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Abstract Background Visceral leishmaniasis (VL), known as Kala-azar on the Indian subcontinent, is a parasitic disease caused by the flagellated protozoa Leishmania donovani and can be fatal if left untreated. The sand fly Phlebotomus argentipes is the only proven vector of VL in the Southeast Asia region, and VL control in this region has relied on the use of synthetic insecticides for indoor residual spraying (IRS). The use of DDT in VL control programmes has led to the development of resistance to this insecticide in sand flies, resulting in DDT being replaced with the insecticide alpha-cypermethrin. However, alpha-cypermethrin has a similar mode of action as DDT and, therefore, the risk of resistance development in sand flies increases under the pressure of regular exposure to this insecticide. In the present study we assessed the susceptibility status of wild-caught sand flies and F1 progeny using the CDC bottle bioassay. Methods Sand flies were collected from 10 villages in Muzaffarpur District, Bihar, India. Eight of these villages are receiving continuous IRS with alpha-cypermethrin, one village had discontinued IRS with alpha-cypermethrin and one village had never received IRS with alpha-cypermethrin. The collected sand flies were exposed to a pre-determined diagnostic dose for a specific time duration (3 µg/ml for 40 min), and knockdown and mortality at 24 h post-exposure were recorded. Results Knockdown ranged from 91.19% to 99.47% for wild-caught sand flies and from 91.70% to 98.89% for their F1 progeny. At 24 h post-exposure, mortality ranged from 89.34% to 98.93% for wild-caught sand flies and from 90.16% to 98.33% for F1 progeny. Conclusions The results of this study showed that P. argentipes is potentially developing resistance, signalling the need for continuous monitoring and vigilance to sustain the validation of elimination once achieved. Graphical Abstract

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

Abstract The fast expansion of mobile networks has sparked worries regarding base station EM radiation's health impacts. Traffic load is commonly ignored when evaluating EM radiation levels using maximum power output. This study proposes utilizing AI and ML on real network traffic data to optimize GSM base station EM radiation estimations. We obtained EM radiation measurements and traffic data from selecting GSM base stations by location and configuration. To predict EM radiation levels, traffic patterns were used to train linear regression, random forests, and neural networks. Base stations were clustered by radiation profile using unsupervised learning. Considering regulatory restrictions and measurement feasibility, an optimization methodology was created to minimize EM radiation estimate inaccuracy. The results show better prediction accuracy than power-based estimations and high generalisability across base station types. Site-specific factors influenced daily EM radiation patterns after clustering. EM radiation levels can be monitored using traffic data and the optimized AI/ML model. This research helps telecom operators and regulators analyze EM radiation more accurately and efficiently. Future projects should include 5G and small cell network extensions and intelligent city platform integration. The suggested method develops data-driven, AI-powered Public Safety and mobile network trust solutions.

Abstract Groundwater poisoning by heavy metals has caused serious health hazards in the exposed population globally. Manganese (Mn) poisoning causing human health hazards is very meagerly reported worldwide. The present research elucidates for the first time the catastrophic effect of manganese causing cancer in the Gangetic plains of Bihar (India). The blood samples of n = 1146 cancer patients were voluntarily obtained for the study, after their consent. Their household water samples were also collected for the study. All the samples were analysed for Mn contamination by Atomic Absorption Spectrophotometer. The study indicates high Mn contamination in the cancer patient blood samples with highest content as 6022 µg/L. Moreover, the cancer patient’s household handpump water samples also contained elevated Mn contamination. The correlation coefficient study finds significant association between Mn contamination in blood of cancer patients and their handpump water. The carcinoma group of cancer patients mostly in Stage III & IV had significant Mn contamination in their blood (above WHO/BIS permissible limit). The geospatial study depicts Mn contamination in handpump water in the state of Bihar in correlation with cancer patient’s blood samples. This novel finding is being reported in India for the first time, which correlates cancer with handpump drinking water. The long-term Mn exposure could be one of the causative agents for elevating cancer incidences. However, other confounding risk factors cannot be denied.

Abstract Background The prevalence of cognitive diseases, including Alzheimer’s disease and other forms of dementia, poses a significant global health challenge due to the limited availability of effective therapeutic options. Recent years have witnessed a growing emphasis in research on the exploration of natural compounds and their derivatives as prospective therapeutic agents for cognitive impairments. Main body Xanthotoxin, a furanocoumarin compound derived from botanical sources, exhibits promising therapeutic promise in several neurological conditions such as depression, neuronal inflammation, Alzheimer’s disease, vascular cognitive impairment, epilepsy, and Parkinson’s disease. This potential stems from its notable neuroprotective, antioxidant, and anti-inflammatory characteristics. The present study offers a comprehensive examination of the acquisition of XAT from both natural sources and synthetic means. It delves into the significance of XAT in the treatment of cognitive disorders and delineates potential avenues for future research in the domain of XAT and cognitive disorders. Conclusion Ongoing research and advancements in the field of XAT have the potential to enhance its use as a potent therapeutic intervention for cognitive impairments, consequently enhancing the holistic welfare of those afflicted by these incapacitating disorders.

Nowadays, digital technologies are being used to transform the agriculture sector into a more effective and environmentally friendly one by including technologies such as the Internet of Things (IoT), cloud computing, machine learning, and artificial intelligence (AI). These techniques are used to improve sustainability through more productive farming practices. Internet of Things is one of the most revolutionary techniques to provide improved agricultural services by efficiently managing and analyzing related processes. Traditional methods of a few agricultural services cannot satisfy the intricate needs of a growing population. Hence, a combination of multiple services or service composition is needed to meet user demand. This study addresses this problem by considering various agricultural services and integrating them into a composite service. The proposed work is divided into two phases. To ascertain the non-linear relationship between the cost and time of different services, Lagrange's interpolation model has been employed in the first phase. Subsequently, in the second phase, the Non-dominated Sorting Genetic Algorithm (NSGA-II), a multi-objective evolutionary algorithm, has been utilized to optimize the time and cost of services. The efficacy of the work has been evaluated by analyzing the results of the proposed method using the same multi-objective evolutionary technique, which has a linear relationship between the cost and time of various services.

Background: Wireless Holter monitors can be a great alternative to the traditional wired holter monitoring potentially giving better patient outcomes. However, the technology is new and less explored for the quality of ECG wave forms. Objective: This study was taken up to compare the quality of electrocardiogram (ECG) and arrhythmia detection using a traditional Holter and a wireless ambulatory smart ECG – Vigo SmartHeart (VSH) that functions with a Mobile application. Materials and Methods: The present study was cross-sectional in nature. We enrolled the patients indicated for continuous ECG monitoring. All the enrolled patients were connected to VSH wireless Holter solution and a conventional Holter monitor simultaneously. The ECGs generated were compared through descriptive statistics such as mean, standard deviation, and correlation by Pearson’s correlation method. Results: Seventy-one patients had simultaneous ECG recordings by both systems. The Pearson correlation for P wave, QRS, PR, QT, and ST was measured as 0.93, 0.93, 0.99, 0.36, and 0.98, respectively. The minimum heart rate (HR), maximum HR, RR interval, P wave, QRS complex, PR, and ST segments showed a statistically significant correlation between Smart Heart and Conventional Holter. 17 ECG events were reported, of which 14 were detected by both. The events missed by conventional Holter and detected by VSH were Atrioventricular block (2), Supraventricular tachycardia (1), and Intraventricular conduction delay (1). Conclusions: The quality of the report generated by both the methods was comparable to ECG wave quality, However, arrhythmia was picked up by the SmartHeart with better precision compared to conventional Holter. Thus, VSH can serve as a viable and potential alternative tool to screen and help in reducing the morbidity and mortality related to arrhythmias.

