Wealth-based disparities in the prevalence of short birth interval in India: insights from NFHS-5.

BACKGROUND: Short birth interval (SBI) has profound implications for the health of both mothers and children, yet there remains a notable dearth of studies addressing wealth-based inequality in SBI and its associated factors in India. This study aims to address this gap by investigating wealth-based disparities in SBI and identifying the underlying factors associated with SBI in India. METHODS: We used information on 109,439 women of reproductive age (15-49 years) from the fifth round of the National Family Health Survey (2019-21). We assessed wealth-based inequality in SBI for India and its states using the Erreygers Normalised Concentration Index (ECI). Additionally, we used a multilevel binary logistic regression to assess the factors associated with SBI in India. RESULTS: In India, the prevalence of SBI was 47.8% [95% CI: 47.4, 48.3] during 2019-21, with significant variation across states. Bihar reported the highest prevalence of SBI at 61.2%, while Sikkim the lowest at 18.1%. SBI prevalence was higher among poorer mothers compared to richer ones (Richest: 33.8% vs. Poorest: 52.9%). This wealth-based inequality was visible in the ECI as well (ECI= -0.13, p < 0.001). However, ECI varied considerably across the states. Gujarat, Punjab, and Manipur exhibited the highest levels of wealth-based inequality (ECI= -0.28, p < 0.001), whereas Kerala showed minimal wealth-based inequality (ECI= -0.01, p = 0.643). Multilevel logistic regression analysis identified several factors associated with SBI. Mothers aged 15-24 (OR: 12.01, p < 0.001) and 25-34 (2.92, < 0.001) were more likely to experience SBI. Women who married after age 25 (3.17, < 0.001) and those belonging to Scheduled Caste (1.18, < 0.001), Scheduled Tribes (1.14, < 0.001), and Other Backward Classes (1.12, < 0.001) also had higher odds of SBI. Additionally, the odds of SBI were higher among mothers in the poorest (1.97, < 0.001), poorer (1.73, < 0.001), middle (1.62, < 0.001), and richer (1.39, < 0.001) quintiles compared to the richest quintile. Women whose last child had passed away were also significantly more likely to have SBI (2.35, < 0.001). Furthermore, mothers from communities with lower average schooling levels (1.18, < 0.001) were more likely to have SBI. Geographically, mothers from eastern (0.67, < 0.001) and northeastern (0.44, < 0.001) regions of India were less likely to have SBI. CONCLUSION: The significant wealth-based inequality in SBI in India highlights the need for targeted interventions focusing on economically disadvantaged women, particularly in states with high SBI prevalence. Special attention should be given to younger mothers and those from socially disadvantaged groups to enhance maternal and child health outcomes across the country.

Bedaquiline: An Insight Into its Clinical Use in Multidrug-Resistant Pulmonary Tuberculosis.

Every year, the World Health Organization reports 500,000 new cases of drug-resistant tuberculosis (TB), which poses a serious global danger. The increased number of XDR-TB and MDR-TB cases reported worldwide necessitates the use of new therapeutic approaches. The main issues with the antitubercular medications now in use for the treatment of multidrug-resistant tuberculosis are their poor side effect profile, reduced efficacy, and antimicrobial resistance. One possible remedy for these problems is bedaquiline. The need for better treatment strategies is highlighted by the strong minimum inhibitory concentrations that bedaquiline (BDQ), a novel anti-TB medicine, exhibits against both drug-resistant and drug-susceptible TB. Bedaquiline may be able to help with these problems. Bedaquiline is a medication that is first in its class and has a distinct and particular mode of action. Bedaquiline is an ATP synthase inhibitor that is specifically directed against Mycobacterium tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4. Bedaquiline preclinical investigations revealed intralesional drug biodistribution. The precise intralesional and multi-compartment pharmacokinetics of bedaquiline were obtained using PET bioimaging and high-resolution autoradiography investigations. Reduced CFU counts were observed in another investigation after a 12-week course of therapy. Meta-analyses and systematic reviews of phase II trials on bedaquiline's efficacy in treating drug-resistant tuberculosis in patients reported higher rates of cure, better culture conversion, and lower death rates when taken in conjunction with a background regimen. Here is a thorough medication profile for bedaquiline to aid medical professionals in treating individuals with tuberculosis.

