Characterization and removal of microplastics in the Guheshwori Wastewater Treatment Plant, Nepal.

Contamination of river water systems by microplastic particles (MPPs) is one of the emerging global environmental concerns with potentially widespread ecological, socioeconomic, and health implications. A wastewater treatment plant (WWTP) processes and treats wastewater to remove pollutants and release safe water into the environment. There has been limited research on the characterization of microplastics and their removal in WWTP in South Asia. In this work, we report on the characterization of microplastics in wastewater and sludge samples (n = 300) from Guheshwori WWTP located on the bank of the Bagmati River in Kathmandu city, Nepal representing inlet, secondary aeration tank (SAT), outlet, and sludge from November 2021 to November 2022. On average, we detected 31.2 ± 17.3 MPPs/L, 11.2 ± 9.4 MPPs/L, 8.5 ± 5.6 MPPs/L, and 6.6 ± 4.8 MPPs/g in the samples collected from inlet, SAT, outlet, and sludge, respectively. Commonly found MPPs were in the form of fiber, fragments, foam, and pellets. Largely, MPPs were red, yellow, white, blue, and black. Among the 44 µm - 150 µm, 150 µm - 500 µm and 500 µm - 5 mm categories of size fractions, the most dominant fractions were 500 µm - 150 µm in inlet, SAT, and sludge, and 150 µm - 44 µm in the outlet sampling unit. The Guheshwori WWTP was able to remove 72.5 % of MPPs on average, that mostly occurred in the inlet. The effluent released into the river and the sludge still contained a significant number of MPPs.

Identifying long non-coding RNAs involved in heat stress response during wheat pollen development.

Introduction: Wheat is a staple food crop for over one-third of the global population. However, the stability of wheat productivity is threatened by heat waves associated with climate change. Heat stress at the reproductive stage can result in pollen sterility and failure of grain development. Methods: This study used transcriptome data analysis to explore the specific expression of long non-coding RNAs (lncRNAs) in response to heat stress during pollen development in four wheat cultivars. Results and discussion: We identified 11,054 lncRNA-producing loci, of which 5,482 lncRNAs showed differential expression in response to heat stress. Heat-responsive lncRNAs could target protein-coding genes in cis and trans and in lncRNA-miRNA-mRNA regulatory networks. Gene ontology analysis predicted that target protein-coding genes of lncRNAs regulate various biological processes such as hormonal responses, protein modification and folding, response to stress, and biosynthetic and metabolic processes. We also noted some paired lncRNA/protein-coding gene modules and some lncRNA-miRNA-mRNA regulatory modules shared in two or more wheat cultivars. These modules were related to regulating plant responses to heat stress, such as heat-shock proteins and transcription factors, and protein domains, such as MADS-box, Myc-type, and Alpha crystallin/Hsp20 domain. Conclusion: Our results provide the basic knowledge and molecular resources for future functional studies investigating wheat reproductive development under heat stress.

Overexpression of GmPIF4b affects morpho-physiological traits to reduce heat-induced grain loss in soybean.

Heat waves associated with climate change seriously threaten crop productivity. Crop seed yield depends on the success of reproduction. However, reproductive development is most vulnerable to heat stress conditions. Perception of heat and its conversion into cellular signals is a complex process. The basic helix loop helix (bHLH) transcription factor, Phytochrome Interacting Factor 4 (PIF4), plays a significant role in this process. However, studies on PIF4- mediated impacts on crop grain yield at a higher temperature are lacking. We investigated the overexpression of GmPIF4b in soybean to alleviate heat-induced damage and yield using a transgenic approach. Our results showed that under high-temperature conditions (38°C/28°C), overexpressing soybeans plants had higher chlorophyll a and b, and lower proline accumulation compared to WT. Further, overexpression of GmPIF4b improved pollen viability under heat stress and reduced heat-induced structural abnormalities in the male and female reproductive organs. Consequently, the transgenic plants produced higher pods and seeds per plant at high temperatures. Quantitative RT-PCR analysis showed that the overexpressing GmPIF4b soybeans had higher transcripts of heat shock factor, GmHSF-34, and heat-shock protein, GmHSP90A2. Collectively, our results suggest that GmPIF4b regulates multiple morpho-physiological traits for better yield under warmer climatic conditions.

Pokkali: A Naturally Evolved Salt-Tolerant Rice Shows a Distinguished Set of lncRNAs Possibly Contributing to the Tolerant Phenotype.