Introduction: Coeliac Disease (CD) is a systemic immune disorder caused by gluten in genetically susceptible individuals. A serological screening assay for CD has been designed to detect Immunoglobulin A (IgA) and IgG anti-tissue Transglutaminase (a-tTG) and IgA and IgG Deamidated Gliadin Peptide antibodies (a-DGP) simultaneously. The seronegative gap can be closed when these two antigens are combined on a single solid phase. This is primarily because untreated CD children who are negative for antibodies of one of the antigens may exhibit a positive result for the other. Aim: To determine the diagnostic parameters {sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV)} of tTG-IgA and htTG-DGP (Coeliac fusion- a combination of IgA and IgG to human tTG and synthetic DGP) for the diagnosis of CD in clinically symptomatic children. Materials and Methods: This cross-sectional study was conducted at the Paediatric Outpatient Department (OPD) of Santokhba Durlabhji Memorial Hospital, Jaipur, Rajasthan, India from April 2023 to November 2023. The study population comprised 45 children (age >6 months and

Introduction: Children who are born with disability, more so intellectual disability are dependant on their parents for their daily needs. The presence of disabled child in the family adds to the caregiver burden which may read to emotional distress manifesting as anger, depression, stigma, etc. The study aimed to assess both the positive and negative impacts of having a disabled child in the family on caregivers. Methodology: The present, cross-sectional study was conducted in a rural area of Jammu district using simple random sampling, two health zones out of eight were selected for the conduct of the study. All the disabled children were identified and their parents were interviewed using National Institute of Mental Health-Disability Impact Scale Scale after taking an informed consent from them (IECGJ)(NO: IEC/GMC/2019/892). Results: During the course of the study, a total of 101 caregivers of disabled children were interviewed. Both negative and positive impact on the caregivers was found to be in close approximation to the tune of 15%–16%. Among the negative impacts, financial burden was the most dominant domain followed by physical care of the child and caregiver health being affected. Conclusion: It would be pertinent to conclude that we need to empower the caregivers as an important step for the inclusion of these special children in the society. In this context, few recommendations have been discussed in the present study.

Soil management is pivotal in optimizing crop production, directly influencing agricultural sustainability and food security. Traditional soil management practices, while effective, often lack the integration of interdisciplinary approaches necessary to address contemporary agricultural challenges. This review paper explores recent advancements in soil management, emphasizing the synergy of various disciplines to enhance soil health and crop productivity. Conservation agriculture, precision farming, organic farming, and integrated nutrient management are highlighted as key practices that have evolved through technological and scientific innovations. Interdisciplinary collaborations between soil science, agronomy, biotechnology, microbiology, and environmental science are examined, showcasing their collective impact on soil management strategies. Furthermore, the paper discusses the role of socio-economic and policy perspectives in promoting sustainable soil management practices. Real-world applications and case studies are presented to illustrate the practical benefits and outcomes of these advanced practices. The review identifies current challenges and outlines future research directions needed to further optimize soil management and crop production. The findings underscore the necessity for a holistic approach that integrates scientific, technological, environmental, and socio-economic dimensions to achieve sustainable agricultural systems.

The ongoing transition from a supply chain (SC) to net-zero emission (NZE) in SC performance must align with Sustainable Development Goal 13 to address climate change using life cycle assessment (LCA). Effective management of LCA significantly impacts an organization's competitiveness. With a lack of technology oversight and its connections with other enabling parameters that increase competitiveness, practices in the manufacturing industry remain limited. This study identifies and evaluates key enablers for LCA adoption in the manufacturing industry to achieve NZE in SC. Based on 123 responses, an exploratory factor analysis (EFA) was employed, followed by the Best-Worst Method (BWM). Further, a Fuzzy-Decision-Making Trial and Evaluation Laboratory (Fuzzy-DEMATEL) was used. The results revealed ‘organizational integration’, ‘data availability and quality, and ‘policy and regulation’ as significant group enablers that support NZSC to compete in the market. It provides insights for industry practitioners and policymakers on optimizing sustainable SC practices. The essential practical recommendations for resource optimization and carbon footprint reduction are also suggested.

In a Sustainable Supply Chain (SSC) context, information management offers a unique perspective on the digital economy and information management. Artificial intelligence (AI) is developing into a more robust digital field to facilitate quick information access and intelligent decisions in expanding commercial contexts. These days, Supply Chains (SC) would crumble without robust information systems. Applying AI and information management is crucial in determining the direction of sustainable supply chain management (SSCM). A systematic literature review (SLR) of the use of AI in SSCM is conducted in this research. The authors can identify crucial factors of the present literature using bibliometric and network analysis. AI is essential to the SSC to address sustainability challenges and manage the large volumes of data produced by numerous industrial processes. In the corpus of research that is already accessible, there is currently no comprehensive and bibliometric analysis of the potential for AI techniques for information management in SSC. Scientific publications were analysed from an objective point of view. Based on our results, we have drafted a proposal for an AI supply chain framework. Researchers, policymakers, and SCM practitioners may all benefit from the approach. This study is the first to analyse AI applications for information management in SSCM. In consideration of this, organizations are now exploring AI capabilities to improve operational efficiency and innovate their processes. This will assist industry people in understanding how AI methods support SC processes in their optimization to attain sustainability in SC practices.

Global market competitiveness and standards are pushing the manufacturing supply chain to adopt sustainable approaches to enhance quality, reduce waste, improve environmental practices, and optimize product costs. Blockchain technology has emerged as a promising tool for improving supply chain transparency and manufacturing sustainability. However, various challenges to the mainstream use of blockchain must be identified and addressed. In this regard, the study aims to identify and comprehend the challenges of adopting blockchain technology in the manufacturing sector to improve sustainable standards. To bridge this gap, the study used a three-step procedure. First, through a comprehensive literature review, 19 potential challenges were identified. Then, with the experts' discussion, a total of 18 challenges were finalized. In the second phase, data was collected from 15 professionals with industrial backgrounds. Lastly, the collected data was analyzed using Combined Compromise Solution methodologies and the Fuzzy-Decision-Making Trial and Evaluation Laboratory (fuzzy DEMATEL). This hybrid methodology prioritizes the challenges in blockchain adoption and categorizes them into causal groups. This improves the decision-making process by evaluating how the mutual impact of challenges in blockchain adoption affects achieving sustainability in the manufacturing supply chain. The outcomes of the presented work are validated through a sensitivity analysis of the outranked dimensions of blockchain adoption challenges. Results show that 'High Initial Investment Cost' and 'Lack of Digital Skills’ are the top challenges in its adoption. The findings of this work provide a roadmap to make the manufacturing supply chain sustainable and accomplish sustainability.

