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Background: Rabies is a viral zoonosis that occurs in more than 100 countries and territories Although a number of carnivores and bat species serve as natural reservoirs, rabies in dogs is the source of 99% human infections and poses a potential threat to more than 3.3 billion people. In humans, rabies is highly fatal once clinical symptoms have developed. According to the World Health Organization, human rabies can be prevented completely by proper post exposure prophylaxis. In India alone, 20,000 deaths (i.e., about 2/100,000 population at risk) and 2 million bites, mostly by dogs, are estimated to occur annually. India has 36% global and 65% Asian rabies burden in terms of cases. Local treatment of wounds is of maximal value when applied immediately after exposure (within minutes if possible). Animal experiments have shown that local wound treatment can reduce the chances of developing rabies by up to 80%. Objectives: To find out the status of post exposure prophylaxis and associated factors among animal bite cases in Raipur city Chhattisgarh. Methodology: Type of study: A community based cross sectional survey Conducted at: Raipur District. Duration of study: Over a period of 3 months (November 2023- January 2024). Study Subjects: General Population. Inclusion criteria: General population, Raipur. Exclusion Criteria: 1) Patients who do not give consent. 2)Unconscious Very ill patients or patients with Mental illness. Results: Total of 1124 participants 41 had animal bite, 63.41% were males and 36.59% were females. Among the biting animals 83% were dogs, while cats were 15% and 2% were monkeys. Out of 41 cases 90.24% had Category II bite while 9.75% had Category III bite. 33 out of 41 i.e. 80.48% victims took Anti Rabies vaccine, while rest 19.52% preferred treatment from traditional healer. Conclusion: Majority of animal bite were of dog bite and were classified under Category II. Improved awareness, forestalling animal rabies, and better access to affordable and potent human rabies vaccines are essential for the elimination of human rabies.

Plants are central to global food production, and the pursuit of sustainability aims to enhance or preserve food quality while safeguarding the environment. Due to their immobility, plants are unable to evade unfavourable climatic setups or interactions with other living creatures. Upon their interaction with insect herbivores, plants face biotic stress, which is a constant challenge for plants, causing molecular, physiological, and biochemical changes and reducing their productivity. To combat biotic stress caused by herbivores, plants have evolved intricate defence mechanisms through growth regulators such as auxins, cytokinins, gibberellins, salicylic acid (SA), jasmonic acid (JA), ethylene (ET), abscisic acid (ABA), strigolactones and brassinosteroids. The intricate network of specific proteins, metabolites and certain phytohormones orchestrates plant defensive reactions, leading to their skilful coordination in responding to insect attacks. Comprehending the defence mechanisms holds the key to mitigating significant crop and economic losses. This review entails a comprehensive analysis of the role of growth regulators in enhancing plant immunity against herbivory, highlighting the substantial efforts by the scientific community to manage and mitigate damages from biotic stress in plants, ultimately contributing to the advancement of sustainable agriculture., (© 2024 Scandinavian Plant Physiology Society.)

As one of the most prevalent malignancies, lung cancer displays considerable biological variability in both molecular and clinical characteristics. Lung cancer is broadly categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) with the latter being most prevalent. The primary histological subtypes of NSCLC are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In the present work, we primarily extracted mRNA count data from a publicly accessible database followed by differentially expressed genes (DEGs) and differentially expressed mitophagy-related genes (DEMRGs) identification in case of both LUAD and LUSC cohorts. Next, we identified important DEMRGs via clustering approach followed by enrichment, survival, and mutational analyses. Lastly, the finalized prognostic biomarker was validated using wet-lab experimentations. Primarily, we obtained 986 and 1714 DEGs across LUAD and LUSC cohorts. Only 7 DEMRGs from both cohorts had significant membership values as indicated by the clustering analysis. Most significant pathway, Gene Ontology (GO)-biological process (BP), GO-molecular function (MF), GO-cellular compartment (CC) terms were macroautophagy, GTP metabolic process, magnesium ion binding, mitochondrial outer membrane. Among all, only TDRKH reported significant overall survival (OS) and 14% amplification across LUAD patients. Lastly, we validated TDRKH via immunohistochemistry (IHC) and semi-quantitative polymerase chain reaction (PCR). In conclusion, our findings advocate for the exploration of TDRKH and their genetic alterations in precision oncology therapeutic approaches for LUAD, emphasizing the potential for target-driven therapy and early diagnostics ., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04127-y., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Influenza A virus, particularly the H5N1 strain, poses a significant threat to public health due to its ability to cause severe respiratory illness and its high mortality rate. Traditional antiviral drugs targeting influenza A virus have faced challenges such as drug resistance and limited efficacy. Therefore, new antiviral compounds are needed to be discovered and developed. This study concentrated on examining the stability and behavior of the H5N1 polymerase PB2 CAP-binding domain when interacting with natural compounds, aiming to identify potential candidates for antiviral drug discovery. Through the virtual screening process, four lead compounds, ZINC000096095464, ZINC000044404209, ZINC000001562130, and ZINC000059779788, were selected, and these compounds showed binding energies -9.6, -9.4, -9.3, and -9.2 kcal/mol, respectively. When complexed with PB2, the ligand showed acceptable binding stability due to significant bond formation. However, during the 200ns MD simulation analysis, three (ZINC000096095464, ZINC000044404209, and ZINC000059779788) showed significant stability, which was proven by the trajectory analysis. The Rg-RMSD-based FEL plot showed significant structural stability due to stable conformers. The free-binding energy calculation also validates the stability of these complexes. This study offers valuable insights into the stability and dynamics of the H5N1 polymerase PB2 CAP-binding domain in complexes with natural compounds. These findings highlight the potential of these natural compounds as antiviral agents against the H5N1 influenza virus. Furthermore, this research contributes to the broader field of influenza virus treatment by demonstrating the effectiveness of computational methods in predicting and evaluating the stability and dynamics of potential drug candidates., (Copyright © 2024 Elsevier Inc. All rights reserved.)

There are significant psychosocial burdens in patients with hyperpigmentation, which emphasizes the importance of treatment. Current gold standard for treatment is hydroquinone; however, alternatives have been developed given the concern for side effects of hydroquinone. Melanogenesis is responsible for the production of eumelanin and pheomelanin; there are many factors that will determine whether eumelanin or pheomelanin will be produced. Eumelanin is known for its photoprotective qualities, while pheomelanin is implicated in photocarcinogenesis and photoaging. Multiple treatment modalities for hyperpigmentation that shift eumelanin to pheomelanin synthesis exist. Cysteamine, glutathione, kojic acid, and methyl sulfonyl methane are four agents used to treat hyperpigmentation by shifting the production of eumelanin to pheomelanin. It is critical to discuss photoprotection with patients to help reduce the potential impact of increased pheomelanin production and to expand research in this area., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rare diseases and conditions have thus far received relatively less attention in the field of precision/personalized medicine than common chronic diseases. There is a dire need for orphan drug discovery and therapeutics in ways that are informed by the precision/personalized medicine scholarship. Moreover, people with rare conditions, when considered collectively across diseases worldwide, impact many communities. In this overarching context, Activin A Receptor Type 1 (ACVR1) is a transmembrane kinase from the transforming growth factor-β superfamily and plays a critical role in modulating the bone morphogenetic protein signaling. Missense variants of the ACVR1 gene result in modifications in structure and function and, by extension, abnormalities and have been predominantly linked with two rare conditions: fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma. We report here an extensive bioinformatic analyses assessing the pool of 50,951 variants and forecast seven highly destabilizing mutations (R206H, G356D, R258S, G328W, G328E, R375P, and R202I) that can significantly alter the structure and function of the native protein. Protein-protein interaction and ConSurf analyses revealed the crucial interactions and localization of highly deleterious mutations in highly conserved domains that may impact the binding and functioning of the protein. cBioPortal, CanSAR Black, and existing literature affirmed the association of these destabilizing mutations with posterior fossa ependymoma, uterine corpus carcinoma, and pediatric brain cancer. The current findings suggest these deleterious nonsynonymous single nucleotide polymorphisms as potential candidates for future functional annotations and validations associated with rare conditions, further aiding the development of precision medicine in rare diseases.

