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Introduction: Laparoscopic transperitoneal adrenalectomy was first described by Gagner M et al. Here, we present our experience of more than two decades of laparoscopic adrenalectomy performed in a single surgical unit at a tertiary care centre. Patients and Methods: A prospectively collected database of patients undergoing laparoscopic adrenalectomy from December 1994 to May 2020 was analysed retrospectively. The demographic profile, details of clinical workup and laboratory parameters were recorded in a pre-structured pro forma. Functional workup and anatomical imaging were performed for all the patients. Patients were taken up for surgery after adequate pre-operative optimisation using a multidisciplinary approach. All the patients were operated by a single surgical team of experienced laparoscopic surgeons. Results: A total of 158 patients underwent laparoscopic transperitoneal adrenalectomy. The majority patients were females (64.5%). The median tumour size was 5 cm (range, 1–18 cm). The diagnosis in the majority of the patients was pheochromocytoma (56.3%). The mean operative time was 80 min (range: 45–210 min). The most common complication was bleeding in 6 (3.7%) patients, which required laparotomy. The median duration of post-operative hospital stay was 3 days (range: 1–13). There was no 30-day mortality. The mean follow-up period was 15 months (range: 6–72 months), during which two patients developed local recurrence. Conclusion: The advantages of laparoscopic surgery are well established and have been extensively explored for the management of adrenal lesions. A multidisciplinary approach to management, consisting of endocrinologists, surgeons and anaesthesiologists is preferred. Pre-operative evaluation, optimisation and accurate selection of patients are crucial for successful laparoscopic adrenalectomy.

Purpose: Outcomes of peripheral arterial injury (PAI) depend on various factors, such as warm ischemia time and concomitant injuries. Suboptimal prehospital care may lead to delayed presentation, and a lack of dedicated trauma system may lead to poorer outcome. Also, there are few reports of these outcomes. The study aims to review our experience of PAI management for more than a decade, and identify the predictors of limb loss in these patients. Methods: This is a retrospective analysis of prospectively maintained database of trauma admissions at a level I trauma center from January 2008 to December 2019. Patients with acute upper limb arterial injuries or lower limb arterial injuries at or above the level of popliteal artery were included. Association of limb loss with ischemia time, mechanism of injury, and concomitant injuries was studied using multiple logistic regressions. Statistical analysis was performed using STATA version 15.0 (Stata Corp LLC, Texas). Results: Out of 716 patients with PAI, the majority (91.9%) were young males. Blunt trauma was the most common mechanism of injury. Median ischemia time was 4 h (interquartile range 2–7 h). Brachial artery (28.5%) was the most common injured vessel followed by popliteal artery (17.5%) and femoral artery (17.3%). Limb salvage rate was 78%. Out of them, 158 (22.1%) patients needed amputation, and 53 (7.4%) had undergone primary amputation. The majority (88.6%) of patients who required primary or secondary amputations had blunt trauma. On multivariate analysis, blunt trauma, ischemia time more than 6 h and concomitant venous, skeletal, and soft tissue injuries were associated with higher odds of amputation. Conclusion: Over all limb salvage rates was 77.9% in our series. Blunt mechanism of injury and associated skeletal and soft tissue injury, ischemia time more than 6 h portend a poor prognosis. Injury prevention, robust prehospital care, and rapid referral to specialized trauma center are few efficient measures, which can decrease the morbidity associated with vascular injury.

Abstract Yersinia pestis, a Gram-negative bacterium is the causative agent of the fatal communicable disease plague. The disease had a profound impact on human history. Plague bacteria are usually transmitted to humans through the bite of an infected rat flea. Earlier studies have indicated that Y. pestis can survive in environmental matrices e.g. water and soil. This study aimed to generate a peptide-based screen for identification of Y. pestis particularly from environmental matrices. We employed a shotgun proteomic approach using nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) to discover Y. pestis-specific peptides. The pure cultures of Y. pestis and related species were grown, their proteome were delineated and analyzed by in silico tools to discover 61 Y. pestis specific peptides. Additionally, 148 peptides were discovered from proteins of Y. pestis-specific plasmids and chromosomal-associated virulence markers. To validate this screen of 209 peptides, various concentrations of Y. pestis (ranging from 1.3 × 108 to 1.3 × 105 cfu) were spiked into garden soil. Y. pestis could be identified in all samples except un-spiked negative control soil sample. This study offers a valuable method for the identification of Y. pestis, by tandem mass spectrometry which may be used in environmental and clinical matrices.

Background: Postpartum depression (PPD) is a serious concern with multifactorial etiology. Association between prenatal anxiety, pain, and depression has been theorized. Aim: In this randomized controlled trial, we studied the effect of pain relief by combined spinal epidural (CSE) and other factors influencing PPD. Methods: After thorough assessment and obtaining prenatal baseline parameters, parturients were randomly assigned to group 1 (CSE) and group 2 (control) (n = 31 each). Group 1 received 0.5 ml of 0.5% hyperbaric bupivacaine with 12.5 mcg of fentanyl intrathecally and 6 ml of 0.1% levobupivacaine with 2 mcg/ml fentanyl programmed intermittent epidural bolus every 60 min and patient-controlled epidural analgesia (PCEA) bolus of the same drug with a lockout interval of 15 min. Group 2 underwent normal vaginal delivery without neuraxial analgesia. Patients in both the groups were assessed for PPD using Edinburgh Postnatal Depression Scale (EPDS) at day 3 and 6 weeks postpartum. Results: The EPDS score at 6 weeks postpartum was significantly lower in group 1 than in group 2 (P < 0.05). The pain score assessed using visual analog scale was significantly lesser in group 1 than in group 2 (P < 0.001). Multivariate linear regression analysis showed that prenatal anxiety, greater pain interference scores, and perceived stress were major determinants of PPD. Conclusion: CSE analgesia using PCEA pump with PIEB facility in laboring parturients resulted in lesser EPDS scores and hence lesser postpartum depression. Effective pain control may be an important component to prevent PPD.

This review paper explores the integration of phase change materials (PCMs) in building insulation systems to enhance energy efficiency and thermal comfort. Through an extensive analysis of existing literature, the thermal performance of PCM-enhanced building envelopes is evaluated under diverse environmental conditions. This review highlights that PCMs effectively moderate indoor temperatures by absorbing and releasing heat during phase transitions, maintaining a stable indoor climate. This paper also delves into the detailed concepts of PCMs, including their classification and various applications within building insulation. It is noted that different types of PCMs have unique thermal properties and potential uses, which can be tailored to specific building requirements and climatic conditions. Furthermore, cost–benefit and environmental assessments presented in the reviewed studies suggest that incorporating PCMs into building materials offers significant potential for reducing energy consumption and mitigating environmental impacts. These assessments indicate that PCMs can lead to substantial energy savings by decreasing the reliance on heating and cooling systems, thereby lowering overall energy costs and carbon emissions. However, despite the promising outlook, this review identifies a need for further research to optimize PCM formulations and integration methods. This optimization is essential for overcoming current challenges and facilitating the widespread adoption of PCMs in the construction industry. Addressing issues such as long-term durability, compatibility with existing building materials, and cost-effectiveness will be crucial for maximizing the benefits of PCMs in enhancing energy efficiency and sustainability in buildings. Overall, this review underscores the transformative potential of PCMs in building insulation practices. By providing a comprehensive overview of PCM classifications, applications, and their impacts on energy efficiency and environmental sustainability, this paper lays the groundwork for future advancements and research directions in the field of PCM-enhanced building technologies.

