite the challenge posed by the blood-brain barrier (BBB), which limits the efficacy of first-line anti-TB drugs (ATDs). Nose-to-brain (N2B) drug delivery offers a promising solution for achieving high ATD concentrations directly at infection sites in the brain while bypassing the BBB. This study aimed to develop chitosan nanoparticles encapsulating ATDs, specifically isoniazid (INH) and rifampicin (RIF). These nanoparticles were further processed into micro-sized chitosan nano-aggregates (NA) via spray drying. Both INH-NA and RIF-NA showed strong mucoadhesion and significantly higher permeation rates across RPMI 2650 cells compared to free ATDs. Intranasal administration of these NAs to TB-infected mice for four weeks resulted in a significant reduction of mycobacterial load by approximately ∼2.86 Log 10 CFU compared to the untreated group. This preclinical data highlights the efficacy of intranasal chitosan nano-aggregates in treating CNS-TB, demonstrating high therapeutic potential, and addressing brain inflammation challenges. To our knowledge, this study is the first to show nasal delivery of ATD nano-formulations for CNS-TB management.

In this study, we present two fully characterized nickel tetrathiocyanocorroles, representing a novel class of 3d-metallocorroles. These nickel(II) ions form square planar complexes, exhibiting a d 8 -electronic configuration. These anionic complexes are stabilized by the electron-withdrawing SCN groups on the bipyrrole unit of the corrole. The reduced aromaticity in these anionic nickel(II) corrole complexes is evidenced by single crystal X-ray diffraction (XRD) data and a markedly altered absorption profile, with stronger Q bands compared to Soret bands. Notably, the UV-Vis and electrochemical data exhibit significant differences from previously reported nickel(II) corrole radical cation and nickel(II) porphyrin complexes. While these electrochemical data bear a resemblance to those of the anionic nickel(II) corrole by Gross et al. , the UV-Vis data show substantial distinctions. Additionally, we explore the utilization of nickel(II)-corrole@CC (where CC denotes carbon cloth) as an electrocatalyst for the oxygen evolution reaction (OER) in an alkaline medium. During electrochemical water oxidation, the molecular catalyst is partially converted to nickel (oxy)hydroxide, Ni(O)OH. The structure reveals the coexistence of the molecular complex and Ni(O)OH in the active catalyst, achieving a turnover frequency (TOF) of 3.32 × 10 -2 s -1 . The synergy between the homogeneous and heterogeneous phases improves the OER activity, providing more active sites and edge sites and enhancing interfacial charge transfer.

Gall bladder cancer (GBC) is common among the socioeconomically deprived populations of certain geographical regions. Aflatoxin is a genotoxic hepatocarcinogen, which is recognized to have a role in the pathogenesis of hepatocellular carcinoma. However, the role of aflatoxin in the pathogenesis of GBC is largely unknown. We determined serum AFB1-Lys albumin adduct (AAA) levels as a marker of aflatoxin exposure in the patients with GBC and compared to those without GBC. The relationship of AAA levels to cytogenetic (TP53mutation&HER2/neu amplification) and radiological characteristics of the tumor was assessed. We included GBC cases (n = 51) and non-GBC controls (n = 100). Mean serum AAA levels were higher in the GBC group (n = 51) than those without GBC (n = 100) (26.1 ± 12.2 vs. 13.1 ± 11.9 ng/mL; p < .001). HER2/neu expression was associated with higher AAA levels compared to those with equivocal or negative expression (43.9 ± 3 vs. 28.6 ± 10 vs. 19.3 ± 7 ng/mL; p < .001). Older age (age >50 years) (odds ratio [OR] = 3.2 [CI: 1.3-8.2]; p = .013), positive Helicobacter pylori serology (OR = 5.1 [CI: 1.4-17.8]; p = .012), presence of GS (OR = 5 [CI: 1.5-16.9]; p = .009) and detectable AAA levels (OR = 6.8 [CI: 1.3-35.7]; p = .024) were independent risk factors for the presence of the GBC among all study subjects. Among patients harboring GS, older age (age >50 years) (OR = 4.5 [CI: 1.3-14.9]; p = .015), female gender (OR = 3.8 [CI: 1.2-12.5]; p = .027), presence of multiple GS (OR = 21.9 [CI: 4.8-100.4]; p < .001) and high serum AAA levels (OR = 5.3 [CI: 1.6-17.3]; p = .006) were independent risk factors for the presence of the GBC. Elderly age >50 years (OR = 2.6 [CI: 1.3-5.2]; p = .010) and frequent peanut consumption (OR = 2.3 [CI: 1.1-4.9]; p = .030) were independent risk factors for high serum AAA levels. The current study has implications for the prevention of GBC through the reduction of dietary aflatoxin exposure., (© 2024 UICC.)