Brassinosteroids (BRs) play a vital role in plant growth and stress response, operating through a well-defined signaling pathway. Yet, the export of BRs through plasma membranes poses significant challenges. Ying et al. recently identified the essential role of the ATPase activity of ABCB19 (Arabidopsis thaliana ATP-binding cassette transporter) in BR transport., Competing Interests: Declaration of interests The authors have no competing/financial/ or any other interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

With the advent of transcriptomic techniques involving single-stranded RNA sequencing and chromatin isolation by RNA purification-based sequencing, transcriptomic studies of coding and non-coding RNAs have been executed efficiently. These studies acknowledged the role of non-coding RNAs in modulating gene expression. Long non-coding RNAs (lncRNAs) are a kind of non-coding RNAs having lengths of >200 nucleotides, playing numerous roles in plant developmental processes such as photomorphogenesis, epigenetic changes, reproductive tissue development, and in regulating biotic and abiotic stresses. Epigenetic changes further control gene expression by changing their state to "ON-OFF" and also regulate stress memory and its transgenerational inheritance. With well-established regulatory mechanisms, they act as guides, scaffolds, signals, and decoys to modulate gene expression. They act as a major operator of post-transcriptional modifications such as histone and epigenetic modifications, and DNA methylations. The review elaborates on the roles of lncRNAs in plant immunity and also discusses how epigenetic markers alter gene expression in response to pest/pathogen attack and influences chromatin-associated stress memory as well as transgenerational inheritance of epigenetic imprints in plants. The review further summarizes some research studies on how histone modifications and DNA methylations resist pathogenic and pest attacks by activating defense-related genes., Competing Interests: Declaration of competing interest The authors declare that they have no competing/financial/any other interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-β, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Herbivorous insects such as Spodoptera litura, pose a constant threat to agricultural crops. The incompetence of contemporary pest management tools and techniques stipulates unravelling of molecular dogma, that drives pest-plant interaction. From our previous observations, we inferred that despite being a voracious polyphagous herbivore, S. litura growth and adaptability is severely hampered on maize foliage diet. In this investigation we explored further and demonstrated the impact of maize diet on the insect gut peritrophic membrane (PM, a crucial membrane involved in compartmentalizing digestive events and absorption of nutrients), its structural analysis using scanning electron microscopy (SEM) revealed damaged and perforated PM. Further, this study delves into the intricate resistance mechanism adapted by Z. mays against S. litura by conducting a comparative proteome analysis. We have detected 345 differentially abundant proteins (DAPs) at p < 0.05 and fold change ≥1. The DAPs were categorized as plant defense, secondary metabolite synthesis, redox homeostasis, cytoskeleton/cell wall biosynthesis, primary metabolism, transport and molecular processes. We remarkably report differential expression of proteolysis- and defense-related proteins that have potential to target insect gut, digestion and absorption of nutrients. Our findings contribute to a deeper understanding of the molecular dynamics governing maize resistance against S. litura. Understanding of such intricate molecular dialogues at these interfaces could provide valuable information on the arms race between plants and herbivores, it may pave the way for innovative pest management strategies., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Triple-negative breast cancer (TNBC) poses a significant global health challenge due to its highly aggressive nature and invasive characteristics. Dysregulation of the Hippo pathway, a key regulator of various biological processes, is observed in TNBC, and its inhibition holds promise for impeding cancer growth. This in-silico analysis investigates the role of Transcriptional Enhanced Associate Domain 4 (TEAD4) in TNBC and its interaction with Yes Associated Protein (YAP) in cancer progression. Our results demonstrate that TEAD4 upregulation is linked to poor prognosis in TNBC, emphasizing its critical role in the disease. Moreover, we identify CID44521006, an analog of Flufenamic acid, as a potential therapeutic compound capable of disrupting the TEAD4-YAP interaction by binding to the YAP-binding domain of TEAD4. These findings underscore the significance of TEAD4 in TNBC and propose CID44521006 as a promising candidate for therapeutic intervention. The study contributes valuable insights to advance treatment options for TNBC, offering a potential avenue for the development of targeted therapies against this aggressive form of breast cancer., Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00239-8., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Terpenoids are a vast class of plant specialized metabolites (PSMs) manufactured by plants and are involved in their interactions with environment. In addition, they add health benefits to human nutrition and are widely used as pharmaceutically active compounds. However, native plants produce a limited amount of terpenes restricting metabolite yield of terpene-related metabolites. Exponential growth in the plant metabolome data and the requirement of alternative approaches for producing the desired amount of terpenoids, has redirected plant biotechnology research to plant metabolic engineering, which requires in-depth knowledge and precise expertise about dynamic plant metabolic pathways and cellular physiology. Metabolic engineering is an assuring tool for enhancing the concentration of terpenes by adopting specific strategies such as overexpression of the key genes associated with the biosynthesis of targeted metabolites, controlling the modulation of transcription factors, downregulation of competitive pathways (RNAi), co-expression of the biosynthetic pathway genes in heterologous system and other combinatorial approaches. Microorganisms, fast-growing host plants (such as Nicotiana benthamiana), and cell suspension/callus cultures have provided better means for producing valuable terpenoids. Manipulation in the biosynthetic pathways responsible for synthesis of terpenoids can provide opportunities to enhance the content of desired terpenoids and open up new avenues to enhance their production. This review deliberates the worth of metabolic engineering in medicinal plants to resolve issues associated with terpenoid production at a commercial scale. However, to bring the revolution through metabolic engineering, further implementation of genome editing, elucidation of metabolic pathways using omics approaches, system biology approaches, and synthetic biology tactics are essentially needed., Competing Interests: Declaration of competing interest The authors declare that they have no competing/financial/any other interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The advancement of metabolomics has assisted in the identification of various bewildering characteristics of the biological system. Metabolomics is a standard approach, facilitating crucial aspects of system biology with absolute quantification of metabolites using minimum samples, based on liquid/gas chromatography, mass spectrometry and nuclear magnetic resonance. The metabolome profiling has narrowed the wide gaps of missing information and has enhanced the understanding of a wide spectrum of plant-environment interactions by highlighting the complex pathways regulating biochemical reactions and cellular physiology under a particular set of conditions. This high throughput technique also plays a prominent role in combined analyses of plant metabolomics and other omics datasets. Plant metabolomics has opened a wide paradigm of opportunities for developing stress-tolerant plants, ensuring better food quality and quantity. However, despite advantageous methods and databases, the technique has a few limitations, such as ineffective 3D capturing of metabolites, low comprehensiveness, and lack of cell-based sampling. In the future, an expansion of plant-pathogen and plant-pest response towards the metabolite architecture is necessary to understand the intricacies of plant defence against invaders, elucidation of metabolic pathway operational during defence and developing a direct correlation between metabolites and biotic stresses. Our aim is to provide an overview of metabolomics and its utilities for the identification of biomarkers or key metabolites associated with biotic stress, devising improved diagnostic methods to efficiently assess pest and pathogen attack and generating improved crop varieties with the help of combined application of analytical and molecular tools., (© 2024 Scandinavian Plant Physiology Society.)