Assessing the accuracy and reliability of satellite-derived precipitation products in the Kosi River basin (India).

The present research endeavors to examine the effectiveness of four gridded precipitation datasets, namely Integrated Multi-satellite Retrievals for GPM (IMERG), Tropical Precipitation Measuring Mission (TRMM), Modern-Era Retrospective Analysis for Research and Applications Version 2 (MERRA-2), and Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks (PERSIANN), with the observed rainfall data of eight rain gauge stations of India Meteorological Department (IMD) from 2001 to 2019 in Kosi River basin, India. Various statistical metrics, contingency tests, trend analysis, and rainfall anomaly index were utilized at daily, monthly, seasonal, and annual time scales. The categorical metrics namely probability of detection (POD) and false alarm ratio (FAR) indicate that MERRA-2 and IMERG datasets have the highest level of concurrence with the observed daily data. Statistical analysis of gridded datasets with observed dataset of IMD showed that the performance of the IMERG dataset is better than MERRA-2, PERSIANN, and TRMM datasets with "very good" coefficient of determination (R2) and Nash-Sutcliffe Efficiency values for monthly data. Trend analysis of gridded seasonal data of IMERG showed similar trends of observed seasonal data whereas other dataset differs. IMERG also performed well in identifying wet and dry years based on annual data. Discrepancies of the satellite sensor in capturing the precipitation have also been discussed. Thus, the IMERG dataset can be effectively used for hydro-meteorological and climatological investigations in cases of lack of observed datasets.

Unveiling the Journey from the Gut to the Brain: Decoding Neurodegeneration-Gut Connection in Parkinson's Disease.

Parkinson's disease, a classical motor disorder affecting the dopaminergic system of the brain, has been as a disease of the brain, but this classical notion has now been viewed differently as the pathology begins in the gut and then gradually moves up to the brain regions. The microorganisms in the gut play a critical role in maintaining the physiology of the gut from maintaining barrier integrity to secretion of microbial products that maintain a healthy gut state. The pathology subsequently alters the normal composition of gut microbes and causes deleterious effects that ultimately trigger strong neuroinflammation and nonmotor symptoms along with characteristic synucleopathy, a pathological hallmark of the disease. Understanding the complex pathomechanisms in distinct and established preclinical models is the primary goal of researchers to decipher how exactly gut pathology has a central effect; the quest has led to many answered and some open-ended questions for researchers. We summarize the popular opinions and some contrasting views, concise footsteps in the treatment strategies targeting the gastrointestinal system.

Alteration of gastric microbiota in Helicobacter pylori-infected individuals suffering from GERD, DU, and gastritis.

BACKGROUND/AIM: Helicobacter pylori (H. pylori) colonization affects the gastric microbiome, causing gastrointestinal (GI) diseases. Modern sequencing technology provides insights into GI microbe interaction with H. pylori and their metabolic pathways in causing GI diseases. We aim to compare the gastric microbiota alteration due to H. pylori infection in patients suffering from GI diseases. MATERIALS AND METHODS: Genomic DNA were isolated from gastric antrum tissue from 37 H.pylori-infected patients diagnosed with GERD, duodenal ulcers, and gastritis. We conducted the genomic library preparation and sequencing of the amplified product using 16S rRNA NGS analysis. Using microbiome analyst tool diversity analysis, random forest analysis and ANOVA were conducted to find out the comparison of microbial abundance. We have also conducted functional pathway prediction analysis using PICRUSt. RESULTS: Metagenomic analysis shows high bacterial diversity in H. pylori-positive gastritis patients. Streptococcus infantis and Neisseria subflava were significantly higher in duodenal ulcer (DU) and gastritis groups. Acinetobacter lwoffii and Helicobacter pullorum were significantly high in the gastritis group only. The functional metabolic pathway analyses revealed that gastroesophageal reflux disease (GERD) samples were significantly enriched with the energy metabolism and xenobiotic biodegradation and metabolism pathways, whereas fructose-1,6-bisphosphatase III was found less in gastritis and DU groups. CONCLUSION: There is a difference in microbiota composition in different disease outcomes. We found positive association between microbial diversity and H. pylori in gastritis group only, whereas negative association was found in DU and GERD groups. The functional metabolic pathway analysis revealed significant differences in various disease outcomes.