Tropical cyclone (TC) is a rapidly intensifying storm over warm water of oceans, critically studied for its potential to inflict severe damage and pose life-threatening hazards. The present study focuses on exploring the pre- and post-cyclone characteristics of TC Amphan and Nisarga using ECMWF Reanalysis v5 (ERA5) reanalysis. Our analysis reveals that the TC features, such as its intensity, life cycle, wind circulations, the warm-core structure evolution, and the related environmental factors, are consistent with India Meteorological Department observations. The presented results have indicated that maximum sustainable wind speed, central sea level pressure, lower troposphere temperature and lower stratosphere temperature along the radius from the TC center create a favourable condition that eventually leads to the formation and intensification of super and severe cyclonic storms, for example, Amphan and Nisarga, respectively. The analysis suggests that the atmospheric instability, TC formation, development, and energy for intensification are controlled mainly by the warmer-than-average Arabian Sea and Bay of Bengal basin sea surface temperature anomalies in the Indian Ocean region. The results indicated that the TC genesis and movement are well captured by ERA5, close to the observed best tracks provided by the India Meteorological Department, with an RMSE of ∼31 km. The vorticity budget analysis illustrates that in the developing and mature stages of TC, the tilting term converts horizontal vorticity into vertical vorticity via upward motion. During the dissipation phase, the tilting term reverses, resulting in a fall in vertical vorticity, which weakens or dissipates the TC intensity. Overall, the circulation pattern appears to reproduce most of the essential characteristics of the mature stage of TCs, like the eye and eyewall, highlighting the importance of near real-time high-resolution reanalysis datasets for exploring the details of extreme events.

In this investigation, we effectively fabricated zinc sulphide (ZnS) nanoparticles doped with cobalt (Co) using the facial synthesis method at different concentrations (3 %, 6 %, and 9 %). The Co doping-dependent structural, morphological, magnetic, optical, and electrochemical properties of the ZnS nanostructures were systematically explored. The analysis of magnetic properties revealed that the ferromagnetic ZnS nanoparticles exhibited superparamagnetic behaviour, showing an increased magnetization with higher Co doping content. Electrochemical assessments of the electrodes were conducted in 1 mol L−1 Na2SO4 liquid electrolyte. The 3 % Co doped ZnS variant, which demonstrated the highest energy density (14.27 Whkg−1) at 10 mAcm−2 and capacity retention (94.76 %) after 2000 cycles at 50 mAcm−2. Further, a trend of a decrease in specific capacitances and energy density with an increase in Co doping is observed. This outcome implies that optimal levels of Co doping can enhance the electrochemical and magnetic performances of ZnS nanoparticles, underscoring their potential for applications in energy storage.

The bulk amount of power generated from the present-day large-scale DFIG-installed wind farms are preferably transmitted to utility grid through series compensated transmission lines. Currently, TCSC compensation is more attractive compared to fixed series compensation due to its numerous technical advantages. However, the nonlinear relationship of the output power verses wind speed and the different operating modes of the DFIG and TCSC cause rapid variation in the line impedance during both normal as well as fault conditions. Consequently, the widely used fixed impedance-based distance relays when used for protection of such lines find limitation. In this paper, a fast discrete S-transform feature-assisted back propagation neural network technique is proposed using the relay end current measurements for effective detection and classification of faults in such crucial transmission lines. The efficacy of the scheme is evaluated on numerous fault and non-fault cases simulated through MATLAB/Simulink on different standard test systems under varying system operating conditions. The results clearly show the superiority of the proposed method in comparision to the existing approaches in terms of its low computational burden, fast fault detection time (< 10 ms) and accuracies (= 100 %) and fast fault classification time (< 10 ms) and accuracies (99.99 %).

Wheat is one of the most important food crop cultivated across the globe which ensures sustainability and food security to massive world’s population, but its production is threatened by both biotic factors like rust (caused by Puccinia species) and abiotic stresses such as salinity. In this study, 41 salt-tolerant wheat lines were screened for rust resistance at both seedling and adult plant stages. Rust resistance genes were characterized through gene matching technique and molecular markers analysis. Yr2 was confirmed in 23 lines, while Yr9 along with Lr26/Sr31 were postulated in six lines with the help of SRT and molecular markers. Except for KRL2013, none showed complete resistance to all Puccinia striiformis f. sp. tritici (Pst). Lr24/Sr24 genes were confirmed in HD2851 and KRL2029, and Lr13 was detected in a maximum of 24 wheat lines, with varying reaction responses to different leaf rust pathotypes. Several lines carried additional resistance genes such as Sr11, Sr28, and Lr68. Lr68 an effective race non-specific APR gene identified in 15 wheat lines with the help of CsGs-STS marker. Although many salt-tolerant wheat lines were susceptible to yellow rust during the seedling stage, a few lines showed APR in the years during 2020 and 2021. Three lines (KRL213, KRL219 and KRL238) showed complete resistance at adult plant stage to leaf rust. These findings offer insights into the genetic basis of rust resistance in salt-tolerant wheat, aiding breeding strategies.

Introduction: Traumatic hemothorax is accounted for about 20% of traumatic chest injuries. Although majority can be managed with the timely placement of intercostal tube (ICT) drainage, the remaining pose a challenge owing to high complication rates associated with retained hemothorax. Although various treatment modalities including intrapleural instillation of fibrinolytics, radioimage guided drainage, VATS guided evacuation and thoractomy do exist to address the retained hemothorax, but indications along with timing to employ a specific treatment option is still unclear and ambiguous. Methods: Patient with residual hemothorax (>200 mL) on ultrasonography after 48 h of indwelling ICT was randomized into either early video-assisted thoracic surgery (VATS) or conventional approach cohort. Early VATS cohort was subjected to video-assisted thoracoscopic evacuation of undrained blood along with normal saline irrigation and ICT placement. The conventional cohort underwent intrapleural thrombolytic instillation for 3 consecutive days. The outcome measures were the duration of indwelling ICT, removal rate of tube thoracostomy, length of hospital stay, duration of intensive care unit (ICU) monitoring, need for mechanical ventilation, incidence of pulmonary and pleural complications, and requirement of additional intervention to address undrained hemothorax and mortality rate. Results: The early VATS cohort had shorter length of hospital stay (7.50 ± 0.85 vs. 9.50 ± 3.03, P = 0.060), reduced duration of indwelling ICT (6.70 ± 1.25 vs. 8.30 ± 2.91, P = 0.127) with higher rate of tube thoracostomy removal (70% vs. 30%, P = 0.003) and lesser need of additional interventions (0% vs. 30%, P = 0.105). Thoracotomy (3 patients) and image-guided drainage (4 patients) were additional interventions to address retained hemothorax in the conventional cohort. However, similar length of ventilator assistance (0.7 ± 0.48 vs. 0.60 ± 1.08, P = 0.791) and prolonged ICU monitoring (1.30 ± 1.06 vs. 0.90 ± 1.45, P = 0.490) was observed in early VATS cohort. Both the cohorts had no mortality. Conclusion: VATS-guided early evacuation of traumatic hemothorax is associated with shorter length of hospital stay along with abbreviated indwelling ICT duration, reduced incidence of complications, lesser readmissions, and improved rate of tube thoracostomy removal. However, the duration of ventilator requirement, ICU stay, and mortality remain unchanged.