Despite significant efforts, currently, there is no particular drug available to treat Zika virus (ZIKV) infection, highlighting the urgent need for effective therapeutic interventions. To identify putative inhibitors of the ZIKV RdRp protein's RNA binding function, the present study applied an extensive in-silico drug discovery methodology. The initial phase involved virtual screening using Lipinski's rule of five as a filter, ensuring the selection of molecules with favorable pharmacokinetic properties. This process yielded 238 compounds with promising docking scores, ranging from -6.0 to -7.48 kcal/mol, indicative of their potential binding affinity to the ZIKV RdRp. To refine the selection, these compounds underwent a re-docking process, comparing their binding energies with a reference molecule known for its inhibitory action against RdRp. Remarkably, five compounds, labeled CMNPD30598, CMNPD27464, CMNPD25971, CMNPD27444, and CMNPD16599, demonstrated superior re-docking energies compared to the reference, suggesting a stronger interaction with the RdRp allosteric site. Subsequent molecular dynamics (MD) simulations provided insights into the stability of these complexes over time, reinforcing their potential as RdRp inhibitors. Additionally, the calculation of free binding energies and principal component analysis (PCA) of the free energy landscape offered a deeper understanding of the binding dynamics and energetics. This study not only highlights the utility of marine fungi compounds in antiviral drug discovery but also showcases the power of computational tools in identifying novel therapeutics. The identified compounds represent promising candidates for further experimental validation and development as ZIKV RdRp inhibitors.Communicated by Ramaswamy H. Sarma.

Neuroblastoma is a tumour of the sympathetic nervous system mainly prevalent in children. Many strategies have been employed to target several drug-targetable proteins for the clinical management of neuroblastoma. However, the heterogeneous nature of neuroblastoma presents serious challenges in drug development for its treatment. Albeit numerous medications have been developed to target various signalling pathways in neuroblastoma, the redundant nature of the tumour pathways makes its suppression unsuccessful. Recently, the quest for neuroblastoma therapy resulted in the identification of human ALYREF, a nuclear protein that plays an essential role in tumour growth and progression. Therefore, this study used the structure-based drug discovery method to identify the putative inhibitors targeting ALYREF for the Neuroblastoma treatment. Herein, a library of 119 blood-brain barrier crossing small molecules from the ChEMBL database was downloaded and docked against the predicted binding pocket of the human ALYREF protein. Based on docking scores, the top four compounds were considered for intermolecular interactions and molecular dynamics simulation analysis, which revealed CHEMBL3752986 and CHEMBL3753744 with substantial affinity and stability with the ALYREF. These results were further supported by binding free energies and essential dynamics analysis of the respective complexes. Hence, this study advocates the sorted compounds targeting ALYREF for further in vitro and in vivo assessment to develop a drug against neuroblastoma.Communicated by Ramaswamy H. Sarma.

Plant yields are compromised due to abiotic and biotic stresses. A crucial biotic stress instigated by insect attack, is a major concern that limits crop production. To overcome the deleterious effect of herbivory, pesticides are used but long-term usage of pesticides can be harmful to the environment and human health. Understanding the plants' inherent defense mechanism by interpreting the interaction pattern of defense-related proteins and signalling components and manipulating them to strengthen defense status, is one of the alternative approaches of green biotechnology. During insect attack, host plants initiate innumerable signalling pathways to activate defense response; Mitogen Activated Protein Kinase (MAPK) Pathway is a crucial component of signalling pathway that regulate the expression of downstream defense-related genes. MAPK pathway has three components: MAPKKK, MAPKK and MAPK. Earlier studies have shown participation of SIPK and WIPK (MAPKs) as well as MEK2 (MAPKK) during insect infestation and its association with plant defense. However, information on the third component and elucidation of the complete MAPK pathway are still elusive. Therefore, this study aims to identify the unknown component and decipher MAPK pathway in Nicotiana attenuata involved in plant defense against herbivory by identifying herbivory-inducible MAPKKKs and and their interaction with known partners of the MAPK pathway by docking and MD simulation. The possible pathway was predicted to be MAPKKK Na 12134/ Na 04522-MEK2-SIPK/WIPK. Further, validation of the above interaction by in vitro and in vivo methods is highly recommended.Communicated by Ramaswamy H. Sarma.

Breast cancer (BC) accounts for 30% of all diagnosed cases of cancer in women and remains a leading cause of cancer-related deaths among women worldwide. The current study looks for a protein from the anti-apoptotic/pro-survival BCL-2 family whose overexpression reduces survivability in BC patients and a potential inhibitor for the protein. We found BCL-2A1/BFL1 protein with high expression linked to low survivability in BC. The protein shows prognosis in 8 out of 29 categories, whereas no other family member manifests this property. Out of 7379 compounds, three small molecules (CHEMBL9509, CHEMBL2104550 and CHEMBL3545011) form an H-bond with BCL-2A1/BFL1 protein's unique residue Cys55. Of the three small molecules, we found CHEMBL9509 (Silibinin) to be a potent inhibitor. The compound forms a stable H-bond with the residue Cys55 with the lowest binding energy compared to the other two compounds. It remains stable in the BH3 binding region for more than 100 ns, whereas the other two detach from the region. Additionally, the compound is found to be better than Venetoclax and Nematoclax. We firmly believe in the compound CHEMBL9509 potency to halt BC's progression by inhibiting the BCL-2A1/BFL1 protein, increasing patients' survivability.Communicated by Ramaswamy H. Sarma.

Plants being sessile organisms and lacking both circulating phagocytic cells and somatic adaptive immune response, have thrived on various defense mechanisms to fend off insect pests and invasion of pathogens. CYP450s are the versatile enzymes, which thwart plants against insect pests by ubiquitous biosynthesis of phytohormones, antioxidants, and secondary metabolites, utilizing them as feeding deterrents and direct toxins. Therefore, a comprehensive analysis of biotic stress-responsive CYPs from Glycine max was performed to ascertain their function against S. litura -infestation. Phylogenetic analysis and evolutionary studies on conserved domains and motifs disclosed the evolutionary correspondence of these GmCYPs with already characterized members of the CYP450 superfamily and close relatedness to Medicago truncatula. These GmCYPs were mapped on 13 chromosomes; they possess 1-8 exons; they have evolved due to duplication and are localized in endoplasmic reticulumn. Further, identification of methyl-jasmonate, salicylic acid, defense responsive and flavonoid biosynthesis regulating cis -acting elements, their interaction with biotic stress regulating proteins and their differential expression in diverse types of tissues, and during herbivory, depicted their responsiveness to biotic stress. Three-dimensional homology modelling of GmCYPs , docking with heme cofactor required for their catalytic activity and enzyme-substrate interactions were performed to understand the functional mechanism of their action. Moreover, to gain insight into their involvement in plant defense, gene expression analysis was evaluated, which revealed differential expression of 11 GmCYPs upon S. litura -infestation, 12 GmCYPs on wounding while foliar spray of ethylene, methyl-jasmonate and salicylic acid differentially regulated 11 GmCYPs , 6 GmCYPs , and 10 GmCYPs respectively. Our study comprehensively analysed the underlying mechanism of GmCYPs function during S. litura -infestation, which can be further utilized for functional characterization to develop new strategies for enhancing soybean resistance to insect pests., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yadav, Panwar, Rustagi, Chakraborty, Roy, Singh and Singh.)

