Discovering the regulators of heat stress tolerance in Ziziphus nummularia (Burm.f) wight and walk.-arn.

Ziziphus nummularia an elite heat-stress tolerant shrub, grows in arid regions of desert. However, its molecular mechanism responsible for heat stress tolerance is unexplored. Therefore, we analysed whole transcriptome of Jaisalmer (heat tolerant) and Godhra (heat sensitive) genotypes of Z. nummularia to understand its molecular mechanism responsible for heat stress tolerance. De novo assembly of 16,22,25,052 clean reads yielded 276,029 transcripts. A total of 208,506 unigenes were identified which contains 4290 and 1043 differentially expressed genes (DEG) in TGO (treated Godhra at 42 °C) vs. CGO (control Godhra) and TJR (treated Jaisalmer at 42 °C) vs. CJR (control Jaisalmer), respectively. A total of 987 (67 highly enriched) and 754 (34 highly enriched) pathways were obsorved in CGO vs. TGO and CJR vs. TJR, respectively. Antioxidant pathways and TFs like Homeobox, HBP, ARR, PHD, GRAS, CPP, and E2FA were uniquely observed in Godhra genotype and SET domains were uniquely observed in Jaisalmer genotype. Further transposable elements were highly up-regulated in Godhra genotype but no activation in Jaisalmer genotype. A total of 43,093 and 39,278 simple sequence repeats were identified in the Godhra and Jaisalmer genotypes, respectively. A total of 10 DEGs linked to heat stress were validated in both genotypes for their expression under different heat stresses using quantitative real-time PCR. Comparing expression patterns of the selected DEGs identified ClpB1 as a potential candidate gene for heat tolerance in Z. nummularia. Here we present first characterized transcriptome of Z. nummularia in response to heat stress for the identification and characterization of heat stress-responsive genes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01431-y.

Copper ion incorporation in α-synuclein amyloids.

Copper ion dys-homeostasis is linked to neurodegenerative diseases involving amyloid formation. Even if many amyloidogenic proteins can bind copper ions as monomers, little is known about copper interactions with the resulting amyloid fibers. Here, we investigate copper interactions with α-synuclein, the amyloid-forming protein in Parkinson's disease. Copper (Cu(II)) binds tightly to monomeric α-synuclein in vitro involving the N-terminal amine and the side chain of His50. Using purified protein and biophysical methods in vitro, we reveal that copper ions are readily incorporated into the formed amyloid fibers when present at the start of aggregation reactions, and the metal ions also bind if added to pre-formed amyloids. Efficient incorporation is observed for α-synuclein variants with perturbation of either one of the high-affinity monomer copper-binding residues (i.e., N-terminus or His50) whereas a variant with both N-terminal acetylation and His50 substituted with Ala does not incorporate any copper into the amyloids. Both the morphology of the resulting α-synuclein amyloids (amyloid fiber pitch, secondary structure, proteinase sensitivity) and the copper chemical properties (redox activity, chemical potential) are altered when copper is incorporated into amyloids. We speculate that copper chelation by α-synuclein amyloids contributes to the observed copper dys-homeostasis (e.g., reduced bioavailable levels) in Parkinson's disease patients. At the same time, amyloid-copper interactions may be protective to neuronal cells as they will shield aberrantly free copper ions from promotion of toxic reactive oxygen species.

Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection.