Silent estrus results in spread-out kidding and extended inter-kidding interval in goats. Progesterone (P4) priming for 12-14 days could be one of the approaches for estrus induction with optimum fertility. The present work was carried to comparatively assess the duration of P4 priming on estrus and fertility in silent estrus goats. Sirohi does (n=18) with a history of anestrus and high basal P4 in paired samples were equally divided into three groups. Does in P-0 d group received 200 IU of equine chorionic gonadotropin by intramuscular route. Does in group second and third were subjected to per-vaginal P4 sponges for 7 (P-7 d) and 14 (P-14 d) days, respectively and were given 200 IU equine chorionic gonadotropin following sponge withdrawal. Estrus was monitored for 72 h at 12 h intervals using teaser buck to record estrus per cent, induction time and duration. Estrus induction was highest in P-14 d (6/6) than P-0 d and P-7 d (4/6 and 5/6), respectively. Estrus induction time was shorter in P-7 d and P-14 d than P-0 d. The estrus duration was shortest in P-14 d group. The conception and pregnancy rate did not differ significantly among the groups, though all the does in P-14 d conceived. The fertility was non-significantly higher in P-14 d (6/6) and P-7 d group (5/5) than P-0 d (3/4). It could be concluded that P4 priming for 7-14 days in silent estrus does results in improved reproductive performances.

Egyptian clover/Berseem (Trifolium alexandrinum L.) is the most popular winter leguminous multi-cut fodder crop widely cultivated in the northwest and central parts of India. Quality seed significantly impacts farm productivity, farmers’ profitability, and socioeconomic welfare. Foundation and certified seeds enable high-quality seed production, making breeder seed (BS) the most important link in the seed supply chain. In India, berseem BS indent had increased from 1998 - 99 to 2012–13; afterwards, it followed a constant but decreasing trend. Of the 27 notified cultivars, 24 came into the seed supply chain between 1998–1999 and 2021–2022, indicating high varietal availability to stakeholders. The study examines the potential causes of the national decline in BS indent and production and the differences in these figures over time. The highest BS indent was received for the variety JB-1 (276.1 q), followed by BL-10 (205.1 q), Mescavi (165.6 q) and Wardan (153.7 q) from 1998 - 99 to 2021–22. The varietal replacement rate (VRR) is high, 43.30 %, for the varieties that have reached the age of five or less in the recent three years (2019–20 to 2021–22). Additionally, it has been calculated that if the seed chain operates at 100 % efficiency, the BS generated (48.1q) in 2021–22 can cover an area of almost 0.12 million hectares in 2024–25. The study offers an in-depth overview of berseem BS indent and production, an analysis of the difficulties encountered in BS production, and future directions for expanding variety and producing excess BS in the nation.

PURPOSEStandard-dose immune checkpoint inhibitors (SD-ICIs) are the standard of care as initial therapy in microsatellite instable-high (MSI-H) advanced/metastatic colorectal adenocarcinomas (mCRC), but there are preclinical data to suggest that low-dose ICIs (LD-ICI) might also have similar efficacy.MATERIALS AND METHODSA retrospective study of patients with MSI-H mCRC receiving ICIs between June 2017 and January 2023 was conducted. The primary end point of the study was 12-month progression-free survival (PFS), which was computed using the Kaplan-Meier method.RESULTSA total of 65 patients were available for analysis during the study period. Sixty patients (92%) received nivolumab, whereas the remaining received pembrolizumab. First-line ICIs were received by 18 patients (28%), whereas 47 patients (72%) received ICIs during later lines. Thirty patients (47%) received LD-ICIs (all received nivolumab), with the remaining receiving SD-ICIs (53%). At a median follow-up of 16.5 (95% CI, 11.8 to 21.2) months, median PFS was not reached in the entire cohort. The 12-month PFS rate in the LD-ICI cohort was 90%, whereas it was 75.8% in the SD-ICI cohort. There were no statistical differences in patients receiving ICIs as first-line therapy (12 months PFS—94.4%) or during later lines of therapy (12-month PFS—77.9%; P = .56).CONCLUSIONICIs in the current study show survivals which are similar to those seen in seminal trials in patients with MSI-H mCRC. Low-dose ICIs appear to work in MSI-H mCRC and should be explored prospectively in clinical trials. Patients with MSI-H status should be exposed to ICIs, whether initially or later during treatment, whenever feasible.

Summary: Lung cancer varies between Caucasians and Asians. There have been differences recorded in the epidemiology, genomics, standard therapies and outcomes, with variations according to the geography and ethnicity which affect the decision for optimal treatment of the patients. To better understand the profile of lung cancer in Southeast Asia, with a focus on India, we have comprehensively reviewed the available data, and discuss the challenges and the way forward. A substantial proportion of patients with lung cancer in Southeast Asia are neversmokers, and adenocarcinoma is the common histopathologic subtype, found in approximately a third of the patients. EGFR mutations are noted in 23–30% of patients, and ALK rearrangements are noted in 5–7%. Therapies are similar to global standards, although access to newer modalities and molecules is a challenge. Collaborative research, political will with various policy changes and patient advocacy are urgently needed.

Background: Postpartum depression refers to non-psychotic depressive episode that begins immediately after childbirth. Although delivering a baby is a happy event but many females develop depressive symptoms. About 13% of postpartum women experience a mental disorder, primarily depression worldwide. The aim is to estimate the prevalence of Postpartum depression among the mothers and to determine the association of Perceived Social Support, socio demographic and other obstetric variables with Postpartum depression. Methodology: The study was conducted among the Postpartum mothers attending the immunization section of a Tertiary care hospital, Jammu, India. Tools used are- Edinburgh Postnatal Depression Scale (EPDS), Hamilton depression Rating Scale (HDRS) and Multidimensional Scale of Perceived Social Support (MSPSS). SPSS software was used to analyse the data. Results: Prevalence of Postpartum Depression was found to be 16.1%. Variables like residence, occupation, h/o domestic violence, family h/o mental illness, eventful antenatal period, h/o hospitalization of baby, unwanted parenthood and low social support emerged to be independent predictors of Post Partum depression. Conclusions: Postpartum mothers particularly those, who were having poor social support are highly vulnerable to depression. Every postpartum mother should be screened for postpartum depression and timely referred to the psychiatrists. Also, family members need to be counselled.

This special issue is part of an ongoing project by the Institute of Indian Studies at Hankuk University of Foreign Studies, titled Great Transitions in India: A Korean Perspective on Indian Studies. Launched in 2017 with the support of a significant research grant from the National Research Foundation of Korea (NRF) under the prestigious Humanities Korea Plus (HK[Formula: see text]) program, the project aims to explore India’s major transformations from a multidisciplinary viewpoint. Building on the momentum of the Journal of Indian and Asian Studies (JIAS) special issue series introduced in 2021, which focused on key changes in India, this issue continues that exploration. It brings fresh insights by integrating perspectives from the humanities and social sciences. This special issue is the result of an international conference on Great Transitions in India, held in May 2024 at the Institute of Indian Studies, Hankuk University of Foreign Studies, Seoul. The conference gathered scholars from various disciplines, each contributing to a broader understanding of India’s profound changes. By offering a multidisciplinary perspective, this issue seeks to advance the current body of literature and encourage scholars of Indian and South Asian studies to adopt cross-disciplinary approaches, fostering deeper insights into India’s transformations.