HIV self-testing in India: implementation and qualitative evaluation of a web-based programme with virtual counsellor support.

INTRODUCTION: To achieve epidemic control of infectious diseases, engaging higher-burden populations with accessible diagnostic services is critical. HIV self-testing (HIVST) is a promising option. METHODS: We implemented an online HIVST programme for key populations across India. Eligible clients were 18 years or older, self-reported a negative or unknown HIV status and reported not taking antiretroviral therapy. Clients who reported a prior HIV diagnosis were not eligible to receive an HIVST kit. HIVST clients received kits via courier or in person at pre-determined pick-up points supported by trained counselling staff. Virtual counsellors engaged clients online and by phone and offered support to register, access, and complete HIVST free of cost. Virtual counsellors supported clients to report results and engage with follow-up services. Follow-up included linking clients with a positive result to confirmatory testing and HIV care services. We assessed programmatic data across HIV continuum outcomes and conducted a qualitative evaluation through interviews with purposively sampled clients. RESULTS: Between 30 June 2021 and 30 September 2022, 5324 clients ordered an HIVST kit (76% men, 13% women, 7% transgender people, 4% unknown gender). Of the 4282 clients reporting results (94% of those who received a kit), 6% screened positive, among whom 72% (n = 184) completed confirmatory testing. Themes from 41 client interviews included satisfaction about the convenience and privacy of services and the discreet nature of kit delivery. Respondents were drawn to the convenience of HIVST and appreciated gaining courage and comfort throughout the process from virtual counsellor support. For respondents who screened positive, challenges to care linkage included fearing judgemental questions from public providers and wanting more time before starting treatment. Clients shared concerns about kit accuracy and suggested that instructional materials be provided with more diverse language options. CONCLUSIONS: Web-based HIVST services with tailored support appeared to facilitate HIV service access and engagement of harder-to-reach populations across India. Assistance from a community-oriented counsellor proved important to overcome literacy barriers and mistrust  in order to support the HIVST process and service linkage. Learnings can inform global efforts to improve the critical step of diagnosis in achieving epidemic control for HIV and other infectious diseases.

Role of STIMULAN in chronic osteomyelitis-A randomised blinded study on 95 patients comparing 3 antibiotic compositions, bead quality, forming & absorption time.

Introduction: Chronic Osteomyelitis is a well-known clinical entity affecting patients holistically and presents with multiple treatment challenges. Local antibiotic delivery with biodegradable drug carriers has shown promising results. Materials and methods: Prospective multicenter study performed at 2 centers from November 2021 to January 2023 on 95 osteomyelitis patients treated with surgical debridement & STIMULAN™ for local antibiotic delivery. Patients were randomized into 3 groups. Authors compared antibiotic combinations, bead quality, bead setting, and resorption time for calcium sulfate beads- STIMULAN™. Additionally, organisms isolated, WBC Turnover time, Hypersensitivity Reactions, Recurrence, and Revision Rates were documented. Results: 95 patients underwent surgical debridement and STIMULAN™ bead application for chronic osteomyelitis. The proximal 1/3rd tibia was commonly affected. The most common symptoms were sinus and pus discharge in 96.84 % & 86.31 % of patients respectively (p < 0.001). Staphylococcus aureus & MRSA were isolated in 37.8 % & 29.4 % of the patient's wound culture respectively. Bead setting time in Descending order was Group 3 > Group 2 > Group 1 (p < 0.001). Bead setting first in Group 1 followed by Group 3 & 2. On compression, Group-1 beads withstood maximum compression forces & had smooth even bead surfaces. On radiographs, 1/3rd bead volume in ascending order was Group 3 > Group 2 > Group 1 (p < 0.001). 2/3rd reduction in ascending order was Group 3 > Group 2 > Group 1. Complete bead absorption was earliest seen in Group 3 followed by Group 2 & Group 1 (p < 0.001). Recurrence in 2 patients (Group 2) at 6 weeks. Revision rate: 2.10 %. There were no incidences of hypersensitivity. Suture removal was done at 16 ± 2 days. Conclusion: STIMULAN™ combination with tobramycin, vancomycin, and gentamycin is stable, and forms uniform beads with predictable drug elution & bead resorption with negligible side effects. A mixture with higher liquid content sets later, forms softer beads, and resorbs earlier.