The pathologic consequences of Coronavirus Disease-2019 (COVID-19) include elevated inflammation and dysregulated vascular functions associated with thrombosis. In general, disruption of vascular homeostasis and ensuing prothrombotic events are driven by activated platelets, monocytes, and macrophages, which form aggregates (thrombi) attached to the endothelium lining of vessel walls. However, molecular pathways underpinning the pathological interactions between myeloid cells and endothelium during COVID-19 remain undefined. Here, we tested the hypothesis that modulations in the expression of cellular receptors angiotensin-converting enzyme 2 (ACE2), CD147, and glucose-regulated protein 78 (GRP78), which are involved in homeostasis and endothelial performance, are the hallmark responses induced by SARS-CoV-2 infection. Cultured macrophages and lungs of hamster model systems were used to test this hypothesis. The results indicate that while macrophages and endothelial cells are less likely to support SARS-CoV-2 proliferation, these cells may readily respond to inflammatory stimuli generated by the infected lung epithelium. SARS-CoV-2 induced modulations of tested cellular receptors correlated with corresponding changes in the mRNA expression of coagulation cascade regulators and endothelial integrity components in infected hamster lungs. Among these markers, tissue factor (TF) had the best correlation for prothrombotic events during SARS-CoV-2 infection. Furthermore, the single-molecule fluorescence in situ hybridization (smFISH) method alone was sufficient to determine the peak and resolution phases of SARS-CoV-2 infection and enabled screening for cellular markers co-expressed with the virus. These findings suggest possible molecular pathways for exploration of novel drugs capable of blocking the prothrombotic shift events that exacerbate COVID-19 pathophysiology and control the disease.

Alpha-Synuclein and GM1 Ganglioside Co-Localize in Neuronal Cytosol Leading to Inverse Interaction-Relevance to Parkinson's Disease.

Research on GM1 ganglioside and its neuroprotective role in Parkinson's disease (PD), particularly in mitigating the aggregation of α-Synuclein (aSyn), is well established across various model organisms. This essential molecule, GM1, is intimately linked to preventing aSyn aggregation, and its deficiency is believed to play a key role in the initiation of PD. In our current study, we attempted to shed light on the cytosolic interactions between GM1 and aSyn based on previous reports demonstrating gangliosides and monomeric aSyn to be present in neuronal cytosol. Native-PAGE and Western blot analysis of neuronal cytosol from mouse brains demonstrated the presence of both GM1 and monomeric aSyn in the neuronal cytosol of normal mouse brain. To demonstrate that an adequate level of GM1 prevents the aggregation of aSyn, we used NG108-15 and SH-SY5Y cells with and without treatment of 1-phenyl-2-palmitoyl-3-morpholino-1-propanol (PPMP), which inhibits the synthesis/expression of GM1. Cells treated with PPMP to reduce GM1 expression showed a significant increase in the formation of aggregated aSyn compared to untreated cells. We thus demonstrated that sufficient GM1 prevents the aggregation of aSyn. For this to occur, aSyn and GM1 must show proximity within the neuron. The present study provides evidence for such co-localization in neuronal cytosol, which also facilitates the inverse interaction revealed in studies with the two cell types above. This adds to the explanation of how GM1 prevents the aggregation of aSyn and onset of Parkinson's disease.

Identification of quantitative trait loci (QTLs) regulating leaf SPAD value and trichome density in mungbean (Vigna radiata L.) using genotyping-by-sequencing (GBS) approach.

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.

Prevalence of Diabetes, Hypertension, and Obesity in Punjab: A Comparison between NFHS-4 and NFHS-5 Surveys.

Diseases that are caused by a person's everyday habits are known as lifestyle diseases. Habits that devoid people of their daily activities and direct them towards a sedentary lifestyle cause numerous health problems that can lead to non-communicable diseases. Noncommunicable diseases, or NCDs, kill more than 41 million individuals per year, accounting for 74% of all deaths worldwide. In India, 63% of all fatalities were attributed to NCDs in 2016, with 23% of those deaths being early. Compared to the current state of various lifestyle diseases, the prevalence of adult obesity, hypertension, and other lifestyle disorders in Punjab was determined by the National Family Healthcare Surveys (NFHS-4 and NFHS-5). NFHS-5 survey conducted in Punjab was used to examine the general distribution of these disorders. The National Family Health Survey 2019-21 (NFHS-5), the fifth survey in the NFHS series, provides information on the population, health, and nutritional status of all states and union territories (UT) in India. NFHS-5 also gives district-level estimates for several crucial variables, similar to the NFHS-4 survey 2015-16.

Immunopathology of Pulmonary Mycobacterium tuberculosis Infection in a Humanized Mouse Model.