The world is witnessing a new technological order as major powers restructure their national strategies to dominate the supply chains of semiconductors, which have emerged as the most critical technology in the post-COVID era. In this context, the origins of the India-US semiconductor alliance represent a significant development. This paper explores the drivers and defining characteristics of this partnership. By combining geo-economic and geopolitical perspectives, the paper explains India's emerging semiconductor strategies and the rationale behind the India-US semiconductor collaboration. Geo-economic factors—such as India's recognition of economic security risks during the pandemic-induced chip shortages, the crucial role of semiconductors in India's future economic growth, and its ambitions to become a chip exporter—have driven the formation of India’s new semiconductor strategy and its quest to strengthen ties with the US. Geopolitical factors, including India's heightened threat perception regarding its dependence on chip imports from China and concerns about China's technological advancements, have further bolstered this technological partnership. The India-US semiconductor alliance in the post-COVID era is defined by three major characteristics: first, unprecedented high-level political commitment to building chip partnerships; second, significant enhancement of chip-related agreements and institutional collaborations between the two countries; and third, the promotion of US semiconductor companies' presence in India. The paper also examines the future prospects of this alliance, emphasizing the substantial convergence between India and the US in the semiconductor sector and identifying key challenges that will shape the future trajectory of this partnership.

The scarcity of high-quality forage has a significant influence on the productivity and profitability of livestock. Addressing this concern, an investigation was undertaken to assess the effects of distinct Italian ryegrass genotypes, namely, Punjab ryegrass-1, Kashmir collection, and Makhan grass, in conjunction with varying seeding ratios of Italian ryegrass to Egyptian clover. The seeding ratios considered were 100:0 (Italian ryegrass to Egyptian clover), 75:25, 50:50, and 25:75. All possible combinations of Italian ryegrass and Egyptian clover with seeding ratios were set up in a randomized complete block design and replicated thrice. Co-cultivating Italian ryegrass and Egyptian clover at a 75:25 seeding ratio yields the best yield benefit, as determined by the land equivalent ratio. It is noteworthy that in this configuration, real yield loss is higher for Egyptian clover and for Italian ryegrass when the seeding ratio is 25:75. The higher competitiveness of Italian ryegrass in comparison to Egyptian clover is highlighted by the competitive ratio. Notably, the nutritive parameter, crude protein yield, was significantly higher in the Makhan grass-based 50:50 and 75:25 seeding ratio. Results of the study ascertained the compatibility of grass-legume co-cultivation with significantly higher quantity and quality forage harvested under mixed cropping systems whereas Makhan grass as the superior and dominant genotype in comparison to Kashmir collection. The outcomes of this study revealed that the 100:0 seeding ratio, coupled with the Makhan grass genotype, exhibited superior performance in terms of cumulative forage harvest, dry matter accumulation, net returns, and benefit–cost ratio.

Agriculture is the second largest contributor (20 %) to total anthropogenic greenhouse gas (GHG) emissions in the world. There is a need to identify energy and carbon efficient cropping systems that reduce GHG emission and improve environmental quality. Using life cycle assessment (LCA), we evaluated the four cropping systems namely fallow – chickpea (F–C); Sesbania – mustard (Ses–M); blackgram – chickpea (B–C); sorghum + cowpea – mustard (S + C–M) cultivated during the 2018–2022 period. The energy use pattern and the input-output relationship were analysed. Three measures were utilized to quantify carbon footprints: CFa, which denotes emissions per unit area; CFb, indicating emissions per kilogram of yield; and CFe, representing emissions per unit of economic output. The result indicates that non-renewable sources of energy (diesel and fertilizer) contributed more than ∼80 % of the total energy consumed in the different cropping systems. The total energy requirement was the highest for S + C–M (16,972 MJ ha–1), followed by Ses–M (14,365 MJ ha–1), B–C (11,132 MJ ha–1) and F–C (8679 MJ ha–1) cropping systems. The S + C–M cropping system also had the highest energy use efficiency (9.13) followed by F–C (6.03), B–C (5.41) and Ses–M (5.41). The fallow–chickpea cropping system had the lowest values of CFa, CFb, and CFe however, the highest carbon efficiency (10.7) and the carbon sustainability index (9.7) were computed in S + C–M cropping system. Our findings indicate that thoughtfully structured, varied crop systems that integrate legumes and forage crops have the potential to significantly reduce energy consumption and carbon emissions, while sustaining or potentially improving overall productivity within these systems.

Introduction: The aim of the study was to evaluate the feasibility and outcome of laparoscopic surgery in complicated choledochal cyst (CDC) with previous interventions (laparotomy or biliary drainage). Patients and Methods: Patients with CDC who underwent surgery from July 2014 to July 2019 were evaluated. CDC without previous interventions (Group A) was compared with CDC that had previous interventions (Group B) to assess the feasibility and outcome of laparoscopic surgery. Results: In 5 years' period, 38 patients were operated for CDC. The mean age was similar in both groups (3.78 ± 2.27 in Group A and 4.08 ± 2.73 in Group B). Out of six CDC with previous intervention (Group B), five patients were previously managed at other institutions as follows: (1) Laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) stenting. (2) Laparotomy for biliary peritonitis and ERCP. (3) Percutaneous drainage of the large cyst. (4) Laparoscopic cholecystectomy. (5) ERCP stenting. (6) Percutaneous drainage for biliary ascites. All patients underwent laparoscopic CDC excision and hepatico-duodenostomy. The mean duration of surgery was 160.3 ± 17.22 in Group A and 169.2 ± 17.5 in Group B (P = 0.258). None required intraoperative blood transfusion. None had a bile leak. Drain was removed at 4.47 ± 0.98 in Group A, while at 4.17 ± 0.75 days in Group B (P = 0.481). There was statistically no significant difference in feed starting time or length of stay. In follow-up of 6 months–3 years, all patients are asymptomatic. Conclusions: Laparoscopy in complicated CDC with previous intervention is technically tedious but is feasible. The procedure is safe and delivers a good outcome.

