Search Results (23,198)

Background: Sucrose metabolism plays a crucial role in plant responses to abiotic stresses such as drought and high temperatures, significantly influencing plant growth and yield formation. In higher plants, the second step in sucrose bioconversion involves sucrose phosphate phosphatase (SPP) hydrolyzing sucrose-6-phosphate to form sucrose. This study determined the number of SPP gene family members in upland cotton (Gossypium hirsutum), systematically analyzed their fundamental characteristics, physicochemical properties, phylogenetic relationships, chromosomal localization, and expression patterns across different tissues and under various abiotic stresses. Methods: The SPP gene family in hirsutum was identified using Hidden Markov Models (HMMER) and the NCBI Conserved Domain Database (NCBI CDD), and its physico-chemical properties were analyzed via the SOPMA online analysis website. Phylogenetic relationships were determined using MEGA 12.0 software. Promoter regions were analyzed with PlantCARE, sequence patterns were identified via MEME, and transcriptome data were downloaded from the CottonMD database. Results: This study identified four members of the hirsutum SPP gene family, with amino acid lengths ranging from 335 to 1015, molecular weights between 38.38 and 113.28 kDa, and theoretical isoelectric points (pI) between 5.39 and 6.33. These genes are localized across four chromosomes. The SPP gene family in hirsutum exhibits closer phylo-genetic relationships with SPP genes in Arabidopsis thaliana and Chenopodium quinoa. Their promoter regions are rich in cis-elements associated with multiple abiotic stress resistance functions, and their expression patterns vary across different tissues and under different abiotic stress conditions. Conclusions: The GhSPP gene may play an important role in the growth and development of upland cotton and its responses to salt stress and drought. Therefore, it could be considered as a candidate gene for future functional analysis of cotton resistance to salt and drought stress. Full article

Human infections caused by pathogenic bacteria remain a major global health concern. Among them, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Salmonella typhi are particularly prevalent and associated with significant morbidity and mortality. While antibiotics have long been the cornerstone of bacterial infection treatment, the widespread and often inappropriate use of these drugs has led to the emergence of multidrug-resistant (MDR) strains. This escalating resistance crisis underscores the urgent need for alternative therapeutic strategies. Amid the escalating global antimicrobial-resistance crisis, a genome-wide screen of 1800 Saccharomyces cerevisiae knockouts identified a TAD1-deficient mutant whose cell-free supernatant (CFS) rapidly eradicates multidrug-resistant E. coli, S. aureus, K. pneumoniae, and S. typhi in vitro. CFS disrupts pathogenic biofilms, downregulates biofilm-associated genes, and exerts bactericidal activity by triggering intracellular reactive oxygen species (ROS) accumulation and compromising envelope integrity. Probiotic profiling revealed robust tolerance to an acidic pH and physiological bile, high auto-aggregation, and efficient co-aggregation with target pathogens. In both Galleria mellonella and murine infectious models, administration of CFS or live yeast significantly increased survival, attenuated intestinal histopathology, and reduced inflammatory infiltration. These data establish the TAD1-knockout strain and its secreted metabolites as dual-function antimicrobial-probiotic entities, offering a sustainable therapeutic alternative to conventional antibiotics against multidrug-resistant bacterial infections. Full article

Chloroplast-to-nucleus ROS retrograde signaling is essential for acclimation of the photosynthetic apparatus to environmental stresses. One of the key mechanisms is the regulation of the photosystem II antenna size depending on light conditions and other environmental factors. However, the molecular components linking chloroplast redox status to nuclear gene regulation remain poorly defined. Here, we demonstrate that H₂O₂, generated in chloroplasts, in particular with involvement of the plastoquinone pool components, enhances the protease activity in the chloroplast envelope. As it is known, protease activity leads to the processing of the chloroplast envelope-bound transcription factor PTM, enabling its relocation to the nucleus, where it induces ABI4 expression. ABI4, in turn, represses transcription of lhcb genes, resulting in downsizing of the PS II antenna. Gene expression analysis confirms the coordinated upregulation of ABI4, and PTM, as well as metallo-ASP and serine SPPA1 envelope proteases in high light. We further show that H₂O₂ at physiologically relevant concentrations specifically stimulates the serine protease activity, since this activation is inhibited by PMSF. Our findings indicate a link between redox changes in the plastoquinone pool and the H₂O₂ level in chloroplasts with protease-mediated signaling cascades. Therefore, the obtained data reveal the connection between chloroplast and nuclear control of photosynthetic light harvesting, highlighting a signaling strategy for the photosystem II antenna size regulation in higher plants. Full article