Despite the availability of antibiotic therapy, tuberculosis (TB) is prevailing as a leading killer among human infectious diseases, which highlights the need for better intervention strategies to control TB. Several animal model systems, including mice, guinea pigs, rabbits, and non-human primates have been developed and explored to understand TB pathogenesis. Although each of these models contributes to our current understanding of host-Mycobacterium tuberculosis (Mtb) interactions, none of these models fully recapitulate the pathological spectrum of clinical TB seen in human patients. Recently, humanized mouse models are being developed to improvise the limitations associated with the standard mouse model of TB, including lack of necrotic caseation of granulomas, a pathological hallmark of TB in humans. However, the spatial immunopathology of pulmonary TB in humanized mice is not fully understood. In this study, using a novel humanized mouse model, we evaluated the spatial immunopathology of pulmonary Mtb infection with a low-dose inoculum. Humanized NOD/LtSscidIL2Rγ null mice containing human fetal liver, thymus, and hematopoietic CD34+ cells and treated with human cytokines were aerosol challenged to implant <50 pathogenic Mtb (low dose) in the lungs. At 2 and 4 weeks post infection, the tissue bacterial load, disease pathology, and spatial immunohistology were determined in the lungs, liver, spleen, and adipose tissue using bacteriological, histopathological, and immunohistochemical techniques. The results indicate that implantation of <50 bacteria can establish a progressive disease in the lungs that transmits to other tissues over time. The disease pathology in organs correspondingly increased with the bacterial load. A distinct spatial distribution of T cells, macrophages, and natural killer cells were noted in the lung granulomas. The kinetics of spatial immune cell distribution were consistent with the disease pathology in the lungs. Thus, the novel humanized model recapitulates several key features of human pulmonary TB granulomatous response and can be a useful preclinical tool to evaluate potential anti-TB drugs and vaccines.

Antiviral fibrils of self-assembled peptides with tunable compositions.

The lasting threat of viral pandemics necessitates the development of tailorable first-response antivirals with specific but adaptive architectures for treatment of novel viral infections. Here, such an antiviral platform has been developed based on a mixture of hetero-peptides self-assembled into functionalized ß-sheets capable of specific multivalent binding to viral protein complexes. One domain of each hetero-peptide is designed to specifically bind to certain viral proteins, while another domain self-assembles into fibrils with epitope binding characteristics determined by the types of peptides and their molar fractions. The self-assembled fibrils maintain enhanced binding to viral protein complexes and retain high resilience to viral mutations. This method is experimentally and computationally tested using short peptides that specifically bind to Spike proteins of SARS-CoV-2. This platform is efficacious, inexpensive, and stable with excellent tolerability.

Diabetic Retinopathy Leading to Blindness- A Review.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes that damages the retina, leading to blindness. People with type 1 diabetes are at greater risk of developing DR than people with type 2 diabetes. Diabetic retinopathy may be divided into two primary categories: proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR). There are multiple risk factors for the onset and progression of diabetic retinopathy, such as hypertension, obesity, smoking, duration of diabetes, and genetics. Numerous investigations have evaluated the levels of a wide range of inflammatory chemokines within DR patients' serum, vitreous, and aqueous fluids. In diabetic retinopathy, the vitreous fluid exhibited rises in angiogenic factors like platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF) or declines in antiangiogenic factors like pigment epithelium-derived factor (PEDF). For prevention of diabetic retinopathy, more physical activity as well as less sedentary behavior were linked to a reduced likelihood of DR. Supplementing with nutraceuticals containing vitamins (B1, B2, B6, B12, C, D, E, and l-methyl folate) and mineral (zinc) can help decrease or avoid an outbreak of DR. Only laser photocoagulation and Anti-vascular endothelial growth factor (Anti-VEGF) injections are advised as favorable therapies in severe retinopathy. When it comes to treating DR's VEGF levels, inflammation, oxidative stress, apoptosis, and angiogenesis, traditional Chinese medicine (TCM) has an excellent future.

Genome-wide association studies for earliness, MYMIV resistance, and other associated traits in mungbean (Vigna radiata L. Wilczek) using genotyping by sequencing approach.