Peptides are short linear molecules consisting of amino acids that play an essential role in most biological processes. They can treat diseases by working as a vaccine or antimicrobial agent and serves as a cancer molecule to deliver the drug to the target site for the treatment of cancer. They have the potential to solve the drawbacks of current medications and can be industrially produced in large quantities at low cost. However, poor chemical and physical stability, short circulating plasma half-life, and solubility are some issues that need solutions before they can be used as therapeutics. PepAnalyzer tool is a user-friendly tool that predicts 15 different properties such as binding potential, half-life, transmembrane patterns, test tube stability, charge, isoelectric point, molecular weights, and molar extinction coefficients only using the sequence. The tool is designed using BioPython utility and has even results with standard tools, such as Expasy, EBI, Genecorner, and Geneinfinity. The tool assists students, researchers, and the pharmaceutical sector. The PepAnalyzer tool's online platform is accessible at the link: http://www.iksmbrlabdu.in/peptool ., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Breast cancer is the most common cancer in women, with roughly 10-15% of new cases classified as triple-negative breast cancer (TNBC). Traditional chemotherapies are often toxic to normal cells. Therefore, it is important to discover new anticancer compounds that target TNBC while causing minimal damage to normal cells. Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is an oncofetal protein overexpressed in numerous human malignancies, including TNBC. This study investigated potential small molecules targeting ROR1. Methodology: Using AutoDock Vina and Glide, we screened 70,000 chemicals for our investigation. We obtained 10 representative compounds via consensus voting, deleting structural alerts, and clustering. After manual assessment, compounds 2 and 4 were chosen for MD simulation and cell viability experiment. Compound 4 showed promising results in the viability assay, which led us to move further with the apoptosis assay and immunoblotting. Results: Compound 4 (CID1261330) had docking scores of -6.635 and -10.8. It fits into the pocket and shows interactions with GLU64, ASP174, and PHE93. Its RMSD fluctuates around 0.20 nm and forms two stable H-bonds indicating compound 4 stability. It inhibits cell proliferation in MDA-MB-231, HCC1937, and HCC1395 cell lines, with IC 50 values of approximately 2 μM to 10 μM, respectively. Compound 4 did not kill non-malignant epithelial breast cells MCF-10A (IC 50 > 27 μM). These results were confirmed by the significant number of apoptotic cells in MDA-MB-231 cells (47.6%) but not in MCF-10A cells (7.3%). Immunoblot analysis provided additional support in the same direction. Discussion: These findings collectively suggest that compound 4 has the potential to effectively eliminate TNBC cells while causing minimal harm to normal breast cells. The promising outcomes of this study lay the groundwork for further testing of compound 4 in other malignancies characterized by ROR1 upregulation, serving as a proof-of-concept for its broader applicability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gupta, Ta, Khan, Singh, Singh and Peethambaran.)

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are lung complications diagnosed by impaired gaseous exchanges leading to mortality. From the diverse etiologies, sepsis is a prominent contributor to ALI/ARDS. In the present study, we retrieved sepsis-induced ARDS mRNA expression profile and identified 883 differentially expressed genes (DEGs). Next, we established an ARDS-specific weighted gene co-expression network (WGCN) and picked the blue module as our hub module based on highly correlated network properties. Later we subjected all hub module DEGs to form an ARDS-specific 3-node feed-forward loop (FFL) whose highest-order subnetwork motif revealed one TF ( STAT6 ), one miRNA (miR-34a-5p), and one mRNA ( TLR6 ). Thereafter, we screened a natural product library and identified three lead molecules that showed promising binding affinity against TLR6. We then performed molecular dynamics simulations to evaluate the stability and binding free energy of the TLR6-lead molecule complexes. Our results suggest these lead molecules may be potential therapeutic candidates for treating sepsis-induced ALI/ARDS. In-silico studies on clinical datasets for sepsis-induced ARDS indicate a possible positive interaction between miR-34a and TLR6 and an antagonizing effect on STAT6 to promote inflammation. Also, the translational study on septic mice lungs by IHC staining reveals a hike in the expression of TLR6. We report here that miR-34a actively augments the effect of sepsis on lung epithelial cell apoptosis. This study suggests that miR-34a promotes TLR6 to heighten inflammation in sepsis-induced ALI/ARDS., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03700-1., Competing Interests: Conflict of interestThe authors declare that they have are no conflict of interest., (© King Abdulaziz City for Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Lipid Transfer Proteins (LTPs) play a crucial role in synthesizing lipid barrier polymers and are involved in defense signaling during pest and pathogen attacks. Although LTPs are conserved with multifaceted roles in plants, these are not yet identified and characterized in Cicer arietinum . In this study, a genome-wide analysis of LTPs was executed and their physiochemical properties, biochemical function, gene structure analysis, chromosomal localization, promoter analysis, gene duplication, and evolutionary analysis were performed using in silico tools. Furthermore, tissue-specific expression analysis and gene expression analysis during pest attack was also conducted for the LTPs. A total of 48 LTPs were identified and named as CaLTPs . They were predicted to be small unstable proteins with "Glycolipid transfer protein" and "Alpha-Amylase Inhibitors, Lipid Transfer and Seed Storage" domains, that are translocated to the extracellular region. CaLTPs were predicted to possess 3-4 introns and were located on all the eight chromosomes of chickpea with half of the CaLTPs being localized on chromosomes 4, 5, and 6, and found to be closely related to LTPs of Arabidopsis thaliana and Medicago trancatula . Gene duplication and synteny analysis revealed that most of the CaLTPs have evolved due to tandem or segmental gene duplication and were subjected to purifying selection during evolution. The promoters of CaLTPs had development-related, phytohormone-responsive, and abiotic and biotic stress-related cis-acting elements. A few CaLTP transcripts exhibited differential expression in diverse tissue types, while others showed no/very low expression. Out of 20 jasmonate-regulated CaLTPs , 14 exhibited differential expression patterns during Helicoverpa armigera -infestation, indicating their role in plant defense response. This study identified and characterized CaLTPs from an important legume, C. arietinum , and indicated their involvement in plant defense against H. armigera -infestation, which can be further utilized to explore lipid signaling during plant-pest interaction and pest management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Saxena, Negi, Keshan, Chitkara, Kumar, Chakraborty, Roy, Singh and Singh.)

Drought is the most prevalent environmental stress that affects plants' growth, development, and crop productivity. However, plants have evolved adaptive mechanisms to respond to the harmful effects of drought. They reprogram their: transcriptome, proteome, and metabolome that alter their cellular and physiological processes and establish cellular homeostasis. One of the crucial regulatory processes that govern this reprogramming is post-transcriptional regulation by microRNAs (miRNAs). miRNAs are small non-coding RNAs, involved in the downregulation of the target mRNA via translation inhibition/mRNA degradation/miRNA-mediated mRNA decay/ribosome drop off/DNA methylation. Many drought-inducible miRNAs have been identified and characterized in plants. Their main targets are regulatory genes that influence growth, development, osmotic stress tolerance, antioxidant defense, phytohormone-mediated signaling, and delayed senescence during drought stress. Overexpression of drought-responsive miRNAs (Osa-miR535, miR160, miR408, Osa-miR393, Osa-miR319, and Gma-miR394) in certain plants has led to tolerance against drought stress indicating their vital role in stress mitigation. Similarly, knock down (miR166/miR398c) or deletion (miR169 and miR827) of miRNAs has also resulted in tolerance to drought stress. Likewise, engineered Arabidopsis plants with miR165, miR166 using short tandem target mimic strategy, exhibited drought tolerance. Since miRNAs regulate the expression of an array of drought-responsive genes, they can act as prospective targets for genetic manipulations to enhance drought tolerance in crops and achieve sustainable agriculture. Further investigations toward functional characterization of diverse miRNAs, and understanding stress-responses regulated by these miRNAs and their utilization in biotechnological applications is highly recommended.

