Neuroprotective Effects of Cannabispirenone A against NMDA-Induced Excitotoxicity in Differentiated N2a Cells.

The endocannabinoid system is found throughout the central nervous system, and its cannabinoids receptor 1 is critical in preventing neurotoxicity caused by N-methyl-D-aspartate receptor activation (NMDARs). The activity of NMDARs places demands on endogenous cannabinoids to regulate their calcium currents. Endocannabinoids keep NMDAR activity within safe limits, protecting neural cells from excitotoxicity. Cannabinoids are remembered to deliver this outcome by repressing presynaptic glutamate discharge or obstructing postsynaptic NMDAR-managed flagging pathways. The endocannabinoid system must exert a negative influence proportional to the strength of NMDAR signaling for such control to be effective. The goal of this paper is to draw the attention towards the neuroprotective mechanism of constituents of Cannabis sativa against NMDA-induced excitotoxic result. Phytochemical investigation of the cannabis flowers led to the isolation of nine secondary metabolites. A spiro-compound, Cannabispirenone A, which on treatment of the cells prior to NMDA exposure significantly increases cell survival while decreasing ROS production, lipid peroxidation, and intracellular calcium. Our findings showed that this compound showed neuroprotection against NMDA-induced excitotoxic insult, has antioxidative properties, and increased cannabinoid receptor 1 expression, which may be involved in the signaling pathway for this neuroprotection.

Toward Rational Design of Mononuclear Nickel Complexes as Water Oxidation Catalysts Exploring the Ligand Effects on the Rate-Determining Step.

The major impediment in realizing a carbon-neutral hydrogen fuel economy is the cost and inadequacy of contemporary electrochemical water splitting approaches towards the energy intensive oxygen evolution reaction (OER). The O-O bond formation in the water oxidation half-cell reaction is both kinetically and thermodynamically challenging and amplifies the overpotential requirement in most of the active water oxidation catalysts. Herein, density functional theory is employed to interrogate 20 Ni(II) complexes, out of which 17 are in silico designed molecular water oxidation catalysts, coordinated to electron-rich tetra-anionic redox non-innocent phenylenebis(oxamidate) and dibenzo-1,4,7,10-tetraazacyclododecane-2,3,8,9-tetraone parent ligands and their structural analogues, and identify the role of substituent changes or ligand effects in the order of their reactivity. Importantly, our computational mechanistic analyses predict that the activation free energy of the rate-determining O-O bond formation step obeys an inverse scaling relationship with the global electrophilicity index of the intermediate generated on two-electron oxidation of the starting complex. Additionally, the driving force is directly correlated with this OER descriptor which enables two-dimensional volcano representation and thereby extrapolation towards the ideal substitution with the chosen ligand. Our study, therefore, establish fundamental insights to overcome the imperative overpotential issue with simple and precise computational rationalization preceding experimental validation.

Ultrafast Dynamics of Self-Trapped Excitons in Cs2AgInCl6:Al3+ Double Perovskite Nanocrystals.

It is a huge challenge to increase the photoluminescence (PL) of lead-free halide perovskites, and understanding the mechanism behind exciton dynamics can provide a valuable solution. Herein, we achieved enhanced broad-band emission at ambient conditions in Cs2AgInCl6 by tuning self-trapped excitons (STEs) through Al3+ doping. Cryogenic measurements showed an inhomogeneous nature of STE emission due to the presence of defect states and is subject to thermal quenching. An increased Huang-Rhys factor (S-factor) resulted in better electron-phonon coupling and high-density STE states post Al3+ doping. Femtosecond transient absorption (fs-TA) results provided insights into the distribution dynamics of excitons, which occurs through gradient energy levels from free excitons (FE) to STEs, where each STE state potentially possesses higher quantized energy states. Overall, this study aims to comprehend the origins of self-trapping and decay of STEs in Cs2AgInCl6:Al3+ and emphasizes the potential of compositional engineering to mitigate self-trapping in this material.

Exploring landscape of measles vaccination coverage: A step towards measles elimination goal in India.