Introduction: Severity of systemic inflammatory response to surgical trauma may predict those at increased risk of postoperative complications. Serum albumin level falls early postoperatively and its measurement is cheap and widely available. This study evaluates the role of postoperative fall in albumin to predict postoperative complications of colorectal resections. Methods: This is a prospective observational study of 56 consecutive patients undergoing colorectal resections in the department of Surgical Gastroenterolgy of Bir Hospital, NAMS from 2020 December to 2022 May. Postoperative albumin drop (Δ Albumin) was defined as ‘Preoperative albumin – Albumin on Postoperative Day 1’. The primary outcome was 30-day postoperative complications. Multivariate analysis was performed to identify factors associated with postoperative complications. Receiver operating characteristic (ROC) curve analysis was done for determining the value of postoperative albumin drop in identifying patients with complications. Results: Postoperative albumin drop > 0.5 g/dl (OR 4.26, CI 3.6-39.99, p = 0.018) and emergency surgery (OR 3.25, CI 1.06-95.79, p = 0.046) were independent predictors of postoperative complications. Patients with complications had higher ‘Δ Albumin’ (0.6 g/dl vs. 0.27 g/dl, p =0.001) compared to those without complications. The ROC curve Area under the curve of Δ Albumin to discriminate patients with complications was 0.865. Cut-off value of ‘Δ Albumin’ ≥ 0.35 g/dl resulted in highest accuracy of 80.36%, sensitivity of 95.2% and specificity of 71.4%. Patients with postoperative albumin drop > 0.5 g/dl had significantly higher rate of surgery specific complications (61.9% vs. 11.4%, p = 0.001) compared to those with albumin drop ≤ 0.5 g/dl. Conclusion: Early postoperative fall in albumin level may identify patients at risk for overall as well as surgery specific complications after colorectal resections.

Barley stripe or yellow rust (BYR) caused by Puccinia striiformis f. sp. hordei (Psh) is a significant constraint to barley production. The disease is best controlled by genetic resistance, which is considered the most economical and sustainable component of integrated disease management. In this study, we assessed the diversity of resistance to Psh in a panel of international barley genotypes (n = 266) under multiple disease environments (Ecuador, India, and Mexico) using genome-wide association studies (GWASs). Four quantitative trait loci (QTLs) (three on chromosome 1H and one on 7H) associated with resistance to Psh were identified. The QTLs were validated by mapping resistance to Psh in five biparental populations, which detected key genomic regions on chromosomes 1H (populations Pompadour/Zhoungdamei, Pompadour/Zug161, and CI9214/Baudin), 3H (Ricardo/Gus), and 7H (Fumai8/Baronesse). The QTL RpshQ.GWA.1H.1 detected by GWAS and RpshQ.Bau.1H detected using biparental mapping populations co-located were the most consistent and stable across environments and are likely the same resistance region. RpshQ.Bau.1H was saturated using population CI9214/Baudin by enriching the target region, which placed the resistance locus between 7.9 and 8.1 Mbp (flanked by markers sun_B1H_03, 0.7 cM proximal to Rpsh_1H and sun_B1H_KASP_02, 3.2 cM distal on 1HS) in the Morex reference genome v.2. A Kompetitive Allele Specific PCR (KASP) marker sun_B1H_KASP_01 that co-segregated for RpshQ.Bau.1H was developed. The marker was validated on 50 Australian barley cultivars, showing well-defined allelic discrimination and presence in six genotypes (Baudin, Fathom, Flagship, Grout, Sakurastar, and Shepherd). This marker can be used for reliable marker-assisted selection and pyramiding of resistance to Psh and in diversifying the genetic base of resistance to stripe rust.

In this report, we have investigated the CsMgCl3 compound with the help of the WIEN2K software package. The structural and electronic properties are performed using the full potential augmented plane wave (FP-LAPW) method with the generalised gradient approximation (GGA) approximation as exchange correlation potentials. We used the Birch-Murnaghan equation (BME) to find the structural properties of the material. These include the lattice parameter, the bulk modulus, the first derivative of the bulk modulus, the minimum energy, and the volume. The structural properties match up with the experimental data. Electronic properties in terms of the band structure (BS) and total and partial density of state (T-DOS and P-DOS) profiles of CsMgCl3 using GGA potentials exhibit an indirect wide energy band gap of 5.35 eV. All these properties show that the CsMgCl3 compound is used as a perovskite in solar cells.

Introduction:Sarcoidosis is an idiopathic systemic granulomatous disorder that can affect multiple organs, including rare extrapulmonary sites like the premaxilla. This case report presents a rare occurrence of premaxillary sarcoidosis, a condition scarcely reported in medical literature.Case Report:The patient, a 62-year-old male, presented with a progressively enlarging painless swelling on the right cheek over a three-year period. Despite multiple Fine Needle Aspiration Cytology (FNAC) examinations yielding no conclusive diagnosis, a contrast-enhanced computed tomographic (CT) scan revealed an ill-defined lesion in the premaxillary soft tissue. Biopsy and subsequent excision procedures confirmed the presence of non-caseating granulomas with asteroid bodies, indicative of sarcoidosis. With no systemic involvement and complete excision of the disease, further treatment was not necessary.Conclusion:This case highlights the challenges in diagnosing premaxillary (Extrapulmonary Sarcoidosis) sarcoidosis due to its rarity and resemblance to other dental and maxillofacial conditions and granulomatous lesions. Accurate diagnosis requires a high index of suspicion, multidisciplinary approach, involving clinical assessment, histopathological analysis, and imaging modalities. By deepening our understanding of these uncommon presentations, this report aims to enhance clinical awareness and contribute to improved patient outcomes.

Gamma-aminobutyric acid (GABA)ergic neurons, the most abundant inhibitory neurons in the human brain, have been found to be reduced in many neurological disorders, including Alzheimer’s disease and Alzheimer’s disease-related dementia. Our previous study identified the upregulation of microRNA-502-3p (miR-502-3p) and downregulation of GABA type A receptor subunit α-1 in Alzheimer’s disease synapses. This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function. In vitro studies were performed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs. In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunit α-1 mRNA. Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunit α-1 gene and suppresses the luciferase activity. Furthermore, quantitative reverse transcription-polymerase chain reaction, miRNA in situ hybridization, immunoblotting, and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunit α-1 level, while suppression of miR-502-3p increased the level of GABA type A receptor subunit α-1 protein. Notably, as a result of the overexpression of miR-502-3p, cell viability was found to be reduced, and the population of necrotic cells was found to be increased. The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney (HEK) recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function, suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function. Additionally, the levels of proteins associated with Alzheimer’s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression. The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p. We propose that micro-RNA, in particular miR-502-3p, could be a potential therapeutic target to modulate GABAergic synapse function in neurological disorders, including Alzheimer’s disease and Alzheimer’s disease-related dementia.

Administration of anesthesia is essential in surgical procedures, ensuring patient unconsciousness and safety. Traditional Depth of Anesthesia (DoA) assessment methods rely heavily on the clinical expertise of anesthesiologists and patient physiological responses, which can vary widely due to age, weight, and ethnicity. This variability poses significant challenges in maintaining appropriate anesthesia levels and making timely decisions in critical situations. To address these challenges, we propose XAI-VSDoA, an explainable AI model using vital signs designed to augment DoA assessment by providing accurate predictions and interpretable insights. In this work, we experimented with various machine learning classifiers, including XGBoost, CatBoost, LightGBM, Random Forest, ResNet, and Feed-forward Neural Networks. Among these, the XGBoost model achieved the highest accuracy, with 99.34% on the University of Queensland dataset and 93.07% on the VitalDB dataset. Statistical testing confirmed that XGBoost outperformed the other models. We employed explainable AI techniques such as LIME and SHAP to identify the top 10 features significantly influencing the model’s predictions, ensuring the model’s transparency and reliability. These methods consistently highlighted the same influential features, reinforcing the model’s interpretability. Our proposed scheme demonstrated exceptional performance using numeric vital signs, with XAI techniques validating the key features. This interpretability boosts confidence in the model, enhancing its utility to augument and support the clininal observations of anethesiologiss in anesthesia management. Our findings underscore the potential of XAI-VSDoA as a valuable tool for clinical use, enhancing patient safety and decision-making in anesthesia.