Chimeric antigen receptor (CAR)-T cell therapies represent a promising therapeutic approach for refractory autoimmune diseases. Although autologous CAR-T cells have achieved success thus far, they require expensive, individualised manufacturing, limiting their commercialisation potential. Allogeneic alternatives could overcome these scalability barriers, providing ‘off-the-shelf’ treatments, although they raise the issues of graft-vs-host reactions and host-mediated rejection. To mitigate such risks, gene-edited αβ T cells or non-alloreactive host cells (e.g., NK cells, γδ T cells) may be used. This review evaluates evidence of the functionality and commercial potential of various allogeneic CAR-T solutions for autoimmunity. Searches were conducted of PubMed, EMBASE and Web of Science to extract clinical and preclinical studies of allogeneic CAR-T cells, for the treatment of autoimmune diseases and B or T cell malignancies. In light of the paucity of data on autoimmune disease, the latter were included to facilitate extrapolation to the autoimmune setting. A total of 107 studies were included. The available clinical outcomes of efficacy and safety, as well as preclinical key findings, are reported. Current developments and potential future improvements for safety, effectiveness and cost-effective manufacture are then discussed. The findings of this review demonstrate the promising therapeutic potential of allogeneic CAR-T for autoimmune disease, with scope for the further optimisation of safety and scalable manufacture to facilitate commercialisation. Full article

Background: Snipe eels (family Nemichthyidae) are a group of pelagic fishes with unique specializations; yet, species within this study are not well-studied due to a lack of molecular data. As typical mesopelagic-to-bathypelagic fishes, snipe eels exhibit extreme body elongation, reduced skeletal ossification, and highly specialized beak-like jaws that facilitate survival in deep-sea midwater environments. Methods: The complete mitochondrial genome of the deep-sea eel Nemichthys curvirostris (Anguilliformes: Nemichthyidae) was sequenced and annotated, representing the first mitogenomic resource for this species. The phylogenetic position of N. curvirostris was also explored. Results: The circular genome of N. curvirostris was determined to be 16,911 bp in length and contained 37 genes, including 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and a single control region, with an overall A + T bias of 56.67%. The maximum-likelihood phylogeny inferred from concatenated mitochondrial protein-coding genes recovered a well-supported monophyletic Nemichthys clade, with N. curvirostris positioned as the sister taxon to N. scolopaceus. The genera Avocettina and Labichthys were recovered as sister taxa, and Nemichthys clustered within a broader clade alongside them. The COX1 haplotype phylogeny showed that the two public database sequences (HQ563894.1 and MN123435.1) appeared as long, isolated branches outside the main N. curvirostris lineage, with COX1 genetic distances from typical N. curvirostris haplotypes reaching 12–13%, far exceeding the expected range of intraspecific variation. Conclusions: This mitogenome provides a valuable molecular resource for phylogenetic, evolutionary, and population genetic studies of deep-sea Anguilliformes. Full article

Background: Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer, but only 15–30% of patients achieve a pathological complete response. Single nucleotide polymorphisms represent stable genetic markers with potential predictive value for treatment response. This systematic review synthesizes current evidence on the association between SNPs and the response to nCRT in rectal cancer. Methods: PubMed and Web of Science databases were searched for relevant English studies. Two reviewers independently screened the titles and abstracts using the DistillerSR tool. Full-text articles were assessed for their eligibility. Data extraction followed the PRISMA guidelines, and the risk of bias was assessed. Results: Thirty-two studies (4116 patients) assessed 304 SNPs across 126 genes in 407 analyses. DNA repair genes (XRCC1, XRCC3, ERCC1, ERCC2) and folate metabolism genes (MTHFR, TYMS) were most frequently investigated. Only two SNPs demonstrated predictive value in multiple studies: rs25487 (XRCC1) and rs1801133 (MTHFR); however, the associations were inconsistent. The remaining SNPs showed isolated associations in single studies. No SNP demonstrated predictive value across independent cohorts. Conclusions: Current evidence does not support the clinical use of individual SNPs to predict nCRT response in rectal cancer patients. Although XRCC1 and MTHFR polymorphisms have been extensively studied, their predictive utility remains inconclusive. Future research should prioritize large, multicenter prospective studies with standardized treatment and outcome definitions, and consider polygenic risk models or integrated multi-omic approaches. Full article