Introduction: Long COVID is commonly encountered by many individuals during the coronavirus 2019 pandemic. It is best diagnosed by a history consistent with acute coronavirus disease 2019 (COVID-19) followed by a prolonged recovery. An attempt has been made to enlist the sequel of long COVID clinically and to assess their risk factors. Materials and Methods: Confirmed COVID-19 patients admitted to our hospital were enquired about their persistent symptoms following infection after 3– 12 weeks for acute symptoms and after 12 weeks for chronic symptoms through the predesigned questionnaire schedule about their manifestations and followed up every month for 6 months. Results: A total of 152 patients were included in our study and found acute long COVID symptoms related to neurological (72.2%), respiratory (64.7%), and musculoskeletal (61.4%) system being most commonly affected. Chronic symptoms were comprised predominantly musculoskeletal (63.1%) followed by fatigue (43.4%) and neurological (29.6) manifestations. Risk factors estimate of postacute COVID-19 symptoms showed that females had increased risk with odds ratio (OR) (and 95% confidence intervals) (OR) of 2.412 (1.239–4.692), sedentary lifestyle OR 1.775 (1.345–2.762), body mass index (BMI) >23 OR 3.877 (1.613–6.144), and presence of comorbidities OR 2.526 (1.277–4.997). Similarly, risk factor estimate of Postchronic COVID-19 symptoms showed that females had increased risk with OR 1.879 (0.952–3.709), sedentary lifestyle OR 5.091 (2.853–9.085), BMI >23 OR 2.082 (1.005–4.134), and presence of comorbidities OR 1.851 (0.925–3.705). Conclusions: Long COVID symptoms noted were mainly related to musculoskeletal disorders, neurological, respiratory, and fatigue. This enumeration will help us to bring the further pathway to include this long COVID entity for preventive strategies in our regular setup at the primary care level.

Background: Food insecurity is a matter of public health concern as it is associated with adverse health outcomes particularly among vulnerable population. Accessibility and availability of nutritious and culturally appropriate food is paramount to achieve zero hunger. To assess the prevalence of household food insecurity, to estimate the household dietary diversity and its association with household food insecurity. Material and Methods: Using multistage sampling 381 rural households were surveyed. Household Food Insecurity Access Scale and House hold Dietary Diversity Scale were used as study instruments. Chi square test was used to compare the two groups and P < 0.05 was considered to be statistically significant. Results: Prevalence of household insecurity was 33.3% (127) among the surveyed households and 8.1% (31) had severe food insecurity. The mean HFIS score was 6.85 ± 4.82. The household Dietary diversity score was 8.14 ± 1.54 for food secure and 6.51 ± 1.38 for severely food insecure households. There was a statistically significant difference in intake of milk and milk products, fruits, eggs and meat/poultry among food secure and insecure households (P < 0.001 respectively). Conclusion: Food insecurity was high in rural households and was associated with lower dietary intake of foods from protein group, necessitating a need to reinforce the food security programmes in rural India with focus to enhance protein rich diet.

The democratic welfare government is equally committed to quality-driven, impartial, and egalitarian education. The major contribution of this study is to examine the problems and opportunities posed by the incorporation of digital technology in the classroom via the lens of Classroom 4.0 (CLSR4) and education 4.0. The commitment of the democratic welfare government to equitable and quality education is investigated, in line with the Global Agenda SDG 4 goal of ensuring comprehensive and lifelong education for everyone. The modern classroom is witnessing a clash between traditional teaching methods and the digital competency of today’s tech-savvy generation. The goal of this study is to examine the connections between education 4.0 and classroom 4.0 by looking at developments in classroom architecture and the use of digital platforms. The biggest issue found is instructors’ inability to adjust to changing conditions. In terms of methodology, confirmatory factor analysis is used in this work to investigate the dynamics of correlations in the context of Classroom 4.0. This method offers insights into the variables influenced by metaverse technology, resulting in a thorough comprehension of the evolving educational scene. This study’s findings shed insight into how students see the changing classroom and the role that various platforms play in engaging them. The study underscores the need for educators to effectively integrate these tools and address this digital transformation to improve teaching and learning experiences. However, there are study constraints, most notably the limited contextual scope, which is exclusively focused on the Indian educational setting. Further research in other worldwide contexts is required to generalize the findings. In the future, it is critical to investigate and build creative instructional practices that effectively synergize with Classroom 4.0. Furthermore, further research should be conducted to determine how governments and educational institutions might adapt to this paradigm shift, ensuring a smooth and effective transition into the digital era of education.

Abstract The growing popularity of nano-fertilization around the world for enhancing yield and nutrient use efficiency has been realized, however its influence on soil microbial structure is not fully understood. The purpose of carrying out this study was to assess the combined effect of nano and conventional fertilizers on the soil biological indicators and crop yield in a wheat–maize system. The results indicate that the at par grain yield of wheat and maize was obtained with application of 75% of recommended nitrogen (N) with full dose of phosphorus (P) and potassium (K) through conventional fertilizers along with nano-N (nano-urea) or nano-N plus nano-Zn sprays and N100PK i.e. business as usual (recommended dose of fertilizer). Important soil microbial property like microbial biomass carbon was found statistically similar with nano fertilizer-based management (N75PK + nano-N, and N75PK + nano-N + nano-Zn) and conventional management (N100PK), during both wheat and maize seasons. The experimental data indicated that the application of foliar spray of nano-fertilizers along with 75% N as basal is a sustainable nutrient management approach with respect to growth, yield and rhizosphere biological activity. Furthermore, two foliar sprays of nano-N or nano-N + nano-Zn curtailed N requirement by 25%, furthermore enhanced soil microbial diversity and the microbial community structure. The specific microbial groups, including Actinobacteria, Bacteroidia, and Proteobacteria, were present in abundance and were positively correlated with wheat and maize yield and soil microbial biomass carbon. Thus, one of the best nutrient management approaches for sustaining productivity and maintaining sound microbial diversity in wheat–maize rotation is the combined use of nano-fertilizers and conventional fertilizers.

Gliomas are the most common primary brain tumors, representing approximately 28% of all central nervous system tumors. These tumors are characterized by rapid progression and show a median survival of approximately 18 months. The therapeutic options consist of surgical resection followed by radiotherapy and chemotherapy. Despite the multidisciplinary approach and the biomolecular role of targeted therapies, the median progression-free survival is approximately 6–8 months. The incomplete tumor compliance with treatment is due to several factors such as the presence of the blood–brain barrier, the numerous pathways involved in tumor transformation, and the presence of intra-tumoral mutations. Among these, the interaction between the mutations of genes involved in tumor bio-energetic metabolism and the functional response of the tumor has become the protagonist of numerous studies. In this scenario, the main role is played by mitochondria, cellular organelles delimited by a double membrane and containing their own DNA (mtDNA), which participates in numerous cellular processes such as the regulation of cellular metabolism, cellular proliferation, and apoptosis and is also the main source of cellular energy production. Therefore, it is understood that the mitochondrion, specifically its functional alteration, is a leading figure in tumor transformation, including brain tumors. The acquisition of mutations in the mitochondrial DNA of tumor cells and the subsequent identification of the so-called mitochondria-related genes (MRGs), both functional (mutation of Complex I) and structural (mutations of Complex III/IV), have been seen to play an important role in metabolic reprogramming with increased proliferation, resistance to apoptosis, and the progression of tumorigenesis. This demonstrates that these mitochondrial alterations could have a role not only in the intrinsic tumor biology but also in the extrinsic one associated with the therapeutic response. We aim to summarize the main mitochondrial dysfunction interactions present in gliomas and how they might impact prognosis.