Excessive electricity usage in buildings, notably for heating and cooling, accounts for over 30% of energy consumption, creating a pressing need for energy-saving solutions. Electrochromic Smart Windows (ECSW) aims to reduce energy use while maintaining comfort but faces high costs due to materials like tin-doped indium oxide (ITO) and thick electrochromic films. Moreover, achieving full opacity in the colored state of ECSW is a bottleneck for the industry to overcome privacy concerns. Herein, efforts are directed toward finding cost-efficient alternatives, with all-tungsten-based mesh networks showing promise due to enhanced stability. This newly developed ITO-free, all-tungsten ECSW displays minimal transmittance (≈3%) in the colored state using only 260 nm thick sub-stoichiometric tungsten oxide (WO 3-x ) film within a lithium-ion-based electrolyte. The ECSW device of size (25 cm 2 ) also demonstrates areal capacitance of ≈13 mF cm -2 to power a liquid crystal display (LCD) for ≈25 min, showcasing its energy storage capabilities. Additionally, to confirm scalability and cost-effectiveness, a larger 15 × 15 cm 2 ECSW utilized a single hybrid electrode, highlighting the potential for reducing costs when scaling up production processes. This advancement represents a significant stride toward accessible and energy-efficient smart window technology, offering broader applicability within modern architectural practices., (© 2024 Wiley‐VCH GmbH.)

