Unlocking the versatility of Nitric Oxide in plants and insights into its molecular interplays under biotic and abiotic stress.

In plants, nitric oxide (NO) has become a versatile signaling molecule essential for mediating a wide range of physiological processes under various biotic and abiotic stress conditions. The fundamental function of NO under various stress scenarios has led to a paradigm shift in which NO is now seen as both a free radical liberated from the toxic product of oxidative metabolism and an agent that aids in plant sustenance. Numerous studies on NO biology have shown that NO is an important signal for germination, leaf senescence, photosynthesis, plant growth, pollen growth, and other processes. It is implicated in defense responses against pathogensas well as adaptation of plants in response to environmental cues like salinity, drought, and temperature extremes which demonstrates its multifaceted role. NO can carry out its biological action in a variety of ways, including interaction with protein kinases, modifying gene expression, and releasing secondary messengers. In addition to these signaling events, NO may also be in charge of the chromatin modifications, nitration, and S-nitrosylation-induced posttranslational modifications (PTM) of target proteins. Deciphering the molecular mechanism behind its essential function is essential to unravel the regulatory networks controlling the responses of plants to various environmental stimuli. Taking into consideration the versatile role of NO, an effort has been made to interpret its mode of action based on the post-translational modifications and to cover shreds of evidence for increased growth parameters along with an altered gene expression.

Transcriptome analysis and differential expression in Arabidopsis thaliana in response to rohitukine (a chromone alkaloid) treatment.

Rohitukine is a chromone alkaloid and precursor of potent anticancer drugs flavopiridol, P-276-00, and 2,6-dichloro-styryl derivative (11d) (IIIM-290). The metabolite is reported to possess anticancer, anti-inflammatory, antiadipogenic, immunomodulatory, gastroprotective, anti-implantation, antidyslipidemic, anti-arthritic, and anti-fertility properties. However, the physiological role of rohitukine in plant system is yet to be explored. Here, we studied the effect of rohitukine isolated from Dysoxylum gotadhora on Arabidopsis thaliana. The A. thaliana plants grown on a medium fortified with different rohitukine concentrations showed a significant effect on the growth and development. The root growth of A. thaliana seedlings showed considerable inhibition when grown on medium containing 1.0 mM of rohitukine. Transcriptomic analysis indicated the expression of 895 and 932 genes in control and treated samples respectively at a cut-off of FPKM ≥ 1 and P-value < 0.05. Gene ontology (GO) analysis revealed the upregulation of genes related to photosynthesis, membrane transport, antioxidation, xenobiotic degradation, and some transcription factors (TFs) in response to rohitukine. Conversely, rohitukine downregulated several genes including RNA helicases and those involved in nitrogen compound metabolism. The RNA-seq result was also validated by real-time qRT-PCR analysis. In light of these results, we discuss (i) likely ecological importance of rohitukine in parent plant as well as (ii) comparison between responses to rohitukine treatment in plants and mammals.

Prokaryotic communities adapted to microhabitats on the Indian lotus (Nelumbo nucifera) growing in the high-altitude urban Dal Lake.

Indian lotus (Nelumbo nucifera) is one of the dominant aquatic plants cultivated in Dal Lake, situated at 1586 m above mean sea level (MSL) in the northeast of Srinagar, Kashmir. Despite their economic and ecological role, the microbial communities associated with the lotus plant are still unexplored. In this study, we investigated the prokaryotic communities on surfaces of different lotus microhabitats (roots, rhizome, leaves, flowers, and fruits), lake water, and sediments using 16S rRNA gene amplicon sequencing. Overall, prokaryotic diversity decreased significantly on the surface of lotus microhabitats in comparison to the lake water and sediments. Among the microhabitats of lotus, roots and leaves harbored more diverse communities in comparison to rhizomes, fruits, and flowers. A total of 98 genera were shared by lotus and the Dal Lake sediments and water. However, significant differences were found in their relative abundance; for example, Pseudomonas was the most dominant genus on the majority of lotus microhabitats. On the other hand, Flavobacterium was highly abundant in the lake water, while a higher abundance of Acinetobacter was recorded in sediments. Additionally, we also noted the presence of potential human pathogenic genera including Escherichia-Shigella, Enterobacter, Pantoea, Raoultella, Serratia, and Sphingomonas on the lotus microhabitats. Predicted functions of prokaryotic communities revealed a higher abundance of genes associated with nutrient uptake in the microhabitats of the lotus. This study offered first-hand information on the prokaryotic communities harbored by lotus plants and water and sediments of the Dal Lake and demonstrated the adaptation of diverse communities to microhabitats of lotus.