Irrespective of men and women, colorectal cancer (CRC), is the third most common cancer in the population with more than 1.85 million cases annually. Fewer than 20% of patients only survive beyond five years from diagnosis. CRC is a highly preventable disease if diagnosed at the early stage of malignancy. Several screening methods like endoscopy (like colonoscopy; gold standard), imaging examination [computed tomographic colonography (CTC)], guaiac-based fecal occult blood (gFOBT), immunochemical test from faeces, and stool DNA test are available with different levels of sensitivity and specificity. The available screening methods are associated with certain drawbacks like invasiveness, cost, or sensitivity. In recent years, computer-aided systems-based screening, diagnosis, and treatment have been very promising in the early-stage detection and diagnosis of CRC cases. Artificial intelligence (AI) is an enormously in-demand, cost-effective technology, that uses various tools machine learning (ML), and deep learning (DL) to screen, diagnose, and stage, and has great potential to treat CRC. Moreover, different ML algorithms and neural networks [artificial neural network (ANN), k-nearest neighbors (KNN), and support vector machines (SVMs)] have been deployed to predict precise and personalized treatment options. This review examines and summarizes different ML and DL models used for therapeutic intervention in CRC cancer along with the gap and challenges for AI.

Parkinson’s Disease (PD) occurs as a result of the progressive loss of dopaminergic neurons within the substantia nigra causing motor and non-motor symptoms and has become more prevalent within the last several decades. With mitochondria being essential to cellular survival, mitochondrial dysfunction contributes to the disease progression by increasing neuron loss through (1) insufficient ATP production and (2) reactive oxygen species generation. MicroRNAs (miRNAs) are small molecules located throughout cells that regulate gene expression, particularly mitochondrial function. Through their own dysregulation, miRNAs offset the delicate balance of mitochondrial function by altering or dysregulating the expression of proteins, increasing neuroinflammation, increasing retention of toxic substances, limiting the removal of reactive oxygen species, and preventing mitophagy. Improper mitochondrial function places cells at increased risk of apoptosis, a major concern in individuals with PD due to their reduced number of dopaminergic neurons. This article has identified the 17 most promising mitochondrial associated miRNAs within PD: hsa-miR-4639-5p, miR-376a, miR-205, miR-421, miR-34b/c, miR-150, miR-7, miR-132, miR-17-5p, miR-20a, miR-93, miR-106, miR-181, miR-193b, miR-128, miR-181a, and miR-124-3p. These miRNAs alter mitochondrial function and synaptic energy by impeding normal gene expression when up or downregulated. However, there is limited research regarding mitochondria-localized miRNAs that are typically seen in other diseases. Mitochondria-localized miRNA may have a greater impact on mitochondrial dysfunction due to their proximity. Further research is needed to determine the location of these miRNAs and to better understand their regulatory capabilities on mitochondrial and synaptic function within PD.

No licensed vaccine exists for the lethal plague and yersiniosis. Therefore, a combination of recombinant YopE and LcrV antigens of Yersinia pestis was evaluated for its vaccine potential in a mouse model. YopE and LcrV in formulation with alum imparted a robust humoral immune response, with isotyping profiles leaning towards the IgG1 and IgG2b subclasses. It was also observed that a significantly enhanced expression of IFN-γ, TNF-α, IL-6, IL-2, and IL-1β from the splenic cells of vaccinated mice, as well as YopE and LcrV-explicit IFN-γ eliciting T-cells. The cocktail of YopE + LcrV formulation conferred complete protection against 100 LD50 Y. pestis infection, while individually, LcrV and YopE provided 80 % and 60 % protection, respectively. Similarly, the YopE + LcrV vaccinated animal group had significantly lower colony forming unit (CFU) counts in the spleen and blood compared to the groups administered with YopE or LcrV alone when challenged with Yersinia pseudotuberculosis and Yersinia enterocolitica. Histopathologic evidence reinforces these results, indicating the YopE + LcrV formulation provided superior protection against acute lung injury as early as day 3 post-challenge. In conclusion, the alum-adjuvanted YopE + LcrV is a promising vaccine formulation, eliciting a robust antibody response including a milieu of pro-inflammatory cytokines and T-cell effector functions that contribute to the protective immunity against Yersinia infections. YopE and LcrV, conserved across all three human-pathogenic Yersinia species, provide cross-protection. Therefore, our current vaccine (YopE + LcrV) targets all three pathogens: Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica. However, the efficacy should be tested in other higher mammalian models.

Introduction: Glaucoma is a significant cause of ocular morbidity following ocular trauma, particularly Closed Globe Injury (CGI), which frequently leads to elevated Intraocular Pressure (IOP). This type of trauma can result in various tissue damages such as radial sphincter tears, iridodialysis, angle recession, cyclodialysis, trabecular meshwork tears, zonule separation, or peripheral retinal dialysis. Damage in these areas can lead to early or delayed onset glaucoma. Aim: To evaluate the clinical profile, assess visual outcomes, and analyse management strategies in post-traumatic glaucoma with CGI. Materials and Methods: The retrospective cohort study was conducted at a tertiary eye care centre in Department of Ophthalmology, Regional Institute of Ophthalmology (RIO), Sitapur, Uttar Pradesh, India. from January 2020 to December 2022. Retrospective data of patients presenting with CGI and developing elevated IOP (>21 mmHg) were collected. Only patients with a minimum follow-up of three months were included. Various parameters, including demographics, IOP, Best-Corrected Visual Acuity (BCVA), and the effects of medical and surgical treatments on IOP and BCVA, were analysed. The Ocular Trauma Score (OTS) was also calculated. Statistical analysis was performed using Microsoft excel and Statistical Package for Social Sciences software version 21.0, with a significance level of 5%. Continuous variables were described as mean±Standard Deviation (SD), and an unpaired t-test was used for comparisons between pre- and postmanagement visual acuity and IOP. Results: Out of 259 eyes with ocular trauma, 93 (35.90%) were diagnosed with CGI and developed elevated IOP. The most common causes of elevated IOP were hyphema (37.63%) and angle recession mechanisms (32.25%). The median IOP at presentation was 35 mmHg (range: 12 to 71 mmHg) and decreased to 16.5 mmHg (range: 4 to 52 mmHg) at the last follow-up (p-value

Greater advantages of employing hybrid reinforced advanced aluminum matrix composites over single particle reinforced composites have been the highlights of recent times. Herein, Al6082 bimodal hybrid composites embedded with different proportions of SiC and TiO2 particles were fabricated via modified stir-squeeze cast technique. A transmission electron microscopy was used for morphological evaluation of TiO2 particles while microstructure of fabricated composites and fractured surfaces were analyzed by using field emission scanning electron microscopy. Energy dispersive X-ray spectroscopy was used for evaluation of elements and phase analysis was done by using X-ray diffraction technique. Microstructural analysis confirms the homogeneous dispersion of SiC particles up to 3 wt.% and beyond that, clusters of SiC were observed which deteriorates the properties of composites. Maximum enhancement in mechanical properties of Al6082 alloy was noticed for incorporation of 3 wt.% of SiC and 0.5 wt.% of TiO2. 0.5 wt.%TiO2-3 wt.% SiC reinforced Al6082 composites enhanced yield strength, Ultimate tensile strength, and compressive strength by 215.84 ± 1.43 MPa, 268.84 ± 1.75 Mpa and 321.42 MPa, respectively, over as-cast Al6082 alloy.

Background Prolonged mechanical ventilation is associated with weaning failure in severe TBI patients. Ultrasound is a noninvasive modality for evaluating diaphragm function. On ultrasonography (USG), diaphragm thickness is observed to decrease over time in mechanically ventilated patients. However, little literature exists on the severity of diaphragmatic dysfunction in traumatic brain injury (TBI) patients. This study aimed to observe the changes occurring in diaphragmatic function in mechanically ventilated TBI patients.