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.

Sub-volt high-speed silicon MOSCAP microring modulator driven by high-mobility conductive oxide.

Silicon microring modulator plays a critical role in energy-efficient optical interconnect and optical computing owing to its ultra-compact footprint and capability for on-chip wavelength-division multiplexing. However, existing silicon microring modulators usually require more than 2 V of driving voltage (Vpp), which is limited by both material properties and device structures. Here, we present a metal-oxide-semiconductor capacitor microring modulator through heterogeneous integration between silicon photonics and titanium-doped indium oxide, which is a high-mobility transparent conductive oxide (TCO) with a strong plasma dispersion effect. The device is co-fabricated by Intel's photonics fab and our in-house TCO patterning processes, which exhibits a high modulation efficiency of 117 pm/V and consequently can be driven by a very low Vpp of 0.8 V. At a 11 GHz modulation bandwidth where the modulator is limited by the RC bandwidth, we obtained 25 Gb/s clear eye diagrams with energy efficiency of 53 fJ/bit.

Prevalence of Diabetes in India: A Review of IDF Diabetes Atlas 10th Edition.

Diabetes is a severe chronic disease that arises when insulin generation is insufficient, or the generated insulin cannot be used in the body, resulting a long-term metabolic disorder. Diabetes affects an estimated 537 million adults worldwide between the age of 20 to 79 (10.5% of all adults in this age range). By 2030, 643 million people will have diabetes globally, increasing to 783 million by 2045. According to the IDF 10th edition, the incidence of diabetes has been rising in South-East Asia (SEA) nations for at least 20 years, and current estimates have outperformed all previous forecasts. This review aims to provide updated estimates and future projections of diabetes prevalence at the national and global levels by using data from the 10th edition of the IDF Diabetes Atlas 2021. For this review, we studied more than 60 previously published related articles from various sources, such as PubMed and Google Scholar, and we extracted 35 studies out of 60. however, we used only 34 studies directly related to diabetes and its prevalence at the global, SEA, and Indian levels. This review article concludes that in 2021 more than 1 in 10 adults worldwide developed diabetes. The estimated prevalence of diabetes in adults (20 to 79 years) has more than tripled since the first edition in 2000, rising from an estimated 151 million (4.6% of the world's population at the time) to 537.5 million (10.5%) of the world's population today. The prevalence rate will be higher than 12.8% by 2045. In addition, this study indicates that the incidence of diabetes in the world, Southeast Asia, and India was 10.5%, 8.8%, and 9.6%, respectively, throughout 2021 and will rise to 12.5%, 11.5%, and 10.9%, respectively by 2045.

Centenary of Insulin Therapy: A Review.

Insulin is an endocrine hormone produced by the beta cells of islets of Langerhans in the pancreas. It regulates blood sugar levels and various anabolic activities such as glycogenesis and lipid synthesis. Despite the fact that insulin therapy has been around for 100 years, insulin formulations are continually being improved to lower the risk of hypoglycaemia and other adverse effects, including weight gain. The development of insulin pens has significantly reduced the consequences of hypoglycaemia instead of vials and syringes. Both injectable devices were well-received by the patients. In the population under study, the efficacy and safety profiles of the pen appeared to be comparable to those of the vial/syringe. However, more patients reported that they would like to keep using pen devices. This article aimed to summarize the background of insulin, its mechanism, types, needle size, injection technique, adverse drug reactions and various studies related to insulin. It has been recommended intensive treatment of type-1 and type-2 diabetes patients to achieve good metabolic control and avoid chronic complications caused by poor glycaemic control. Healthcare professionals should address concerns about safe and effective implementation of inpatient hypoglycaemic control and insulin usage and they should empower patients to self-manage their diabetes, so they may improve their quality of life as well as avoid potential complications. Much more progress is expected in the future, at a faster pace, based on the implementation of well-organized recovery efforts, advancing technologies, and scientific collaboration.