Phytoliths analysis in root, culm, leaf and synflorescence of Rostraria cristata (Poaceae).

Phytoliths (siliceous structures) present in the plants have been employed in the fields of taxonomy and archaeology for many decades. Rostraria cristata is an economically important grass species (Poaceae) which accumulates silica in its different organs in the form of phytoliths. In order to understand the pattern of phytolith production and biochemical architecture of silica in R. cristata, leaf epidermis (blade) using the clearing solution method and different organs using the dry ashing method, X-ray diffraction and Fourier-transform infrared spectroscopy techniques were analyzed. Both abaxial and adaxial leaf epidermis showed the presence of acute bulbosus, rectangular sinuate and stomata phytolith morphotypes. Leaf including sheath and blade had the highest silica content. Characteristic phytolith morphotypes were present in different organs. A total of 34 phytolith morphotypes were present among which nine (9) were articulated and 25 were isolated forms. The most abundant were elongate scrobiculate (48.20%) in root and rectangular sinuate (26.16%) in leaf part. Other common phytolith morphotypes present in different organs of R. cristata were articulated elongate irregular, articulated elongate scrobiculate, acute bulbosus, and polygonal rondel etc. Leaf and synflorescence had the highest similarity based on presence/absence of phytolith morphotypes (Jaccard's similarity index). XRD studies revealed the presence of cristobalite, quartz, tridymite, zeolite etc. forms of silica in different organs. FTIR spectra showed that inplane stretching vibration of Si-C was unique to root, anti-symmetric stretching vibration of C-H was unique to leaf and Al2O3.SiO2 was found in synflorescence only. Our results show the characteristic pattern of phytoliths production in R. cristata.

Bu4NI-Catalyzed, Radical-Induced Regioselective N-Alkylations and Arylations of Tetrazoles Using Organic Peroxides/Peresters.

Bu4NI-catalyzed regioselective N2-methylation, N2-alkylation, and N2-arylation of tetrazoles have been achieved using tert-butyl hydroperoxide (TBHP) as the methyl source, alkyl diacyl peroxides as the primary alkyl source, alkyl peresters as the secondary and tertiary alkyl sources, and aryl diacyl peroxides as the arylating source. These reactions proceed without pre-functionalization of tetrazole and in the absence of any metal catalysts. Here, peroxides serve the dual role of oxidants as well as alkylating or arylating agents. Based on DFT calculations, it was found that spin density, transition-state barriers (kinetic control), and thermodynamic stability of the products (thermodynamic control) play essential roles in the observed regioselectivity during N-alkylation. This radical-mediated process is amenable to a broad range of substrates and provides products in moderate to good yields.

Cu(I)-Catalyzed Oxygen and Nitrogen Nucleophiles Triggered Regioselective Synthesis of Furo/Pyrrolo-Annulated Quinolines.

Cu(I)-catalyzed intramolecular annulation of o-ethynylquinoline-3-carbaldehydes leads to the synthesis of alkoxy/imidazole-substituted 1,3-dihydrofuro[3,4-b]quinolines via C-O and C-N bond formation. The scope of the reaction was further extended to o-ethynylquinoline-3-carbonitriles for the synthesis of alkoxy-substituted 3H-pyrrolo[3,4-b]quinolines using alcohols as nucleophiles. These reactions are regioselectively favoring the 5-exo-dig cyclizations in all the annulation processes.

In vitro propagation and withaferin A production in Withania ashwagandha, a rare medicinal plant of India.

