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Abstract Today's world is facing a criticalglobal challenge of rising temperatures and disrupted ecosystems, primarily driven by increased carbon emissions. The study aims to determine the major factors leading to carbon emissions in five major carbon-emitting countries: China, the United States, India, Russia, and Japan. Specifically, it explores the interplay between economic growth, natural resource rent (Natural Resource Rent: The economic benefit a country gains from its natural resources, such as oil or minerals, after subtracting the cost of extracting and using them), technological change, renewable energy use, and carbon emissions. The study postulates that economic growth and natural resource extraction bear a substantial interaction that contributes to carbon emissions. At the same time, technological change and the usage of renewable energy could probably become imperative to alleviate such emissions. This research, therefore, provides a good insight into the determinants of CO2 emissions in these key economies and the probable pathways toward emission reduction through innovation and harnessing of renewable sources of energy. Utilizing the comprehensive dataset between 1990 and 2021 and employing the ARDL [Panel ARDL (Autoregressive Distributed Lag): A statistical method used to analyze how different factors affect each other over time in a dataset that includes multiple subjects (e.g., countries)] model on the panel data, this study examines both the short- and long-term effects of these variables on carbon emissions, considering cross-country heterogeneity. The results underscore the significance related to guidelines for sustainable development practices and the necessity for these leading economies to lead the shift towards sustainability. By identifying factors that can mitigate emissions and enhance resilience, this research provides useful inputs to the policymakers who intend to promote renewable sources of energy usage along with technological upgrades. This study’s results contribute to the existing literature by making it a significant resource for future policy formulation and academic research in the field of mitigating climate change.

Abstract Background Breast cancer, the most prevalent cancer in women worldwide, faces treatment challenges due to drug resistance, posing a serious threat to patient survival. The present study aimed to identify the key molecules that drive drug resistance and aggressiveness in breast cancer cells and validate them as therapeutic targets. Methods Transcriptome microarray and analysis using PANTHER pathway and StemChecker were performed to identify the most significantly expressed genes in tamoxifen-resistant and adriamycin-resistant MCF-7 breast cancer cells. Clinical relevance of the key genes was determined using Kaplan-Meier survival analyses on The Cancer Genome Atlas dataset of breast cancer patients. Gene overexpression/knockdown, spheroid formation, flow cytometric analysis, chromatin immunoprecipitation, immunocytochemistry, wound healing/transwell migration assays, and cancer stem cell transcription factor activation profiling array were used to elucidate the regulatory mechanism of integrin α11 expression. Tumour-bearing xenograft models were used to demonstrate integrin α11 is a potential therapeutic target. Results Integrin α11 was consistently upregulated in drug-resistant breast cancer cells, and its silencing inhibited cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) while restoring sensitivity to anticancer drugs. HIF1α, GLI-1, and EZH2 contributed the most to the regulation of integrin α11 and EZH2 expression, with EZH2 being more necessary for EZH2 autoinduction than HIF1α and GLI-1. Additionally, unlike HIF1α or EZH2, GLI-1 was the sole transcription factor activated by integrin-linked focal adhesion kinase, indicating GLI-1 as a key driver of the EZH2-integrin α11 axis operating for cancer stem cell survival and EMT. Kaplan-Meier survival analysis using The Cancer Genome Atlas (TCGA) dataset also revealed both EZH2 and integrin α11 could be strong prognostic factors of relapse-free and overall survival in breast cancer patients. However, the superior efficacy of integrin α11 siRNA therapy over EZH2 siRNA treatment was demonstrated by enhanced inhibition of tumour growth and prolonged survival in murine models bearing tumours. Conclusion Our findings elucidate that integrin α11 is upregulated by EZH2, forming a positive feedback circuit involving FAK-GLI-1 and contributing to drug resistance, cancer stem cell survival and EMT. Taken together, the results suggest integrin α11 as a promising prognostic marker and a powerful therapeutic target for drug-resistant breast cancer.