Pokkali is a strong representation of how stress-tolerant genotypes have evolved due to natural selection pressure. Numerous omics-based investigations have indicated different categories of stress-related genes and proteins, possibly contributing to salinity tolerance in this wild rice. However, a comprehensive study towards understanding the role of long-noncoding RNAs (lncRNAs) in the salinity response of Pokkali has not been done to date. We have identified salt-responsive lncRNAs from contrasting rice genotypes IR64 and Pokkali. A total of 63 and 81 salinity-responsive lncRNAs were differentially expressed in IR64 and Pokkali, respectively. Molecular characterization of lncRNAs and lncRNA-miRNA-mRNA interaction networks helps to explore the role of lncRNAs in the stress response. Functional annotation revealed that identified lncRNAs modulate various cellular processes, including transcriptional regulation, ion homeostasis, and secondary metabolite production. Additionally, lncRNAs were predicted to bind stress-responsive transcription factors, namely ERF, DOF, and WRKY. In addition to salinity, expression profiling was also performed under other abiotic stresses and phytohormone treatments. A positive modulation in TCONS_00035411, TCONS_00059828, and TCONS_00096512 under both abiotic stress and phytohormone treatments could be considered as being of potential interest for the further functional characterization of IncRNA. Thus, extensive analysis of lncRNAs under various treatments helps to delineate stress tolerance mechanisms and possible cross-talk.

Circular RNAs modulate the floral fate acquisition in soybean shoot apical meristem.

BACKGROUND: Soybean (Glycine max), a major oilseed and protein source, requires a short-day photoperiod for floral induction. Though key transcription factors controlling flowering have been identified, the role of the non-coding genome is limited. Circular RNAs (circRNAs) recently emerged as a novel class of RNAs with critical regulatory functions. However, a study on circRNAs during the floral transition of a crop plant is lacking. We investigated the expression and potential function of circRNAs in floral fate acquisition by soybean shoot apical meristem in response to short-day treatment. RESULTS: Using deep sequencing and in-silico analysis, we denoted 384 circRNAs, with 129 exhibiting short-day treatment-specific expression patterns. We also identified 38 circRNAs with predicted binding sites for miRNAs that could affect the expression of diverse downstream genes through the circRNA-miRNA-mRNA network. Notably, four different circRNAs with potential binding sites for an important microRNA module regulating developmental phase transition in plants, miR156 and miR172, were identified. We also identified circRNAs arising from hormonal signaling pathway genes, especially abscisic acid, and auxin, suggesting an intricate network leading to floral transition. CONCLUSIONS: This study highlights the gene regulatory complexity during the vegetative to reproductive transition and paves the way to unlock floral transition in a crop plant.

Melatonin and Abiotic Stress Tolerance in Crop Plants.

Increasing food demand by the growing human population and declining crop productivity due to climate change affect global food security. To meet the challenges, developing improved crops that can tolerate abiotic stresses is a priority. Melatonin in plants, also known as phytomelatonin, is an active component of the various cellular mechanisms that alleviates oxidative damage in plants, hence supporting the plant to survive abiotic stress conditions. Exogenous melatonin strengthens this defence mechanism by enhancing the detoxification of reactive by-products, promoting physiological activities, and upregulating stress-responsive genes to alleviate damage during abiotic stress. In addition to its well-known antioxidant activity, melatonin protects against abiotic stress by regulating plant hormones, activating ER stress-responsive genes, and increasing protein homoeostasis, heat shock transcription factors and heat shock proteins. Under abiotic stress, melatonin enhances the unfolded protein response, endoplasmic reticulum-associated protein degradation, and autophagy, which ultimately protect cells from programmed cell death and promotes cell repair resulting in increased plant survival.

Evaluation of the Effectiveness and Perceived Benefits of Interventional Structured Infection Prevention and Control Training Module Introduced in the Undergraduate Medical Curricula.