Withania ashwagandha, belonging to the family Solanaceae, is an important medicinal herb of India with restricted geographic distribution. It is a rich source of withaferin A (WA) and other bioactive withanolides. In the present study a rapid in vitro mass propagation protocol of W. ashwagandha was developed from nodal explants. Nodal explants were cultured on MS medium supplemented with various concentrations and combinations of plant growth regulators (PGRs). The highest number of regenerated shoots per ex-plant (33 ± 2.7) and highest WA (13.4 ± 1.15 mg/g of DW) production was obtained on MS medium supplemented with 5.0 µM 6-benzyladenine (BA) and 1.0 µM Kinetin (Kn). In vitro raised shoots were further rooted on half-strength MS medium containing 2.0 µM Indole-3-butyric acid (IBA) and analyzed for WA production. The rooted plantlets when transferred to poly bags in the greenhouse showed 90 % survival frequency. Levels of WA were higher in the in vitro and ex vitro derived shoot and root tissues as compared to field grown mother plants. In an attempt to further maximize WA production, shoot cultures were further grown in liquid MS medium supplemented with 5.0 µM 6-benzyladenine (BA) and 1.0 µM Kinetin (Kn). Root cultures were grown on half strength MS liquid medium fortified with 2.0 µM of IBA. WA production in the liquid cultures was significantly higher compared to the static composition of the same media. This protocol, first of its kind in this plant, can be successfully employed for conservation, proliferation and large-scale production of WA. The regenerated plants can also be used in traditional medicine as an alternative to naturally collected plants.

SB-Net: Synergizing CNN and LSTM networks for uncovering retrosynthetic pathways in organic synthesis.

Retrosynthesis is vital in synthesizing target products, guiding reaction pathway design crucial for drug and material discovery. Current models often neglect multi-scale feature extraction, limiting efficacy in leveraging molecular descriptors. Our proposed SB-Net model, a deep-learning architecture tailored for retrosynthesis prediction, addresses this gap. SB-Net combines CNN and Bi-LSTM architectures, excelling in capturing multi-scale molecular features. It integrates parallel branches for processing one-hot encoded descriptors and ECFP, merging through dense layers. Experimental results demonstrate SB-Net's superiority, achieving 73.6 % top-1 and 94.6 % top-10 accuracy on USPTO-50k data. Versatility is validated on MetaNetX, with rates of 52.8 % top-1, 74.3 % top-3, 79.8 % top-5, and 83.5 % top-10. SB-Net's success in bioretrosynthesis prediction tasks indicates its efficacy. This research advances computational chemistry, offering a robust deep-learning model for retrosynthesis prediction. With implications for drug discovery and synthesis planning, SB-Net promises innovative and efficient pathways.

Sarcopenia in cirrhosis: Unraveling the prevalence and relationships with liver disease severity and complications.

BACKGROUND AND OBJECTIVES: Sarcopenia in cirrhosis is associated with poor survival and adverse pre and post-transplant outcomes. The study aimed at determining the prevalence of sarcopenia and its association with the severity, complications and etiology of liver disease. METHODS: As many as 416 cirrhotic patients who met the inclusion criteria underwent muscle strength testing using a dynamometer. As many as 109 probable sarcopenia patients underwent computed tomography (CT) scan to measure skeletal muscle index (SMI) at the L3 vertebral level and gait-speed testing. The gender-specific cut-offs used to define sarcopenia were an SMI of 36.54 cm2/m2 in males and 30.21 cm2/m2 in females. A gait speed ≤ 0.8 m/s was taken as a cut-off to define severe sarcopenia in both genders. RESULTS: The mean age was 54.7 ± 9.51 years and male:female ratio was 2.2:1.The mean body mass index (BMI) was 24.2 ± 1.34 kg/m2. Alcohol and non-alcoholic steatohepatitis (NASH) were the two most common etiologies (45.9% and 31.2%). The proportion of patients belonging to Child-Pugh class A, B and C was 26.6%, 48.6% and 24.8%, respectively. Forty out of 109 (36.7%) patients had a model for end-stage liver disease (MELD) > 14. Ascites, upper gastrointestinal bleeding and hepatic encephalopathy (HE) were present in 59 (54.1%), 60 (55.0%) and 24 (22.0%) patients, respectively. The prevalence of probable sarcopenia, sarcopenia and severe sarcopenia was found to be 26.20%, 10.09% and 6.73%, respectively. Sarcopenia and severe sarcopenia were associated with Child-Pugh class (p < 0.001, p < 0.001), MELD (p = 0.007, 0.002), upper gastrointestinal bleed (p = 0.007, 0.004), ascites (p = 0.038, 0.025) and HE (0.001, < 0.001). CONCLUSION: The prevalence of sarcopenia and severe sarcopenia was found to be 10.09% and 6.73%, respectively. Sarcopenia and severe sarcopenia had a significant association with the severity and complications of cirrhosis. However, no association was observed with etiology of liver disease.

Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19.

COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context, the review meticulously delves into the potential of plant-based folk remedies and existing molecules. These substances have showcased substantial viral inhibition in diverse in vivo, in silico, and in vitro studies, particularly against critical viral protein targets, including SARS-CoV-2. The findings position these plant-based molecules as promising antiviral drug candidates for the swift advancement of treatments for COVID-19. It is noteworthy that the inherent attributes of these plant-based molecules, such as their natural origin, potency, safety, and cost-effectiveness, contribute to their appeal as lead candidates. The review advocates for further exploration through comprehensive in vivo studies conducted on animal models, emphasizing the potential of plant-based compounds to help in the ongoing quest to develop effective antivirals against COVID-19.

Improving Enhancer Identification with a Multi-Classifier Stacked Ensemble Model.

Enhancers are DNA regions that are responsible for controlling the expression of genes. Enhancers are usually found upstream or downstream of a gene, or even inside a gene's intron region, but are normally located at a distant location from the genes they control. By integrating experimental and computational approaches, it is possible to uncover enhancers within DNA sequences, which possess regulatory properties. Experimental techniques such as ChIP-seq and ATAC-seq can identify genomic regions that are associated with transcription factors or accessible to regulatory proteins. On the other hand, computational techniques can predict enhancers based on sequence features and epigenetic modifications. In our study, we have developed a multi-classifier stacked ensemble (MCSE-enhancer) model that can accurately identify enhancers. We utilized feature descriptors from various physiochemical properties as input for our six baseline classifiers and built a stacked classifier, which outperformed previous enhancer classification techniques in terms of accuracy, specificity, sensitivity, and Mathew's correlation coefficient. Our model achieved an accuracy of 81.5%, representing a 2-3% improvement over existing models.

Interactive effect of 24-epibrassinolide and plant growth promoting rhizobacteria inoculation restores photosynthetic attributes in Brassica juncea L. under chlorpyrifos toxicity.

Chlorpyrifos (CP) is a commonly used organophosphorous pesticide that is frequently utilised in the agricultural industry because of its great efficiency and inexpensive cost. The focus of the present study was to assess the impact of CP toxicity on Brassica juncea L. and to unravel the ameliorative potential of phytohormone, 24-epibrassinolide (EBL) mediated plant-microbe (Pseudomonas aeruginosa (B1), Burkholderia gladioli (B2)) interaction in B. juncea L. The maximum significant increment in the total chlorophyll, carotenoids, xanthophyll, anthocyanin and flavonoid content with EBL and B2 treatment in CP stressed B. juncea seedlings on spectrophotometric analysis were observed. Autofluorescence imaging of photosynthetic pigments i.e. chlorophyll, carotenoids, and total phenols with confocal microscopy showed maximum fluorescence with EBL and B2. Furthermore, when compared to CP stressed seedlings, scanning electron microscopy (SEM) study of the abaxial surface of leaves revealed a recovery in stomatal opening. The supplementation of EBL and PGPR (plant growth promoting rhizobacteria) improved the level of psb A (D1 subunit PSII) and psb B (CP 47 subunit of PSII) genes expression. The expression analysis of chalcone synthase (CHS), Phenylalanine ammonialyase (PAL), Phyotene synthase (PSY) with RT-PCR system showed up-regulation in the expression when supplemented with EBL and PGPR. As a result, the current study suggests that EBL and PGPR together, can reduce CP-induced toxicity in B. juncea seedlings and recovering the seedling biomass.