To address the limitations of the traditional Coati Optimization Algorithm (COA), such as insufficient global exploration, poor population cooperation, and low convergence efficiency in global optimization and photovoltaic (PV) model parameter identification, this paper proposes a Multi-strategy Enhanced Coati Optimization Algorithm (MECOA). MECOA improves performance through three core strategies: (1) Elite-guided search, which replaces the single global best solution with an elite pool of three top individuals and incorporates the heavy-tailed property of Lévy flights to balance large-step exploration and small-step exploitation; (2) Horizontal crossover, which simulates biological gene recombination to promote information sharing among individuals and enhance cooperative search efficiency; and (3) Precise elimination, which discards 20% of low-fitness individuals in each generation and generates new individuals around the best solution to improve population quality. Experiments on the CEC2017 (30/50/100-dimensional) and CEC2022 (20-dimensional) benchmark suites demonstrate that MECOA achieves superior performance. On CEC2017, MECOA ranks first with an average rank of 1.87, 2.07, 1.83, outperforming the second-best LSHADE (2.03, 2.43 and 2.63) and the original COA (9.93, 9.93 and 9.96). On CEC2022, MECOA also maintains the leading position with an average rank of 1.58, far surpassing COA (8.92). Statistical analysis using the Wilcoxon rank-sum test (significance level 0.05) confirms the superiority of MECOA. Furthermore, MECOA is applied to parameter identification of single-diode (SDM) and double-diode (DDM) PV models. Experiments based on real measurement data show that the SDM model achieves an RMSE of 9.8610 × 10⁻⁴, which is only 1/20 of that of COA. For the DDM model, the fitted curves almost perfectly overlap with the experimental data, with a total integrated absolute error (IAE) of only 0.021555 A. These results fully validate the effectiveness and reliability of MECOA in solving complex engineering optimization problems, providing a robust and efficient solution for accurate modeling and optimization of PV systems. Full article

Breast cancer is a substantial and growing public health issue in India, with epidemiological data demonstrating distinct and often severe disease characteristics in contrast to Western countries. Contrary to the global trend, Indian women frequently develop the disease at an earlier age and tend to present with more advanced stages, emphasizing important variations in disease pathophysiology. This review compiles and critically evaluates the current literature to describe the specific pathophysiology of breast cancer in the Indian population. We investigate the unique cellular and molecular landscapes, evaluate the impact of specific Indian demographic and genetic features, and highlight crucial gaps in knowledge, diagnostic tools, and therapeutic approaches. The assessment reveals a molecular landscape determined by the incidence of specific tumor subtypes; triple-negative breast cancer, for instance, is frequently diagnosed in younger women, and genetic profiling research suggests variations in its susceptibility genes and mutation patterns when compared to global populations. While this paper brings together recent advancements, it highlights the challenges of adopting global diagnostic and treatment guidelines in the Indian healthcare system. These challenges are largely due to variances and specific demographic and socioeconomic discrepancies that create substantial hurdles for timely diagnosis and patient care. We highlight significant gaps, such as the need for more complete multi-omics profiling of Indian patient cohorts, an absence of uniform and readily available screening programs, and shortcomings in healthcare infrastructure and qualified oncology experts. Furthermore, the review highlights the crucial need for therapeutic strategies tailored to the distinct genetic and demographic profiles of Indian breast cancer patients. We present significant strategies for addressing these challenges, with a focus on integrating multi-omics data and clinical characteristics to gain deeper insight into the underlying causes of the disease. Promising avenues include using artificial intelligence and advancements in technology to improve diagnostics, developing indigenous and affordable treatment options, and establishing context-specific research frameworks for the Indian population. This review also underlines the necessity for personalized strategies to improve breast cancer outcomes in India. Full article

Type 2 diabetes (T2D) is a chronic metabolic disorder with an estimated prevalence of over 422 million individuals affected globally. Since the advent of genomics, numerous studies have been conducted to elucidate T2D pathogenetic mechanisms and define genetic loci affecting T2D susceptibility. Transcriptomic studies, including bulk and single-cell RNA sequencing, play an important role both in discerning molecular mechanisms of the disease and in identifying potential T2D biomarkers. In this study, we performed bulk RNA-seq of whole blood of nine T2D patients and nine control subjects and performed meta-analysis of these data with seven publicly available blood RNA-seq datasets of T2D patients. Our analysis showed that the changes in the gene expression between different studies show very low concordance; moreover, a substantial number of differentially expressed genes (DEGs) was identified in only three out of eight datasets, with only five DEGs—FBLN2, TPCN1, PC, SHANK1, and PLD4—identified in all three of those datasets. Nevertheless, cross-study meta-analysis identified a broad set of 2065 DEGs, including 713 genes that have not been identified in any of the source studies. These genes showed a significant enrichment of GO terms indicating neutrophil activation and proliferation and included several genes that have not been implicated in type 2 diabetes previously. Taken together, our study highlights challenges associated with biomarker discovery from blood transcriptomics in T2D and suggests novel genes that may be considered as such biomarkers. Full article