The overgrowth condition known as Sotos syndrome is distinguished by its characteristic facial gestalt, macrocephaly, excessive development during childhood, varying degrees of learning problems, and a variety of other abnormalities. Due to abnormally high height, occipitofrontal circumference (OFC), advanced bone age, neonatal problems such as hypotonia and feeding issues, and facial gestalt, the diagnosis is typically recognized after birth. The current work aims to identify potential therapeutic treatments through bioinformatics analysis, focusing on key genes and pathways implicated in the disease. Text mining techniques were employed to identify 41 genes associated with Sotos syndrome, 37 of which were enriched with Gene Ontology (GO) terms and 24 with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Using protein-protein interaction (PPI) network analysis, two gene modules were extracted using the Molecular Complex Detection (MCODE) algorithm, highlighting 15 hub genes as central candidates. Furthermore, leveraging drug-gene interaction databases and network pharmacology tools, 23 FDA-approved drugs were identified that target 11 of these core hub genes, suggesting potential therapeutic avenues for Sotos syndrome. Only bioinformatics tools were used in this study further in-vitro and in-vivo studies are required because phenotypic differences will vary from person to person depending on the expressivity of the gene. In future this approach may help to collaborate with clinical researchers to integrate bioinformatics findings with real-world clinical data. This will enhance understanding of clinical relevance of the identified genes and pathways and validate bioinformatics predictions with patient-derived samples and clinical histories.

Objective: The severe acute type of respiratory distress caused by Coronavirus disease 2019 (COVID-19) was responsible for the global pandemic of 2019. While most of the focus of vaccine/drug molecules is on the receptor, there are certain enzymes that also need to be checked. Cell surface proteases are one of these. Activation of the virus spike protein becomes more complicated when many host proteases are involved. As many Variants of Concerns have been reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this study aimed to understand the proteolytic function of Furin in each, and its involvement in virus-host interaction. Material and Methods: Spike Protein sequence alignment, furin cleavage site prediction of variants: Wuhan, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529), and protein-protein docking studies have been undertaken using appropriate bioinformatics tools. Results: It was observed that when compared to previous variations, the November 2021, outbreak of Omicron variant showed 50 amino acid substitutions in the Spike protein. Thus, in addition to the Angiotensin Converting Enzyme 2 (ACE-2) receptor, the role of virus binding sites to act as “Addition Receptors” for viral entry has been reported here. Conclusion: It was observed that substitution of basic amino acids in the Omicron variant may be responsible for the recognition of furin cleavage sites and the presence of furin cleavage site in the receptor binding domain (RBD) region will thus enhance viral transmission. If these sites are utilized in formulation of new drugs/vaccine molecules to target the furin hydrolyse sites, we may be able to add to the existing course of COVID-19 treatment.

Background: Medications, including chemotherapeutic drugs, contribute to male infertility as external factors by inducing oxidative stress in testicular cells. Shilajit is a naturally occurring bioactive antioxidant used in Ayurvedic medicine to treat a variety of ailments. Objective: This study examines the potential of Shilajit to counteract the negative effects of the chemotherapeutic drug cyclophosphamide (CPA) on testicular germ cell dynamics. Material and methods: Male Parkes mice received single intraperitoneal CPA injection (200 mg/kg BW) on day one, followed by daily supplementation of Shilajit (100 and 200 mg/kg BW) for one spermatogenic cycle. Results: CPA adversely affected testicular germ cell dynamics by inhibiting the conversion of spermatogonia-to-spermatids, altering testicular histoarchitecture, impairing Sertoli cell function and testicular steroidogenesis, and disturbing the testicular oxido-apoptotic balance. Shilajit supplementation restores testicular germ cell dynamics in CPA-exposed mice, as evidenced by improved histoarchitecture of the testis. Shilajit improves testicular daily production and sperm quality by promoting the conversion of spermatogonia (2C) into spermatids (1C), stimulating germ cell proliferation (PCNA), improving Sertoli cell function (N-Cadherin and β-Catenin), and maintaining the Bax/Bcl2 ratio. Additionally, Shilajit enhances testosterone biosynthesis by activating enzymes like 3β-HSD, and 17β-HSD. Shilajit also reduces testicular oxidative stress by increasing antioxidant enzyme activity (SOD) and decreasing lipid peroxidation (LPO). These effects are mediated by upregulation of the antioxidant protein Nrf-2 and downregulation of Keap-1. Conclusion: The findings underscore the potent androgenic and antioxidant characteristics of Shilajit, as well as its ability to enhance fertility in cases of testicular damage caused by chemotherapeutic drugs.