Background: Signal transducer and activator of transcription 3 (STAT3) is a member of the cytoplasmic inducible transcription factors and plays an important role in mediating signals from cytokines, chemokines, and growth factors. We and others have found that STAT3 directly regulates pro-fibrotic signaling in the kidney. The STAT3 protein–protein interaction plays an important role in activating its transcriptional activity. It is necessary to identify these interactions to investigate their function in kidney disease. Here, we investigated the protein–protein interaction among three species to find crucial interactions that can be targeted to alleviate kidney disease. Method: In this study, we examined common protein–protein interactions leading to the activation or downregulation of STAT3 among three different species: humans (Homo sapiens), mice (Mus musculus), and rabbits (Oryctolagus cuniculus). Further, we chose to investigate the P300 and STAT3 interaction and performed studies of the activation of STAT3 using IL-6 and inhibition of the P300 by its specific inhibitor A-485 in pericytes. Next, we performed immunoprecipitation to confirm whether A-485 inhibits the binding of P300 to STAT3. Results: Using the STRING application from ExPASy, we found that six proteins, including PIAS3, JAK1, JAK2, EGFR, SRC, and EP300, showed highly confident interactions with STAT3 in humans, mice, and rabbits. We also found that IL-6 treatment increased the acetylation of STAT3 and increased histone 3 lysine acetylation (H3K27ac). Furthermore, we found that the disruption of STAT3 and P300 interaction by the P300 inhibitor A-485 decreased STAT3 acetylation and H3K27ac. Finally, we confirmed that the P300 inhibitor A-485 inhibited the binding of STAT3 with P300, which inhibited its transcriptional activity by reducing the expression of Ccnd1 (Cyclin D1). Conclusions: Targeting the P300 protein interaction with STAT3 may alleviate STAT3-mediated fibrotic signaling in humans and other species.

Emergence of newer variants of SARS-CoV-2 underscores the need for effective antivirals to complement the vaccination program in managing COVID-19. The multi-functional papain-like protease (PLpro) of SARS-CoV-2 is an essential viral protein that not only regulates the viral replication but also modulates the host immune system, making it a promising therapeutic target. To this end, we developed an in vitro interferon stimulating gene 15 (ISG15)-based Förster resonance energy transfer (FRET) assay and screened the National Cancer Institute (NCI) Diversity Set VI compound library, which comprises 1584 small molecules. Subsequently, we assessed the PLpro enzymatic activity in the presence of screened molecules. We identified three potential PLpro inhibitors, namely, NSC338106, 651084, and 679525, with IC50 values in the range from 3.3 to 6.0 µM. These molecules demonstrated in vitro inhibition of the enzyme activity and exhibited antiviral activity against SARS-CoV-2, with EC50 values ranging from 0.4 to 4.6 µM. The molecular docking of all three small molecules to PLpro suggested their specificity towards the enzyme’s active site. Overall, our study contributes promising prospects for further developing potential antivirals to combat SARS-CoV-2 infection.

A 55-year-old female presented with recent exacerbation of the chronic cough, dyspnea, and copious expectoration. The symptoms worsened during the winter months. In the past, she was misdiagnosed with pulmonary tuberculosis. A computed tomography scan revealed bronchiectasis changes, high attenuated mucus, and hypereosinophilia. The diagnosis of Allergic Bronchopulmonary Aspergillosis (ABPA) with subacute invasion was confirmed through bronchoscopy and fungal culture. Treatment with oral voriconazole significantly improved lung function and quality of life. This case highlights the importance of considering invasive pulmonary aspergillosis in patients with exacerbations of asthma and bronchiectasis. Early diagnosis and appropriate treatment are essential for improved outcomes in such cases.

Quantitative trait loci (QTL) mapping is used for the precise localization of genomic regions regulating various traits in plants. Two major QTLs regulating Soil Plant Analysis Development (SPAD) value (qSPAD-7-1) and trichome density (qTric-7-2) in mungbean were identified using recombinant inbred line (RIL) populations (PMR-1×Pusa Baisakhi) on chromosome 7. Functional analysis of QTL region identified 35 candidate genes for SPAD value (16 No) and trichome (19 No) traits. The candidate genes regulating trichome density on the dorsal leaf surface of the mungbean include VRADI07G24840, VRADI07G17780, and VRADI07G15650, which encodes for ZFP6, TFs bHLH DNA-binding superfamily protein, and MYB102, respectively. Also, candidate genes having vital roles in chlorophyll biosynthesis are VRADIO7G29860, VRADIO7G29450, and VRADIO7G28520, which encodes for s-adenosyl-L-methionine, FTSHI1 protein, and CRS2-associated factor, respectively. The findings unfolded the opportunity for the development of customized genotypes having high SPAD value and high trichome density having a possible role in yield and mungbean yellow vein mosaic India virus (MYMIV) resistance in mungbean.

Yellow mosaic disease (YMD) is a major constraint for the low productivity of mungbean, mainly in South Asia. Addressing this issue requires a comprehensive approach, integrating field and challenge inoculation evaluations to identify effective solutions. In this study, an infectious clone of Begomovirus vignaradiataindiaense (MYMIV) was developed to obtain a pure culture of the virus and to confirm resistance in mungbean plants exhibiting resistance under natural field conditions. The infectivity and efficiency of three Agrobacterium tumefaciens strains (EHA105, LBA4404, and GV3101) were evaluated using the susceptible mungbean genotype PS16. Additionally, a recombinant inbred line (RIL) population comprising 175 lines derived from Pusa Baisakhi (MYMIV susceptible) and PMR-1 (MYMIV resistant) cross was developed and assessed for YMD response. Among the tested Agrobacterium tumefaciens strains, EHA105 exhibited the highest infectivity (84.7%), followed by LBA4404 (54.7%) and GV3101 (9.80%). Field resistance was evaluated using the coefficient of infection (CI) and area under disease progress curve (AUDPC), identifying seven RILs with consistent resistant reactions (CI≤9) and low AUDPC (≤190). Upon challenge inoculation, six RILs exhibited resistance, while RIL92 displayed a resistance response, with infection occurring in less than 10% of plants after 24 to 29 days post inoculation (dpi). Despite some plants remaining asymptomatic, MYMIV presence was confirmed through specific PCR amplification of the MYMIV coat protein (AV1) gene. Quantitative PCR revealed a very low relative viral load (0.1-5.1% relative fold change) in asymptomatic RILs and the MYMIV resistant parent (PMR1) compared to the susceptible parent (Pusa Baisakhi). These findings highlight the potential utility of the developed infectious clone and the identified MYMIV-resistant RILs in future mungbean breeding programs aimed at cultivating MYMIV-resistant varieties.

This case study has made an effort to show the impact of improved ocean initial conditions (ICs) in a coupled forecast system (CFSv2) simulation on the seasonal prediction of Indian summer monsoon rainfall (ISMR). CFSv2 is used as an operational dynamical model for the seasonal prediction of ISMR. Here, we show an improved ISMR skill by initializing the ocean component of CFSv2 using new improved ocean ICs based on Global Ocean Data Assimilation System (GODAS) analysis. This new analysis is better than the NCEP GODAS, which uses the earlier-generation ocean model MOM4p0d and assimilates observed temperature and synthetic salinity using the 3DVar assimilation scheme. However, the new, improved GODAS analysis uses the MOM4p1 ocean model and assimilates observed salinity instead of synthetic salinity. We performed twin sets of nearly identical model experiments differing only in their ICs, with one set using NCEP ICs and the other using the new ICs (NIC). The NIC experiment consistently shows better El Niño–Southern Oscillation prediction skill than the NCEP IC experiment. This advancement leads to improvement in the ISMR skill. We found that the substantial improvements in both oceanic and atmospheric variables in a coupled feedback system contributed to the improved ISMR skills. The enhanced ISMR skill score of the NIC experiment might be the result of improved teleconnections, better depiction of large-scale monsoon circulations, and reduced model drift.