To investigate the effect of epigenetic modifications on sex determination and differentiation in northern pike (Esox lucius), we employed Whole-Genome Bisulfite Sequencing (WGBS) to analyze the DNA methylation patterns in gonadal tissues of females, males, and neomales. First, we obtained high-quality sequencing data, including a total of 410.16 Gb of raw reads and 361.48 Gb of clean reads, with an 86% unique mapping rate, and a bisulfite conversion efficiency of 99.6%. Subsequently, comparative analysis revealed that 66,581 differentially methylated CG regions (i.e., DNA regions with a high frequency of CG dinucleotides), 1215 differentially methylated CHG regions (i.e., DNA regions where CG is followed by another nucleotide), and 3185 differentially methylated CHH regions (i.e., regions where cytosine is methylated in a CHH sequence, with ‘H’ representing A, T, or C) were identified among the three groups. Furthermore, we identified four key differentially methylated candidate genes (Rspo1, hsd11b2, CYP27A1 and smad3) associated with sex determination and differentiation processes in E. lucius. Finally, by integrating GO and KEGG enrichment analyses, we explored the role of epigenetic modification regulatory networks in the sex determination and differentiation of E. lucius and identified multiple metabolic pathways related to sex determination and differentiation processes (Notch signaling pathway, Wnt signaling pathway and Ovarian steroidogenesis). This study thereby lays a foundation for subsequent functional verification. Full article

Banana (Musa spp.) is a typical climacteric fruit. Xyloglucan endotransglucosylase/hydrolase (XTH) is a key factor regulating plant cell wall dynamic remodeling and participates in fruit ripening. To clarify the core physiological traits of banana ripening, four ripening stages of banana cultivar (Musa AAA ‘Minai No. 1’) fruits in the fully green stage (S1), green-yellow stage (S2), fully yellow stage (S3), and yellow with brown spots stage (S4) were used in this study’s experimental materials, to examine dynamic changes in key physiological–biochemical properties. The results showed that fruit firmness decreased continuously, starch content first increased then decreased, and soluble protein and total soluble solids (TSS) accumulated gradually during the ripening stages of banana fruits. Transcriptome analysis of the four stages found that there were 14,315 differentially expressed genes (DEGs) in S1 versus S4, the GO enrichment pathway is enriched in “protein dephosphorylation”, and the KEGG enrichment pathway is enriched in the “Protein processing in endoplasmic reticulum” and “Ubiquitin mediated proteolysis” pathways. The fruit ripening process involves the processing of numerous proteins. The heatmap revealed that MaXTH32.5 was significantly up-regulated during banana ripening and the result of RT-qPCR is consistent with the transcriptome data. A total of 989 XTH members across 16 Musa varieties of the XTH gene family were further identified. Among them, MaXTH32.5 localized at the chloroplast, and transient overexpression of MaXTH32.5 significantly reduced banana fruit firmness and may be involved in regulating ripening in banana fruits. This study indicated that the differential expression of XTH gene family members may regulate ripening-related processes in banana and MaXTH32.5 as a key candidate, providing insights into banana ripening mechanisms and a foundation for subsequent Musa XTH research. Full article

Antiretroviral therapy (ART) effectively suppresses HIV replication but fails to eradicate latent reservoirs, leading to viral rebound after interruption. Chimeric antigen receptor (CAR) T-cell therapy offers a potential strategy to achieve durable remission. A systematic PubMed search (July 2020–June 2025) identified 253 studies on CAR-T therapy in HIV; 74 met inclusion criteria and were qualitatively analyzed. Preclinical data showed that CAR-T cells can recognize and eliminate infected cells, reach viral reservoirs, and persist long term, particularly when derived from hematopoietic stem cells. Dual-target and combination approaches with checkpoint inhibitors or latency-reversing agents enhanced antiviral efficacy. Early clinical studies confirmed safety and modest reservoir reduction. CAR-T cell therapy represents a promising step toward a functional HIV cure. Further optimization of design, integration with gene-editing technologies, and standardized clinical evaluation are required to confirm durable efficacy and safety. Full article