The Hippo signaling pathway is a master regulator of development, cell proliferation, and apoptosis in particular, and it plays an important role in tissue regeneration, controlling organ size, and cancer suppression. Dysregulation of the Hippo signaling pathway has been implicated in breast cancer, a highly prevalent cancer affecting 1 out of every 15 women worldwide. While the Hippo signaling pathway inhibitors are available, they are suboptimal, for example, due to chemoresistance, mutation, and signal leakage. Inadequate knowledge about the Hippo pathway connections and their regulators limits our ability to uncover novel molecular targets for drug development. We report here novel microRNA (miRNA)-gene and protein-protein interaction networks in the Hippo signaling pathway. We employed the GSE miRNA dataset for the present study. The GSE57897 dataset was normalized and searched for differentially expressed miRNAs, and their targets were searched using the miRWalk2.0 tool. From the upregulated miRNAs, we observed that the hsa-miR-205-5p forms the biggest cluster and targets four genes involved in the Hippo signaling pathway. Interestingly, we found a novel connection between two Hippo signaling pathway proteins, angiomotin (AMOT) and mothers against decapentaplegic homolog 4 (SMAD4). From the downregulated miRNAs, hsa-miR-16-5p , hsa-miR-7g-5p , hsa-miR-141-3p , hsa-miR-103a-3p , hsa-miR-21-5p , and hsa-miR-200c-3p , target genes were present in the pathway. We found that PTEN , EP300 , and BTRC were important cancer-inhibiting proteins, form hubs, and their genes interact with downregulating miRNAs. We suggest that targeting proteins from these newly unraveled networks in the Hippo signaling pathway and further research on the interaction of hub-forming cancer-inhibiting proteins can open up new avenues for next-generation breast cancer therapeutics.

Background: Mechanical wounding (MW) is mainly caused due to high wind, sand, heavy rains and insect infestation, leading to damage to crop plants and an increase in the incidences of pathogen infection. Plants respond to MW by altering expression of genes, proteins, and metabolites that help them to cope up with the stress., Methods and Results: In order to characterize maize transcriptome in response to mechanical wounding, a microarray analysis was executed. The study revealed 407 differentially expressed genes (DEGs) (134 upregulated and 273 downregulated). The upregulated genes were engaged in protein synthesis, transcription regulation, phytohormone signaling-mediated by salicylic acid, auxin, jasmonates, biotic and abiotic stress including bacterial, insect, salt and endoplasmic reticulum stress, cellular transport, on the other hand downregulated genes were involved in primary metabolism, developmental processes, protein modification, catalytic activity, DNA repair pathways, and cell cycle., Conclusion: The transcriptome data present here can be further utilized for understanding inducible transcriptional response during mechanical injury and their purpose in biotic and abiotic stress tolerance. Furthermore, future study concentrating on the functional characterization of the selected key genes (Bowman Bird trypsin inhibitor, NBS-LRR-like protein, Receptor-like protein kinase-like, probable LRR receptor-like ser/thr-protein kinase, Cytochrome P450 84A1, leucoanthocyanidin dioxygenase, jasmonate O-methyltransferase) and utilizing them for genetic engineering for crop improvement is strongly recommended., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

In the current scenario of global warming and climate change, plants face many biotic stresses, which restrain growth, development and productivity. Nanotechnology is gaining precedence over other means to deal with biotic and abiotic constraints for sustainable agriculture. One of nature's most beneficial metalloids, silicon (Si) shows ameliorative effect against environmental challenges. Silicon/Silica nanoparticles (Si/SiO 2 NPs) have gained special attention due to their significant chemical and optoelectronic capabilities. Its mesoporous nature, easy availability and least biological toxicity has made it very attractive to researchers. Si/SiO 2 NPs can be synthesised by chemical, physical and biological methods and supplied to plants by foliar, soil, or seed priming. Upon uptake and translocation, Si/SiO 2 NPs reach their destined cells and cause optimum growth, development and tolerance against environmental stresses as well as pest attack and pathogen infection. Using Si/SiO 2 NPs as a supplement can be an eco-friendly and cost-effective option for sustainable agriculture as they facilitate the delivery of nutrients, assist plants to mitigate biotic stress and enhances plant resistance. This review aims to present an overview of the methods of formulation of Si/SiO 2 NPs, their application, uptake, translocation and emphasize the role of Si/SiO 2 NPs in boosting growth and development of plants as well as their conventional advantage as fertilizers with special consideration on their mitigating effects towards biotic stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Activin A receptor type I (ACVR1), a transmembrane serine/threonine kinase, belongs to the transforming growth factor-β superfamily, which signals via phosphorylating the downstream effectors and SMAD transcription factors. Its central role in several biological processes and intracellular signaling is well known. Genetic variation in ACVR1 has been associated with a rare disease, fibrodysplasia ossificans progressive, and its somatic alteration is reported in rare cancer diffuse intrinsic pontine glioma. Furthermore, altered expression or variation of ACVR1 is associated with multiple pathologies such as polycystic ovary syndrome, congenital heart defects, diffuse idiopathic skeletal hyperostosis, posterior fossa ependymoma and other malignancies. Recent advancements have witnessed ACVR1 as a potential pharmacological target, and divergent promising approaches for its therapeutic targeting have been explored. This review highlights the structural and functional characteristics of receptor ACVR1, associated signaling pathways, genetic variants in several diseases and cancers, protein-protein interaction, gene expression, regulatory miRNA prediction and potential therapeutic targeting approaches. The comprehensive knowledge will offer new horizons and insights into future strategies harnessing its therapeutic potential., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

While the world is still recovering from the Covid-19 pandemic, monkeypox virus (MPXV) awaits to cause another global outbreak as a challenge to all of mankind. However, the Covid-19 pandemic has taught us a lesson to speed up the pace of viral genomic research for the implementation of preventive and treatment strategies. One of the important aspects of MPXV that needs immediate insight is its evolutionary lineage based on genomic studies. Utilizing high-quality isolates from the GISAID (Global Initiative on Sharing All Influenza Data) database, primarily sourced from Europe and North America, we employed a SNP-based whole-genome phylogeny method and identified four major clusters among 628 MPXV isolates. Our findings indicate a distinct evolutionary lineage for the first MPXV isolate, and a complex epidemiology and evolution of MPXV strains across various countries. Further analysis of the host-pathogen interaction network revealed key viral proteins, such as E3, SPI-2, K7 and CrmB, that play a significant role in regulating the network and inhibiting the host's cellular innate immune system. Our structural analysis of proteins E3 and CrmB revealed potential disruption of stability due to certain mutations. While this study identified a large number of mutations within the new outbreak clade, it also reflected that we need to move fast with the genomic analysis of newly detected strains from around the world to develop better prevention and treatment methods.

Biotic stresses threaten to destabilize global food security and cause major losses to crop yield worldwide. In response to pest and pathogen attacks, plants trigger many adaptive cellular, morphological, physiological, and metabolic changes. One of the crucial stress-induced adaptive responses is the synthesis and accumulation of plant secondary metabolites (PSMs). PSMs mitigate the adverse effects of stress by maintaining the normal physiological and metabolic functioning of the plants, thereby providing stress tolerance. This differential production of PSMs is tightly orchestrated by master regulatory elements, Transcription factors (TFs) express differentially or undergo transcriptional and translational modifications during stress conditions and influence the production of PSMs. Amongst others, microRNAs, a class of small, non-coding RNA molecules that regulate gene expression post-transcriptionally, also play a vital role in controlling the expression of many such TFs. The present review summarizes the role of stress-inducible TFs in synthesizing and accumulating secondary metabolites and also highlights how miRNAs fine-tune the differential expression of various stress-responsive transcription factors during biotic stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kajla, Roy, Singh and Singh.)