Background: Hyperreflective foci (HRF) are biomarkers in detection of diabetic retinopathy (DR). Presence of HRF on spectral domain optical coherence tomography (SD-OCT) can give a correlation with visual acuity change and grades of DR. Purpose of this study is to determine the presence, location, and role of HRF in the retina of DM patients with and without retinopathy., Methods: A total of 192 eyes of patients suffering from type II DM were evaluated. Patients were divided into 2 groups, with Group A having diabetes without retinopathy (20 patients) and group B (76 patients) having diabetes and various grades of retinopathy. SD-OCT was performed in all patients, passing through the center of fovea. On OCT, presence and absence of HRF were noted. Characteristics of the hyper-reflective spots were evaluated: location, shape, size, back shadowing and association with central macular thickness (CMT), visual acuity, and grades of retinopathy., Results: HRF were present in 169 eyes (88%) out of 192 eyes. The shape and location of HRF tend to change with disease progression. HRF were significantly associated with increasing grades of retinopathy (χ2 = 57.586, p < 0.01) Association of macular edema was significant with both retinopathy (χ2 = 8.895, p < 0.05) and HRF (χ2 = 34.720, p < 0.01). Association of best-corrected visual acuity with HRF (χ2 = 21.232, p < 0.01), macular edema (χ2 = 86.960, p < 0.01), and CMT (χ2 = 47.959, p< 0 .01) was significant., Conclusion: HRF is a great indicator for early diagnosis of subclinical retinopathy and can be used to monitor the progression of disease and development of macular edema. Significant difference is present in HRF distribution and morphology., (© 2024 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Oculomotor nerve supplies all extraocular muscles (medial rectus, inferior oblique, superior rectus, and inferior rectus) except superior oblique and lateral rectus. Thus, isolated medial rectus palsy only in a healthy individual is very rare and may indicate underlying systemic pathology. Here we present such rare and only case report of a healthy young female who presented with sudden onset deviation in her left eye and on investigations was detected to have mid-brain lesion. Thus, extraocular muscle palsies in a young patient needs thorough investigation to rule out any causative systemic disorder so that early intervention can be sought., Competing Interests: The authors have none to declare, (© 2022 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Introduction: Ischemia/reperfusion cascade can cause severe tissue damage as documented in myocardial infarction, stroke, and peripheral occlusive vascular; however, Chin et al. first identified unexplained neurological deterioration after decompressive spinal surgery and attributed this to reperfusion injury of the spinal cord. As this appears as hyperintense signal changes in post-operative T2-weighted magnetic resonance image (MRI) sequences, it is termed as "white cord syndrome.", Case Report: A 63-year-old man presented with cervical myelopathy due to an ossified posterior longitudinal ligament and ossified ligamentum flavum, having Nurick's Grade IV posted for surgery. The patient underwent posterior instrumented decompression from 2nd cervical to 5th dorsal spine. Postoperatively, he had neurological deterioration and was investigated and found to have extensive cervical cord edema on MRI. There was no implant malposition., Conclusion: WCS has to be ruled out in a case of unexplained neurological deterioration after decompressive spinal surgery, especially in the cervical and dorsal spine. The exact mechanism and treatment of WCS remain unexplained; spine surgeons should warn patients about WCS before surgery to prevent ethical and medicolegal issues., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Host-directed therapy (HDT) with vitamin D in tuberculosis (TB) is beneficial only if the subject is deficient in vitamin D. We investigated pulmonary delivery of 1,25-dihydroxy vitamin D 3 (calcitriol) in mice infected with Mycobacterium tuberculosis (Mtb). We made two kinds of dry powder inhalations (DPI)- soluble particles or poly(lactide) (PLA) particles. We compared treatment outcomes when infected mice were dosed with a DPI alone or as an adjunct to standard oral anti-TB therapy (ATT). Mice infected on Day 0 were treated between Days 28-56 and followed up on Days 57, 71, and 85. Neither DPI significantly reduced Mtb colony forming units (CFU) in the lungs. Combining DPI with ATT did not significantly augment bactericidal activity in the lungs, but CFU were 2-log lower in the spleen. CFU showed a rising trend on stopping treatment, sharper in groups that did not receive calcitriol. Lung morphology and histology improved markedly in animals that received PLA DPI; with or without concomitant ATT. Groups receiving soluble DPI had high mortality. DPI elicited cathelicidin, interleukin (IL)-1 and induced autophagy on days 57, 71, and 85. Macrophage-targeted calcitriol is therefore bacteriostatic, evokes innate microbicidal mechanisms, and mitigates pathology arising from the host response to Mtb., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cytokines regulate immune responses essential for maintaining immune homeostasis, as deregulated cytokine signaling can lead to detrimental outcomes, including inflammatory disorders. The antioxidants emerge as promising therapeutic agents because they mitigate oxidative stress and modulate inflammatory pathways. Antioxidants can potentially ameliorate inflammation-related disorders by counteracting excessive cytokine-mediated inflammatory responses. A comprehensive understanding of cytokine-mediated inflammatory pathways and the interplay with antioxidants is paramount for developing natural therapeutic agents targeting inflammation-related disorders and helping to improve clinical outcomes and enhance the quality of life for patients. Among these antioxidants, curcumin, vitamin C, vitamin D, propolis, allicin, and cinnamaldehyde have garnered attention for their anti-inflammatory properties and potential therapeutic benefits. This review highlights the interrelationship between cytokines-mediated disorders in various diseases and therapeutic approaches involving antioxidants., Competing Interests: Declaration of Competing Interest The Authors declare no conflict of interests, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Copper and Mercury ions have vital role to play in biological world as their excess or deficiency can cause different type of diseases in human being as well as biological species including plants and animals. Therefore, their detection at trace level becomes very important in term of biological. The current studies embody the fabrication, structural characterization and recognition behavior of a novel rhodamine B hydrazone formed when hydrazide of rhodamine B was condensed with 5-Allyl-3-methoxy salicylaldehyde (RBMA). RBMA was found to be responsive towards the very trace level of Cu 2+ and Hg 2+ among other tested cations so far. The sensing procedure is based on the classical opening of the spiroatom ring of rhodamine. The limit of detection (LOD) and binding constant is 5.35 ppm, 2.06 × 10 4  M -1 and 5.16 ppm, 1.26 × 10 4  M -1 for Cu 2+ and Hg 2+ ions respectively. The probable mechanism correlates the specific binding of RBMA with Cu 2+ and Hg 2+ ions. The 1:1 stoichiometry of RBMA with Cu 2+ and Hg 2+ ions have been supported by HRMS, FT-IR data, Job's plot, and binding constant data. Reversibility is well exhibited by RBMA by the involvement of CO 3 2- ions via demetallation process. The real time application is well demonstrated by the use of paper strip test. The DFT study also carried out which agrees well with the experimental findings. The results displayed the novelty of this current work towards the trace level analysis of the Cu 2+ and Hg 2+ of the cations which are play the crucial role in industry., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Mental and physical non-communicable diseases (NCDs) coexist, because they share common environmental and behavioral risk factors. The treatment gap for common mental disorders, such as depression, anxiety, and substance use, is large compared to other NCDs., Objective: To determine the prevalence and treatment gap of common mental disorders among patients with non-communicable diseases., Methodology: The community-based cross-sectional study was conducted in the rural parts of East India, in people aged 30 years and older with NCDs. A simple random sample was chosen to select the villages and participants. Eligible participants administered with screening and diagnostic questionnaire for depression, anxiety, and substance use. Those diagnosed with mental disorders were again assessed for treatment status in the last 12 months. Non-receipt of treatment was considered as treatment gap., Results: A total of 515 participants were included in the analysis. The overall prevalence of common mental disorders among the study population was 46.4% (95% CI 42.0-50.8), and excluding substance use, the prevalence was 11.7% (95% CI 9.0-14.7). The treatment gap for common mental disorders among patients with non-communicable diseases, including and excluding substance use, was 98.3% (95% CI 95.8-99.5) and 93.3% (95% CI 83.8-98.2), respectively., Conclusion: The prevalence and treatment gap of common mental disorders among persons with NCDs was high. Public health interventions need to be emphasized for the integration of mental health care into NCD care., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The human cytochrome P450 (CYP) 1, 2 and 3 families of enzymes are responsible for the biotransformation of a majority of the currently available pharmaceutical drugs. The highly polymorphic CYP2C9 predominantly metabolizes many drugs including anticoagulant S-warfarin, anti-hypertensive losartan, anti-diabetic tolbutamide, analgesic ibuprofen, etc. There are >80 single nucleotide changes identified in CYP2C9, many of which significantly alter the clearance of important drugs. Here we report the structural and biophysical analysis of two polymorphic variants, CYP2C9*14 (Arg125His) and CYP2C9*27 (Arg150Leu) complexed with losartan. The X-ray crystal structures of the CYP2C9*14 and *27 illustrate the binding of two losartan molecules, one in the active site near heme and another on the periphery. Both losartan molecules are bound in an identical conformation to that observed in the previously solved CYP2C9 wild-type complex, however, the number of losartan differs from the wild-type structure, which showed binding of three molecules. Additionally, isothermal titration calorimetry experiments reveal a lower binding affinity of losartan with *14 and *27 variants when compared to the wild-type. Overall, the results provide new insights into the effects of these genetic polymorphisms and suggests a possible mechanism contributing to reduced metabolic activity in patients carrying these alleles., 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 © 2023. Published by Elsevier Inc.)