Background: Polycystic ovary syndrome (PCOS)-related infertility remains a major challenge and the efficacy of conventional treatments is limited in certain patient groups and often fails to address the underlying causes of ovarian dysfunction. Platelet-rich plasma (PRP) is rich in growth factors and cytokines and has emerged as a potential regenerative therapy for women with a diminished ovarian reserve. Methods: A literature search for studies pertaining to intraovarian PRP administration and PCOS was performed on PubMed. Results: Preclinical studies in PCOS animal models have demonstrated that intraovarian PRP can improve folliculogenesis, enhance antioxidant defenses, normalize steroid hormone levels, and downregulate pro-apoptotic pathways. Early clinical reports suggest that intraovarian PRP may restore ovulation and improve ovarian reserve in women with long-standing amenorrhea and poor responses to standard fertility treatments. The proposed mechanisms of how PRP could improve folliculogenesis include the modulation of local ovarian gene expression, the activation of dormant follicles, angiogenesis, and a reduction in oxidative stress and inflammation. Conclusions: Although preliminary data are promising, larger studies are needed to establish the efficacy, if any, of intraovarian PRP administration as a potential novel therapeutic adjunct in women with PCOS. Full article

Background: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal stem cell disorders in which disrupted post-transcriptional regulation contributes to aberrant hematopoiesis and leukemic transformation. The miRNA biogenesis machinery, which comprises Drosha, DGCR8, Dicer, TARBP2, and AGO1, ensures the precise maturation of miRNAs that control lineage commitment and proliferation. However, the extent to which alterations in this pathway reshape hematopoietic gene networks during myeloid disease evolution remains largely unexplored. Methods: Bone marrow samples from newly diagnosed, untreated MDS and AML patients and matched healthy controls were analyzed for the expression of five key miRNA biogenesis genes using quantitative real-time PCR. Statistical comparisons, correlation matrices, and ROC analyses were performed to characterize gene-expression differences. These results were integrated with multigene logistic modeling, decision-curve analysis, and exploratory random forest/SHAP approaches to evaluate molecular interactions and diagnostic relevance. Results: DROSHA, DICER1, and TARBP2 were significantly downregulated in both MDS and AML, suggesting impaired miRNA maturation and a loss of global post-transcriptional control. DGCR8 expression increased across higher-risk MDS groups, suggesting compensatory activation of the Microprocessor complex, whereas AGO1 levels remained relatively stable, consistent with partial maintenance of RISC function. Correlation analyses revealed a co-regulated DROSHA–TARBP2–AGO1 module. ROC, logistic, and machine learning models identified DGCR8 and DICER1 as the strongest diagnostic discriminators. The integrated five-gene signature achieved high discriminative performance (AUC ≈ 0.98) and showed promise but remains preliminary potential for clinical application. Conclusions: Our findings suggest that defects in miRNA biogenesis disrupt hematopoietic homeostasis, reflecting common mechanisms in MDS and AML. The dysregulation of DICER1, DGCR8, and TARBP2 offers insights into miRNA-driven leukemogenesis and may pave the way for miRNA-based diagnostic and therapeutic strategies, pending validation in larger cohorts. Although transcript-level data are provided, future studies should include functional validation to determine the impact on downstream miRNA processing and hematopoietic pathways. Full article

Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis due to aggressive invasion and therapy resistance. Cancer-associated fibroblasts (CAFs) are key stromal components that promote tumor progression; however, their specific roles in ESCC remain unclear. Using a direct co-culture model of ESCC cell lines (TE-9, -10, and -15) and mesenchymal stem cells (MSCs) to generate CAF-like cells, we identified biglycan (BGN) as a significantly upregulated gene in CAF-like cells via cDNA microarray analysis. Public single-cell RNA sequencing data also demonstrated elevated BGN expression in CAF clusters. We confirmed that CAF-like cells exhibited elevated BGN expression and secretion at both the mRNA and protein levels. Recombinant human BGN enhanced ESCC cell proliferation and migration by activating Erk and NF-κB signaling pathways, effects abrogated by TLR4 blockade. Furthermore, BGN promoted CAF marker expression in MSCs, M2-like macrophage polarization, and enhanced proliferation and migration abilities in both cell types. Immunohistochemical analysis of 66 ESCC tissues revealed that high stromal BGN expression correlated with greater tumor invasion, lymphatic invasion, and shorter disease-free survival. These findings indicate that CAF-derived BGN promotes ESCC progression via TLR4-mediated signaling and modulates stromal cell behavior, highlighting its potential as a prognostic biomarker and therapeutic target. Full article