Lipid-transfer proteins (LTPs) are lipid-binding small proteins, ubiquitously distributed amongst plant kingdom. Apart from their involvement in plant defense, it has also been discovered that they induce allergic reactions in humans. A plethora of LTPs have been identified in vegetables, fruits, pollens, nuts, and latex, among which Pru p 3, a LTP allergen from peach fruit, is extensively studied and exhibits cross-reactivity with potential allergens from different species. In Cicer arietinum , a family of LTPs (CaLTPs) has been identified and their importance in plant defense during Helicoverpa armigera- infestation has been recognized. However, the determination of the allergenicity potential of CaLTPs has not been attempted. In this study, we aim to decipher the allergenicity potential of defense-related CaLTPs. The allergenicity potential prediction, and identification of B-cell epitope binding regions showed that the CaLTPs had conserved domains and B-cell epitopes in the same regions as Prup3 (a marker allergen for LTPs). Using molecular docking and simulations, we observed that the CaLTPs successfully interacted with the Immunoglobin E(IgE)with docking energies ranging from -315.5 to -268.4 and the structures were stabilized within 10 ns of simulation. Through this study, we intend to embellish our present knowledge and understanding of the sensitization and allergenicity potential of CaLTPs.Communicated by Ramaswamy H. Sarma.

Dhurrin, a cyanogenic glucoside, is a plant defensive chemical synthesized from aliphatic amino acids and consists of β-d-glucopyranose linked to α-hydroxy nitrile. It is catabolized by the consecutive action of hydroxynitrilase and β-glucosidase to release hydrogen cyanide on tissue disruption during herbivory. These phytoanticipins are widely distributed across various monocot and dicot plants such as Sorghum, Macadamia, Ostrya sp., and many other plant species with ornamental, pharmaceutical, medicinal, and food value. Although repellent properties of dhurrin against herbivores are often reported, less is known about its distribution, metabolism, mode of action against insects, and application for pest control. Herein, we highlight recent updates on dhurrin distribution, biosynthesis, and catabolism along with the cyanide detoxification pathway. Additionally, this article focuses on biological activities of dhurrin against various herbivores and opportunities to explore the utilization of dhurrin as a natural pest control agent and a substitute for chemically synthesized pesticides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Plasmepsin V (Plm V) is an essential aspartic protease required for survival of the malaria parasite, Plasmodium falciparum (Pf) . Plm V is required for cleaving the PEXEL motifs of many Pf proteins and its inhibition leads to a knockout effect, indicating its suitability as potential drug target. To decipher new inhibitors of Pf Plm V, molecular docking of four HIV-1 protease inhibitors active against Pf PlmV was performed on Glide module of Schrödinger suite that supported saquinavir as a lead drug, and therefore, selected as a control. Saquinavir contains an important hydroxyethylamine (HEA) pharmacophore, which was utilized as backbone coupled with piperazine scaffold to build new library of compounds. Newly designed HEA compounds were screened virtually against Plm V. Molecular docking led to a few hits ( 1 and 3 ) with higher docking score over the control drug. Notably, compound 1 showed the highest docking score (-11.90 kcal/mol) and XP Gscore (-11.948 kcal/mol). The Prime MMGBSA binding free energy for compound 1 (-60.88 kcal/mol) and 3 (-50.96 kcal/mol) was higher than saquinavir (-37.51 kcal/mol). The binding free energy for the last frame of molecular dynamic simulation supported compound 1 (-92.88 kcal/mol) as potent inhibitor of Pf Plm V over saquinavir (-72.77 kcal/mol), and thus, deserves experimental validations in culture and subsequently in animal models.Communicated by Ramaswamy H. Sarma.

Single amino-acid substitution in a protein affects its structure and function. These changes are the primary reasons for the advent of many complex diseases. Analyzing single point mutations in a protein is crucial to see their impact and to understand the disease mechanism. This has given many biophysical resources, including databases and web-based tools to explore the effects of mutations on the structure and function of human proteins. For a given mutation, each tool provides a score-based outcomes which indicate deleterious probability. In recent years, developments in existing programs and the introduction of new prediction algorithms have transformed the state-of-the-art protein mutation analysis. In this study, we have performed a systematic study of the most commonly used mutational analysis programs (10 sequence-based and 5 structure-based) to compare their prediction efficiency. We have carried out extensive mutational analyses using these tools for previously known pathogenic single point mutations of five different proteins. These analyses suggested that sequence-based tools, PolyPhen2, PROVEAN, and PMut, and structure-based web tool, mCSM have a better prediction accuracy. This study indicates that the employment of more than one program based on different approaches should significantly improve the prediction power of the available methods., Competing Interests: The authors have declared that no competing interests exist.

The calcium (Ca 2+ ) signaling is a crucial event during plant-herbivore interaction, which involves a transient change in cytosolic Ca 2+ concentration, which is sensed by Ca 2+ -sensors, and the received message is transduced to downstream target proteins leading to appropriate defense response. Calmodulin-like proteins ( CMLs ) are calcium-sensing plant-specific proteins. Although CMLs have been identified in a few plants, they remained uncharacterized in leguminous crop plants. Therefore, a wide-range analysis of CMLs of soybean was performed, which identified 41 true CMLs with greater than 50% similarity with Arabidopsis CMLs . The phylogenetic study revealed their evolutionary relatedness with known CMLs . Further, the identification of conserved motifs, gene structure analysis, and identification of cis -acting elements strongly supported their identity as members of this family and their involvement in stress responses. Only a few Glycine max CMLs (GmCMLs) exhibited differential expression in different tissue types, and rest of them had minimal expression. Additionally, differential expression patterns of GmCMLs were observed during Spodoptera litura -feeding, wounding, and signaling compound treatments, indicating their role in plant defense. The three-dimensional structure prediction, identification of interactive domains, and docking with Ca 2+ ions of S. litura -inducible GmCMLs, indicated their identity as calcium sensors. This study on the characterization of GmCMLs provided insights into their roles in calcium signaling and plant defense during herbivory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yadav, Pandey, Chakraborty, Hassan, Kundu, Roy, Singh and Singh.)

With the advent of human civilization and anthropogenic activities in the shade of urbanization and global climate change, plants are exposed to a complex set of abiotic stresses. These stresses affect plants' growth, development, and yield and cause enormous crop losses worldwide. In this alarming scenario of global climate conditions, plants respond to such stresses through a highly balanced and finely tuned interaction between signaling molecules. The abiotic stresses initiate the quick release of reactive oxygen species (ROS) as toxic by-products of altered aerobic metabolism during different stress conditions at the cellular level. ROS includes both free oxygen radicals {superoxide (O 2 •- ) and hydroxyl (OH - )} as well as non-radicals [hydrogen peroxide (H 2 O 2 ) and singlet oxygen ( 1 O 2 )]. ROS can be generated and scavenged in different cell organelles and cytoplasm depending on the type of stimulus. At high concentrations, ROS cause lipid peroxidation, DNA damage, protein oxidation, and necrosis, but at low to moderate concentrations, they play a crucial role as secondary messengers in intracellular signaling cascades. Because of their concentration-dependent dual role, a huge number of molecules tightly control the level of ROS in cells. The plants have evolved antioxidants and scavenging machinery equipped with different enzymes to maintain the equilibrium between the production and detoxification of ROS generated during stress. In this present article, we have focused on current insights on generation and scavenging of ROS during abiotic stresses. Moreover, the article will act as a knowledge base for new and pivotal studies on ROS generation and scavenging.