The crop water requirement of rice in different agroclimatic zones of Jharkhand, India was estimated using the CROPWAT 8.0 and CLIMWAT 2.0 models with data collected through NASA data-access-viewer on climate, soil, crop, and water availability. The evapotranspiration (ETo), effective rainfall (Peff), and crop water requirement (CWR) for the four zones of the Jharkhand State were calculated. Results revealed that the reference evapotranspiration (ETo) varied from 420.4 mm to 516.5 mm during the crop growing season of rice in different zones. The effective precipitation varied from 748.4 mm to 760.8 mm. The crop water requirement of rice varied from 482.5 mm to 592.4 mm. Effective rainfall was sufficient to meet the water requirement of rice in most of the zones except Alluvial zone wherein the net irrigation water requirement was only 67.6 mm.

The pathogenesis of the inflammatory, chronic, and common skin disease psoriasis involves immune cells, skin cells (keratinocytes), and the cytokines they secrete. Hyperproliferation and abnormal differentiation of keratinocytes are hallmarks of the disease. The roles of cytokines such as TNFα, IL-15, IL-17, and IL-23 in psoriasis have been studied through mathematical/computational models as well as experiments. However, the role of proinflammatory cytokine IL-36 in the onset and progression of psoriasis is still elusive. To explore the role of IL-36, we construct a network embodying indirect cell–cell interactions of a few immune and skin cells mediated by IL-36 based on existing knowledge. We also develop a mathematical model for the network and perform a global sensitivity analysis. Our results suggest that the model is most sensitive to a parameter that represents the level of cytokine IL-36. In addition, a steady-state analysis of the model suggests that an increase in the level of IL-36 could lead to the hyperproliferation of keratinocytes and, thus, psoriasis. Our analysis also highlights that the plaque formation and progression of psoriasis could occur through either a gradual or a switch-like increase in the keratinocyte population. We propose that the switch-like increase would be due to a bistable behavior of the network toward either a psoriatic or healthy state and could be used as a novel treatment strategy.

Abstract The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30–150‐nm‐sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto‐lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV‐treated macrophages. Due to this, both macro‐autophagy and caspase‐linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT–mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV‐mediated immune suppression revealed that the EV can protect the mice from DSS‐induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential.

A field experiment was conducted during the rainy seasons (kharif) of 2021 and 2022 at research farm of ICAR- Indian Agricultural Research Institute, New Delhi to study the effect of irrigation regimes and integrated use of prilled urea and nano-urea as a source of N, on productivity and profitability of basmati rice (Oryza sativa L.). The experiment was conducted in a three-time replicated split-plot design (SPD) comprised of 3 irrigation regimes, viz. irrigation at 1, 3 and 6 days after disappearance of surface water (DADSW) assigned to main-plots and 4 N-management variants including; 100% RDN (recommended dose of N, 120 kg/ha); 75% RDN + 4% nano-urea (NU) 2 sprays (75% RDN + 2 NU); 50% RDN + 2 NU; and no-N (control) in sub-plots. Irrigating basmati rice 1 DADSW exhibited the highest panicle weight (2.67–3.09 g) and number of grains/panicle (115.9, 109.8), across the years, respectively that were significantly higher than 3 and 6 DADSW. The most delayed irrigation at 6 DADSW caused significant reduction in grain yield, the magnitude of reduction was 13–19% over irrigation at 3 DADSW and substantially by 23–28% over 1 DADSW. Fertilizing rice crop with 100% RDN and 75% RDN + 2 NU resulted in statistically similar yield attributes and grain yield; however, both were, significantly superior to 50% RDN + 2 NU and no-N. Net returns, benefit cost (B:C) ratio and monetary efficiency were significantly higher when crop was irrigated 1 DADSW than 3 and 6 DADSW. The N-management options followed the trend as RDN>75% RDN + 2 NU ˃50% RDN > no-N for all studied economic parameters.

Visceral leishmaniasis (VL) is a potentially fatal parasitic infection caused by Leishmania donovani in India. L. donovani is an obligate intracellular protozoan residing mostly in macrophages of the reticuloendothelial system throughout chronic infection. Monocytic phagocytes are critical in the pathogenesis of different forms of leishmaniasis. Subsets of monocytes are distinguished by their surface markers into CD14+CD16- classical monocytes, CD14+CD16+ intermediate monocytes, and CD16++CD14low non-classical monocyte subsets. During cutaneous leishmaniasis (CL), intermediate monocyte are reported to be a source of inflammatory cytokines IL-1β and TNF, and they express CCR2 attracting them to sites of inflammatory pathology. We examined monocyte subsets in the blood and bone marrow of patients with VL from an endemic site in Bihar, India, and found these contrasted with the roles of monocytes in CL. During VL, intermediate and non-classical CD16+ monocyte subsets expressed instead a non-inflammatory phenotype with low CCR2, high CX3CR1 and low microbicidal oxidant generation, making them more similar to patrolling monocytes than inflammatory cells. Bone marrow CD16+ monocyte subsets expressed a phenotype that might be more similar to the inflammatory subsets of CL, although our inability to obtain bone marrow from healthy donors in the endemic region hampered this interpretation Overall the data suggest that CD16+ intermediate monocyte subsets in VL patients express a phenotypes that contributes to an immunosuppressed pathologic immune state, but in contrast to CL, these do not mediate localized inflammatory responses.

Among cancer-related disorders, lung carcinoma is one of the leading causes of mortality. Anaplastic lymphoma kinase (ALK) belongs to tyrosine kinase receptor family and exhibits similar characteristics to insulin type receptors. The treatment of advanced non-small cell lung cancer (NSCLC) associates with ALK gene rearrangement has significantly improved since the approval of Crizotinib in 2011 as the first generation ALK inhibitor. In continuation, the second-generation drugs like ceritinib, alectinib, and brigatinib were developed to address and counteract resistance that was associated with the first-generation agents. However, resistance can develop over time, necessitating ongoing research to enhance their effectiveness. Therefore, the third-generation drug lorlatinib, which has demonstrated broad-spectrum potency against the majority of known resistance mutations and better lipophilicity, has been developed. According to current reports, the USFDA has approved five ALK-TKIs crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib for ALK-associated lung cancer. Currently, several clinical trials are underway in search of better ALK inhibitors. Trials such as TPX-0131 and NVL-655 are considered fourth-generation ALK inhibitors for the treatment of patients with advanced ALK-positive or metastatic NSCLC. This review aims to provide specifics information on research works involving various ALK tyrosine kinase inhibitors, clinical studies, and the development of ALK TKIs. Additionally, we suggest potential future strategies involving sequential therapy and combination techniques for managing non-small cell carcinoma.