Assessment of quality-of-life in cancer patients at tertiary care hospital in North India

Introduction: Cancer is a disease that emerges as a result of abnormal cell proliferation and their propensity to spread from one bodily region to another. There are over a hundred different types of cancer that impact individuals all over the world. It is difficult to identify in the early stages, but there are certain warning signals that the cells will turn malignant. Quality of life (QOL) is described by the World Health Organisation as "individuals' perception of life, values, objectives, standards, and interests within the cultural framework of the social environment in which they live and in relation to their goals, expectations, standards, and concerns." QOL assessment in health system is a multidimensional construct that can be measured by evaluating objective levels of health status filtered by the subjective perceptions and expectations of the individual. Aim and Objective: To assess socio-demographic factors and quality of life among cancer patients in tertiary care hospital. Materials and Methods: A hospital-based prospective observational study was conducted at Guru Gobind Singh Medical College and Hospital Faridkot district, Punjab (India). The study was conducted for a period of six months after getting approval from Institutional Ethical Committee (IEC). Generic instrument, SF-36 was used to assess the QOL. The study was analyzed on SPSS version 26.0 software. Descriptive and analytical analysis was used to describe the results. Results: Linear regression was conducted to see the relationship of physical functioning score with age and weight of the patients. The descriptive statistics shows the mean and standard deviation of the variable. The mean of physical functioning score was found to be (M = 27.82, SD = 15.635). The physical functioning score and age, weight of the patients in linear regression shows that the age and weight explain 17.5% Conclusion: Treatment revealed that severe and moderate activities restricted nearly half of the assessed patients, with body pain interfering with employment and routine activities. According to the findings of the current study, QOL deteriorates as the disease progresses. Cancer unquestionably has a detrimental influence on patients' quality of life, which is connected to the illness process itself, the therapy administered, and the length of the disease. (AU)

Ten-year risk assessment for cardiovascular diseases using ASCVD risk estimator plus: outcomes from hypertension and diabetes patients.

BACKGROUND: Cardiovascular risk prediction models encompass numerous CVD risk factors. Available prediction models were developed from non-Asian cohorts hence we decided to evaluate the performance of the ASCVD risk estimator model and the associated 10-year CVD predisposing factors in Punjab. METHODS: We carried out a cross-sectional study among patients having hypertension and diabetes mellitus in a tertiary hospital in Punjab, India. 201 participants without ASCVD who were ≥ 40 years old and had been admitted to the medical ward were assessed. a pre-validated questionnaire was used to collect data on the socio-demographics and behavioral patterns. Lipid profile and blood pressure measurements were collected as per standard protocols. The respondents' CVD risk was assessed using ASCVD Risk Estimator Plus. Data were analyzed using IBM SPSS version 26; bivariate analysis was done using Chi-square and binary logistic regression was used to identify the predictors of 10-year risk for CVD at a 5% level of significance. MEASUREMENTS: We examined the stratification of the predicted outcomes and evaluated the associations between individual risk factors and the predicted cardiovascular events. Our study categorized the results of these outcomes into 4 categories: low category (1-5%), borderline category (6-9%) intermediate category (10-20%), and high category (21-95%). RESULTS: Out of the 201 participants that enrolled in our study, the majority 76 (37.8%) were in the intermediate category, 56 (27.9%) were in the high category, 41 (20.4%) were in the borderline category, 28 (13.9%) were in the low category. The median ASCVD percentage was 14.20%. Respondents who were alcoholics, smokers, and drug abusers (OR = 5.8, 95% CI 0.397-83.584) were associated with the highest likelihood of developing CVDs. Furthermore, males had a significantly higher mean predicted CVD outcome % (M = 23.18%) compared to females (M = 14.91%). CONCLUSION: According to our prediction study, it was discovered that 145 (72.1%) participants were not likely to have had an ASCVD in the next 10 years. However, middle-aged males should be more cautious with their lifestyle habits, particularly in dealing with risk factors that can expose them to CVDs.

Plant salinity stress, sensing, and its mitigation through WRKY.

