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Melanoma is a metastatic, drug-refractory cancer with the ability to evade immunosurveillance. Cancer immune evasion involves interaction between tumor intrinsic properties and the microenvironment. The transcription factor E2F1 is a key driver of tumor evolution and metastasis. To explore E2F1’s role in immune regulation in presence of aggressive melanoma cells, we established a coculture system and utilized transcriptome and cytokine arrays combined with bioinformatics and structural modeling. We identified an E2F1-dependent gene regulatory network with IL6 as a central hub. E2F1-induced IL-6 secretion unleashes an autocrine inflammatory feedback loop driving invasiveness and epithelial-to-mesenchymal transition. IL-6-activated STAT3 physically interacts with E2F1 and cooperatively enhances IL-6 expression by binding to an E2F1-STAT3-responsive promoter element. The E2F1-STAT3/IL-6 axis strongly modulates the immune niche and generates a crosstalk with CD4+ cells resulting in transcriptional changes of immunoregulatory genes in melanoma and immune cells that is indicative of an inflammatory and immunosuppressive environment. Clinical data from TCGA demonstrated that elevated E2F1, STAT3, and IL-6 correlate with infiltration of Th2, while simultaneously blocking Th1 in primary and metastatic melanomas. Strikingly, E2F1 depletion reduces the secretion of typical type-2 cytokines thereby launching a Th2-to-Th1 phenotype shift towards an antitumor immune response. The impact of activated E2F1-STAT3/IL-6 axis on melanoma-immune cell communication and its prognostic/therapeutic value was validated by mathematical modeling. This study addresses important molecular aspects of the tumor-associated microenvironment in modulating immune responses, and will contribute significantly to the improvement of future cancer therapies.

Cancer cells have a remarkable ability to evade recognition and destruction by the immune system. At the same time, cancer has been associated with chronic inflammation, while certain autoimmune diseases predispose to the development of neoplasia. Although cancer immunotherapy has revolutionized antitumor treatment, immune-related toxicities and adverse events detract from the clinical utility of even the most advanced drugs, especially in patients with both, metastatic cancer and pre-existing autoimmune diseases. Here, the combination of multi-omics, data-driven computational approaches with the application of network concepts enables in-depth analyses of the dynamic links between cancer, autoimmune diseases, and drugs. In this review, we focus on molecular and epigenetic metastasis-related processes within cancer cells and the immune microenvironment. With melanoma as a model, we uncover vulnerabilities for drug development to control cancer progression and immune responses. Thereby, drug repurposing allows taking advantage of existing safety profiles and established pharmacokinetic properties of approved agents. These procedures promise faster access and optimal management for cancer treatment. Together, these approaches provide new disease-based and data-driven opportunities for the prediction and application of targeted and clinically used drugs at the interface of immune-mediated diseases and cancer towards next-generation immunotherapies.

During the last two decades several nanoscale materials were engineered for industrial and medical applications. Among them carbon nanotubes (CNTs) are the most exploited nanomaterials with global production of around 1000 tons/year. Besides several commercial benefits of CNTs, the fiber-like structures and their bio-persistency in lung tissues raise serious concerns about the possible adverse human health effects resembling those of asbestos fibers. In this review, we present a comparative analysis between CNTs and asbestos fibers using the following four parameters: (1) fibrous needle-like shape, (2) bio-persistent nature, (3) high surface to volume ratio and (4) capacity to adsorb toxicants/pollutants on the surface. We also compare mechanisms underlying the toxicity caused by certain diameters and lengths of CNTs and asbestos fibers using downstream pathways associated with altered gene expression data from both asbestos and CNT exposure. Our results suggest that indeed certain types of CNTs are emulating asbestos fiber as far as associated toxicity is concerned.

Abstract Angiogenesis is a critical process in tumor progression. Inhibition of angiogenesis by blocking VEGF signaling can impair existing tumor vessels and halt tumor progression. However, the benefits are transient, and most patients who initially respond to these therapies develop resistance. Accordingly, there is a need for new anti-angiogenesis therapeutics to delay the processes of resistance or eliminate the resistive effects entirely. This manuscript presents the results of a screen of the National Institutes of Health Clinical Collections Libraries I & II (NIHCCLI&II) for novel angiogenesis inhibitors. The 727 compounds of the NIHCCLI&II library were screened with a high-throughput drug discovery platform (HTP) developed previously with angiogenesis-specific protocols utilizing zebrafish. The screen resulted in 14 hit compounds that were subsequently narrowed down to one, with PD 81,723 chosen as the lead compound. PD 81,723 was validated as an inhibitor of angiogenesis in vivo in zebrafish and in vitro in human umbilical vein endothelial cells (HUVECs). Zebrafish exposed to PD 81,723 exhibited several signs of a diminished endothelial network due to the inhibition of angiogenesis. Immunochemical analysis did not reveal any significant apoptotic or mitotic activity in the zebrafish. Assays with cultured HUVECs elucidated the ability of PD 81,723 to inhibit capillary tube formation, migration, and proliferation of endothelial cells. In addition, PD 81,723 did not induce apoptosis while significantly down regulating p21, AKT, VEGFR-2, p-VEGFR-2, eNOS, and p-eNOS, with no notable change in endogenous VEGF-A in cultured HUVECs.

The world is facing the pandemic situation due to a beta corona virus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The disease caused by this virus known as Corona Virus Disease 2019 (COVID-19) has affected the entire world. The current diagnosis methods are laboratory based and require specialized testing kits for performing the test. Therefore, to overcome the limitations of testing kits a diagnosis method from chest X-ray images is proposed in this paper. Chest X-ray images can be easily obtained by X-ray machines that are readily available at medical centres. The radiological examinations augmented with chest X-ray images is an effective way of disease diagnosis. The automated analysis of the chest X-ray images requires a highly efficient method for identifying COVID-19 from these images. Thus, a novel deep convolution neural network (CNN) optimized using Grasshopper Optimization Algorithm (GOA) is proposed. The deep learning model comprises depth wise separable convolutions that independently look at cross channel and spatial correlations. The optimization of deep learning models is a complex task due the multiple layers and their non-linearities. In image classification problems optimizers like Adam, SGD etc. get stuck in local minima. Thus, in this paper a metaheuristic optimization algorithm is used to optimize the network. Grasshoper Optimization Algorithm (GOA) is a metaheuristic algorithm that mimics the behaviour of grasshoppers for food search. This algorithm is a fast converging and is capable of exploration and exploitation of large search spaces. Maximum Probability Based Cross Entropy Loss (MPCE) loss function is used as it minimizes the back propogation error of cross entropy and improves the training. The experimental results show that the proposed method gives high classification accuracy. The interpretation of results is augmented with class activation maps. Grad-CAM visualization algorithm is used for class activation maps.