Abstract India is the second-highest contributor to the post-2000 global greening. However, with satellite data, here we show that this 18.51% increase in Leaf Area Index (LAI) during 2001–2019 fails to translate into increased carbon uptake due to warming constraints. Our analysis further shows 6.19% decrease in Net Primary Productivity (NPP) during 2001–2019 over the temporally consistent forests in India despite 6.75% increase in LAI. We identify hotspots of statistically significant decreasing trends in NPP over the key forested regions of Northeast India, Peninsular India, and the Western Ghats. Together, these areas contribute to more than 31% of the NPP of India (1274.8 TgC.year−1). These three regions are also the warming hotspots in India. Granger Causality analysis confirms that temperature causes the changes in net-photosynthesis of vegetation. Decreasing photosynthesis and stable respiration, above a threshold temperature, over these regions, as seen in observations, are the key reasons behind the declining NPP. Our analysis shows that warming has already started affecting carbon uptake in Indian forests and calls for improved climate resilient forest management practices in a warming world.

Introduction: Pain from lower abdominal surgeries originates from the abdominal wall incision. The Transversus Abdominis Plane (TAP) is a fascial plane between the internal oblique and the transversus abdominis muscle, which contains the nerve bundles. TAP block involves infiltrating this plane with anaesthetic drugs that block the somatic component of postoperative pain. Traditionally, the TAP block is given by anaesthesiologists as a blind procedure or under Ultrasound (US) guidance. In 2010, an innovative surgical TAP block method was developed, where the surgeon gives TAP block under direct vision before closing the abdomen during abdominal surgery. Many studies have recommended surgical TAP block as an intervention for achieving postoperative pain relief. Aim: To evaluate the efficacy of the surgical TAP block technique for postoperative analgesia following lower abdominal surgeries using Visual Analogue Scale (VAS) scores and by comparing the need for rescue analgesia and the total amount of analgesic drugs utilised within the first 24 hours of surgery. Materials and Methods: This hospital-based prospective interventional study was conducted in the Department of Obstetrics and Gynaecology at The Oxford Medical College Hospital and Research Centre, Bengaluru, Karnataka, India, from January 2022 to December 2022. The study participants included 108 women undergoing lower abdominal surgeries under spinal or epidural or combined regional anaesthesia and belonging to the American Society of Anaesthesiologists (ASA) physical status classification system ASA I or ASA II or ASA IIE. The study group included 54 women who received surgical TAP block with 20 mL 0.25% bupivacaine and 4 mg of dexamethasone, intraoperatively on either side before closure of the abdomen. Postoperative pain was assessed using VAS at regular intervals within 24 hours of surgery. VAS was also recorded whenever the participants demanded rescue analgesia. The control group included 54 women who received intravenous tramadol 50 mg eight hourly for postoperative pain relief, while the study group received rescue analgesia on demand or if the VAS score was recorded as three or more. The time for the first request for rescue analgesia and the total dose of rescue analgesic required in the first 24 hours after surgery were also recorded. Data were analysed using Statistical Package for Social Sciences (SPSS) version 25.0. For inferential statistics, numerical data were analysed by Chi-square test, and for continuous data, the Student’s t-test was used. A p-value

Aim: The aim of this study was to investigate the feasibility of developing a deep learning (DL) algorithm for classifying brain metastases from non-small cell lung cancer (NSCLC) into epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement groups and to compare the accuracy with classification based on semantic features on imaging. Methods: Data set of 117 patients was analysed from 2014 to 2018 out of which 33 patients were EGFR positive, 43 patients were ALK positive and 41 patients were negative for either mutation. Convolutional neural network (CNN) architecture efficient net was used to study the accuracy of classification using T1 weighted (T1W) magnetic resonance imaging (MRI) sequence, T2 weighted (T2W) MRI sequence, T1W post contrast (T1post) MRI sequence, fluid attenuated inversion recovery (FLAIR) MRI sequences. The dataset was divided into 80% training and 20% testing. The associations between mutation status and semantic features, specifically sex, smoking history, EGFR mutation and ALK rearrangement status, extracranial metastasis, performance status and imaging variables of brain metastasis were analysed using descriptive analysis [chi-square test (χ2)], univariate and multivariate logistic regression analysis assuming 95% confidence interval (CI). Results: In this study of 117 patients, the analysis by semantic method showed 79.2% of the patients belonged to ALK positive were non-smokers as compared to double negative groups (P = 0.03). There was a 10-fold increase in ALK positivity as compared to EGFR positivity in ring enhancing lesions patients (P = 0.015) and there was also a 6.4-fold increase in ALK positivity as compared to double negative groups in meningeal involvement patients (P = 0.004). Using CNN Efficient Net DL model, the study achieved 76% accuracy in classifying ALK rearrangement and EGFR mutations without manual segmentation of metastatic lesions. Analysis of the manually segmented dataset resulted in improved accuracy of 89% through this model. Conclusions: Both semantic features and DL model showed comparable accuracy in classifying EGFR mutation and ALK rearrangement. Both methods can be clinically used to predict mutation status while biopsy or genetic testing is undertaken.

Background: Snakebite envenoming, a neglected tropical disease (NTD), is an important public health problem that is responsible for more than 1 lakh deaths annually across the world. However, the majority of the data in this regard is from health institutions and data from community settings are scarce. The aim of the current study was to develop valid and reliable qualitative tools for assessing the burden of snakebites and the health-seeking behavior of the community. The tools developed thus will serve in creating a community connection and thereby strengthen primary care teams engaged in managing snakebites at the primary care level. Methods: A four-step design was used; (a) review of the available literature on the burden of disease, tools used to assess the burden, and the guidelines on snakebite (b) development, laying out, and contextualization of questions/items for the tools (c) pilot testing and establishment of validity. Results: A focus group discussion guide, key informant interview schedule for health professionals, community leaders, and traditional faith healers were matured for the implementation. Conclusion: A reliable and valid qualitative tool was developed to discern the speculations related to snakebites and its management in rural field settings.

The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the major enzyme that deposits N6-methyladenosine (m6A) modifications on messenger RNA (mRNA) in humans. METTL3-14 plays key roles in various biological processes through its methyltransferase (MTase) activity. However, little is known about its substrate recognition and methyl transfer mechanism from its cofactor and methyl donor S-adenosylmethionine (SAM). Here, we study the MTase mechanism of METTL3-14 by a combined experimental and multiscale simulation approach using bisubstrate analogues (BAs), conjugates of a SAM-like moiety connected to the N6-atom of adenosine. Molecular dynamics simulations based on crystal structures of METTL3-14 with BAs suggest that the Y406 side chain of METTL3 is involved in the recruitment of adenosine and release of m6A. A crystal structure with a BA representing the transition state of methyl transfer shows a direct involvement of the METTL3 side chains E481 and K513 in adenosine binding which is supported by mutational analysis. Quantum mechanics/molecular mechanics (QM/MM) free energy calculations indicate that methyl transfer occurs without prior deprotonation of adenosine-N6. Furthermore, the QM/MM calculations provide further support for the role of electrostatic contributions of E481 and K513 to catalysis. The multidisciplinary approach used here sheds light on the (co)substrate binding mechanism, catalytic step, and (co)product release, and suggests that the latter step is rate-limiting for METTL3. The atomistic information on the substrate binding and methyl transfer reaction of METTL3 can be useful for understanding the mechanisms of other RNA MTases and for the design of transition state analogues as their inhibitors.