Increasing circulating levels of Tenascin C in response to the Wingate anaerobic test.

AIM: Tenascin C (TNC) is a large extracellular matrix glycoprotein. It is involved in development and upregulated both during tissue repair and in several pathological conditions, including cardiovascular disease. Extracellular matrix proteins play a role in promoting exercise responses, leading to adaptation, regeneration, and repair. The main goal of this study was to investigate whether a short anaerobic effort leads to increased levels of TNC in serum. METHODS: Thirty-nine healthy men performed a Wingate test followed by a muscle biopsy. Myoblasts were isolated from the muscle biopsies and differentiated to myotubes ex vivo. TNC RNA was quantified in the biopsies, myotubes and myoblasts using RNA sequencing. Blood samples were drawn before and 5 min after the Wingate test. Serum TNC levels were measured using enzyme-linked immunosorbent assay. RESULTS: After the Wingate test, serum TNC increased on average by 23% [15-33], median [interquartile range]; PWilcoxon < 0.0001. This increase is correlated with peak power output and power drop, but not with VO2max . TNC RNA expression is higher in myoblasts and myotubes compared to skeletal muscle tissue. CONCLUSION: TNC is secreted systemically as a response to the Wingate anaerobic test in healthy males. The response was positively correlated with peak power and power drop, but not with VO2max which implicates a relation to mechanical strain and/or blood flow. With higher expression in undifferentiated myoblast cells than muscle tissue, it is likely that TNC plays a role in muscle tissue remodelling in humans. Our findings open for research on how TNC contributes to exercise adaptation.

Environmental Factors Affecting Monoterpene Emissions from Terrestrial Vegetation.

Monoterpenes are volatile organic compounds that play important roles in atmospheric chemistry, plant physiology, communication, and defense. This review compiles the monoterpene emission flux data reported for different regions and plant species and highlights the role of abiotic environmental factors in controlling the emissions of biogenic monoterpenes and their emission fluxes for terrestrial plant species (including seasonal variations). Previous studies have demonstrated the role and importance of ambient air temperature and light in controlling monoterpene emissions, likely contributing to higher monoterpene emissions during the summer season in temperate regions. In addition to light and temperature dependence, other important environmental variables such as carbon dioxide (CO2), ozone (O3), soil moisture, and nutrient availability are also known to influence monoterpene emissions rates, but the information available is still limited. Throughout the paper, we identify knowledge gaps and provide recommendations for future studies.

Increased expression of HPV-E7 oncoprotein correlates with a reduced level of pRb proteins via high viral load in cervical cancer.

Human Papillomavirus (HPV) is the most common cause of sexually transmitted diseases and causes a wide range of pathologies including cervical carcinoma. Integration of the HR-HPV DNA into the host genome plays a crucial role in cervical carcinoma. An alteration of the pRb pathways by the E7 proteins is one of the mechanisms that's account for the transforming capacity of high-risk papillomavirus. For the proper understanding of the underline mechanism of the progression of the disease, the present study investigate the correlation of concentration of host pRb protein, viral E7 oncoprotein and viral load in early and advanced stages of cervical carcinoma. It was found that the viral load in early stages (stage I and II) was less (log10 transformed mean value 2.6 and 3.0) compared to advanced stages (stage III and IV) (Log10 transformed value 5.0 and 5.8) having high expression of HPV E7 onco-protein and reduced level of pRb protein, signifying the role of viral load and expression level of E7 oncoprotein in the progression of cervical cancer.

Traditional uses, phytochemistry, pharmacology, and toxicology of the genus Artemisia L. (Asteraceae): A high-value medicinal plant.