Creativity is motivated by novelty. Curiosity is triggered by uncertainty.

Although creativity and curiosity can be similarly construed as knowledge-building processes, their underlying motivation is fundamentally different. Specifically, curiosity drives organisms to seek information that reduces uncertainty so that they can make a better prediction about the world. On the contrary, creative processes aim to connect distant pieces of information, maximizing novelty and utility.

Funding Pattern Comparison Pre- and Post-Ayushman Bharat National Health Scheme (AB-PMJAY) in Active Females Undergoing TKA for Advanced Knee Arthritis with Clinical, QoL Analysis and AB-PMJAY Technical Data.

Introduction: Patients visiting for Knee Arthroplasty have often been treated at neighborhood clinics and bonesetters. India floated world's largest publicly funded national health insurance program -AB-PMJAY covering Knee Arthroplasty. AB-PMJAY's data for Arthroplasty has not been published. Methods: A Prospective study from Jan 2016- Jan 2023 on females undergoing TKA. Age, DEXA Score, Walking Ability, KSS, 10MWT, SF36 Scores, Funding Pattern before and after AB-PMJAY, Time to Approval, Time to discharge, Time to Query reply and Rejection Rates were documented. Results: 790 patients (91.86%) received treatment previously. 650 (78.54%) patients lived with family & 32 patients lost to follow-up. 37.67% & 62.32% patients had Grade. 3 & 4 osteoarthritis respectively. Commonest comorbidity was Vitamin D deficiency followed by Menopause and Hypertension. Post-treatment Vitamin D deficiency reduced from 68.59% to 2.17% at 3 months. Post-surgery, Functional Scores improved significantly at 1st and 6th month. VAS dropped significantly from 7.8 to 3.6 at 1st month follow up. At 6 months, 81.52% patients were independent outdoor walkers compared to 9.42% (baseline). Average hospital stay-54 hours and Return to work- 42 days. Central health scheme beneficiaries rose significantly from 12% (pre-PMJAY) to 42% (post-PMJAY). With AB-PMJAY, no rejection for surgical procedures, Time to surgery approval was 16 hours (mean) and Time to Discharge was 8 hours (mean). Time to reply was 6 hours (mean). Conclusion: Evident rise in patients getting TKA done through AB-PMJAY. TKA has become an affordable and achievable target for financially deprived patients, post regulation of knee implant prices & AB-PMJAY.

Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures.

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.

Nonadherence to antiepileptic medication and associated factors among persons with epilepsy in India: A systematic review and meta-analysis.