Abstract Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in atherosclerotic plaques and implicated in the development of cardiovascular diseases. Peripheral arterial disease (PAD) is an atherosclerotic disease that often results in major cardiovascular events. This study aimed to prospectively examine the potential of urine NGAL (uNGAL) in predicting worsening PAD status and major adverse limb events (MALE). Baseline urine NGAL (uNGAL) and urine creatinine (uCr) concentrations were measured in PAD (n = 121) and non-PAD (n = 77) patients. Levels of uNGAL were normalized for urine creatinine (uNGAL/uCr). Outcomes included worsening PAD status, which was defined as a drop in ankle brachial index (ABI) > 0.15, and major adverse limb events (MALE), which was defined as a need for surgical revascularization or amputations. PAD patients had 2.30-fold higher levels of uNGAL/uCr [median (IQR) 31.8 (17.0–62.5) μg/g] in comparison to non-PAD patients [median (IQR) 73.3 (37.5–154.7) μg/g] (P = 0.011). Multivariate cox analysis showed that uNGAL/uCr levels were independently associated with predicting worsening PAD status and MALE outcomes. Cumulative survival analysis, over follow up period, demonstrated a direct correlation between elevated uNGAL/uCr levels and PAD disease progression and MALE outcomes. These data demonstrate an association between elevated uNGAL/uCr levels and worsening PAD disease status and MALE outcomes, indicating its potential for risk-stratification of PAD patients.

Bio-inspired computing has progressed so far to deal with real-time multi-objective optimization problems. The Transmission expansion planning of the modern electricity grid requires finding the best and optimal routes for electricity transmission from the generation point to the endpoint while satisfying all the power and load constraints. Further, the transmission expansion cost allocation becomes a critical and pragmatic issue in the deregulated electricity industry. The prime objective is to minimize the total investment and expansion costs while considering N-1 contingency. The most optimal transmission expansion planning problem's solution is calculated using the objective function and the constraints. This optimal solution provides the total number and best locations for the candidates. The presented paper details the mathematical modeling of the shuffled frog leap algorithm with various modifications applied to the method to refine the results and finally proposes an enhanced novel approach to solve the transmission expansion planning problem. The proposed algorithm produces the expansion plans based on target-based evolution. The presented algorithm is rigorously tested on the standard Garver dataset and IEEE 24 bus system. The empirical results of the proposed algorithm led to better expansion plans while effectively considering typical electrical constraints along with modern and realistic constraints.

Abstract With new telecommunications engineering applications, the cognitive radio (CR) network‐based internet of things (IoT) resolves the bandwidth problem and spectrum problem. However, the CR‐IoT routing method sometimes presents issues in terms of road finding, spectrum resource diversity and mobility. This study presents an upgradable cross‐layer routing protocol based on CR‐IoT to improve routing efficiency and optimize data transmission in a reconfigurable network. In this context, the system is developing a distributed controller which is designed with multiple activities, including load balancing, neighbourhood sensing and machine‐learning path construction. The proposed approach is based on network traffic and load and various other network metrics including energy efficiency, network capacity and interference, on an average of 2 bps/Hz/W. The trials are carried out with conventional models, demonstrating the residual energy and resource scalability and robustness of the reconfigurable CR‐IoT.

Abstract Signature biometrics is a widely accepted and used modality to verify the identity of an individual in many legal and financial organisations. A writer and language‐independent signature identification method that can distinguish between the genuine and forged sample irrespective of the language of the signature has been proposed. To extract the distinguishing features, a pre‐trained model GoogLeNet, which is fine‐tuned with the largest signature dataset present till date (GPDS Synthetic), has been used. The proposed method is tested over the BHSig260 (contains images from two regional languages, Bengali and Hindi) dataset. With the help of the above fine‐tuned model, knowledge is transferred to the publicly available datasets – BHSig260 and MCYT‐75. The features extracted using the fine‐tuned model has been fed to the support vector machine (SVM) classifiers. With the proposed method, 96.5% and 95.7% accuracy on Bengali and Hindi datasets, and 93% on MCYT‐75 with skilled forged samples have been achieved respectively.

Prior research argues for a role of increased de novo fatty acid synthesis in pathogenesis of prostate adenocarcinoma, which remains a leading cause of cancer-associated mortality in American men. A safe and effective inhibitor of fatty acid synthesis is still a clinically unmet need. Herein, we investigated the effect of ethanol extract of Withania somnifera root (WRE) standardized for one of its components (withaferin A) on fatty acid synthesis using LNCaP and 22Rv1 human prostate cancer cells. Withania somnifera is a medicinal plant used in the Ayurvedic medicine practiced in India. Western blotting and confocal microscopy revealed a statistically significant decrease in protein levels of key fatty acid metabolism enzymes including ATP citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A) in WRE-treated cells compared with solvent control. The mRNA levels of ACLY, ACC1, FASN, and CPT1A were also lower in WRE-treated cells in comparison with control. Consequently, WRE treatment resulted in a significant decrease in intracellular levels of acetyl-CoA, total free fatty acids, and neutral lipid droplets in both LNCaP and 22Rv1 cells. WRE exhibited greater potency for fatty acid synthesis inhibition at equimolar concentration than cerulenin and etomoxir. Exposure to WRE results in downregulation of c-Myc and p-Akt(S473) proteins in 22Rv1 cell line. However, overexpression of only c-Myc conferred protection against clonogenic cell survival and lipogenesis inhibition by WRE. In conclusion, these results indicate that WRE is a novel inhibitor of fatty acid synthesis in human prostate cancer cells.