INTRODUCTION: Measles remains a critical public health concern causing significant morbidity and mortality globally. Despite the success of measles vaccination programs, challenges persist, particularly in India. This study investigates dose-wise measles vaccination coverage and explores gaps in immunization focusing on zero-dose, one-dose, and two-dose coverage among children aged 24-35 months. DATA SOURCES AND METHODOLOGY: The National Family Health Survey 2019-21 (NFHS-5) served as the data source and the study analyzed information from 43,864 children aged 24-35 months. Sociodemographic variables such as birth order, wealth quintile, gender, social group, religion, residence, mother education, delivery-related factors, and media exposure were considered. Statistical analysis involved weighted estimates, chi-square tests, and multivariate multinomial logistic regression. RESULTS: The study revealed that challenges persist in achieving optimal measles vaccination coverage. Analysis by sociodemographic factors highlighted disparities in coverage, with variations in zero dose prevalence across states and districts. The percentage of zero-dose children was significantly higher, with 11.5% of children in India remaining to receive any measles vaccination. Factors influencing vaccine coverage include birth order, age, wealth quintile, social group, religion, residence, maternal education, place of delivery, media exposure, and mode of delivery. The findings from the spatial analysis show the clustering of zero-dose children is high in the northeastern states of India. DISCUSSION: Measles zero-dose children pose a significant obstacle to achieving elimination goals. Spatial analysis identifies clusters of unvaccinated populations guiding targeted interventions. The study aligns with global initiatives such as the Immunization Agenda 2030 emphasizing equitable vaccine access and discusses how India can tailor its strategies to achieve the goal. Lessons from polio eradication efforts inform strategies for measles elimination, stressing the importance of high-quality data and surveillance. The study underscores the urgency of addressing last-mile measles vaccination gaps in India. Spatially targeted interventions informed by sociodemographic factors can enhance immunization coverage. Achieving measles elimination requires sustained efforts and leveraging lessons from successful vaccination campaigns. The study findings have the potential to contribute to informed decision-making, supporting India's roadmap for the measles and rubella elimination goal.

Co-occurrence of rhino-orbital mucormycosis and acute lymphoblastic leukemia post-COVID-19 infection in a young adolescent male: A case report from a low middle-income country.

Key Clinical Message: Immunosuppression from B-acute lymphoblastic leukemia (B-ALL) chemotherapy and a preceding COVID-19 infection may predispose patients to rare complications such as rhino-orbital mucormycosis. Hence, a high index of suspicion should be maintained by physicians (and oncologists) if patients undergoing B-ALL treatment present with orofacial symptoms and ophthalmological manifestations such as peri-orbital swelling, ophthalmoplegia, and loss of vision, suggestive of infection. Abstract: Mucormycosis is a severe fungal infection that poses significant mortality and morbidity risks, particularly in immunocompromised individuals. We present a rare case of a 16-year-old patient with rhino-orbital mucormycosis following B-acute lymphoblastic leukemia (B-ALL) treatment and concurrent COVID-19 infection. We describe the clinical presentation, diagnosis, treatment, and outcome of this patient, and discuss the possible interactions and implications of these three conditions. A young 16-year-old male patient without significant clinical history was admitted with complaints of low-grade intermittent fever, fatigue, malaise, restlessness, and unexplained weight loss for the past 2 months. A bone marrow biopsy confirmed the diagnosis of B-ALL. Following the diagnosis of B-ALL, the patient underwent initiation of chemotherapy. Following the initial two cycles of chemotherapy, the patient experienced fever and cough and tested positive for COVID-19 infection. Nearly a week later, the patient presented to the chemotherapy emergency department with a clinical picture characterized by a fever up to 39°C associated with left facial swelling, severe headache, purulent rhinorrhea, and foreign body sensation in the ipsilateral nostril. The following day, erythema and left eyelid edema were observed, with ocular opening limitation. The diagnosis was confirmed based on the positive result of polymerase chain reaction for left-sided mucormycosis. Initial administration of liposomal and lipid amphotericin B at 1-1.5 mg/kg/d doses for 4-6 weeks was followed by surgical debridement of necrotic tissue on the left side of the face and nose. Subsequent ophthalmological examinations showed normal conditions of the left eye. The case underscores the importance of heightened clinical suspicion, early diagnosis through imaging and molecular techniques, aggressive multimodal therapy, and close interdisciplinary collaboration for improved outcomes in such rare and challenging clinical scenarios.