BACKGROUND: Nonadherence to antiepileptic drugs (AEDs) is a prevalent issue in India, contributing to suboptimal seizure control, higher morbidity and mortality, increased hospitalization rates, and a substantial effect on the overall quality of life for individuals with epilepsy. OBJECTIVES: This study aimed to measure the prevalence of medication adherence among individuals with epilepsy in India and to identify factors associated with nonadherence. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Embase, and Google Scholar for studies on AED adherence in India. Quality assessment employed Newcastle Ottawa Scale adapted for cross-sectional studies. Pooled prevalence was ascertained using a random-effects model in R software (version 4.2.2), with a 95% confidence interval. Heterogeneity was estimated with the I2 statistic, and publication bias was appraised via a funnel plot. Subgroup analyses, based on study region and adherence measurement tool, were done to investigate heterogeneity. RESULTS: Nine cross-sectional studies with 1772 participants were analyzed. The pooled prevalence of adherence to AEDs in India stood at 49.9% (95% CI: 39.8%-60.1%). Subgroup analyses showed comparable adherence rates in the South (50.9%) and North (46.5%) regions of India. However, adherence rates varied substantially based on the measurement tool: Morisky Medication Adherence Scale-4 (MMAS-4) reported 71.3%, MMAS-8 indicated 45.9%, and Morisky Green Levine (MGL) adherence scale exhibited 42.0%. Factors contributing to non-adherence to antiepileptic therapies involved poor socioeconomic status, lower education levels, polytherapy, drug-related side effects, and substance abuse. CONCLUSIONS: Almost half of persons with epilepsy in India were non-adherent to their AEDs. This underscores the importance for healthcare professionals to pay greater attention to improving the adherence rate to AEDs within the healthcare service.

A Review on Tau Targeting Biomimetics Nano Formulations: Novel Approach for Targeting Alzheimer's Diseases.

Central nervous system disorders are prevalent, profoundly debilitating, and poorly managed. Developing innovative treatments for these conditions, including Alzheimer's disease, could significantly improve patients' quality of life and reduce the future economic burden on healthcare systems. However, groundbreaking drugs for central nervous system disorders have been scarce in recent years, highlighting the pressing need for advancements in this field. One significant challenge in the realm of nanotherapeutics is ensuring the precise delivery of drugs to their intended targets due to the complex nature of Alzheimer's disease. Although numerous therapeutic approaches for Alzheimer's have been explored, most drug candidates targeting amyloid-ß have failed in clinical trials. Recent research has revealed that tau pathology can occur independently of amyloid-ß and is closely correlated with the clinical progression of Alzheimer's symptoms. This discovery suggests that tau could be a promising therapeutic target. One viable approach to managing central nervous system disorders is the administration of nanoparticles to neurons, intending to inhibit tau aggregation by directly targeting p-tau. In Alzheimer's disease, beta-amyloid plaques and neurofibrillary tau tangles hinder neuron transmission and function. The disease also triggers persistent inflammation, compromises the blood-brain barrier, leads to brain shrinkage, and causes neuronal loss. While current medications primarily manage symptoms and slow cognitive decline, there is no cure for Alzheimer's.

Prevalence of self-medication practices among pregnant women in India: A systematic review and meta-analysis.

BACKGROUND: Self-medication practice among pregnant women is a global concern. However, its understanding in the Indian context is limited due to a lack of comprehensive studies. PURPOSE: This study aimed to comprehensively assess the prevalence of self-medication, the medications used for self-medication, diseases/conditions associated with self-medication, and the reasons for self-medication among Indian pregnant women. METHODS: This study was carried out following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A thorough search was done in PubMed, Embase, and Google Scholar to find articles that were published up until May 2023. Inclusion criteria comprised observational studies reporting self-medication prevalence among pregnant women in India. Data were extracted using a standardized sheet, and a random-effects model was applied to determine the overall prevalence of self-medication using R software. The I2 statistic was employed to assess the heterogeneity among the studies. RESULTS: This study analyzed eight studies with a collective sample size of 2208 pregnant women. The pooled prevalence of self-medication among pregnant Indian women was 19.3% (95% CI: 7.5%-41.3%; I2 = 99%; p < 0.01). Common self-treated conditions were cold, cough, fever, headache, and stomach disorders. Antipyretics, analgesics, antihistamines, and antacids were frequently used for self-medication. The perception of mild ailment, immediate alleviation, convenience, time savings, and advice from family, friends, or the media were all reasons for self-medication. Local pharmacies were the most usual source for obtaining drugs, and pharmacists, family, friends, and past prescriptions were common sources of medicine information. CONCLUSIONS: A low yet substantial number of pregnant women in India are engaged in self-medication practices. Appropriate strategies need to be planned to reduce self-medication practices to attain sustainable developmental goals for maternal health in India.