The endothelium maintains and regulates vascular homeostasis mainly by balancing interplay between vasorelaxation and vasoconstriction via regulating Nitric Oxide (NO) availability. Endothelial nitric oxide synthase (eNOS) is one of three NOS isoforms that catalyses the synthesis of NO to regulate endothelial function. However, eNOS's role in the regulation of endothelial function, such as cell proliferation and migration remain unclear. To gain a better understanding, we genetically knocked down eNOS in cultured endothelial cells using sieNOS and evaluated cell proliferation, migration and also tube forming potential in vitro. To our surprise, loss of eNOS significantly induced endothelial cell proliferation, which was associated with significant downregulation of both cell cycle inhibitor p21 and cell proliferation antigen Ki-67. Knockdown of eNOS induced cell migration but inhibited formation of tube-like structures in vitro. Mechanistically, loss of eNOS was associated with activation of MAPK/ERK and inhibition of PI3-K/AKT signaling pathway. On the contrary, pharmacologic inhibition of eNOS by inhibitors L-NAME or L-NMMA, inhibited cell proliferation. Genetic and pharmacologic inhibition of eNOS, both promoted endothelial cell migration but inhibited tube-forming potential. Our findings confirm that eNOS regulate endothelial function by inversely controlling endothelial cell proliferation and migration, and by directly regulating its tube-forming potential. Differential results obtained following pharmacologic versus genetic inhibition of eNOS indicates a more complex mechanism behind eNOS regulation and activity in endothelial cells, warranting further investigation.

Introduction Around 9% of India’s children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants

Abstract Mutations in the tumor suppressor gene BRCA2 (BReast CAncer susceptibility gene 2) predispose carriers to breast, ovarian, and other cancers. In response to DNA damage, BRCA2 participates in homology‐directed DNA damage repair to maintain genome stability. Genome‐wide association studies have identified an association between BRCA2 single nucleotide polymorphisms and plasma‐lipid levels and lipid deregulation in humans. To date, DNA damage, apoptosis, and lipid deregulation are recognized as central pathways for endothelial dysfunction and atherosclerosis; however, the role of BRCA2 in endothelial dysfunction remains to be elucidated. To determine the role of BRCA2 in endothelial dysfunction, BRCA2 was silenced in human umbilical vein endothelial cells (ECs) and assessed for markers of DNA damage, apoptosis, and endothelial function following oxidized low‐density lipoprotein (oxLDL) treatment. OxLDL was found to induce significant reactive oxygen species (ROS) production in BRCA2‐silenced ECs. This increase in ROS production was associated with exacerbated DNA damage evidenced by increased expression and activation of DNA double‐stranded break (DSB) marker γH2AX and reduced RAD51‐foci formation—an essential regulator of DSB repair. Increased DSBs were associated with enhanced expression and activation of pro‐apoptotic p53 and significant apoptosis in oxLDL‐treated BRCA2‐silenced ECs. Loss of BRCA2 in ECs was further associated with oxLDL‐induced impaired tube‐forming potential and eNOS expression. Collectively, the data reveals, for the first time, a novel role of BRCA2 as a regulator of EC survival and function in the setting of oxLDL treatment in vitro. Additionally, the data provide important clues regarding the potential susceptibility of BRCA2 mutation carriers to endothelial dysfunction, atherosclerosis, and other cardiovascular diseases.

The electrical market scenario has changed drastically in the last decade. In the presence of increased competition and less tolerant players, more sophisticated methods are required to balance the diversity and differential pricing while promoting cooperation among the agents. In the monopolistic environment, the central utility incurred the total cost of the transmission expansion. But as the current scenario demands, there are several public and private market players. The growth will benefit all the players, so the total cost in transmission expansion can be divided among players as per the benefit received by each player. In this paper, a transmission system expansion planning problem in the cooperative environment using cooperative game theory (CGT) is framed for the power sector, in which various players can cooperate in a coordinated manner to maximize their benefit but ultimately strengthen the power grid. In this paper, we have modeled, analyzed and compared various cost allocation methods of cooperative game theory specifically for the cost allocation in a transmission expansion planning problem. The present work focuses on forming coalitions to calculate the costs using the forward search and frog leap optimization approach. We have compared the SCRB, BSV, ENSC, and ACA methods for transmission expansion planning while attempting to satisfy the axioms. We have also observed that bilateral Shapely value efficiently allocated the costs due to its decentralized approach and the sequencing of coalition formations to achieve the best possible cost allocations.

The field of ground-based γ-ray astronomy has made very significant advances over the last three decades with the extremely successful operations of several atmospheric Cherenkov telescopes worldwide. The advent of the imaging Cherenkov technique for indirect detection of cosmic γ rays has immensely contributed to this field with the discovery of more than 220 γ-ray sources in the Universe. This has greatly improved our understanding of the various astrophysical processes involved in the non-thermal emission at energies above 100 GeV. In this paper, we summarize the important results achieved by the Indian γ-ray astronomers from the GeV-TeV observations using imaging Cherenkov telescopes over the last two decades. We mainly emphasize the results obtained from the observations of active galactic nuclei with the TACTIC (TeV Atmospheric Cherenkov Telescope with Imaging Camera) telescope, which has been operational since 1997 at Mount Abu, India. We also discuss the future plans of the Indian γ-ray astronomy program with special focus on the scientific objectives of the recently installed 21 m diameter MACE (Major Atmospheric Cherenkov Experiment) telescope at Hanle, India.

Chronic limb-threatening ischemia (CLTI) results in devastating complications such as lower-limb amputations. In this study, a genome-wide plasma microRNAs (miRNA) sequencing was performed to identify miRNA(s) associated with CLTI. Blood samples were collected from early stage CLTI patients (ABI < 0.9) and non-PAD controls (ABI ≥ 0.9) for 3 experiments: discovery phase (n = 23), confirmatory phase (n = 52) and validation phase (n = 20). In the discovery phase, next generation sequencing (NGS) was used to identify miRNA circulating in the plasma CLTI (n = 13) patients, compared to non-PAD controls (n = 10). Two down-regulated miRNAs (miRNA-6843-3p and miRNA-6766-5p) and three upregulated miRNAs (miRNA-1827, miRNA-320 and miRNA-98-3p) were identified (≥2-fold change). In the confirmatory phase, these 5 deregulated miRNAs were further investigated in non-PAD (n = 21) and CTLI (n = 31) patients using qRT-PCR. Only miRNA-1827 was found to be significantly upregulated (≥3-fold, p-value < 0. 001) in the CLTI group. Lastly, to minimize the influence of confounding factors, miRNA-1827 plasma levels were validated in a third cohort of CLTI patients (n = 10) matched to non-PAD controls (n = 10). Our analysis demonstrated that miRNA-1827 expression was increased in the CLTI cohort (≥2-folds, p-value < 0.001). In summary, circulating miRNA-1827 is significantly elevated in patients with CLTI.

Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is a widely used anticonvulsant drug that is currently undergoing clinical evaluation for anticancer therapy due to its anti-angiogenic potential. Endothelial cells (ECs) can transition into mesenchymal cells and this form of EC plasticity is called endothelial-to-mesenchymal transition (EndMT), which is widely implicated in several pathologies including cancer and organ fibrosis. However, the effect of VPA on EC plasticity and EndMT remains completely unknown. We report herein that VPA-treatment significantly inhibits tube formation, migration, nitric oxide production, proliferation and migration in ECs. A microscopic evaluation revealed, and qPCR, immunofluorescence and immunoblotting data confirmed EndMT-like phenotypic switching as well as an increased expression of pro-fibrotic genes in VPA-treated ECs. Furthermore, our data confirmed important and regulatory role played by TGFβ-signaling in VPA-induced EndMT. Our qPCR array data performed for 84 endothelial genes further supported our findings and demonstrated 28 significantly and differentially regulated genes mainly implicated in angiogenesis, endothelial function, EndMT and fibrosis. We, for the first time report that VPA-treatment associated EndMT contributes to the VPA-associated loss of endothelial function. Our data also suggest that VPA based therapeutics may exacerbate endothelial dysfunction and EndMT-related phenotype in patients undergoing anticonvulsant or anticancer therapy, warranting further investigation.

Cereals are key contributors to global food security. Genes involved in the uptake (transport), assimilation and utilization of macro- and micronutrients are responsible for the presence of these nutrients in grain and straw. Although many genomic databases for cereals are available, there is currently no cohesive web resource of manually curated nutrient use efficiency (NtUE)-related genes and quantitative trait loci (QTLs). In this study, we present a web-resource containing information on NtUE-related genes/QTLs and the corresponding available microRNAs for some of these genes in four major cereal crops (wheat (Triticum aestivum), rice (Oryza sativa), maize (Zea mays), barley (Hordeum vulgare)), two alien species related to wheat (Triticum urartu and Aegilops tauschii), and two model species (Brachypodium distachyon and Arabidopsis thaliana). Gene annotations integrated in the current web resource were manually curated from the existing databases and the available literature. The primary goal of developing this web resource is to provide descriptions of the NtUE-related genes and their functional annotation. MicroRNAs targeting some of the NtUE related genes and the QTLs for NtUE-related traits are also included. The genomic information embedded in the web resource should help users to search for the desired information.

Marfan syndrome (MFS) is a relatively rare disease of the connective tissue that affects several organs of the body. Cardiovascular abnormalities such as aortic root dilatation and mitral valve prolapse are the two main life-threatening complications associated with MFS. The complete pathogenesis of MFS is yet unclear. However, fibrillin-1 (FBN1) gene mutations and mutations in the transforming growth factor-β (TGFβ) signaling pathway are the leading causes of this lethal disease. Detailed assessment based on several major and minor clinical manifestations has led to the evolution of different nosologies for MFS diagnoses with reliable accuracies. Nevertheless, heterogeneous disease advancement and overlapping clinical outcomes make MFS diagnosis challenging. Rapid strides in research and surgical avenues over the last two decades have improved the life expectancy and the quality of life of MFS patients remarkably. More specific diagnostic criteria have been established, novel therapeutic targets for pharmacotherapy have been identified and validated, and newer surgical techniques have been tested. Current research efforts are focusing on the identification of prognostic biomarkers, gene modifiers, drug targets, and surgical procedures. This review aims to provide a brief overview of these aspects associated with MFS.

Alveolar epithelial cells outnumber alveolar macrophages by ~500 fold and increasing evidence suggests that Mycobacterium tuberculosis may replicate dramatically in these cells during the initial weeks of infecting the lung (Wolf et al., 2008 [1]; Ryndak et al., 2015 [2]). Here, we report in experimental detail the transcriptional profiling of M. tuberculosis replicating at 72 h post-infection in the human type II alveolar epithelial cell line, A549, as compared to M. tuberculosis growing logarithmically in laboratory broth culture (Ryndak et al., 2015 [2]). All resulting transcriptional profiling data was deposited to the Gene Expression Omnibus (GEO) database under the accession number GSE58466.

The CYP1A1 gene encodes for the enzyme, aryl hydrocarbon hydroxylase, which is involved in the biotransformation of various aromatic tobacco precarcinogens. In the present study, the association between CYP1A1 gene polymorphisms (IVS1-728G > A, Thr461Asn and Ile462Val), and the risk of oral cancer, was examined among 157 patients with oral cancer and 132 age-matched controls, in a south Indian population. The strength of the association between CYP1A1 variants and oral cancer was estimated by logistic regression. It was found that Thr461Asn was not polymorphic. Both IVS1-728G > A and Ile462Val frequencies were consistent with Hardy-Weinberg equilibrium in the control group. There were no significant differences in genotype or haplotype frequencies between controls and cases with oral cancer. Hence, CYP1A1 SNPs can be considered as not being associated with oral cancer at either the genotype or haplotype levels in the population studied.

Medicinal plants are the main natural pools for the primary health care system, ethno-medicine, as well as traditional Indian system of several medicines. Uttarakhand also known as ‘Herbal State’, is a rich source of medicinal plants and traditional medicinal knowledge. A great deal of information about medicinal plants of Uttarakhand is scattered in different forms. Although many medicinal plant databases are available, currently there is no cohesive manually curated database of medicinal plants widely distributed in Uttarakhand state. A comprehensive database has been developed, known as the Uttarakhand Medicinal Plants Database (UMPDB). UMPDB provides extensive information on botanical name, common name, taxonomy, genomic taxonomy id, habit, habitat, location in Uttarakhand, part use, medicinal use, genomic information (including number of nucleotides, proteins, ESTs), chemical information, and scientific literature. Annotated medicinal plants integrated in the current version of the database were collected from the existing books, databases, and available literature. The current version of UMPDB contains the 1127 records of medicinal plants which belong to 153 plant families distributed across 13 districts of Uttarakhand. The primary goal of developing this database is to provide traditional, genomic, and chemical descriptions of the medicinal plants exclusively found in various regions of Uttarakhand. We anticipate that embedded information in the database would help users to readily obtain desired information.