Introduction: Assessing and improving infection prevention and control (IPC) knowledge and practicing skills among medical students who are the future medical practitioners is crucial for reducing the burden of healthcare-associated infections (HAIs). In this study, we assessed the IPC knowledge of undergraduate clinical-year medical students before and after interventional IPC modular training and evaluated the effectiveness and students' perception on structured modular IPC training presented to them. Methods: This cross-sectional interventional study was conducted on single medical cohort comprising of 145 final-year undergraduate medical students of the academic year 2022-23 at COMHS. Pre-test, post-test, and feedback questionnaire were used as the assessing tools. The data were collected, entered into Excel sheet, and analyzed using SPSS software version 22. McNemar and Paired-T tests were carried out, and a p value<0.05 was considered significant. Feedback of the questionnaire was analyzed using 3 Point Likert Scale as agree, neutral, and disagree. Results: Overall, mean IPC knowledge scores after training (37.65±1.37) was significantly higher as compared to before training (25.13±4.51). Prior knowledge scores on certain aspects of IPC such as duration of hand washing, steps of hand washing, sequence of donning and doffing of PPE, use of N95 mask, and appropriate sharp and needle precautions, and biomedical waste management were varied from 13.6% to 65.6%. However, overall participants' knowledge (p value <0.001) on these aspects increased significantly after the training. The majority of the participants (>90%) perceived IPC training as an excellent tool to improve IPC knowledge and practicing skills. Conclusion: IPC training had a significant impact in gaining adequate IPC knowledge and practicing skills among our participants. Therefore, it is recommended that IPC training should be implemented in the undergraduate medical curriculum with greater emphasis on practicing skills.

Influence of γ-irradiation on physicochemical, functional, proximate, and antioxidant characteristics of pigmented rice flours.

In recent years, food irradiation using γ-rays is one of the most valuable practices for insect disinfestation in rice grains for extended shelf life. In this study, flours from four pigmented rice cultivars were exposed to γ-irradiation using 60Co at different doses (0, 5, 10, and 15 kGy). The impact of γ-irradiation on the physico-chemical, functional, and morphological characteristics of pigmented rice flours were analyzed. Results revealed that reduction in amylose content, pH, bulk density, tapped density, and syneresis, while solubility, water absorption capacity, and swelling power values increased significantly (p < 0.05). Pasting characteristics of pigmented rice flours also reduced after exposure to γ-irradiation. Morphological features of pigmented rice flour granules revealed no evidence of physical destruction after irradiation except for black kavuni flour. The structural analysis by FTIR confirms no effect of γ-irradiation on pigmented rice flours. Overall, the study revealed that irradiated pigmented rice flours with enhanced functional properties of less than 10 kGy can be effectively used in the development of value-added rice-based food products considering all the beneficial and safety aspects. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05709-z.

Effect on growth performance, carcass traits, and myostatin gene expression in Aseel chicken fed varied levels of dietary protein in isocaloric energy diets.

A study was conducted to assess the effect of feeding different crude protein (CP) levels with isocaloric metabolizable energy (ME) diets on growth performance, carcass traits, and myostatin (MSTN) gene expression of Aseel chicken during 0 to 16 weeks of age. A total of two hundred and ten day-old Aseel chickens were randomly allotted to seven dietary treatment groups. Each group had thirty chicks distributed into three replicates of ten chicks in each. Experimental diets were formulated to have varying levels of CP, viz. 18.5, 19.0, 19.5, 20.0, 20.5, 21.0, and 21.5%, with isocaloric energy of 2800 kcal ME/kg diets of mash feed fed to birds in a completely randomized design. Different CP levels had a significant effect (P < 0.05) on the body weight gain (BWG) of Aseel chicken. At the end of 16 weeks of age, the group fed 21% CP gained 223.53 g more than the lowest CP (18.5%)-fed group. The different CP levels did not significantly (P > 0.05) influenced the feed intake of all treatment groups, but numerically highest feed intake was observed in the lowest CP (18.5%)-fed group. However, significant differences in feed efficiency (FE) appeared from the 13th week only with the 21.0% CP-fed group showing the best FE until the 16th week (3.86 to 4.06). The maximum dressing % (70.61) was observed by the 21% CP-fed group. The CP 21% diet down-regulated the MSTN gene expression in breast muscle tissue to 0.07 folds when compared to the diet of CP 20%. The best economical coordinates for maximum performance for Aseel chicken appeared to be CP of 21% and ME of 2800 kcal/kg to achieve the best FE of 3.86 at the earliest age of 13 weeks. In conclusion, 21% CP in an isocaloric diet of 2800 kcal ME/kg, in Aseel chickens, would be optimum to improve the growth performance at maximum in terms of BWG and FE up to 16 weeks of age.

Functional analysis of soybean miR156 and miR172 in tobacco highlights their role in plant morphology and floral transition.