Salinity or salt stress has deleterious effects on plant growth and development. It imposes osmotic, ionic, and secondary stresses, including oxidative stress on the plants and is responsible for the reduction of overall crop productivity and therefore challenges global food security. Plants respond to salinity, by triggering homoeostatic mechanisms that counter salt-triggered disturbances in the physiology and biochemistry of plants. This involves the activation of many signaling components such as SOS pathway, ABA pathway, and ROS and osmotic stress signaling. These biochemical responses are accompanied by transcriptional modulation of stress-responsive genes, which is mostly mediated by salt-induced transcription factor (TF) activity. Among the TFs, the multifaceted significance of WRKY proteins has been realized in many diverse avenues of plants' life including regulation of plant stress response. Therefore, in this review, we aimed to highlight the significance of salinity in a global perspective, the mechanism of salt sensing in plants, and the contribution of WRKYs in the modulation of plants' response to salinity stress. This review will be a substantial tool to investigate this problem in different perspectives, targeting WRKY and offering directions to better manage salinity stress in the field to ensure food security.

Transcriptional Regulation of Small Heat Shock Protein 17 (sHSP-17) by Triticum aestivum HSFA2h Transcription Factor Confers Tolerance in Arabidopsis under Heat Stress.

Heat shock transcription factors (HSFs) contribute significantly to thermotolerance acclimation. Here, we identified and cloned a putative HSF gene (HSFA2h) of 1218 nucleotide (acc. no. KP257297.1) from wheat cv. HD2985 using a de novo transcriptomic approach and predicted sHSP as its potential target. The expression of HSFA2h and its target gene (HSP17) was observed at the maximum level in leaf tissue under heat stress (HS), as compared to the control. The HSFA2h-pRI101 binary construct was mobilized in Arabidopsis, and further screening of T3 transgenic lines showed improved tolerance at an HS of 38 °C compared with wild type (WT). The expression of HSFA2h was observed to be 2.9- to 3.7-fold higher in different Arabidopsis transgenic lines under HS. HSFA2h and its target gene transcripts (HSP18.2 in the case of Arabidopsis) were observed to be abundant in transgenic Arabidopsis plants under HS. We observed a positive correlation between the expression of HSFA2h and HSP18.2 under HS. Evaluation of transgenic lines using different physio-biochemical traits linked with thermotolerance showed better performance of HS-treated transgenic Arabidopsis plants compared with WT. There is a need to further characterize the gene regulatory network (GRN) of HSFA2h and sHSP in order to modulate the HS tolerance of wheat and other agriculturally important crops.

A phosphodiesterase-4 inhibitor reduces lung inflammation and fibrosis in a hamster model of SARS-CoV-2 infection.

Introduction: The Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection involves pulmonary inflammation that can progress to acute respiratory distress syndrome, a primary cause of lung damage/fibrosis in patients with Coronavirus Disease-2019 (COVID-19). Currently, there is no efficacious therapy available to alleviate lung fibrosis in COVID-19 cases. In this proof-of-concept study, we evaluated the effect of CC-11050, a small molecule phosphodiesterase-4 inhibitor, in dampening lung inflammation and fibrosis in a hamster model of SARS-CoV-2 infection. Methods: Following intranasal inoculation with SARS-CoV-2/WA- 1/2000 strain, hamsters were treated with CC-11050 or placebo by gavage from day-1 until day-16 post-infection (dpi). Animals were monitored for body weight changes, virus titers, histopathology, fibrotic remodeling, cellular composition in the lungs between 2 and 16 dpi. Results: We observed significant reduction in lung viral titer with concomitant reduction in inflammation and fibrotic remodeling in CC-11050 treated hamsters compared to untreated animals. The reductions in immunopathologic manifestations were associated with significant downregulation of inflammatory and fibrotic remodeling gene expression, reduced infiltration of activated monocytes, granulocytes, and reticular fibroblasts in CC-11050 treated animals. Cellular studies indicate a link between TNF-α and fibrotic remodeling during CC-11050 therapy. Discussion: These findings suggest that CC-11050 may be a potential host-directed therapy to dampen inflammation and fibrosis in COVID-19 cases.