We investigated the occurrence of Factor XI (FXI) deficiency syndrome in the following Indian dairy animals: Bos taurus Holstein-Friesian and Jersey cattle, Bos indicus Indian cattle breeds, B. taurus x B. indicus crossbreds and the river buffalo Bubalus bubalis. Factor XI deficiency is an autosomal recessive bleeding disorder known to affect Holstein cattle worldwide. A total of 1001 dairy animals, mainly bulls, were genotyped to detect the mutation within exon 12 of the gene encoding for factor XI. Two Holstein bulls were detected as heterozygous (carrier) for FXI deficiency, giving a carrier frequency of 0.6% in Indian Holstein cattle. None of the other cattle or buffalo breeds was found to be a carrier for FXI. Sequence comparison between normal and heterozygous animals revealed that there is a 77 base pair insertion fragment (AT (A)29 TAAAG (A)27 GAATTATTAATTCT) within exon 12 of the FXI gene. Both sequences were submitted to the National Center for Biotechnology Information (NCBI) GenBank and assigned the accession numbers DQ438908 for normal Holstein Friesian animals and DQ438909 for heterozygous Holstein Friesian animals.

Mycobacterium tuberculosis (M. tb) infection is initiated by the few bacilli inhaled into the alveolus. Studies in lungs of aerosol-infected mice provided evidence for extensive replication of M. tb in non-migrating, non-antigen-presenting cells in the alveoli during the first 2-3 weeks post-infection. Alveoli are lined by type II and type I alveolar epithelial cells (AEC) which outnumber alveolar macrophages by several hundred-fold. M. tb DNA and viable M. tb have been demonstrated in AEC and other non-macrophage cells of the kidney, liver, and spleen in autopsied tissues from latently-infected subjects from TB-endemic regions indicating systemic bacterial dissemination during primary infection. M. tb have also been demonstrated to replicate rapidly in A549 cells (type II AEC line) and acquire increased invasiveness for endothelial cells. Together, these results suggest that AEC could provide an important niche for bacterial expansion and development of a phenotype that promotes dissemination during primary infection. In the current studies, we have compared the transcriptional profile of M. tb replicating intracellularly in A549 cells to that of M. tb replicating in laboratory broth, by microarray analysis. Genes significantly upregulated during intracellular residence were consistent with an active, replicative, metabolic, and aerobic state, as were genes for tryptophan synthesis and for increased virulence (ESAT-6, and ESAT-6-like genes, esxH, esxJ, esxK, esxP, and esxW). In contrast, significant downregulation of the DevR (DosR) regulon and several hypoxia-induced genes was observed. Stress response genes were either not differentially expressed or were downregulated with the exception of the heat shock response and those induced by low pH. The intra-type II AEC M. tb transcriptome strongly suggests that AEC could provide a safe haven in which M. tb can expand dramatically and disseminate from the lung prior to the elicitation of adaptive immune responses.

Hematogenous dissemination of Mycobacterium tuberculosis (M. tb) occurs during both primary and reactivated tuberculosis (TB). Although hematogenous dissemination occurs in non-HIV TB patients, in ∼80% of these patients, TB manifests exclusively as pulmonary disease. In contrast, extrapulmonary, disseminated, and/or miliary TB is seen in 60-70% of HIV-infected TB patients, suggesting that hematogenous dissemination is likely more common in HIV+ patients. To understand M. tb adaptation to the blood environment during bacteremia, we have studied the transcriptome of M. tb replicating in human whole blood. To investigate if M. tb discriminates between the hematogenous environments of immunocompetent and immunodeficient individuals, we compared the M. tb transcriptional profiles during replication in blood from HIV- and HIV+ donors. Our results demonstrate that M. tb survives and replicates in blood from both HIV- and HIV+ donors and enhances its virulence/pathogenic potential in the hematogenous environment. The M. tb blood-specific transcriptome reflects suppression of dormancy, induction of cell-wall remodeling, alteration in mode of iron acquisition, potential evasion of immune surveillance, and enhanced expression of important virulence factors that drive active M. tb infection and dissemination. These changes are accentuated during bacterial replication in blood from HIV+ patients. Furthermore, the expression of ESAT-6, which participates in dissemination of M. tb from the lungs, is upregulated in M. tb growing in blood, especially during growth in blood from HIV+ patients. Preliminary experiments also demonstrate that ESAT-6 promotes HIV replication in U1 cells. These studies provide evidence, for the first time, that during bacteremia, M. tb can adapt to the blood environment by modifying its transcriptome in a manner indicative of an enhanced-virulence phenotype that favors active infection. Additionally, transcriptional modifications in HIV+ blood may further accentuate M. tb virulence and drive both M. tb and HIV infection.

The rapid appearance of resistant malarial parasites after introduction of atovaquone (ATQ) drug has prompted the search for new drugs as even single point mutations in the active site of Cytochrome b protein can rapidly render ATQ ineffective. The presence of Y268 mutations in the Cytochrome b (Cyt b) protein is previously suggested to be responsible for the ATQ resistance in Plasmodium falciparum (P. falciparum). In this study, we examined the resistance mechanism against ATQ in P. falciparum through computational methods. Here, we reported a reliable protein model of Cyt bc1 complex containing Cyt b and the Iron-Sulphur Protein (ISP) of P. falciparum using composite modeling method by combining threading, ab initio modeling and atomic-level structure refinement approaches. The molecular dynamics simulations suggest that Y268S mutation causes ATQ resistance by reducing hydrophobic interactions between Cyt bc1 protein complex and ATQ. Moreover, the important histidine contact of ATQ with the ISP chain is also lost due to Y268S mutation. We noticed the induced mutation alters the arrangement of active site residues in a fashion that enforces ATQ to find its new stable binding site far away from the wild-type binding pocket. The MM-PBSA calculations also shows that the binding affinity of ATQ with Cyt bc1 complex is enough to hold it at this new site that ultimately leads to the ATQ resistance.

The article discusses the impact of neoliberal globalization and multiculturalism. It states that modernism and the Western concept of multiculturalism ruined the traditional bonds connecting human beings who are now lost in violent market competition and capitalistic economic transformation. It discusses the condition of culture in modern societies like Great Britain where terrorist activities have become rampant.