An experiment was conducted during the rainy (kharif) season of 2022–23 at the ICAR-Indian Agricultural Research Institute, Hazaribagh, Jharkhand to assess how well nano- urea performs in maize under different field conditions and investigate its compatibility with other N sources. Results showed that root weight (fresh and dry), partial factor productivity (N, P2O5 and K2O), N concentration (grain and stover), grain yield, biological yield and harvest index of maize were all significantly affected by the application of various N rates and nano-fertilizers. The grain yield of maize was comparable to the yield obtained under RDF and 75% of the recommended N + two nano-urea sprays. These findings indicate that the concurrent use of these nano-fertilizers has the potential to reduce N fertilization by as much as 25%. Furthermore, the results highlight the prospect of augmenting biological yield of maize by incorporating 2 nano-urea sprays alongside the prescribed N quantity from prilled urea, as well as full applications of P2O5 and K2O.

BackgroundCD4+ T cells play a central role in control of L. donovani infection, through IFN-γ production required for activation of macrophages and killing of intracellular parasites. Impaired control of parasites can in part be explained by hampered CD4+ T cells effector functions in visceral leishmaniasis (VL) patients. In a recent studies that defined transcriptional signatures for CD4+ T cells from active VL patients, we found that expression of the IL-7 receptor alpha chain (IL-7Rα; CD127) was downregulated, compared to CD4+ T cells from endemic controls (ECs). Since IL-7 signaling is critical for the survival and homeostatic maintenance of CD4+ T cells, we investigated this signaling pathway in VL patients, relative to ECs.MethodsCD4+ T cells were enriched from peripheral blood collected from VL patients and EC subjects and expression of IL7 and IL7RA mRNA was measured by real time qPCR. IL-7 signaling potential and surface expression of CD127 and CD132 on CD4+ T cell was analyzed by multicolor flow cytometry. Plasma levels of soluble IL-7 and sIL-7Rα were measured by ELISA.ResultTranscriptional profiling data sets generated previously from our group showed lower IL7RA mRNA expression in VL CD4+ T cells as compared to EC. A significant reduction was, however not seen when assessing IL7RA mRNA by RT-qPCR. Yet, the levels of soluble IL-7Rα (sIL-7Rα) were reduced in plasma of VL patients compared to ECs. Furthermore, the levels of soluble IL-7 were higher in plasma from VL patients compared to ECs. Interestingly, expression of the IL-7Rα protein was higher on VL patient CD4+ T cells as compared to EC, with activated CD38+ CD4+ T cells showing higher surface expression of IL-7Rα compared to CD38- CD4+ T cells in VL patients. CD4+ T cells from VL patients had higher signaling potential baseline and after stimulation with recombinant human IL-7 (rhIL-7) compared to EC, as measured by phosphorylation of STAT5 (pSTAT5). Interestingly, it was the CD38 negative cells that had the highest level of pSTAT5 in VL patient CD4+ T cells after IL-7 stimulation. Thus, despite unaltered or potentially lowered IL7RA mRNA expression by CD4+ T cells from VL patients, the surface expression of the IL-7Rα was higher compared to EC and increased pSTAT5 was seen following exposure to rhIL-7. Accordingly, IL-7 signaling appears to be functional and even enhanced in VL CD4+ T cells and cannot explain the impaired effector function of VL CD4+ T cells. The enhanced plasma IL-7 may serve as part of homeostatic feedback mechanism regulating IL7RA expression in CD4+ T cells.

Intense cultivation with narrow row spacing in wheat, a common practice in the Indo-Gangetic plains of South Asia, renders the crop more susceptible to lodging during physiological maturity. This susceptibility, compounded by the use of traditional crop cultivars, has led to a substantial decline in overall crop productivity. In response to these challenges, a two-year field study on the system of wheat intensification (SWI) was conducted. The study involved three different cultivation methods in horizontal plots and four wheat genotypes in vertical plots, organized in a strip plot design. Our results exhibited that adoption of SWI at 20 cm × 20 cm resulted in significantly higher intercellular CO2 concentration (5.9-6.3%), transpiration rate (13.2-15.8%), stomatal conductance (55-59%), net photosynthetic rate (126-160%), and photosynthetically active radiation (PAR) interception (1.6-25.2%) over the existing conventional method (plant geometry 22.5 cm × continuous plant to plant spacing) of wheat cultivation. The lodging resistance capacity of both the lower and upper 3rd nodes was significantly higher in the SWI compared to other cultivation methods. Among different genotypes, HD 2967 demonstrated the highest recorded value for lodging resistance capacity, followed by HD 2851, HD 3086, and HD 2894. In addition, adoption of the SWI at 20 cm × 20 cm enhanced crop grain yield by 36.9-41.6%, and biological yield by 27.5-29.8%. Significantly higher soil dehydrogenase activity (12.06 μg TPF g-1 soil hr-1), arylsulfatase activity (82.8 μg p-nitro phenol g-1 soil hr-1), alkaline phosphatase activity (3.11 n moles ethylene g-1 soil hr-1), total polysaccharides, soil microbial biomass carbon, and soil chlorophyll content were also noted under SWI over conventional method of the production. Further, increased root volumes, surface root density and higher NPK uptake were recorded under SWI at 20×20 cm in comparison to rest of the treatments. Among the tested wheat genotypes, HD-2967 and HD-3086 had demonstrated notable increases in grain and biological yields, as well as improvements in the photosynthetically active radiation (PAR) and chlorophyll content. Therefore, adoption of SWI at 20 cm ×20 cm (square planting) with cultivars HD 2967 might be the best strategy for enhancing crop productivity and resource-use efficiency under the similar wheat growing conditions of India and similar agro-ecotypes of the globe.

BackgroundHelminth infections are a global health menace affecting 24% of the world population. They continue to increase global disease burden as their unclear pathology imposes serious challenges to patient management. Neurocysticercosis is classified as neglected tropical disease and is caused by larvae of helminthic cestode Taenia solium. The larvae infect humans and localize in central nervous system and cause NCC; a leading etiological agent of acquired epilepsy in the developing world. The parasite has an intricate antigenic make-up and causes active immune suppression in the residing host. It communicates with the host via its secretome which is complex mixture of proteins also called excretory secretory products (ESPs). Understanding the ESPs interaction with host can identify therapeutic intervention hot spots. In our research, we studied the effect of T. solium ESPs on human macrophages and investigated the post-translation switch involved in its immunopathogenesis.MethodologyT. solium cysts were cultured in vitro to get ESPs and used for treating human macrophages. These macrophages were studied for cellular signaling and miR expression and quantification at transcript and protein level.ConclusionWe found that T. solium cyst ESPs treatment to human macrophages leads to activation of Th2 immune response. A complex cytokine expression by macrophages was also observed with both Th1 and Th2 cytokines in milieu. But, at the same time ESPs modulated the macrophage function by altering the host miR expression as seen with altered ROS activity, apoptosis and phagocytosis. This leads to activated yet compromised functional macrophages, which provides a niche to support parasite survival. Thus T. solium secretome induces Th2 phenomenon in macrophages which may promote parasite's survival and delay their recognition by host immune system.