Coronavirus Disease 2019 (COVID-19) is spreading across the world, and vaccinations are running parallel. Coronavirus has mutated into a triple-mutated virus, rendering it deadlier than before. It spreads quickly from person to person by contact and nasal or pharyngeal droplets. The COVID-19 database 'Our World in Data' was analyzed from February 24, 2020, to September 26, 2021, and predictions on the COVID positives and their mortality rate were made. Factors such as Vaccine data for the First and Second Dose vaccinated individuals and COVID positives that influence the fluctuations in the COVID-19 death ratio were investigated and linear regression analysis was performed. Based on vaccination doses (partial or complete vaccinated), models are created to estimate the number of patients who die from COVID infection. The estimation of variance in the datasets was investigated using Karl Pearson's coefficient. For COVID-19 cases and vaccination doses, a quartic polynomial regression model was also created. This predictor model helps to predict the number of deaths due to COVID-19 and determine the susceptibility to COVID-19 infection based on the number of vaccine doses received. SVM was used to analyze the efficacy of models generated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rustagi, Bajaj, Tanvi, Singh, Aggarwal, AlAjmi, Hussain, Hassan, Singh and Singh.)

Insects nurture a panoply of microbial populations that are often obligatory and exist mutually with their hosts. Symbionts not only impact their host fitness but also shape the trajectory of their phenotype. This co-constructed niche successfully evolved long in the past to mark advanced ecological specialization. The resident microbes regulate insect nutrition by controlling their host plant specialization and immunity. It enhances the host fitness and performance by detoxifying toxins secreted by the predators and abstains them. The profound effect of a microbial population on insect physiology and behaviour is exploited to understand the host-microbial system in diverse taxa. Emergent research of insect-associated microbes has revealed their potential to modulate insect brain functions and, ultimately, control their behaviours, including social interactions. The revelation of the gut microbiota-brain axis has now unravelled insects as a cost-effective potential model to study neurodegenerative disorders and behavioural dysfunctions in humans. This article reviewed our knowledge about the insect-microbial system, an exquisite network of interactions operating between insects and microbes, its mechanistic insight that holds intricate multi-organismal systems in harmony, and its future perspectives. The demystification of molecular networks governing insect-microbial symbiosis will reveal the perplexing behaviours of insects that could be utilized in managing insect pests.

Zea mays defense response is well-crafted according to the physical and chemical weapons utilized by their invaders during the coevolutionary period. Maize plants employ diversified defense strategies and alter the spatiotemporal distribution of several classes of defensive compounds to affect insect herbivore performance. However, only little knowledge is available about the defense orchestration of maize in response to Spodoptera litura, a voracious Noctuidae pest. In order to decipher the defense status of Zea mays (African tall variety) against S. litura, a comparative feeding bioassay was executed, which revealed reduced performance of the herbivore on maize. In order to understand the molecular mechanism behind maize tolerance against S. litura, a microarray-based genome-wide expression analysis was performed. The comparative analysis displayed 792 differentially expressed genes (DEGs), wherein 357 genes were upregulated and 435 genes were downregulated at fold change ≥ 2 and p value ≤ 0.05. The upregulated genes were identified and categorized as defense-related, oxidative stress-related, transcription regulatory genes, protein synthesis genes, phytohormone-related, and primary and secondary metabolism-related. In contrast, downregulated genes were mainly associated with plant growth and development, indicating a balance of growth and defense response and utilization of a highly evolved C-diversion response were noticed. Maize plants showed better tolerance against herbivory and maintained its fitness using a combinatorial strategy. This peculiar response of Zea mays against S. litura offers an excellent possibility of managing polyphagous pests by spicing up the plant's defensive response with tolerance mechanism., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Coronavirus disease (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), which is a positive single-stranded RNA virus having a large genome ~30 kb. SARSCoV- 2 is zoonotic and highly contagious, causing severe pneumonia-like symptoms. The efficacy of the different potential drug and drug candidates against COVID-19 has been investigated, which are under various stages of clinical trials. The drugs effective against SARS, and Middle east respiratory syndrome (MERS), have been proposed to have a high potential for the treatment of COVID-19. Here, we selected plant-based materials implicated in the prevention and therapy of COVID-19. The plant produces secondary metabolites in response to viral infection. Different classes of secondary metabolites have different mechanisms to counter virus attacks. Many nanomaterials produced by carbohydrates and lipids have been exploited for their in-vitro and in-vivo delivery of antiviral therapeutics. The vaccine has shown impressive results in producing antibodies against SARS-CoV2 and has been evaluated for safety, tolerance, and preliminary immunogenicity. Similarly, DNA/RNA-based therapy has shown high clinical significance. Various forms of vitamins, minerals, herbs, and phytonutrients help to enhance immunity and be implicated in the control of COVID-19. However, such measures should not replace social distancing, quarantine and special care., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Apoptosis, a major hallmark of cancer cells, regulates cellular fate and homeostasis. BCL-2 (B-cell CLL/Lymphoma 2) protein family is popularly known to mediate the intrinsic mode of apoptosis, of which MCL-1 is a crucial member. Myeloid cell leukemia 1 (MCL-1) is an anti-apoptotic oncoprotein and one of the most investigated members of the BCL-2 family. It is commonly known to be genetically altered, aberrantly overexpressed, and primarily associated with drug resistance in various human cancers. Recent advancements in the development of selective MCL-1 inhibitors and evaluating their effectiveness in cancer treatment establish its popularity as a molecular target. The overall aim is the selective induction of apoptosis in cancer cells by using a single or combination of BCL-2 family inhibitors. Delineating the precise molecular mechanisms associated with MCL-1-mediated cancer progression will certainly improve the efficacy of clinical interventions aimed at MCL-1 and hence patient survival. This review is structured to highlight the structural characteristics of MCL-1, its specific interactions with NOXA, MCL-1-regulatory microRNAs, and at the same time focus on the emerging therapeutic strategies targeting our protein of interest (MCL-1), alone or in combination with other treatments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nanoparticles (NPs) possess specific physical and chemical features and they are capable enough to cross cellular barriers and show their effect on living organisms. Their capability to cross cellular barriers have been noticed for their application not only in medicine, electronics, chemical and physical sciences, but also in agriculture. In agriculture, nanotechnology can help to improve the growth and crop productivity by the use of various nanoscale products such as nanofertilizers, nanoherbicides, nanofungicides, nanopesticides etc. An optimized concentration of NPs can be administered by incubation of seeds, roots, pollen, isolated cells and protoplast, foliar spraying, irrigation with NPs, direct injection, hydroponic treatment and delivery by biolistics. Once NPs come in contact with plant cells, they are uptaken by plasmodesmatal or endocytosed pathways and translocated via apoplastic and / symplastic routes. Once beneficial NPs reach different parts of plants, they boost photosynthetic rate, biomass measure, chlorophyll content, sugar level, buildup of osmolytes and antioxidants. NPs also improve nitrogen metabolism, enhance chlorophyll as well as protein content and upregulate the expression of abiotic- and biotic stress-related genes. Herein, we review the state of art of different modes of application, uptake, transport and prospective beneficial role of NPs in stress management and crop improvement., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cytochrome P450s (CYPs) are a versatile group of enzymes and one of the largest families of proteins, controlling various physiological processes via biosynthetic and detoxification pathways. CYPs perform multiple roles through a critical irreversible enzymatic reaction in which an oxygen atom is inserted within hydrophobic molecules, converting them into the reactive and hydro soluble components. During evolution, plants have acquired significantly more number of CYPs and represent about 1% of the encoded genes . CYPs are highly conserved proteins involved in growth, development and tolerance against biotic and abiotic stresses. Furthermore, CYPs reinforce plants' molecular and chemical defense mechanisms by regulating the biosynthesis of secondary metabolites, enhancing reactive oxygen species (ROS) scavenging and controlling biosynthesis and homeostasis of phytohormones, including abscisic acid (ABA) and jasmonates. Thus, they are the critical targets of metabolic engineering for enhancing plant defense against environmental stresses. Additionally, CYPs are also used as biocatalysts in the fields of pharmacology and phytoremediation. Herein, we highlight the role of CYPs in plant stress tolerance and their applications for human welfare., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aldo-keto reductase 1C1 (AKR1C1) is a hydroxysteroid dehydrogenase, known to inactivate the biologically active progesterone into its corresponding 20 α-hydroxyprogesterone. Increased expression of the AKR1C1 gene in oncogenesis is linked with resistance to various anticancer agents and hence it is considered as an emerging drug target for the design and developing the novel anticancer drugs. We have performed QSAR pharmacophore modeling for AKR1C1 inhibitors followed by a virtual screening of ~ 59,000 compounds present at the Maybridge database. The screened compounds were refined using drug-like filters of Lipinski rule, ADMET plot, molecular docking and scoring and subsequently top 20 hits were selected. Selected compounds were subjected to the in vitro for AKR1C1 inhibition assay and best seven compounds bearing excellent binding affinity to the AKR1C1 were finally selected. The identified compounds may be exploited in hit-to-lead development and may also prove as an interventional strategy in preventing a pre-term birth due to declining levels of progesterone.