Acinetobacter baumannii is an ESKAPE pathogen that causes endocarditis, pneumonia, blood infections, urinary tract infections, and several other illnesses. In addition, it is mainly responsible for nosocomial infection-related mortality. Gram-negative A. baumannii bacterium (AYE Strain) has high MDR and XDR levels. Due to its function in synthesizing purines and amino acids, folic acid is a significant molecule necessary for the growth of bacteria. The metabolic pathway of folate production is therefore a potential therapeutic target to inhibit bacterial growth. In the current study, the three-dimensional model of 6-Hydroxy-methyl dihydropterinpyrophosphokinase (HPPK) was predicted and subsequently processed through a virtual high throughput screening (vHTS) against compounds from Enamine HTSC library, that could bind to its active site. Three lead candidates (Z73322064, Z354558542, and Z906123504) and a control molecule (7,8 dihydro-7,7-dimethyl-6-hydroxymethlypterin; Accession Number: DB02278) were identified using several screening criteria namely estimated binding affinity, estimated inhibition constant, drug-like properties, ADME properties, mode of binding, and interaction patterns of the screened compounds. The physiological behavior of ligand binding on the HPPK enzyme was then studied using molecular dynamics simulations of apo and ligand bound complexes. This study proposed the following three molecules: Z73322064, Z354338542, and Z906123504 as promising lead candidates against the substrate-binding site of the HPPK enzyme from A. baumannii using global, essential dynamics studies along with MM/PBSA based binding free energy analysis.Communicated by Ramaswamy H. Sarma.