Soybean (Glycine max), a significant oilseed and protein source for humans and livestock feed, needs short day photoperiod for floral induction. Further, soybean has a paleopolyploid genome with multiple copies of flowering genes adding to the complexity of genetic regulation of flowering, and seed set, especially in investigating the role of the noncoding genome. microRNAs, a class of noncoding RNA, play a regulatory role in plant development. miR156 and miR172 are major components of the essential regulatory hub controlling juvenile and vegetative developments and initiation of reproductive phase change leading to flowering. These microRNAs have been originally isolated and studied from model plant, Arabidopsis. However, a study on soybean microRNAs is lacking. We investigated the temporal expression patterns of gma-miR156a and gma-miR172a and found inversely related - gma-miR156a expression was higher in the vegetative stage, and gma-miR172a expression was elevated under inductive flowering conditions. The functions of gma-miR156a and gma-miR172a were evaluated via heterologous expressions in transgenic tobacco plants (Nicotiana tabacum L.). The analysis of overexpression transgenic lines highlighted that gma-miR156a plays a role in juvenile development via repression of the SPL transcription factor family. In contrast, gma-miR172a plays a pivotal role in the reproductive development phase by down-regulating its target genes, AP2. In addition, ectopic expression of gma-miR156a and gma-miR172a affected plant morphology and physiology during plant growth. Collectively, our results suggest that gma-miR156a and gma-miR172a regulate multiple morpho-physiological traits that could be used to enhance crop yield under changing climate conditions.

Genome-wide analysis reveals the crucial role of lncRNAs in regulating the expression of genes controlling pollen development.

KEY MESSAGE: The genomic location and stage-specific expression pattern of many long non-coding RNAs reveal their critical role in regulating protein-coding genes crucial in pollen developmental progression and male germ line specification. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 bp with no apparent protein-coding potential. Multiple investigations have revealed high expression of lncRNAs in plant reproductive organs in a cell and tissue-specific manner. However, their potential role as essential regulators of molecular processes involved in sexual reproduction remains largely unexplored. We have used developing field mustard (Brassica rapa) pollen as a model system for investigating the potential role of lncRNAs in reproductive development. Reference-based transcriptome assembly performed to update the existing genome annotation identified novel expressed protein-coding genes and long non-coding RNAs (lncRNAs), including 4347 long intergenic non-coding RNAs (lincRNAs, 1058 expressed) and 2,045 lncRNAs overlapping protein-coding genes on the opposite strand (lncNATs, 780 expressed). The analysis of expression profiles reveals that lncRNAs are significant and stage-specific contributors to the gene expression profile of developing pollen. Gene co-expression networks accompanied by genome location analysis identified 38 cis-acting lincRNA, 31 cis-acting lncNAT, 7 trans-acting lincRNA and 14 trans-acting lncNAT to be substantially co-expressed with target protein-coding genes involved in biological processes regulating pollen development and male lineage specification. These findings provide a foundation for future research aiming at developing strategies to employ lncRNAs as regulatory tools for gene expression control during reproductive development.

Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Role of medical thoracoscopy in the diagnosis of pleural effusions.

BACKGROUND: Medical thoracoscopy (semi-rigid and rigid thoracoscopy) have revolutionized the management of undiagnosed pleural effusions. Though semi-rigid thoracoscopy has a good diagnostic yield in malignant and tubercular effusions, its role in the management of a complicated pleural effusions is debatable. Hence, rigid thoracoscopy becomes handy in these cases. The present study looked into the role of medical thoracoscopy in the diagnosis of pleural effusions in different conditions. METHODS: This study included all patients who underwent medical thoracoscopy at our center between May-2010 and March-2020. Basic demographics data, type of medical thoracoscopy used, and histopathology details were collected and analyzed. RESULTS: A total of 373 patients were subjected to medical thoracoscopy (202 semi-rigid thoracoscopy and 171 rigid thoracoscopy). Out of whom 246 (66%) were males, the mean age was 51.9 ± 13.2 years. Diagnosis was achieved in 370 patients with a yield of 99.2%. The diagnostic yield in semi-rigid thoracoscopy was 99.5% with lung malignancy being the most common diagnosis (41%; n = 81), followed by tuberculosis (31%; n = 61). The diagnostic yield in rigid thoracoscopy was 100% in our study. Along with high diagnostic yield, complete drainage and lung expansion was seen in 93.5% (160 out of 171 patients) without requiring a second procedure. CONCLUSIONS: Semi-rigid thoracoscopy and rigid thoracoscopy should complement each other in the diagnosis of pleural effusions. Rigid thoracoscopy should be considered as the procedure of choice in a complicated pleural effusion.