The emergence of SARS-CoV-2 created a havoc worldwide, causing high morbidity, serious complications and mortality. The ORF1ab of SARS-CoV-2 has 16 non-structural proteins which are required for genome replication and transcription. All of these are druggable targets, of which NSP12 (RNA-dependent RNA polymerase), was selected as a potential target for drug molecules. Remdesivir is a recommended drug for SARS-CoV-2 and it targets the RdRp protein. Although Remdesivir was given to COVID-19 patients based on their clinical manifestations, yet the transmission and spread of the virus continued and to add to its pandemicity, new variants emerged from time to time. This necessitates the need for molecular modification of existing antiviral drugs so that more precise targets for halting viral replication can be selected. For this, the approach used was repurposing of the existing drugs. In the present study, ten FDA-approved drugs were chosen on the basis of their properties of inhibiting the RdRp protein. These drugs were subjected for checking the docking score with the target protein. Of these, Remdesivir, Ribavirin, Favipiravir and Baloxavir were taken for further analysis on the basis of their best scores. These drugs were then modified to check the efficiency to inhibit the RdRp and to stop the replication rate of the virus. We docked the modified drugs with the macrodomain of RdRp by using the CB-Dock web server and checked the binding affinity and amino acid contact residues. The modified drugs were also checked for bioactivity in the Molinspiration cheminformatics online tool. Our results showed increased affinity for RdRp of SARS-CoV-2 when compared to the original compound. We also checked the synthetic accessibility of the drugs using the SwissADME tool. The study showed promising results when modified. The findings reported need further confirmation through wet lab studies.

In India and other affected countries, Omicron variant of SARS-CoV-2 has shown faster transmission but less clinical severities when compared to Delta strain. Present study was aimed to investigate how molecular changes in the spike proteins of Omicron variant has increased its transmission but reduced the disease severity. We report molecular interactions of Spike proteins of Delta and Omicron variants with ACE-2 receptor to explain how change in chemical and physical nature of mutated amino acids of Omicron variant has affected the internalization competence of virus into host cell. The Research Collaboratory Structural Bioinformatics (RCSB) and Protein Data Bank (PDB) were used to construct ACE2-Spike Protein interaction. The binding affinity of both omicron and delta variant spike proteins with human ACE2 receptor was observed. Spike protein of Omicron variants has revealed total number of 93 dissimilarities of amino acids from Delta strain,15 of which are in its Receptor Binding Domain (RBD). Our study showed that RBD of Delta variant contained only one hydrophobic amino acid whereas there were 6 hydrophobic amino acids in the RBD of Omicron variant. We report that increased number of Hydrophobic Amino Acids in RBD of Omicron variant affects its binding with ACE2 receptor to enter into the cell. The failure of internalization of virus has increased concentration of extracellular virions at nasopharyngeal region leading to faster expulsion of infective droplets during coughing or sneezing to increase transmission but has reduced the severity of infection. The reported observations could prove to be of public health and therapeutic significance.

Investigating the strain and pressure dependence of perovskite materials can provide valuable insights into their structural and electronic responses, enabling the fine-tuning of their properties for various technological applications. This study investigates the influence of controlled lattice compression and expansion on the acoustic phonon-limited carrier mobility in CsBCl3 (B = Pb, Sn, Ge) perovskites, revealing tunable electronic bandgaps ranging from 0.3 to 1.2 eV by varying the B cation type and applied triaxial strain. The research demonstrates significant and monotonic carrier mobility modulation under pressure, with changes of up to 124% even at modest strain levels of −2%, along with linearly increasing exciton binding energy with lattice parameter expansion.

Introduction: Hearing impairment is caused by damage in the inner ear (can be even birth defect), ear infection, ruptured eardrum and so on. It can be prevented using early detection thus, helps in avoiding severe psychosocial, educational, and linguistic repercussions. Infants, who are not diagnosed of hearing impairment before six months of age, will have delays in speech and language development. Aim: To determine the prevalence of hearing impairment in high-risk neonates and to establish the fact that, these neonates have higher prevalence of hearing impairment as compared to normal population. Materials and Methods: A cross-sectional study was conducted in the Department of Paediatrics at Jawaharlal Nehru Medical College and Hospital, Ajmer, Rajasthan, India. The duration of the study was six months, from December 2012 to May 2013. A total of 500 babies including 297 normal and 203 high-risk babies were enrolled into the study. All the neonates were screened using Behavioural Observation Audiometry (BOA) and Distortion Product Oto-acoustic Emission (DPOAE) preferably within three days of life. Those, who failed under this test, underwent for Brain stem Evoked Response Audiometry (BERA). Data was collected in the Microsoft Excel and analysis done by Statistical Package for Social Sciences (SPSS) version 23.0. Results: The mean age of the newborns on admission, was 3.86±4.25 days and the mean weight was 2560±510 g. Out of 500 newborns screened, 58 babies had abnormal results with the first screening test. When these 58 babies subjected to BERA, eight babies showed Hearing Loss (HL). Sepsis, Neonatal Intensive Care Unit (NICU) stay >5 days and use of aminoglycosides >7 days were the important risk factors associated with hearing impairment. Prevalence of hearing impairment in the present study was came out to be 16/1000. This finding was statistically significant with p-value5 days and use of aminoglycosides >7 days should have mandatory audiologic evaluation at discharge.