Microplastics generated from fragmentation of leftover plastics and industrial waste has reached in the remotely located Asian water tower (AWT) region, the 3rd pole of earth and origin site of several freshwater rivers. The accumulation of microplastics in AWT ecosystem has potential to alter the climatic condition contributing in global warming and disturbing the biodiversity structural dynamics. The present paper provides a comprehensive critical discussion over quantitative assessment of microplastics in different ecosystems (i.e. river, lakes, sediment and snow or glacier) of AWT. The hydrodynamic fate and transport of microplastics and their ecological impact on hydromorphology and biodiversity of AWT has been exemplified. Furthermore, key challenges, perspectives and research directions are identified to mitigate microplastics associated problems. During survey, the coloured polyethylene and polyurethane fibers are the predominant microplastics found in most areas of AWT. These bio-accumulated MPs alter the rhizospheric community structure and deteriorate nitrogen fixation process in plants. Significance in climate change, MPs pollution is enhancing the emissions of greenhouse gases (NH 3 by ∼34% and CH 4 by ∼9%), contributing in global warming. Considering the seriousness of MPs pollution, this review study can enlighten the pathways to investigate the effect of MPs and to develop monitoring tools and sustainable remediation technologies with feasible regulatory strategies maintaining the natural significance of AWT region., 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.)

Tissue on a chip or organ-on-chip (OOC) is a technology that's dignified to form a transformation in drug discovery through the use of advanced platforms. These are 3D in -vitro cell culture models that mimic micro-environment of human organs or tissues on artificial microstructures built on a portable microfluidic chip without involving sacrificial humans or animals. This review article aims to offer readers a thorough and insightful understanding of technology. It begins with an in-depth understanding of chip design and instrumentation, underlining its pivotal role and the imperative need for its development in the modern scientific landscape. The review article explores into the myriad applications of OOC technology, showcasing its transformative impact on fields such as radiobiology, drug discovery and screening, and its pioneering use in space research. In addition to highlighting these diverse applications, the article provides a critical analysis of the current challenges that OOC technology faces. It examines both the biological and technical limitations that hinder its progress and efficacy and discusses the potential advancements and innovations that could drive the OOC technology forward. Through this comprehensive review, readers will gain a deep appreciation of the significance, capabilities, and evolving landscape of OOC technology., (© 2024 The Authors.)