Growth-regulated co-occupancy of Mediator and Lsm3 at intronic ribosomal protein genes.

Mediator is a well-known transcriptional co-regulator and serves as an adaptor between gene-specific regulatory proteins and RNA polymerase II. Studies on the chromatin-bound form of Mediator revealed interactions with additional protein complexes involved in various transcription-related processes, such as the Lsm2-8 complex that is part of the spliceosomal U6 small nuclear ribonucleoprotein complex. Here, we employ Chromatin Immunoprecipitation sequencing (ChIP-seq) of chromatin associated with the Lsm3 protein and the Med1 or Med15 Mediator subunits. We identify 86 genes co-occupied by both Lsm3 and Mediator, of which 73 were intron-containing ribosomal protein genes. In logarithmically growing cells, Mediator primarily binds to their promoter regions but also shows a second, less pronounced occupancy at their 3'-exons. During the late exponential phase, we observe a near-complete transition of Mediator from these promoters to a position in their 3'-ends, overlapping the Lsm3 binding sites ∼250 bp downstream of their last intron-exon boundaries. Using an unbiased RNA sequencing approach, we show that transition of Mediator from promoters to the last exon of these genes correlates to reduction of both their messenger RNA levels and splicing ratios, indicating that the Mediator and Lsm complexes cooperate to control growth-regulated expression of intron-containing ribosomal protein genes at the levels of transcription and splicing.

Isolated perinephric abscess as the initial manifestation of filariasis-an unusual presentation.

Key Clinical Message: Filariasis may present as an isolated perinephric abscess. Hence, a high index of suspicion should be maintained in endemic settings. Abstract: In cases with unexplained fever, eosinophilia and perinephric collection, it is necessary to do detailed infectious disease work up. High index of suspicion is required to diagnose filariasis due to its wide range of clinical presentation and laboratory findings. It may present as perinephric abscess, which can be diagnosed through ultrasonography.

Evolution in the Design of Water Oxidation Catalysts with Transition-Metals: A Perspective on Biological, Molecular, Supramolecular, and Hybrid Approaches.

Increased demand for a carbon-neutral sustainable energy scheme augmented by climatic threats motivates the design and exploration of novel approaches that reserve intermittent solar energy in the form of chemical bonds in molecules and materials. In this context, inspired by biological processes, artificial photosynthesis has garnered significant attention as a promising solution to convert solar power into chemical fuels from abundantly found H2O. Among the two redox half-reactions in artificial photosynthesis, the four-electron oxidation of water according to 2H2O → O2 + 4H+ + 4e- comprises the major bottleneck and is a severe impediment toward sustainable energy production. As such, devising new catalytic platforms, with traditional concepts of molecular, materials and biological catalysis and capable of integrating the functional architectures of the natural oxygen-evolving complex in photosystem II would certainly be a value-addition toward this objective. In this review, we discuss the progress in construction of ideal water oxidation catalysts (WOCs), starting with the ingenuity of the biological design with earth-abundant transition metal ions, which then diverges into molecular, supramolecular and hybrid approaches, blurring any existing chemical or conceptual boundaries. We focus on the geometric, electronic, and mechanistic understanding of state-of-the-art homogeneous transition-metal containing molecular WOCs and summarize the limiting factors such as choice of ligands and predominance of environmentally unrewarding and expensive noble-metals, necessity of high-valency on metal, thermodynamic instability of intermediates, and reversibility of reactions that create challenges in construction of robust and efficient water oxidation catalyst. We highlight how judicious heterogenization of atom-efficient molecular WOCs in supramolecular and hybrid approaches put forth promising avenues to alleviate the existing problems in molecular catalysis, albeit retaining their fascinating intrinsic reactivities. Taken together, our overview is expected to provide guiding principles on opportunities, challenges, and crucial factors for designing novel water oxidation catalysts based on a synergy between conventional and contemporary methodologies that will incite the expansion of the domain of artificial photosynthesis.