Yellow mosaic disease (YMD) remains a major constraint in mungbean (Vigna radiata (L.)) production; while short-duration genotypes offer multiple crop cycles per year and help in escaping terminal heat stress, especially during summer cultivation. A comprehensive genotyping by sequencing (GBS)-based genome-wide association studies (GWAS) analysis was conducted using 132 diverse mungbean genotypes for traits like flowering time, YMD resistance, soil plant analysis development (SPAD) value, trichome density, and leaf area. The frequency distribution revealed a wide range of values for all the traits. GBS studies identified 31,953 high-quality single nucleotide polymorphism (SNPs) across all 11 mungbean chromosomes and were used for GWAS. Structure analysis revealed the presence of two genetically distinct populations based on ΔK. The linkage disequilibrium (LD) varied throughout the chromosomes and at r2 = 0.2, the mean LD decay was estimated as 39.59 kb. Two statistical models, mixed linear model (MLM) and Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) identified 44 shared SNPs linked with various candidate genes. Notable candidate genes identified include FPA for flowering time (VRADI10G01470; chr. 10), TIR-NBS-LRR for mungbean yellow mosaic India virus (MYMIV) resistance (VRADI09G06940; chr. 9), E3 ubiquitin-protein ligase RIE1 for SPAD value (VRADI07G28100; chr. 11), WRKY family transcription factor for leaf area (VRADI03G06560; chr. 3), and LOB domain-containing protein 21 for trichomes (VRADI06G04290; chr. 6). In-silico validation of candidate genes was done through digital gene expression analysis using Arabidopsis orthologous (compared with Vigna radiata genome). The findings provided valuable insight for marker-assisted breeding aiming for the development of YMD-resistant and early-maturing mungbean varieties.

The systematic identification of insertion/deletion (InDel) length polymorphisms from the entire lentil genome can be used to map the quantitative trait loci (QTL) and also for the marker-assisted selection (MAS) for various linked traits. The InDels were identified by comparing the whole-genome resequencing (WGRS) data of two extreme bulks (early- and late-flowering bulk) and a parental genotype (Globe Mutant) of lentil. The bulks were made by pooling 20 extreme recombinant inbred lines (RILs) each, derived by crossing Globe Mutant (late flowering parent) with L4775 (early flowering parent). Finally, 734,716 novel InDels were identified, which is nearly one InDel per 5,096 bp of lentil genome. Furthermore, 74.94% of InDels were within the intergenic region and 99.45% displayed modifier effects. Of these, 15,732 had insertions or deletions of 20 bp or more, making them amenable to the development of PCR-based markers. An InDel marker I-SP-356.6 (chr. 3; position 356,687,623; positioned 174.5 Kb from the LcFRI gene) was identified as having a phenotypic variance explained (PVE) value of 47.7% for earliness when validated in a RIL population. Thus, I-SP-356.6 marker can be deployed in MAS to facilitate the transfer of the earliness trait to other elite late-maturing cultivars. Two InDel markers viz., I-SP-356.6 and I-SP-383.9 (chr. 3; linked to LcELF3a gene) when tested in 9 lentil genotypes differing for maturity duration, clearly distinguished three early (L4775, ILL7663, Precoz) and four late genotypes (Globe Mutant, MFX, L4602, L830). However, these InDels could not be validated in two genotypes (L4717, L4727), suggesting either absence of polymorphism and/or presence of other loci causing earliness. The identified InDel markers can act as valuable tools for MAS for the development of early maturing lentil varieties.

Abstract Protein–protein interactions (PPIs) play a critical role in all biological processes. Menin is tumor suppressor protein, mutated in multiple endocrine neoplasia type 1 syndrome and has been shown to interact with multiple transcription factors including (RPA2) subunit of replication protein A (RPA). RPA2, heterotrimeric protein required for DNA repair, recombination and replication. However, it’s still remains unclear the specific amino acid residues that have been involved in Menin-RPA2 interaction. Thus, accurately predicting the specific amino acid involved in interaction and effects of MEN1 mutations on biological systems is of great interests. The experimental approaches for identifying amino acids in menin-RPA2 interactions are expensive, time-consuming, and challenging. This study leverages computational tools, free energy decomposition and configurational entropy scheme to annotate the menin-RPA2 interaction and effect on menin point mutation, thereby proposing a viable model of menin-RPA2 interaction. The menin–RPA2 interaction pattern was calculated on the basis of different 3D structures of menin and RPA2 complexes, constructed using homology modeling and docking strategy, generating three best-fit models: Model 8 (− 74.89 kJ/mol), Model 28 (− 92.04 kJ/mol) and Model 9 (− 100.4 kJ/mol). The molecular dynamic (MD) was performed for 200 ns and binding free energies and energy decomposition analysis were calculated using Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) in GROMACS. From binding free energy change, model 8 of Menin-RPA2 exhibited most negative binding energy of − 205.624 kJ/mol, followed by model 28 of Menin-RPA2 with − 177.382 kJ/mol. After S606F point mutation in Menin, increase of BFE (ΔGbind) by − 34.09 kJ/mol in Model 8 of mutant Menin-RPA2 occurs. Interestingly, we found a significant reduction of BFE (ΔGbind) and configurational entropy by − 97.54 kJ/mol and − 2618 kJ/mol in mutant model 28 as compared the o wild type. Collectively, this is the first study to highlight the configurational entropy of protein–protein interactions thereby strengthening the prediction of two significant important interaction sites in menin for the binding of RPA2. These predicted sites could be vulnerable for structural alternation in terms of binding free energy and configurational entropy after missense mutation in menin.

PURPOSE: The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1st, 2nd, and 3rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used. RESULTS: A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], −1.78 [−2.71, −0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, −0.10 [−0.14, −0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity. CONCLUSION: CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years.

Introduction: Acute large traumatic wounds require temporary dressing prior to the definitive soft tissue reconstruction, as the physiological derangement during the immediate postinjury period delays the definitive surgical intervention. Selecting an ideal dressing material from numerous available synthetic dressings and skin substitutes poses a challenge. Although amniotic membrane (AM) scaffold has a definitive role in promoting wound healing in burns and chronic wounds, however, its efficacy in acute large traumatic wound is lacking. The present trial aimed to evaluate the safety and efficacy of AM in wound bed preparation before the definitive soft-tissue reconstruction in acute large traumatic wounds. Methods: Sixty patients with acute large traumatic wounds (>10 cm × 10 cm) were divided into two groups (conventional dressing and AM dressing) using simple mixed block randomization. Wounds were assessed using the Bates Jensen Score at various timelines for the signs of early wound healing. The primary outcome was to evaluate the time taken for the wound bed preparation for definitive soft-tissue reconstruction. The secondary outcome was the pain assessment and complications, if any. Results: There was significant reduction in the wound exudate as well as peripheral tissue edema in the intervention group (P = 0.01). AM dressing was significantly less painful (P = 0.01). The incidence of wound infection and need for debridement was decreased in the intervention group. However, the time interval to definitive soft-tissue coverage was statistically insignificant and comparable in both the groups. No adverse reactions were seen in either group. Conclusion: AM dressings are safe and efficacious with significant reduction in wound exudates and peripheral edema. However, these dressings do not hasten the wound maturation as compared to conventional dressings. AM dressings can be used as a less painful alternative to conventional dressing in the management of large acute posttraumatic wounds.

In India, financial literacy among health professionals is a topic of growing importance, as these professionals often earn a significant income but may not have the necessary knowledge or skills to manage their finances effectively. To address this issue, there is a need for financial literacy programs that are specifically designed for health professionals in India. These programs can provide education on topics such as budgeting, saving, investing, retirement planning, and debt management. They can also help health professionals develop better financial habits and improve their overall financial well-being.