Role of long non-coding RNAs in rice reproductive development.

Rice is a staple crop, feeding over half of the global population. The future demand of population growth and climate change requires substantial rice improvement. Recent advances in rice genomics have highlighted the vital role of the non-coding part of the genome. The protein-coding regions account for only a tiny portion of the eukaryotic genome, and most of the genomic regions transcribe copious amounts of non-coding RNAs. Of these, the long non-coding RNAs, including linear non-coding RNAs (lncRNAs) and circular non-coding RNAs (circRNAs), have been shown to play critical roles in various developmental processes by regulating the expression of genes and functions of proteins at transcriptional, post-transcriptional and post-translational levels. With the advances in next-generation sequencing technologies, a substantial number of long non-coding RNAs have been found to be expressed in plant reproductive organs in a cell- and tissue-specific manner suggesting their reproductive development-related functions. Accumulating evidence points towards the critical role of these non-coding RNAs in flowering, anther, and pollen development, ovule and seed development and photoperiod and temperature regulation of male fertility. In this mini review, we provide a brief overview of the role of the linear and circular long non-coding RNAs in rice reproductive development and control of fertility and crop yield.

The adverse effects of solid biomass fuel exposure on lung functions in non-smoking female population.

Background: Though, smoking is the leading cause of chronic obstructive pulmonary disease worldwide, the household air pollution due to use of solid biomass fuel is considered as a major risk factor for the development of obstructive lung disease. The aim of the study was to assess the effect of solid biomass fuel exposure on lung functions in non-smoking female population. Methods: A hospital based, descriptive cross sectional study was carried out among 140 non-smoking female patients aged 40 or more and who had been exposed to solid biomass fuel. These patients underwent spirometry to assess their lung function and were classified as obstructive, restrictive or mixed. Modified medical research council (mMRC) dyspnoea scale for symptom assessment, 6-minute walk test (6 MWT) to determine the exercise capacity and Cumulative exposure index to assess the duration of exposure were also done. Results: All 140 (100%) patients having abnormal lung function, 4 (2.86%) had restrictive pattern, 5 (3.57%) had mixed pattern and 131 (93.57%) had obstructive pattern. Of 131 patients having obstructive pattern, 11 had mild obstruction, 49 had moderate obstruction, 39 had severe obstruction and 32 had very severe obstruction. Most commonly used biomass fuel was wood (43.57%). All the patients had shortness of breath, whereas cough was present in only 35.71% cases. 77 (55%) patients presented with a dyspnoea of mMRC grade 3 and above. Conclusion: Cumulative exposure index for solid biomass fuel is directly proportional to the severity of lung impairment as well as the symptom severity.

Concept maps in immunology: A metacognitive tool to promote collaborative and meaningful learning among undergraduate medical students.

Introduction: Concept maps are graphical representations of knowledge that connect concepts, ideas, and relationships. The present study aims at assessing the perception of medical students in utilization of concept maps as a tool to foster their lifelong learning skills in immunology. Methods: The current study was approved by Institutional Ethics and Review Committee. Third-year undergraduate (MD3) medical students of the academic year 2021-22 were sensitized about the concept map study and included after obtaining their informed consent. The students worked in teams to find answers and link the different words or phrases of the concept maps. At the end of the immunology course, students' perception on concept map-based learning strategy was assessed. A pre-designed, self-administered questionnaire, pre-validated by subject experts for relevance and feasibility, was used for the study. The questionnaire included some quantitative questions assessed by using 3-point Likert Scale and an open-ended question to receive students' comments on concept map-based learning strategy. The responses were collected and analyzed using SPSS version 22. Descriptive statistics was used for the quantitative variables, tabulated as numbers and percentages while the qualitative data was analyzed by thematic analysis. The quantitative data results were prioritized but supported by students' comments on open ended question. Results: Out of 133 eligible participants, 109 students who volunteered and completed the study were included. Majority of our participants (>80%) welcomed the concept map-based learning strategy. Almost 4 out of 5 expressed that concept maps are interesting and enjoyable, encourage active participation, peer discussion, and enhance critical thinking and problem-solving skills. More than 80% of the students agreed that concept maps promoted deep understanding of the topic and lifelong learning. Nearly 3 out of 4 students suggested including concept maps in many immunology topics in future. Majority of students penned down positive comments indicating concept map tool facilitates metacognitive skills. Conclusion: From the study, it can be concluded that concept maps are effective active learning strategies to improve the metacognitive domain of medical students in immunology course, thus assisting them to become better lifelong learners.