Role of Patch Testing in Facial Contact Dermatitis: A Cross-Sectional Study from Central India.

Background: Facial contact dermatitis is an emerging skin disorder due to the use of a large array of materials over the face. It leads to psychological distress in patients, impacting their quality of life. Most of the allergens applied over the face vary as per cosmetic or herbal products' availability, usage, or religious practices. Identifying and discontinuing the implicated allergens will lead to a better prognosis and reduced morbidity in clinical practice. Objectives: To determine the frequency of different allergens responsible for causing facial contact dermatitis, in an urban part of central India, using patch test with the help of Indian standard and cosmetic series. Materials and Methods: All suspected patients (>18 years) of facial contact dermatitis visiting the outpatient department of dermatology were patch tested with both Indian standard and cosmetic series. Results: Out of 38/58 patch-test-positive patients, 71.06% were females, and 28.94% were males. Most patch-test-positive females were housewives. The most common allergens implicated were thiomersal (17.24%), followed by fragrance mix (15.51%), and paraphenylene diamine (12.06%). Conclusion: In our study, forehead and malar areas were most commonly involved indicating fairness creams and perfumes as the important contributors to facial contact dermatitis. Antigen batteries need to be updated with changing social and cultural trends, as many with a consistent history of aggravation with some products tested negative in patch tests.

Exploring Clinical Subgroups of Participants with Major Depressive Disorder that may Benefit from Adjunctive Minocycline Treatment.

Objective: : To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT). Methods: : This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA. Results: : There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects. Conclusion: : Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications.

Activated Mn-MACHO Complexes Form Stable CO2 Adducts.

Manganese(I) carbonyl complexes bearing a MACHO-type ligand (HN(CH2 CH2 PR2 )2 ) readily react in their amido form with CO2 to generate 4-membered {Mn-N-C-O} metallacycles. The stability of the adducts decreases with the steric demand of the R groups at phosphorous (R=isopropyl>adamantyl). The CO2 -adducts display generally a lower reactivity as compared to the parent amido complexes. These adducts can thus be interpretated as masked forms of the active amido catalysts and potentially play important roles as off-loop species or branching points in catalytic transformations of carbon dioxide.

Comprehensive profiling of rRNA-derived small RNAs in Arabidopsis thaliana using rsRNAfinder pipeline.

Ribosomal RNA (rRNA) gives rise to non-random small RNA fragments known as ribosomal-derived small RNAs (rsRNAs), which despite their biological importance, have been relatively understudied in comparison to other short non-coding RNAs. There exists a compelling necessity to develop a methodology for the identification, categorization, and quantification of rsRNAs from small RNA sequencing (sRNA-seq) data sets, considering the unique characteristics of ribosomal RNA (rRNA). To bridge this gap, we introduce 'rsRNAfinder' a specialized pipeline designed within the Snakemake framework. This analytical approach enables robust identification of rsRNAs using sRNA-seq datasets from Arabidopsis thaliana. Our methodology constitutes an integrated bioinformatic pipeline designed for different kinds of analysis.1.sRNA-seq data analysis: It performs in-depth analysis of reference-aligned sRNA-seq data, facilitating rsRNA annotation and quantification.2.Parametric reporting: Our pipeline provides comprehensive reports encompassing key parameters such as rsRNA size distributions, strandedness, genomic origin, and source rRNA origin.3.Illustrative validation: We have demonstrated the utility of our approach by conducting comprehensive rsRNA annotation in Arabidopsis thaliana. This validation reveals unique rsRNAs originating from all rRNA types, each of them distinguished by distinct identity, abundance, and length.

Balancing Routine and Pandemic: The Synergy of India's Universal Immunization Program and COVID-19 Vaccination Program.