Modern cancer diagnostics and treatment options have greatly improved survival rates; the illness remains a major cause of mortality worldwide. Current treatments for cancer, such as chemotherapy, are not cancer-specific and may cause harm to healthy cells; therefore, it is imperative that new drugs for cancer be developed that are both safe and effective. It has been found that lactic acid bacteria (LAB) have the potential to produce bacteriocins, which could potentially offer a promising alternative for cancer treatment. They have been shown in several studies to be effective against cancer cells while having no effect on healthy cells. More research is needed to fully understand the potential of LAB bacteriocins as anti-cancer medicines, to find the appropriate dose and delivery route, and to conduct clinical trials to evaluate the effectiveness and safety of the products in human patients, as is suggested by this work. Furthermore, LAB bacteriocins may evolve into a significant new class of anti-cancer drugs and food products. Patients with cancer may have a safe and effective alternative treatment option in the form of anti-cancer foods and drugs. Therefore, the aim of this study is to provide an in-depth analysis of the recent breakthroughs and potential future technical advancements of significant bacteriocins that are produced by LAB, how these bacteriocins function, and how these bacteriocins may be utilized as an anti-cancer agent. In addition, the current analysis emphasizes the significant constraints and boundaries that bacteriocins face when they are used as an anti-cancer factor., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Diabetic nephropathy (DN) is a progressive kidney disorder that develops as a complication of diabetes due to long-term exposure to elevated blood glucose levels (BGLs). In this case, an intervention of therapeutic moieties is needed to target the specific elements involved in diabetes to prevent/delay the deterioration of kidney function. Therefore, the present study focused on designing and evaluating a potent nano-formulation of a combination of C-peptide (CPep) and the anti-diabetic drug lisofylline (LSF) to prevent streptozotocin (STZ)-induced DN. As a strategic intervention, an LSF-oleic acid prodrug (LSF-OA) was initially synthesized and further encapsulated in an in-house-synthesized cationic polymer [(mPEG- b -P(CB-{g-DMDP}- co -LA)); mPLM] to prepare polymeric nano-complexes of CPep via electrostatic interaction, possessing a size of 218.6 ± 14.4 nm and zeta potential of +5.2 mV together with stability for 30 days at 25 °C. mPLM-LSF-OA-CPep nanoparticles demonstrated hemocompatibility with RBCs and exhibited potent anti-oxidant activity by reducing nitrite levels, inducing the release of anti-oxidant GSH and protecting metabolically stressed rat kidneys and murine insulinoma cells from apoptosis. In vivo pharmacokinetics depicted an increase in t ½ and mean residence time in rats, which further improved the BGL and renal conditions and reduced plasma IL-6 and TNF-α levels in the STZ-induced DN animal model when treated with mPLM-LSF-OA-CPep compared to free LSF and CPep. Moreover, an increase in the plasma insulin level and detection of proliferative marker cells in pancreatic islets suggested the regeneration of β-cells in diabetic animals.

Worldwide, colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related deaths. Thymidylate synthase (TS) is a crucial component of DNA biosynthesis and has drawn interest as an essential target for cancer treatment. In the current work, we have designed and synthesized twenty-eight new diaryl-based pyrido[2,3-d]pyrimidine/alkyl-substituted pyrido[2,3-d]pyrimidine derivatives and evaluated their anticancer activity against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines cell lines. Additionally, we have carried out TS inhibitory activity and in silico studies for compounds 1n and 2j. All the synthesized compounds exhibited good anticancer activity, but among them, compounds 1n and 2j showed excellent anticancer activity, having IC 50 values of 1.98 ± 0.69, 2.18 ± 0.93, 4.04 ± 1.06, and 4.18 ± 1.87 µM; and 1.48 ± 0.86, 3.18 ± 0.79, 3.44 ± 1.51, and 5.18 ± 1.85 µM, against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines respectively with control raltitrexed (IC 50 1.07 ± 1.08, 1.98 ± 0.72, 1.34 ± 1.0, and 3.09 ± 0.96 µM, respectively) and hTS inhibitory activity with IC 50 values of 20.47 ± 1.09 and 13.48 ± 0.96 nM with control raltitrexed (IC 50 14.95 ± 1.01 nM). Further, the mechanism of inhibition was revealed by molecular docking, which showed the binding pattern of 1n and 2j to the catalytic site of TS with docking scores of -10.6 and - 9.5 kcal/mol, respectively, with reference raltitrexed (-9.4 kcal/mol). Additionally, the assessment of physicochemical, biochemical, structural, and toxicological characteristics were also in the acceptable range for these compounds. Based on the anticancer activity of compounds, SAR was also performed for lead optimization., (© 2024. The Author(s).)