Background: Yoga is an emerging intervention causing improvement in physical, mental, and spiritual well-being. Its role in improving outcomes in patients with amputation was investigated. Methodology: Patients with traumatic lower limb amputation (n = 50) were enrolled and randomized to the Yoga group (n = 26) against control (n = 24). Sociodemographic details, quality of life (QOL) (World Health Organization QOL-BREF), Depression anxiety stress scale (DASS), Rosenberg self-esteem scale, and amputee body image score were applied at baseline, 6,–18 weeks of amputation. Results: Sociodemographic and clinical variables were comparable between groups. At 18 weeks, the Yoga group had better QOL (P = 0.005) than the control group. Symptoms of depression (0.02) and anxiety (

SARS-CoV-2 has caused a global pandemic with significant humanity and economic loss since 2020. Currently, only limited options are available to treat SARS-CoV-2 infections for vulnerable populations. In this study, we report a universal fluorescence polarization (FP)-based high throughput screening (HTS) assay for SAM-dependent viral methyltransferases (MTases), using a fluorescent SAM-analogue, FL-NAH. We performed the assay against a reference MTase, NSP14, an essential enzyme for SARS-CoV-2 to methylate the N7 position of viral 5’-RNA guanine cap. The assay is universal and suitable for any SAM-dependent viral MTases such as the SARS-CoV-2 NSP16/NSP10 MTase complex and the NS5 MTase of Zika virus (ZIKV). Pilot screening demonstrated that the HTS assay was very robust and identified two candidate inhibitors, NSC 111552 and 288387. The two compounds inhibited the FL-NAH binding to the NSP14 MTase with low micromolar IC50. We used three functional MTase assays to unambiguously verified the inhibitory potency of these molecules for the NSP14 N7-MTase function. Binding studies indicated that these molecules are bound directly to the NSP14 MTase with similar low micromolar affinity. Moreover, we further demonstrated that these molecules significantly inhibited the SARS-CoV-2 replication in cell-based assays at concentrations not causing cytotoxicity. Furthermore, NSC111552 significantly synergized with known SARS-CoV-2 drugs including nirmatrelvir and remdesivir. Finally, docking suggested that these molecules bind specifically to the SAM-binding site on the NSP14 MTase. Overall, these molecules represent novel and promising candidates to further develop broad-spectrum inhibitors for the management of viral infections.

Polyamines (PAs) play a vital role in plants' response to various abiotic stresses, including high temperature (HT) stress. The present study was carried out during 2020–23 at the Indian Agricultural Research Institute, New Delhi to explores how spermidine treatment affects rice (Oryza sativa L.) seeds' ability to withstand heat and the availability of sugars for seedling growth during the radicle stage in heat-susceptible (IR64) and tolerant (N22) varieties. The seeds were primed with 1 mM spermidine using PEG (-1 MPa) as the priming medium, followed by exposure to heat stress. Results showed that in unprimed seeds, heat stress significantly reduces the seed germination, vigour and sugar availability in both the varieties and to a greater extent in IR64 compared to N22. This difference resulted in a substantially lower percentage of normal seedlings and seed vigour index in IR64 than in N22. However, spermidine seed priming enhanced thermotolerance in both varieties, more in IR64, equating the normal seedling percentage and seedling growth with control, i.e. without heat stress. The priming treatment also notably augmented α-amylase activity and reducing sugar availability, particularly in N22, enabling better seedling growth under heat stress conditions. This study underscores the importance of seed priming with spermidine to allow the seedlings to tolerate elevated temperatures and maintain better seedling growth due to the enhanced availability of reducing sugars during germination and early seedling growth.

Wheat stripe rust caused by Puccinia striiformis Westend. f.sp. tritici (Pst) is a global threat to wheat production. Genetic modification of defense-responsive factors in wheat rust interactions could help devise strategies to control stripe rust on wheat. This experiment studied the interaction between Pst pathotype 78S84 in PBW343 and FLW-3 by evaluating the quantitative temporal transcription profiles of defense-related genes at different time points. This is the first attempt to exhibit inter-connections among different proteins and depict a hypothetical model for the mechanism of R gene-mediated resistance. Transcript levels of LTP, AQP1, PR1, PR2, PR4, and PR10 were relatively higher under compatible interaction, while under incompatible interaction, transcript levels of COMT1, PRA2, WCAB, and PR9 were significantly high. This study projected the role of defense-responsive genes, inter-networking of proteins, and R gene-mediated resistance between wheat and stripe rust.

Puccinia spp. causing rust diseases in wheat and other cereals secrete several specialized effector proteins into host cells. Characterization of these proteins and their interaction with host’s R proteins could greatly help to limit crop losses due to diseases. Prediction of effector proteins by combining the transcriptome analysis and multiple in-silico approaches is gaining importance in revealing the pathogenic mechanism. The present study involved identification of 13 Puccinia triticina (Pt) coding sequences (CDSs), through transcriptome analysis, that were differentially expressed during wheat-leaf rust interaction; and prediction of their effector like features using different in-silico tools. NCBI-BLAST and pathogen-host interaction BLAST (PHI-BLAST) tools were used to annotate and classify these sequences based on their most closely matched counterpart in both the databases. Homology between CDSs and the annotated sequences in the NCBI database ranged from 79 to 94% and with putative effectors of other plant pathogens in PHI-BLAST from 24.46 to 54.35%. Nine of the 13 CDSs had effector-like features according to EffectorP 3.0 (≥0.546 probability of these sequences to be effector). The qRT-PCR expression analysis revealed that the relative expression of all CDSs in compatible interaction (HD2329) was maximum at 11 days post inoculation (dpi) and that in incompatible interactions (HD2329 + Lr28) was maximum at 3 dpi in seven and 9 dpi in five CDSs. These results suggest that six CDSs (>0.8 effector probability as per EffectorP 3.0) could be considered as putative Pt effectors. The molecular docking and MD simulation analysis of these six CDSs suggested that candidate Lr28 protein binds more strongly to candidate effector c14094_g1_i1 to form more stable complex than the remaining five. Further functional characterization of these six candidate effectors should prove useful for a better understanding of wheat-leaf rust interaction. In turn, this should facilitate effector-based leaf rust resistance breeding in wheat.

Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), has re-emerged as one of the major concerns for global wheat production since the evolution of Ug99 and other virulent pathotypes of Pgt from East Africa, Europe, Central Asia, and other regions. Host resistance is the most effective, economic, and eco-friendly approach for managing stem rust. Understanding the virulence nature, genetic diversity, origin, distribution, and evolutionary pattern of Pgt pathotypes over time and space is a prerequisite for effectively managing newly emerging Pgt isolates through host resistance. In the present study, we monitored the occurrence of stem rust of wheat in India and neighboring countries from 2016 to 2022, collected 620 single-pustule isolates of Pgt from six states of India and Nepal, analyzed them on Indian stem rust differentials, and determined their virulence phenotypes and molecular genotypes. The Ug99 type of pathotypes did not occur in India. Pathotypes 11 and 40A were most predominant during these years. Virulence phenotyping of these isolates identified 14 Pgt pathotypes, which were genotyped using 37 Puccinia spp.-specific polymorphic microsatellites, followed by additional phylogenetic analyses using DARwin. These analyses identified three major molecular groups, demonstrating fewer lineages, clonality, and long-distance migration of Pgt isolates in India. Fourteen of the 40 recently released Indian wheat varieties exhibited complete resistance to all 23 Pgt pathotypes at the seedling stage. Twelve Sr genes were postulated in 39 varieties based on their seedling response to Pgt pathotypes. The values of slow rusting parameters i.e. coefficient of infection, area under disease progress curve, and infection rates, assessed at adult plant stage at five geographically different locations during two crop seasons, indicated the slow rusting behavior of several varieties. Six Sr genes (Sr2, Sr57, Sr58, Sr24, Sr31, and Sr38) were identified in 24 wheat varieties using molecular markers closely linked to these genes. These findings will guide future breeding programs toward more effective management of wheat stem rust.

NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2’O-methyl-transferase (2’O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM binding site in NSP16 using Food and Drug Administration (FDA)-approved small molecules set from Drug Bank database. Among the 2 456 FDA-approved molecules, framycetin, paromomycin, and amikacin were found to be significant binders against the SAM binding cryptic pocket of NSP16 with docking score of –13.708, –14.997 and –15.841 kcal/mol, respectively. Classical molecular dynamics (MD) simulation and molecular mechanics Poisson−Boltzmann surface area (MM/PBSA)-based binding free energy calculation depicted that all these three framycetin, paromomycin, and amikacin might be promising therapeutic leads towards SARS-CoV-2 infections via host immune escape inhibition pathway.

A total of 138, samples have been collected in both pre and post monsoon season to understand the seasonal variability in groundwater quality and its suitability for drinking and domestic water supply. The samples were analysed for physical parameters, major ions along with fluoride and uranium. The results were integrated with GIS to represent both seasonal and spatial variations of groundwater quality parameters, drinking groundwater quality index (DGQI) and irrigation groundwater quality index (IGQI). Results show that groundwater is alkaline in nature and largely controlled by the silicate weathering, ion exchange and reverse ion exchange processes. However high nitrate concentration exceeding the WHO guideline suggests the influence of anthropogenic activities on groundwater quality. The average values of the major ions concentrations was found higher in pre monsoon season due to change in the recharge. The DGQI values of 6 samples in pre monsoon and 2 samples in post monsoon season falls under poor water quality. However, individual irrigation indices along with the combine IGQI indicate groundwater is suitable for irrigation in both the seasons. These results along with the seasonal and spatial variability map may help the decision makers in planning for better domestic and irrigation water supply. HIGHLIGHTS Silicate weathering and ion exchange controls ionic species in groundwater.; High concentration of nitrate in pre-monsoon season suggests influence of anthropogenic activities on groundwater.; Relatively high ion concentrations are found in pre-monsoon season.; Groundwater is safe in terms of fluoride and uranium.; Both DGQI and IGQI suggests that groundwater is safe for drinking and domestic water supply.;

Abstract MicroRNAs (miRNAs) are found in nerve terminals, synaptic vesicles, and synaptosomes, but it is unclear whether synaptic and cytosolic miRNA populations differ in Alzheimer’s disease (AD) or if synaptosomal miRNAs affect AD synapse activity. To address these questions, we generated synaptosomes and cytosolic fractions from postmortem brains of AD and unaffected control (UC) samples and analyzed them using a global Affymetrix miRNAs microarray platform. A group of miRNAs significantly differed (P 200-fold) in their expressions in different comparisons: (1) UC synaptosome vs UC cytosol, (2) AD synaptosomes vs AD cytosol, (3) AD cytosol vs UC cytosol, and (4) AD synaptosomes vs UC synaptosomes. MiRNAs data analysis revealed that some potential miRNAs were consistently different across sample groups. These differentially expressed miRNAs were further validated using AD postmortem brains, brains of APP transgenic (Tg2576), Tau transgenic (P301L), and wild-type mice. The miR-501-3p, miR-502-3p, and miR-877-5p were identified as potential synaptosomal miRNAs upregulated with disease progression based on AD Braak stages. Gene Ontology Enrichment and Ingenuity Pathway Analysis of synaptosomal miRNAs showed the involvement of miRNAs in nervous system development, cell junction organization, synapse assembly formation, and function of GABAergic synapse. This is the first description of synaptic versus cytosolic miRNAs in AD and their significance in synapse function.

Food waste (FW) is a significant global issue with a carbon footprint of 3.3 billion tonnes (Bt), primarily generated due to improper food supply chain management, storage issues, and transportation problems. Acidogenic processes like dark fermentation, anaerobic digestion, and a combination of DF-AD can produce renewable biofuels (Bio-CH4, Bio-H2) by valorising FW, aligning with the UN SDGs. FW is an ideal substrate for acidogenic processes due to its high moisture content, organic matter, and biodegradability. However, the choice of FW valorisation pathways depends on energy yield, conversion efficiency, and cost effectiveness. Acidogenic processes are not economically viable for industrial scale FW treatment due to reduced energy recovery from stand-alone processes. So, this study reviews comparative studies on biogas, biohydrogen, and biohythane production from FW via acidogenic processes, focusing on energy yield, energy recovery, and environmental and economic impact to provide a clear understanding of energy recovery and yield from all acidogenic processes. Additionally, this review also explores the recent advancements in digestate slurry management and the synergistic effects of AD and HTC processes. Lastly, a futuristic integrated bio-thermo-chemical process is proposed for maximum energy recovery, valuing food waste to energy vectors (Bio-H2, Bio-CH4, and hydro-char) along with digestate management and biofertilizer production.

Background: The deadly second wave of coronavirus disease-2019 (COVID-19) pandemic swept through the whole of India during the month of April–May 2021. Restrictions like lockdowns and social distancing impacted the normal functioning of life. It is in this backdrop that we need to understand the perceived stress and quality of life among people. Aim and objective: The aim and objective of this study was to evaluate and study the relationship between perceived stress and quality of life among adults living in Delhi NCR, during the second wave of the COVID-19 pandemic. Materials and methods: A 10-item perceived stress scale (PSS-10) was used to assess perceived stress among adults. The 26-item World Health Organization Quality of Life Brief Version (WHOQOL-BREF) was used to assess the quality of life. The data were collected online and analyzed using statistical methods, like independent samples t-test and Spearman's rank correlation. Results: The study found no significant difference in the perceived stress between males and females (p >0.05). There was no significant difference in various domains of quality of life, like physical health, psychological health, social relationships, and environmental health between males and females (p >0.05). Also, the overall quality of life had a significant negative correlation (p

Abstract Background Dyspnea is one of the common symptoms patients present to the emergency department (ED). The broad spectrum of differentials often requires laboratory and radiological testing in addition to clinical evaluation, causing unnecessary delay. Point of care ultrasound (PoCUS) has shown promising results in accurately diagnosing patients with dyspnea, thus, becoming a popular tool in ED while saving time and maintaining safety standards. Our study aimed to determine the utilization of point of care ultrasound in patients with acute dyspnea as an initial diagnostic tool in our settings. Methodology The study was conducted at the emergency department of a tertiary healthcare center in Northern India. Adult patients presenting with acute dyspnea were prospectively enrolled. They were clinically evaluated and necessarily investigated, and a provisional diagnosis was made. Another EP, trained in PoCUS, performed the scan, blinded to the laboratory investigations (not the clinical parameters), and made a PoCUS diagnosis. Our gold standard was the final composite diagnosis made by two Emergency Medicine consultants (who had access to all investigations). Accuracy and concordance of the ultrasound diagnosis to the final composite diagnosis were calculated. The time to formulate a PoCUS diagnosis and final composite diagnosis was compared. Results Two hundred thirty-seven patients were enrolled. The PoCUS and final composite diagnosis showed good concordance (κ = 0.668). PoCUS showed a high sensitivity for acute pulmonary edema, pleural effusion, pneumothorax, pneumonia, pericardial effusion, and low sensitivity for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). High overall specificity was seen. A high positive predictive value for all except left ventricular dysfunction, pericardial effusion, non-cardiopulmonary causes of dyspnea, and a low negative predictive value was seen for pneumonia. The median time to make a PoCUS diagnosis was 16 (5–264) min compared to the 170 (8–1346) min taken for the final composite diagnosis. Thus, time was significantly lower for PoCUS diagnosis (p value