Biologically active secondary metabolites, essential oils, and volatile compounds derived from medicinal and aromatic plants play a crucial role in promoting human health. Within the large family Asteraceae, the genus Artemisia consists of approximately 500 species. Artemisia species have a rich history in traditional medicine worldwide, offering remedies for a wide range of ailments, such as malaria, jaundice, toothache, gastrointestinal problems, wounds, inflammatory diseases, diarrhoea, menstrual pains, skin disorders, headache, and intestinal parasites. The therapeutic potential of Artemisia species is derived from a multitude of phytoconstituents, including terpenoids, phenols, flavonoids, coumarins, sesquiterpene lactones, lignans, and alkaloids that serve as active pharmaceutical ingredients (API). The remarkable antimalarial, antimicrobial, anthelmintic, antidiabetic, anti-inflammatory, anticancer, antispasmodic, antioxidative and insecticidal properties possessed by the species are attributed to these APIs. Interestingly, several commercially utilized pharmaceutical drugs, including arglabin, artemisinin, artemether, artesunate, santonin, and tarralin have also been derived from different Artemisia species. However, despite the vast medicinal potential, only a limited number of Artemisia species have been exploited commercially. Further, the available literature on traditional and pharmacological uses of Artemisia lacks comprehensive reviews. Therefore, there is an urgent need to bridge the existing knowledge gaps and provide a scientific foundation for future Artemisia research endeavours. It is in this context, the present review aims to provide a comprehensive account of the traditional uses, phytochemistry, documented biological properties and toxicity of all the species of Artemisia and offers useful insights for practitioners and researchers into underutilized species and their potential applications. This review aims to stimulate further exploration, experimentation and collaboration to fully realize the therapeutic potential of Artemisia in augmenting human health and well-being.

MicroRNA-100 Reduced Fetal Bovine Muscle Satellite Cell Myogenesis and Augmented Intramuscular Lipid Deposition by Modulating IGF1R.

Previously, microRNA-100 (miR-100) and its putative mRNA target, insulin-like growth factor receptor-1 (IGF1R) were identified as differentially and inversely expressed in bovine longissimus dorsi (LD) muscles with divergent intramuscular fat (IMF) content by our group. While IGF1R signaling is implicated in myogenesis and muscle lipid metabolism, the underlying regulatory mechanisms are poorly understood. In the present study, we aimed to investigate the regulation of IGF1R by miR-100 during bovine muscle satellite cell (BMSC) myogenesis and lipid deposition. MiR-100 was confirmed to target the IGF1R 3'-untranslated region (3'-UTR) by luciferase reporter assay. Furthermore, expression of miR-100 and IGF1R was reciprocal during BMSC differentiation, suggesting a crosstalk between the two. Correspondingly, miR-100 mimic (agomiR) suppressed the levels of IGF1R, PI3K/AKT pathway signaling, myogenic gene MYOG, muscle structural components MYH7 and MYH8, whereas the inhibitor (antagomiR) had no clear stimulating effects. The IGF1R inhibitor (BMS-754807) curtailed receptor levels and triggered atrophy in muscle myotubes but did not influence miR-100 expression. AgomiR increased oleic acid-induced lipid deposition in BMSC myotubes supporting its involvement in intramuscular fat deposition, while antagomiR had no effect. Moreover, mitochondrial beta-oxidation and long-chain fatty acid synthesis-related genes were modulated by agomiR addition. Our results demonstrate modulatory roles of miR-100 in BMSC development, lipid deposition, and metabolism and suggest a role of miR-100 in marbling characteristics of meat animals and fat oxidation in muscle.

Emerging Biomarkers for Screening and Management of Celiac Disease.

Celiac disease (CeD) is a chronic, immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals expressing HLA-DQ2 and/or HLA-DQ8. In the current clinical practice, there are many serologic studies to aid in the diagnosis of CeD which include autoantibodies like IgA antitissue transglutaminase, antiendomysium, and antideamidated forms of gliadin peptide antibodies. Small intestinal biopsy has long been considered an essential step for the diagnosis of CeD. However, in the recent era, researchers have explored the possibility of CeD screening and diagnosis without endoscopy or biopsy. The newer emerging biomarkers of CeD appear promising in diagnostic evaluation and subsequent monitoring of disease. In this review of literature, we have explored the emerging biomarker-based diagnostic evaluation and monitoring of CeD.