In search of new opportunities to develop Trypanosoma brucei phosphodiesterase B1 (TbrPDEB1) inhibitors that have selectivity over the off-target human PDE4 (hPDE4), different stages of a fragment-growing campaign were studied using a variety of biochemical, structural, thermodynamic, and kinetic binding assays. Remarkable differences in binding kinetics were identified and this kinetic selectivity was explored with computational methods, including molecular dynamics and interaction fingerprint analyses. These studies indicate that a key hydrogen bond between GlnQ.50 and the inhibitors is exposed to a water channel in TbrPDEB1, leading to fast unbinding. This water channel is not present in hPDE4, leading to inhibitors with a longer residence time. The computer-aided drug design protocols were applied to a recently disclosed TbrPDEB1 inhibitor with a different scaffold and our results confirm that shielding this key hydrogen bond through disruption of the water channel represents a viable design strategy to develop more selective inhibitors of TbrPDEB1. Our work shows how computational protocols can be used to understand the contribution of solvent dynamics to inhibitor binding, and our results can be applied in the design of selective inhibitors for homologous PDEs found in related parasites., (© 2024 Wiley‐VCH GmbH.)

The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic-pituitary-adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR's functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body's ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders., (© 2024. The Author(s).)

Grave's disease affects numerous patients globally, but its impact on health-related quality of life (HR-QoL) in relation to geographical disparities remains under-explored. This cross-sectional study aimed to assess the influence of urban versus rural residence on HR-QoL among patients diagnosed with Graves' Disease in Rajasthan, India. One hundred seven Graves' disease patients from rural and urban endocrine centers were analyzed. The rural group included 52 patients (24 males, 28 females), averaging 38.9 ± 10.9 years of age, while the urban group had 55 (13 males, 42 females) with an average age of 39.1 ± 14.2 years. We found differences between rural and urban patients in terms of gender ratio, BMI, smoking habits, and obesity. Multivariable linear regression was used in both groups to determine the association between the baseline characteristics of Graves' patients from both areas and HR-QOL. Health-related quality of life, assessed via the SF-36 questionnaire, indicated higher general health and role emotional scores among urban patients. Our study found that the duration of Graves' disease in rural centers negatively impacted physical health scores. In urban patients, age and BMI influenced physical health, while gender and disease duration affected mental health scores in rural patients. Age impacted mental health in urban patients. Rural patients had a poorer quality of life compared to urban patients. Differences in gender distribution, BMI, smoking habits, and obesity rates revealed disparities in Graves' disease between rural and urban patients in India, highlighting the need for better healthcare infrastructure and awareness in rural areas., 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 Mishra, Singh, Rajotiya, Debnath, Kumar, Singh, Snehpreet, Raj, Singh, Bareth, Nathiya and Singh Tomar.)

Introduction: We aimed at evaluating the safety and efficacy of self-expandable metallic stent (SEMS) insertion for managing patients with benign gastric outlet obstruction (GOO)., Methods: This prospective interventional study included 23 patients. All consecutive treatment-naïve symptomatic patients with benign GOO were recruited. Fully covered SEMS were deployed across the stricture under fluoroscopic and endoscopic guidance. Technical success, clinical success and sustained treatment response (STR) were assessed. Technical success was defined as the successful deployment of SEMS at the desired anatomic location. Clinical success was defined as the resolution of symptoms and an increase in Gastric Outlet Obstruction Scoring System (GOOSS) of at least 1 point from the baseline score on Day 7. STR was assessed at four and eight weeks post stent removal in patients who had a response at week four. Factors associated with stent migration and non-response at week four were also assessed., Results: The median age of the study population was 30 years (range 19-65 years). Males constituted 65.22%. Most patients presented with vomiting (100%) and abdominal pain (95.65%). Peptic stricture was most common etiology for GOO (60.9%) followed by tubercular (26.1%) and corrosive (13%). Most common site of obstruction was junction of first and second part of duodenum (69.57%) followed by pyloric (30.43%). Median length of stricture was 2 cm (range 1.5-4). Technical success was achieved in all 23 patients (100%). Clinical success was achieved in 21 patients (91.3%). Response at Day 28 was seen in 20 patients (86.95%). Eighteen of 20 (90%) patients who had a response at week four had STR at week four and week eight after stent removal. Stent migration occurred in five (21.7%) patients. On univariate analysis, stricture length, calibre and stent length were found to predict migration., Conclusions: Fully covered SEMS was an effective and safe management modality in patients with benign GOO. Stent migration remains a troublesome disadvantage., (© 2024. Indian Society of Gastroenterology.)