Sexually transmitted infections (STI) associated with pregnancy poses a great threat to fetal well being due to vertical transmission. This study was conducted to determine the seroprevalence of hepatitis C virus, hepatitis B virus, HIV and syphilis infection in pregnant women. This retrospective study was conducted in Microbiology department over a period of one year from December 2018 to December 2019 at a tertiary care teaching hospital, Uttar Pradesh, India. In this study, hepatitis B surface antigen (HBsAg), antibodies against hepatitis C virus, HIV and syphilis infection were detected in antenatal women. Total 4037 pregnant women attending antenatal clinic were enrolled in this study. The seroprevalence of HBV was 1.34% (54/4037), HCV was 0.52% (21/4037), syphilis was 0.07% (3/4037), and HIV was 0.12% (5/4037). Only one patient had coinfection of HBV and HCV. Regular antenatal screening of all pregnant females for various infections should be done for proper and timely intervention.

Recent years have witnessed a growing interest in the biological activity of metal complexes of α-aminophosphonates. Here for the first time, a detailed DFT study on five α-aminophosphonate ligated mononuclear/dinuclear CuII complexes is reported using the dispersion corrected density functional (B3LYP-D2) method. The electronic structures spin densities, FMO analysis, energetic description of spin states, and theoretical reactivity behaviour using molecular electrostatic potential (MEP) maps of all five species are reported. All possible spin states of the dinuclear species were computed and their ground state S values were determined along with the computation of their magnetic coupling constants. NBO analysis was also performed to provide details on stabilization energies. A molecular docking study was performed for the five complexes against two SARS-CoV-2 coronavirus protein targets (PDB ID: 6LU7 and 7T9K). The docking results indicated that the mononuclear species had a higher binding affinity for the targets compared to the dinuclear species. Among the species investigated, species I showed the highest binding affinity with the SARS-CoV-2 Omicron protease. NPA charge analysis showed that the heteroatoms of model species III had a more nucleophilic nature. A comparative study was performed to observe any variations and/or correlations in properties among all species.

Introduction: Chronic Suppurative Otitis Media (CSOM) is a chronic and persistent inflammation of the mucosal lining of middle ear cleft which presents with recurrent ear discharge through a tympanic membrane perforation. CSOM is a worldwide disease and has higher prevalence in developing countries causing serious local damage and threatening complications. Aim: To determine the profile of CSOM, its causative agents and their antibiotic susceptibility pattern. Materials and Methods: The present study was a retrospective study in which data for culture and antimicrobial susceptibility profile of CSOM cases was retrieved from Microbiology department of Government Medical College, Kannauj, Uttar Pradesh, India, from January 2019 to October 2019 the analysis of data was done in February 2020. Two hundred pus swabs from discharging ears were processed during the study period for aerobic bacterial culture and antimicrobial susceptibility pattern in Microbiology department using standard microbiological techniques. The result analysis of the study was expressed as percentage and proportion for distribution of CSOM cases. Results: Out of 200 patients, 114 (57%) were males and 86 (43%) females. Among the 200 cases, 147 (73.5%) cases showed growth and 53 (26.5%) showed no growth. The most common organism isolated in this study was Pseudomonas aeruginosa, 67 (42.40%) followed by Staphylococcus aureus. 48 (30.37%) and Klebsiella spp. 23 (14.55%). Gentamicin (85%) and amikacin (83%) had high level of antibacterial activity on all the isolates. Meropenem was found to be most effective drug for gram negative isolates. All Staphylococcus spp isolates were sensitive to vancomycin (100%). Conclusion: Pseudomonas aeruginosa was the most predominant organism isolated in otitis media patients. Most of the isolates were sensitive to meropenem.