Shear zones in granular mixtures of hard and soft particles with high and low friction.

Granular materials show inhomogeneous flows characterized by strain localization. When strain is localized in a sheared granular material, rigid regions of a nearly undeformed state are separated by shear bands, where the material yields and flows. The characteristics of the shear bands are determined by the geometry of the system, the micromechanical material properties, and the kinematics at the particle level. For a split-bottom shear cell, recent experimental work has shown that mixtures of hard, frictional and soft, nearly frictionless particles exhibit wider shear zones than samples with only one of the two components. To explain this finding, we investigate the shear zone properties and the stress response of granular mixtures using discrete element simulations. We show that both interparticle friction and elastic modulus determine the shear-band properties and packing density of granular mixtures of various mixing ratios, but their stress response depends strongly on the interparticle friction. Our study provides a fundamental understanding of the micromechanics of shear band formation in granular mixtures.

Targeting Abnormal Tau Phosphorylation for Alzheimer's Therapeutics.

Alzheimer's disease (AD) is a widespread neurodegenerative disorder characterized by progressive memory and cognitive decline, posing a formidable public health challenge. This review explores the intricate interplay between two pivotal players in AD pathogenesis: ß-amyloid (Aß) and tau protein. While the amyloid cascade theory has long dominated AD research, recent developments have ignited debates about its centrality. Aß plaques and tau NFTs are hallmark pathologies in AD. Aducanumab and lecanemab, monoclonal antibodies targeting Aß, have been approved, albeit amidst controversy, raising questions about the therapeutic efficacy of Aß-focused interventions. On the other hand, tau, specifically its hyperphosphorylation, disrupts microtubule stability and contributes to neuronal dysfunction. Various post-translational modifications of tau drive its aggregation into NFTs. Emerging treatments targeting tau, such as GSK-3ß and CDK5 inhibitors, have shown promise in preclinical and clinical studies. Restoring the equilibrium between protein kinases and phosphatases, notably protein phosphatase-2A (PP2A), is a promising avenue for AD therapy, as tau is primarily regulated by its phosphorylation state. Activation of tau-specific phosphatases offers potential for mitigating tau pathology. The evolving landscape of AD drug development emphasizes tau-centric therapies and reevaluation of the amyloid cascade hypothesis. Additionally, exploring the role of neuroinflammation and its interaction with tau pathology present promising research directions.

Understanding the association between intimate partner violence and sexually transmitted infections among women in India: a propensity score matching approach.

BACKGROUND: Intimate partner violence (IPV) against women can significantly impact their overall health. While numerous studies in developing nations highlight the association between IPV and sexually transmitted infections (STIs), the evidence available within the Indian context remains limited. Therefore, this study aims to fill this knowledge gap by investigating the relationship between exposure to different forms of IPV and the occurrence of STIs, using a quasi-experimental approach. METHODS: The study used a sample of 63 851 women aged 15-49 years from the latest National Family Health Survey-5. Propensity score matching (PSM) was employed to assess the 'treatment effect' from exposure to IPV (physical, emotional or sexual) in the past 12 months on STIs. RESULTS: About 12.2% of women (95% CI: 11.7% to 12.8%) reported symptoms of STIs at the time of the survey. Approximately 31.9% (95% CI: 31.2% to 32.7%) of women reported experiencing at least one form of IPV-either physical, emotional or sexual IPV. Of all forms of IPV, physical IPV was the most prevalent, reported by 28.6%, followed by emotional IPV (13.2%) and sexual IPV (5.7%). Women who experienced any form of IPV-whether physical, sexual or emotional-reported a higher prevalence of STIs (17.8%) as compared with those who did not experience any IPV (9.5%). The findings from the PSM analysis indicated that among the three forms of IPV, the impact of sexual IPV on STIs was the most pronounced. The average treatment effect on the treated from exposure to sexual IPV on STIs was 0.15 (95% CI 0.13 to 0.17). CONCLUSION: This study provides evidence of a significant association between IPV and STIs among women in India and underscores the urgent need for intensified efforts and interventions to address both IPV and STIs, to improve the overall health and well-being of women in India.