Cesium lead halide perovskite (CsPbX 3 ; X = Cl, Br, I) nanocrystals showing intense band-edge emission and high photoluminescence quantum yield are known to be a potential candidate for application in optoelectronic devices. However, controlling toxicity due to the presence of Pb 2+ in lead-based halide perovskites is a major challenge for the environment that needs to be tackled cautiously. In this work, we have partially replaced Pb 2+ with Mn 2+ ions in the CsPb(Cl/Br) 3 nanocrystals and investigated their impact on the structural and optical properties. The Rietveld refinement shows that CsPbCl 2 Br nanocrystals possess a cubic crystal structure with Pm 3̅ m space group, the Mn 2+ doping results in the contraction of the unit cell. The CsPb(Cl/Br) 3 : Mn nanocrystals show a substantial change in the optical properties with an additional emission band at ∼588 nm through a d-d transition, changing the emission color from blue to pink. Here, a didodecyldimethylammonium bromide (DDAB) ligand that triggers both anion and ligand exchange in the CsPb(Cl/Br) 3 : Mn nanocrystals have been used to regulate the exchange reaction and tune the emission color of halide perovskites by changing the peak position and the PL intensities of band-edge and Mn 2+ defect states. We have also shown that oleic acid helps in the desorption of oleylamine capping from the CsPb(Cl/Br) 3 : Mn nanocrystal surfaces and DDAB, resulting in the substitution of Cl - with Br - as well as provides capping with shorter branched length ligand which led to increase in the overall PL intensity by many folds., (© 2024 IOP Publishing Ltd.)

Direct-seeded rice (DSR) is gaining popularity among farmers due to its environmentally safe and resource-efficient production system. However, managing the rice root-knot nematode (RRKN), Meloidogyne graminicola , remains a major challenge in DSR cultivation. Developing genetic resistance is a pragmatic and effective approach compared to using hazardous pesticides. Pusa Basmati 1121 (PB1121) is the most popular Basmati rice variety, but it is highly susceptible to RRKN. In contrast, Phule Radha (PR) has shown highly resistant reaction to RRKN, as reported in our earlier study. We generated an F 2:3 population from the cross of PB1121/PR and evaluated it for RRKN resistance-related traits under artificial inoculation conditions. The distribution pattern of traits in the F 2:3 population indicated that resistance may be governed by a few major-effect genes and many minor-effect genes. The molecular markers reported to be associated with QTLs governing RRKN resistance traits were used to test in the current population. Although the simple linear regression identified significant associations between the markers and RRKN resistance-associated traits, these associations were spurious as the LOD score was below the threshold limit. This indicates that PR possesses novel genomic regions for resistance to RRKN as it does not possess any of the earlier reported QTLs.

Binary nanocomposite-based electrodes have been studied extensively in recent times owing to their multiple oxidation states, excellent physico-chemical features, and combined morphology, which are suitable for increasing the electrochemical performance of supercapacitors. The present work deals with Sb 2 O 3 -MoS 2 nanocomposites electrode for supercapacitor applications. The x-ray diffraction (XRD), Raman, scanning electron microscope (SEM), energy dispersive x-ray (EDX), high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED) and x-ray photoelectron spectroscopy (XPS) characterizations have been studied to analyze the phase formation, vibrational modes, morphology, elemental composition and binding energies of the prepared Sb 2 O 3 -MoS 2 nanocomposites electrode material, as well as their electrochemical measurements such as cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), and electrochemical impedance spectroscopy (EIS) have been analyzed. The developed Sb 2 O 3 -MoS 2 nanocomposites electrode provides a high specific capacitance of 454.3 F g -1 at the current density of 1 A g -1 . Further, the hybrid supercapacitor device has been constructed which shows 104.04 F g -1 of specific capacitance at 2 A g -1 and manifests a good energy density of 24.42 Wh kg -1 at a power density of 1299.89 W kg -1 . Additionally, the hybrid device Sb 2 O 3 -MoS 2 //AC exhibits a good capacitive retention of 90.6% and a coulombic efficiency of 100.45% at 10 A g -1 over 8000 cycles., (© 2024 IOP Publishing Ltd.)