Abstract Pneumatic planters are widely adopted in precision agriculture due to their superior field performance and minimal seed damage. However, variations in seed size, shape, and orientation can affect the ability of each orifice to pick and release a single seed accurately. Seed metering units typically incorporate seed cut-off and knock-out devices to improve singulation and ensure timely seed dropping, enhancing the quality feed index and reducing the precision index. These auxiliary devices—whether mechanical, electronic, pneumatic, or magnetic—increase system complexity, require skilled operation, necessitate additional maintenance, consume more energy, and heighten the risk of seed damage. The suctioned seed experiences impact from the seed metering plate during picking, and orifices are not fully sealed after seed pick-up, leading to a need for higher vacuum pressure. Additionally, field vibrations can adversely affect planter performance. To overcome these issues, this study developed a novel flexible orifice seed metering plate and optimised its operating parameters for cotton seed, adopting a central composite rotatable design (CCRD). The plates were developed by adding a layer of elastomeric material on rigid seed metering plate. The experiments were conducted using a developed electronic sticky belt setup in laboratory. An orifice diameter of 3 mm, vacuum pressure of 3.40 kPa, forward speed of 4.67 km/h, extended radius of 1 mm and coating thickness of 0.25 mm were found optimum with a quality feed index of 97.289% and precision index of 4.653%. Minimal difference between laboratory and field performance was noted when operated by an electronic planter. The miss index, multiple index, and precision index obtained under field conditions with rigid seed metering plate were found to be 4.4, 2.8, and 9.08% higher than coated seed metering plate, respectively. A comparatively lower optimal vacuum pressure and higher operation speed was achieved when coated seed metering plate was used in place of rigid seed metering plate. Hence coated seed metering plate can be a low-cost solution to achieve higher speed of precision planting with improved seeding performance. Graphical Abstract

Abstract The geometric features and operational parameters of rotary blades on rotary tillers significantly impact their performance characteristics. The sweepback angle is a geometric feature of the 'L'-shaped rotary blade that has remained unexplored in previous studies. This study aimed to analyze the effect of geometrical and operational parameters on the performance dynamics of the 'L'-shaped rotary blade. The investigation was conducted using the discrete element method (DEM) and further validated through experiments conducted in a soil bin. The simulation experiment was conducted by dividing the particle bed into horizontal particle zones. The effect of the geometrical (sweepback angle) and operational parameters (forward speed, rotational speed, and depth) on the power requirement, disturbance intensity, and mixing index was studied. The novel method was adopted to determine the mixing capability of rotary blades in terms of sub-domain mixing index (SMI) and overall mixing index (OMI). The results revealed that the power requirements for a sweepback angle of 18° were 26.39% and 16.50% lower than those for sweepback angles of 6° and 12°, respectively. The sweepback angle tends to have the least effect on the overall mixing index compared to operational parameters. The average particle velocity decreased by 22.19% and 29.60% with sweepback angles of 12° and 18°, respectively, compared to the sweepback angle of 6°. The relative error during the experiment varied between 1.29% and 13.51%. It was concluded that the sweepback angle was found to be a feasible option for reducing the power requirement with good mixing indices.

Background: Obsessive compulsive disorder (OCD) is a clinically heterogeneous psychiatric disorder in terms of symptom content and insight. Aim: To study the various factors associated with insight in OCD. Materials and Methods: A cross-sectional hospital-based study was conducted among 40 patients with OCD who were evaluated on Yale-Brown Obsessive-Compulsive Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Brown Assessment of Beliefs Scale, Meta-Cognitions Questionnaire, WHOQOL-BREF, and Sheehan Disability Scale. Statistical analysis was done using SPSS version 22. Results: Metacognition, severity of OCD, and associated disability were the significant predictors for insight in patients with OCD. Conclusion: Factors associated with insight in OCD can enhance our understanding in the management of OCD.

Abstract In many Indian regions, paddy wheat is the main crop rotation and facing the problem of straw incorporation for seed bed preparation in short period. The handling of straw in combine harvested paddy fields is a significant issue in the paddy wheat rotation. In order to solve this issue, efforts were carried out to cut paddy straw into small pieces by the newly proposed counter-rotating blades, followed by the simultaneous incorporation of a rotary tiller into the soil. Therefore, a tractor operated chopping cum tilling mixing machine was developed. In the study, three different blades (straw management system (SMS) Serrated, cutter bar and SMS plain) were tested in the terms of torque and required to chop the straw. SMS serrated blade was best suitable for the chopping mechanism as it required minimum cutting torque for the straw bunches. The developed chopping cum tilling mixing machine was tested at three different levels of forward speed (1.77, 2.3, and 3 km h−1), moisture content at three levels (35 ± 3.4, 24 ± 2.2 and 17 ± 2.6%) with fix rotary tiller rotational speed of 810 rev min−1. Optimum operating condition of the machine was obtained at a forward speed of 1.9 km h−1 and a moisture of 24%. At these optimized values, the mixing index (96%), mean weight diameter (7.9 mm), bulk density (1230 g cc−1) and fuel consumption (3 l h−1) were 96%, 7.9 mm, 1230 g cc−1 and 3.0 l h−1 respectively. The developed machine performs three operations i.e., chopping, tilling, and mixing in single pass for effective in-situ straw management.

This study examines the influence of planting mixture variations on the quality of the percolated water of the rain garden with and without plants. Six planting mixtures in experimental rain gardens have been used. It has been noted that pollutant removal efficiency of RG can exhibit variations based on specific parameters. Notably, RG6, utilizing a planting mix of 75% topsoil and 25% compost, demonstrated the highest performance. These results draw attention to the critical role of the specific planting mixtures in influencing the performance of vital parameters related to pollutant removal. The observation shows that RG5 exhibits exceptional removal efficiency in pH, Total Suspended Solids (TSS), Biological Oxygen Demand (BOD), and Chemical Oxygen Demand (COD), and RG6 performs best in electrical conductivity (EC), Total Dissolved Solids (TDS), Total Nitrogen (TN), and Total Phosphorus (TP) removal. In particular, when analyzing pollutant removal on a surface with Madagascar periwinkle plants, RG6 emerges as the most effective, achieving an impressive efficiency of approximately 49%. For the bare surface, pollutant removal efficiency is 40%. The study outcome will be useful in deciding the composition of the planting mixture, which will keep the rain garden to improve quality and quantitatively hydrological performance, lowering urban flooding magnitude. HIGHLIGHTS The rain garden planting mixture influences pollutant removal efficiency.; The performance of rain garden with plant is superior to a bare rain garden.; The rain garden having a planting mixture of topsoil in the range of 75–80% and compost in the range of 20–25% performance is best.;

Abstract Degradation of bromocresol green in alcohol-water solution using ozone micron sized bubbles is reported. A high speed impeller is used to generate micro bubbles of ozone in liquid while ozone is generated using a commercial ozone generator. A 3-level-3-factor Box–Behnken experimental design is used to statistically identify relative importance of the operating parameters studied namely impeller speed, initial concentration of dye and treatment time. Ozone dosage is kept fixed at 4 g/h. Impeller speed is found to be the most dominant factor according to Analysis of Variance (ANOVA) calculations. Kinetics for degradation of bromocresol green in solution is also reported. A second order kinetics is seen to fit the experimental (concentration–time) data, corresponding value of rate constant being 0.0153 L/mg-s. Based on the laboratory scale data a detailed techno-commercial analysis of a scaled up (75 kL/day) plant for ozone based degradation of bromocresol is presented. All relevant economic indicators pertaining to the scaled up plant are reported. A specific treatment cost of Rs. 100/m3 of treated water yields a return on investment (ROI) of 68.77 and discounted payback period of 5 years.