The COVID-19 pandemic posed substantial challenges to healthcare systems globally and severely disrupted essential health services, including routine immunization programs. In India, these disruptions were exacerbated due to the sudden emergence of the pandemic and lockdown measures, leading to mass migrations and a shortage of healthcare workers. Caregivers' concerns about routine immunization sessions further compounded the problem, resulting in a sharp increase in zero-dose children. This review paper examines India's strategies for conducting one of the world's largest COVID-19 vaccination programs while effectively restoring and perpetuating its Universal Immunization Program (UIP). The UIP played a pivotal role in sustaining immunization services during the pandemic, ultimately improving immunization coverage compared to pre-pandemic levels. India's accomplishments in this regard are highlighted through key performance indicators, the reach of immunization services, a reduction in zero-dose children, and antigen-wise coverage. The paper also discusses the successful integration of COVID-19 vaccination within the UIP framework, underscoring the significance of existing infrastructure, technology, and capacity building. India's dedication to concurrently managing routine immunization and COVID-19 vaccination showcases the adaptability and resilience of its healthcare system. India's journey serves as a global example of efficient mass immunization during challenging times, emphasizing the importance of political will, healthcare infrastructure investment, skilled healthcare workforces, and comprehensive vaccination programs. In a world grappling with the dual challenge of COVID-19 and routine immunization, India's experience provides a roadmap for strengthening healthcare systems and promoting public health as the critical agenda in challenging times.

Exploring Vaccine Hesitancy and Uptake during COVID-19: A Review of PM's Mann Ki Baat Dialogue.

Public health programmes are interlinked and intertwined with communication, advocacy and social mobilisation for their success. The unprecedented situation created by COVID-19 brought a medical emergency all over the world, the like of which was probably not seen after the Spanish Flu outbreak, a century ago. First there seemed no solution in sight when tens of thousands of people lost their lives to the coronavirus in various countries, but when the vaccine arrived, there were, in general, doubts about its efficacy and safety. Indian scenario was not any different. When the government launched the vaccine in a campaign mode in January 2021, it was also battling with misperceptions and vaccine hesitancy. Prime Minister Narendra Modi took it upon himself to address the issue through his various addresses to the nation and his signature programme Mann ki Baat (MKB) on the radio. This review paper examines the empirical research on MKB coverage of the COVID-19 pandemic, the media multiplier impact of the MKB, people's voices through their engagement with various social media platforms, and what is the impact on vaccine uptake.

Standardized In Vitro Models of Human Adipose Tissue Reveal Metabolic Flexibility in Brown Adipocyte Thermogenesis.

Functional human brown and white adipose tissue (BAT and WAT) are vital for thermoregulation and nutritional homeostasis, while obesity and other stressors lead, respectively, to cold intolerance and metabolic disease. Understanding BAT and WAT physiology and dysfunction necessitates clinical trials complemented by mechanistic experiments at the cellular level. These require standardized in vitro models, currently lacking, that establish references for gene expression and function. We generated and characterized a pair of immortalized, clonal human brown (hBA) and white (hWA) preadipocytes derived from the perirenal and subcutaneous depots, respectively, of a 40-year-old male individual. Cells were immortalized with hTERT and confirmed to be of a mesenchymal, nonhematopoietic lineage based on fluorescence-activated cell sorting and DNA barcoding. Functional assessments showed that the hWA and hBA phenocopied primary adipocytes in terms of adrenergic signaling, lipolysis, and thermogenesis. Compared to hWA, hBA were metabolically distinct, with higher rates of glucose uptake and lactate metabolism, and greater basal, maximal, and nonmitochondrial respiration, providing a mechanistic explanation for the association between obesity and BAT dysfunction. The hBA also responded to the stress of maximal respiration by using both endogenous and exogenous fatty acids. In contrast to certain mouse models, hBA adrenergic thermogenesis was mediated by several mechanisms, not principally via uncoupling protein 1 (UCP1). Transcriptomics via RNA-seq were consistent with the functional studies and established a molecular signature for each cell type before and after differentiation. These standardized cells are anticipated to become a common resource for future physiological, pharmacological, and genetic studies of human adipocytes.