Rapid Transcriptional Reprogramming Associated With Heat Stress-Induced Unfolded Protein Response in Developing Brassica napus Anthers.

Climate change associated increases in the frequency and intensity of extreme temperature events negatively impact agricultural productivity and global food security. During the reproductive phase of a plant's life cycle, such high temperatures hinder pollen development, preventing fertilization, and seed formation. At the molecular level, heat stress-induced accumulation of misfolded proteins activates a signaling pathway called unfolded protein response (UPR) in the endoplasmic reticulum (ER) and the cytoplasm to enhance the protein folding capacity of the cell. Here, we report transcriptional responses of Brassica napus anthers exposed to high temperature for 5, 15, and 30 min to decipher the rapid transcriptional reprogramming associated with the unfolded protein response. Functional classification of the upregulated transcripts highlighted rapid activation of the ER-UPR signaling pathway mediated by ER membrane-anchored transcription factor within 5 min of heat stress exposure. KEGG pathway enrichment analysis also identified "Protein processing in ER" as the most significantly enriched pathway, indicating that the unfolded protein response (UPR) is an immediate heat stress-responsive pathway during B. napus anther development. Five minutes of heat stress also led to robust induction of the cytosolic HSF-HSP heat response network. Our results present a perspective of the rapid and massive transcriptional reprogramming during heat stress in pollen development and highlight the need for investigating the nature and function of very early stress-responsive networks in plant cells. Research focusing on very early molecular responses of plant cells to external stresses has the potential to reveal new stress-responsive gene networks that can be explored further for developing climate change resilient crops.

Repurposing of FDA Approved Drugs Against SARS-CoV-2 Papain-Like Protease: Computational, Biochemical, and in vitro Studies.

The pandemic caused by SARS-CoV-2 (SCoV-2) has impacted the world in many ways and the virus continues to evolve and produce novel variants with the ability to cause frequent global outbreaks. Although the advent of the vaccines abated the global burden, they were not effective against all the variants of SCoV-2. This trend warrants shifting the focus on the development of small molecules targeting the crucial proteins of the viral replication machinery as effective therapeutic solutions. The PLpro is a crucial enzyme having multiple roles during the viral life cycle and is a well-established drug target. In this study, we identified 12 potential inhibitors of PLpro through virtual screening of the FDA-approved drug library. Docking and molecular dynamics simulation studies suggested that these molecules bind to the PLpro through multiple interactions. Further, IC50 values obtained from enzyme-inhibition assays affirm the stronger affinities of the identified molecules for the PLpro. Also, we demonstrated high structural conservation in the catalytic site of PLpro between SCoV-2 and Human Coronavirus 229E (HCoV-229E) through molecular modelling studies. Based on these similarities in PLpro structures and the resemblance in various signalling pathways for the two viruses, we propose that HCoV-229E is a suitable surrogate for SCoV-2 in drug-discovery studies. Validating our hypothesis, Mefloquine, which was effective against HCoV-229E, was found to be effective against SCoV-2 as well in cell-based assays. Overall, the present study demonstrated Mefloquine as a potential inhibitor of SCoV-2 PLpro and its antiviral activity against SCoV-2. Corroborating our findings, based on the in vitro virus inhibition assays, a recent study reported a prophylactic role for Mefloquine against SCoV-2. Accordingly, Mefloquine may further be investigated for its potential as a drug candidate for the treatment of COVID.

Living-Donor Liver Transplantation for Late-Onset Lysosomal Acid Lipase Deficiency.

Late-onset liposomal acid lipase deficiency (LAL deficiency), previously known as Cholesteryl ester storage disease (CESD) is a rare genetic lysosomal storage disorder caused by deficiency of lysosomal acid lipase (LAL) due to mutations in the LIPA gene. LAL deficiency is a systemic disease that leads to the accumulation of fat and inflammation in the liver, premature atherosclerosis and gastrointestinal disease. Most of the patients require liver transplantation due to decompensated cirrhosis. Enzyme replacement therapy has been approved and is available in many countries. Here we describe a 16-year-old patient who was diagnosed to have late-onset LAL deficiency when he presented to us with ESLD. Subsequently, he underwent a living-donor liver transplant (LDLT) successfully. We discuss the ethical dilemmas in considering LDLT for LAL deficiency.