Abstract Background Chickpea is prone to many abiotic stresses such as heat, drought, salinity, etc. which cause severe loss in yield. Tolerance towards these stresses is quantitative in nature and many studies have been done to map the loci influencing these traits in different populations using different markers. This study is an attempt to meta-analyse those reported loci projected over a high-density consensus map to provide a more accurate information on the regions influencing heat, drought, cold and salinity tolerance in chickpea. Results A meta-analysis of QTL reported to be responsible for tolerance to drought, heat, cold and salinity stress tolerance in chickpeas was done. A total of 1512 QTL responsible for the concerned abiotic stress tolerance were collected from literature, of which 1189 were projected on a chickpea consensus genetic map. The QTL meta-analysis predicted 59 MQTL spread over all 8 chromosomes, responsible for these 4 kinds of abiotic stress tolerance in chickpea. The physical locations of 23 MQTL were validated by various marker-trait associations and genome-wide association studies. Out of these reported MQTL, CaMQAST1.1, CaMQAST4.1, CaMQAST4.4, CaMQAST7.8, and CaMQAST8.2 were suggested to be useful for different breeding approaches as they were responsible for high per cent variance explained (PVE), had small intervals and encompassed a large number of originally reported QTL. Many putative candidate genes that might be responsible for directly or indirectly conferring abiotic stress tolerance were identified in the region covered by 4 major MQTL- CaMQAST1.1, CaMQAST4.4, CaMQAST7.7, and CaMQAST6.4, such as heat shock proteins, auxin and gibberellin response factors, etc. Conclusion The results of this study should be useful for the breeders and researchers to develop new chickpea varieties which are tolerant to drought, heat, cold, and salinity stresses.

Background: Having a child with a serious illness like cancer has a detrimental and negative impact on the parents’ health-related quality of life (HRQOL). Many factors have been identified as being associated with poorer HRQOL. Acquiring knowledge about these factors is essential to enhancing the quality of life (QOL) of children as well as their parents. Aim: This study aims to analyze HRQOL in parents of children with cancer and to explore relationships between parent and child variables and parental quality of life. Materials and Methods: A total of 80 parents of children with cancer were enrolled in this cross-sectional study. To evaluate the parental HRQOL, the Short Form 36 Health Survey Questionnaire (SF-36) was used. Results: Child age and time since diagnosis showed a positive correlation with all domains of HRQOL on Spearman’s correlation. A statistically significant difference in SF-36 scores across four cancer groups was seen on the Kruskal–Wallis test. Mothers showed poorer quality of life in the physical role functioning domain as compared to fathers (U = 248, P < 0.01). Conclusion: The present study shows poor HRQOL for parents of children with cancer, despite learning to cope and adjust over time. Parents of children with retinoblastoma demonstrate a poorer QOL as compared to other cancer groups. The study suggests close monitoring of parents’ QOL and the provision of appropriate treatment and psychosocial support for parents along with the treatment of children.

Background: Poxviruses comprise a group of large double-stranded DNA viruses and are known to cause diseases in humans, livestock animals, and other animal species. The Mpox virus (MPXV; formerly Monkeypox), variola virus (VARV), and volepox virus (VPXV) are among the prevalent poxviruses of the Orthopoxviridae genera. The ongoing Mpox infectious disease pandemic caused by the Mpox virus has had a major impact on public health across the globe. To date, only limited repurposed antivirals and vaccines are available for the effective treatment of Mpox and other poxviruses that cause contagious diseases. Methods: The present study was conducted with the primary goal of formulating multi-epitope vaccines against three evolutionary closed poxviruses i.e., MPXV, VARV, and VPXV using an integrated immunoinformatics and molecular modeling approach. DNA-dependent RNA polymerase (DdRp), a potential vaccine target of poxviruses, has been used to determine immunodominant B and T-cell epitopes followed by interactions analysis with Toll-like receptor 2 at the atomic level. Results: Three multi-epitope vaccine constructs, namely DdRp_MPXV (V1), DdRp_VARV (V2), and DdRp_VPXV (V3) were designed. These vaccine constructs were found to be antigenic, non-allergenic, non-toxic, and soluble with desired physicochemical properties. Protein-protein docking and interaction profiling analysis depicts a strong binding pattern between the targeted immune receptor TLR2 and the structural models of the designed vaccine constructs, and manifested a number of biochemical bonds (hydrogen bonds, salt bridges, and non-bonded contacts). State-of-the-art all-atoms molecular dynamics simulations revealed highly stable interactions of vaccine constructs with TLR2 at the atomic level throughout the simulations on 300 nanoseconds. Additionally, the outcome of the immune simulation analysis suggested that designed vaccines have the potential to induce protective immunity against targeted poxviruses. Conclusions: Taken together, formulated next-generation polyvalent vaccines were found to have good efficacy against closely related poxviruses (MPXV, VARV, and VPXV) as demonstrated by our extensive immunoinformatics and molecular modeling evaluations; however, further experimental investigations are still needed.

Generative Adversarial Networks (GANs) have emerged as a powerful type of generative model, particularly effective at creating images from textual descriptions. Similar to diffusion models, GANs rely on text encoders to extract embeddings from these descriptions. However, this reliance introduces specific vulnerabilities to adversarial attacks. A notable example is a single-character adversarial attack, where altering a single character in the text description can lead to significant performance degradation in the generated image quality and model’s performance. In this study, we systematically evaluate the susceptibility of GANs to such attacks using Generative Adversarial CLIP (GALIP), a single-stage architecture that leverages a pre-trained Contrastive Language-Image Pre-training (CLIP) text encoder for text embeddings. We meticulously selected captions with single-character modifications that exhibit maximum and median-distance embeddings for the attack. Experimental results show up to 310.5% degradation in Fréchet Inception Distance (FID) scores, underscoring the importance of developing improved defenses in text-to-image synthesis.