Mechanistic Investigation of Thiazole-Based Pyruvate Kinase M2 Inhibitor Causing Tumor Regression in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a deadly breast cancer with a poor prognosis. Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme in glycolysis, is abnormally highly expressed in TNBC. Overexpressed PKM2 amplifies glucose uptake, enhances lactate production, and suppresses autophagy, thereby expediting the progression of oncogenic processes. A high mortality rate demands novel chemotherapeutic regimens at once. Herein, we report the rational development of an imidazopyridine-based thiazole derivative 7d as an anticancer agent inhibiting PKM2. Nanomolar range PKM2 inhibitors with favorable drug-like properties emerged through enzyme assays. Experiments on two-dimensional (2D)/three-dimensional (3D) cell cultures, lactate release assay, surface plasmon resonance (SPR), and quantitative real-time polymerase chain reaction (qRT-PCR) validated 7d preclinically. In vivo, 7d outperformed lapatinib in tumor regression. This investigation introduces a lead-based approach characterized by its clear-cut chemistry and robust efficacy in designing an exceptionally potent inhibitor targeting PKM2, with a focus on combating TNBC.

Encyclopaedic Review of Glipizide Pre-clinical and Clinical Status.

Glipizide is an oral glucose-lowering medication that is beneficial for the treatment of type 2 diabetes. This study compiles exhaustively all accessible information on glipizide, from preclinical to clinical studies. Glipizide may be used in concert with TRAIL to treat cancer cells; in vitro studies have shown that it suppresses angiogenesis and vasculogenesis while shielding cells from glycation-induced damage. Anticonvulsant effects and modifications in the pharmacokinetics of other medications, such as Divalproex Sodium, were seen in glipizide in vivo experiments. Propranolol amplifies glipizide's hypoglycemic effect briefly in normal animals but consistently enhances it in diabetic ones. In the treatment of cancer and neurodegenerative poly(Q) illnesses, glipizide has demonstrated to offer potential therapeutic advantages. It is ineffective in preventing DENA-induced liver cancer and may cause DNA damage over time. The way glipizide interacts with genetic variants may increase the risk of hypoglycemia. Combining Syzygium cumini and ARBE to glipizide may enhance glycemic and lipid control in type 2 diabetes. Individuals with coronary artery disease who take glipizide or glyburide have an increased risk of death. The risk of muscular responses and acute pancreatitis is minimal when glipizide and dulaglutide are combined. In conclusion, glipizide has shown promising therapeutic efficacy across a variety of disorders.

Gels in Motion: Recent Advancements in Energy Applications.

Gels are attracting materials for energy storage technologies. The strategic development of hydrogels with enhanced physicochemical properties, such as superior mechanical strength, flexibility, and charge transport capabilities, introduces novel prospects for advancing next-generation batteries, fuel cells, and supercapacitors. Through a refined comprehension of gelation chemistry, researchers have achieved notable progress in fabricating hydrogels endowed with stimuli-responsive, self-healing, and highly stretchable characteristics. This mini-review delineates the integration of hydrogels into batteries, fuel cells, and supercapacitors, showcasing compelling instances that underscore the versatility of hydrogels, including tailorable architectures, conductive nanostructures, 3D frameworks, and multifunctionalities. The ongoing application of creative and combinatorial approaches in functional hydrogel design is poised to yield materials with immense potential within the domain of energy storage.