Plant diseases pose a substantial threat to food availability, accessibility, and security as they account for economic losses of nearly $300 billion on a global scale. Although various strategies exist to reduce the impact of diseases, they can introduce harmful chemicals to the food chain and have an impact on the environment. Therefore, it is necessary to understand and exploit the plants' immune systems to control the spread of pathogens and enable sustainable agriculture. Recently, growing pieces of evidence suggest a functional myriad of lipids to be involved in providing structural integrity, intracellular and extracellular signal transduction mediators to substantial cross-kingdom cell signaling at the host-pathogen interface. Furthermore, some pathogens recognize or exchange plant lipid-derived signals to identify an appropriate host or development, whereas others activate defense-related gene expression. Typically, the membrane serves as a reservoir of lipids. The set of lipids involved in plant-pathogen interaction includes fatty acids, oxylipins, phospholipids, glycolipids, glycerolipids, sphingolipids, and sterols. Overall, lipid signals influence plant-pathogen interactions at various levels ranging from the communication of virulence factors to the activation and implementation of host plant immune defenses. The current review aims to summarize the progress made in recent years regarding the involvement of lipids in plant-pathogen interaction and their crucial role in signal transduction.

Plants protect themselves against pest attack utilizing both direct and indirect modes of defense. The direct mode of defense includes morphological, biochemical, and molecular barriers that affect feeding, growth, and survival of herbivores whereas the indirect mode of defense includes release of a blend of volatiles that attract natural enemies of the pests. Both of these strategies adopted by plants are reinforced if the plants are supplied with one of the most abundant metalloids, silicon (Si). Plants absorb Si as silicic acid (Si(OH)4) and accumulate it as phytoliths, which strengthens their physical defense. This deposition of Si in plant tissue is up-regulated upon pest attack. Further, Si deposited in the apoplast, suppresses pest effector molecules. Additionally, Si up-regulates the expression of defense-related genes and proteins and their activity and enhances the accumulation of secondary metabolites, boosting induced molecular and biochemical defenses. Moreover, Si plays a crucial role in phytohormone-mediated direct and indirect defense mechanisms. It is also involved in the reduction of harmful effects of oxidative stress resulting from herbivory by accelerating the scavenging process. Despite increasing evidence of its multiple roles in defense against pests, the practical implications of Si for crop protection have received less attention. Here, we highlight recent developments in Si-mediated improved plant resistance against pests and its significance for future use in crop improvement., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The most important aspect of controlling COVID-19 is its timely diagnosis. Molecular diagnostic tests target the detection of any of the following markers such as the specific region of the viral genome, certain enzyme, RNA-dependent RNA polymerase, the structural proteins such as surface spike glycoprotein, nucleocapsid protein, envelope protein, or membrane protein of SARS-CoV-2. This review highlights the underlying mechanisms, advancements, and clinical limitations for each of the diagnostic techniques authorized by the Food and Drug Administration (USA). Significance of diagnosis triaging, information on specimen collection, safety considerations while handling, transport, and storage of samples have been highlighted to make medical and research community more informed so that better clinical strategies are developed. We have discussed here the clinical manifestations and hospital outcomes along with the underlying mechanisms for several drugs administered to COVID-19 prophylaxis. In addition to favourable clinical outcomes, the challenges, and the future directions of management of COVOD-19 are highlighted. Having a comprehensive knowledge of the diagnostic approaches of SARS-CoV-2, and its pathogenesis will be of great value in designing a long-term strategy to tackle COVID-19., Competing Interests: Declaration of Competing Interest The authors declared to have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective., Competing Interests: Declaration of competing interest All authors of the manuscript declare to have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pathogenesis related (PR) proteins are defensins expressed upon biotic and abiotic stress by plants. They are also synthesized in specific plant parts such as root, stem, leaves, pollen grains and fruits. According to the current classification, there are 19 different classes of PR-Proteins, 8 out of 19 are proven to exhibit allergic reactions in human. Here, we carried out the allergenicity potential test for the remaining 11 classes of PR-Proteins using in-silico approaches. Our analysis suggests that the other 11 families also have the allergenic potential. We modelled the proteins for which our predictions suggested them to be allergens and for which the crystal structures were not available. We then predicted the B-cell epitope binding regions for all the proteins and used molecular docking approach to study the allergen-antibody interaction. Our findings suggest that all the selected proteins (belonging to 11 families of PR) analysed, can potentially be classified as allergens. We also provide evidence that the number of IgE binding-residues in the allergens is correlated with their respective binding energies with the IgE molecule. This study will be highly relevant to understand the allergenic potential of PR-Proteins to make an informed decision about the consumption of food with high degree of PR-expression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chemosensory perception in insects involves a broad set of chemosensory proteins (CSPs) that identify the bouquet of chemical compounds present in the external environment and regulate specific behaviors. The current study is focused on the Spodoptera litura (Fabricius) chemosensory-related protein, SlitCSP3, a midgut-expressed CSP, which demonstrates differential gene expression upon different diet intake. There is an intriguing possibility that SlitCSP3 can perceive food-derived chemical signals and modulate insect feeding behavior. We predicted the three-dimensional structure of SlitCSP3 and subsequently performed an accelerated molecular dynamics (aMD) simulation of the best-modeled structure. SlitCSP3 structure has six α-helices arranged as a prism and a hydrophobic binding pocket predominated by leucine and isoleucine. We analyzed the interaction of selected host plant metabolites with the modeled structure of SlitCSP3. Out of two predicted binding pockets in SlitCSP3, the plant-derived defensive metabolites 2-b-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1, 4-benzoxazin-3-one (DIMBOA), 6-Methoxy-2-benzoxazolinone (MBOA), and nicotine were found to interact preferably to the hydrophobic site 1, compared to site 2. The current study provides the potential role of CSPs in recognizing food-derived chemical signals, host-plant specialization, and adaptation to the varied ecosystem. Our work opens new perspectives in designing novel pest-management strategies. It can be further used in the development of CSP-based advanced biosensors.