Federated learning uses the concept of decentralized training of n number of local clients for a small number of epochs say 2-5, and then averaging the learned weights of all local clients, and evaluating on test dataset with the average weights loaded to a global model. The train dataset is split into n clusters and each cluster acts as a distributed data for each local model. Each round of weight averaging and then uploading the average weights on each local client for further training is called communication round and it was observed that similar accuracy can be obtained with a lesser amount of training time. In this paper, instead of averaging the weights, a weighted mean concept was developed where the PSO vector helps to find the weight values for the best accuracy of a global model. It was found that PSO can help in two ways by bettering the accuracy and also reducing the training time. The proposed approach can enhance the performance of pre-trained models like AlexNet, VGG16, InceptionV3, and ResNet50 on CIFAR-10 and CIFAR-100 datasets. The maximum increase was found with VGG16 of around 26.01% for CIFAR-10 and 26.84% for CIFAR-100. Similarly, on the Tomato dataset, AlexNet accuracy can be increased by 28.56%. Multi-modal model accuracy on the fake news dataset was also enhanced by 8.21%.

Quantum computers use quantum-mechanical phenomena for knowledge manipulation and depend on quantum bits or qubits. A qubit can be created in several different ways, and out of this, one way of creating a quantum state is by using superconductivity. They must be held very cold to work on these superconductive qubits for long periods. The key to information storage and manipulation is the skill of all computer systems. Current traditional computers handle single bits stored in binary states of 0 and 1 form. Every temperature factor inside the device may be updated; thus, quantum computers are more excellent than the vacuum of space at temperatures similar to absolute null. Consider how the dilution refrigerator of a quantum computer consisting of over 2000 components provides a cold atmosphere for the inside of the qubits. Researchers from all around the world today are using actual quantum processors for validating algorithms for different fields of operation. Yet quantum computation was a strictly speculative topic a couple of decades ago. Quantum cryptography, also known as quantum encoding, uses quantum mechanics principles to encrypt messages in a way nobody else reads. It benefits quantum states, along with its “theory of no transition,” which means that it cannot be disrupted unknowingly. Quantum-improved AI calculations are especially applicable to the area. This work focuses on the implementation patterns of quantum computing in real-time cryptography so that the overall communication will be secured and integrity aware.

Background: Behavioral and psychological symptoms of dementia (BPSD) influence dementia care significantly. BPSD can be affected by factors related to the patient's illness and socio-cultural background. Aim: This study aimed to find a relationship between BPSD with patients' socio-demographic and clinical profiles and their caregivers' distress in a tertiary care center. Materials and Methods: In this hospital-based cross-sectional study, the purposive sampling technique was used to select 100 dementia patients. A comprehensive record of socio-demographic and clinical details was made on a self-prepared semi-structured data sheet. The Neuropsychiatric Inventory Questionnaire was the principal tool to find the BPSD and related caregivers' distress. Results: The sample comprised predominantly Hindu (91%) male patients (66%) with Alzheimer's dementia (76%) coming from rural backgrounds (74%) and joint familial systems (96%), with a mean age of 71.77 ± 7.41 years. Patients' main caregivers were their children/children-in-law (65%). The severity of an overall BPSD and its variable individual domains were directly related to the duration of dementia, patients' age, their cognitive decline, and related decline in activities of living, as well as their caregivers' distress. In comparison to Alzheimer's disease patients, those with other dementia types had more impairment in cognitive functions and activities of daily living and they had a higher number and severity of BPSD. Conclusion: The advancing age, increased duration of dementia, and decline in cognition and related activities of daily living of the patients, as well as their caregivers' distress, are important correlates of BPSD. The findings are essential for the better management of dementia patients.

The advancement of Internet of Everything (IoE) propels the fast growth of next-generation, such as 6G networks, leading to a new era of coverage, connectivity, and technological innovation, which calls for novel approaches to address rising energy consumption and maximize resource use. The proposed article presents a robust hybrid algorithm that combines leader-based optimization and Adaptive Differential Evolution (DE) in the framework of the Energy Efficient Hybrid Evolutionary Algorithm (EEHEA), which is specifically designed for the complex environment of IoE-enabled 6G networks. The scheme EEHEA combines the efficacy of leader-based optimization (LBO) for an effective decision-making process and adaptive differential evolutionary optimization (ADE)’s dynamic network-parameters adaptation, enhanced convergence, and global searching ability, persistently fine-tuning optimization strategies based on the dynamics of the network. Combining these components into the scheme EEHEA allows it to balance local exploitation and global exploration effectively. This implies better resource allocation and improved energy efficiency in ecosystems with IoE-driven 6G (IoE-6G). The outcomes report that the scheme EEHEA can address the rising energy consumption issues and enhance the efficiency of IoE-6G. Based on simulation experiments, the proposed scheme EEHEA can demonstrate faster convergence times, higher accuracy, and superior flexibility concerning changing network conditions. Its capability to handle energy-related challenges and navigate complex network environments with resilience shows the ability to enhance the performance of IoE-6G. The EEHEA scheme reports its efficacy over state-of-the-art schemes regarding localization, latency, coverage, and energy expenditure performance metrics.

Germline mutations in Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) cause breast, ovarian, and other cancers, and the chemotherapeutic drug doxorubicin (Dox) is widely used to treat these cancers. However, Dox use is limited by the latent induction of severe cardiotoxicity known as Dox-induced cardiomyopathy, for which there are no specific treatments currently available. Dox is administered into the systemic circulation, where it readily translocates into sub-cellular compartments and disrupts the integrity of DNA. Accumulating evidence indicates that oxidative stress, DNA damage, inflammation, and apoptosis all play a central role in Dox-induced cardiomyopathy. The BRCA1 and BRCA2 proteins are distinct as they perform crucial yet separate roles in the homologous recombination repair of DNA double-strand breaks, thereby maintaining genomic integrity. Additionally, both BRCA1 and BRCA2 mitigate oxidative stress and apoptosis in both cardiomyocytes and endothelial cells. Accordingly, BRCA1 and BRCA2 are essential regulators of pathways that are central to the development of cardiomyopathy induced by Doxorubicin. Despite extensive investigations, there exists a gap in knowledge about the role of BRCA1 and BRCA2 in Doxorubicin-induced cardiomyopathy. Here, we review the previous findings and associations about the expected role and associated mechanisms of BRCA1 and 2 in Dox-induced cardiomyopathy and future perspectives.