Advancements in bioinformatic tools and breakthroughs in high throughput RNA sequencing have unveiled the potential role of non-coding RNAs in influencing the overall expression of disease-responsive genes. Owing to the increasing need to develop resilient crop varieties against environmental constraints, our study explores the functional relationship of various non-coding RNAs in wheat during leaf rust pathogenesis. MicroRNAs (miRNAs) and circular RNAs (circRNAs) were retrieved from SAGE and RNA-Seq libraries, respectively, in the susceptible (HD2329) and resistant (HD2329 + Lr28) wheat Near-Isogenic Lines (NILs). Here we explored the previously published circRNAs for their differential expression and correlated the data with the differentially expressed miRNAs (DEMs) through various in silico methods to acquire the target miRNAs of circRNAs and the downstream target mRNAs of miRNAs. Finally, a competing endogenous RNA (ceRNAs) regulatory network was constructed and validated through RT-qPCR method. We have identified the ceRNA regulatory network of four differentially expressed circRNAs (DECs) and five DEMs to highlight their crucial roles in the robust enhancement of the temporal expression profiles of five defense responsive genes (mRNAs) in wheat NILs against leaf rust infection. The study confirms the synergistic expression of circRNAs and mRNAs with an antagonistic correlation with the expression profile of the corresponding miRNAs. The vital role of leaf rust-resistant gene Lr28 has also been highlighted for driving the efficiency of the circRNAs to upregulate target gene expression. Thus, understanding the circRNA-miRNA-target gene interaction during leaf rust pathogenesis can help to identify stress-specific regulatory biomarkers to enhance defense responses in wheat for improved resilience through multi-omics integration of transcriptomics, proteomics and metabolomics.

Large-scale, pan-cancer analysis is enabled by data driven knowledge bases that link tumor molecular profiles with phenotypes. A debilitating cancer-related phenotype is skeletal muscle loss, or cachexia, which occurs partly from tumor products secreted into circulation. Using the LinkedOmicsKB knowledge base assembled from the Clinical Proteomics Tumor Analysis Consortium proteogenomic analysis, along with catalogs of human secretome proteins, ligand-receptor pairs and molecular signatures, we sought to identify candidate pan-cancer proteins secreted to blood that could regulate skeletal muscle phenotypes in multiple solid cancers. Tumor proteins having significant pan-cancer associations with muscle were referenced against secretome proteins secreted to blood from the Human Protein Atlas, then verified as increased in paired tumor vs. normal tissues in pan-cancer manner. This workflow revealed seven secreted proteins from cancers afflicting kidneys, head and neck, lungs and pancreas that classified as protein-binding activity modulator, extracellular matrix protein or intercellular signaling molecule. Concordance of these biomarkers with validated molecular signatures of cachexia and senescence supported relevance to muscle and cachexia disease biology, and high tumor expression of the biomarker set associated with lower overall survival. In this article, we discuss avenues by which skeletal muscle and cachexia may be regulated by these candidate pan-cancer proteins secreted to blood, and conceptualize a strategy that considers them collectively as a biomarker signature with potential for refinement by data analytics and radiogenomics for predictive testing of future risk in a non-invasive, blood-based panel amenable to broad uptake and early management.

Post-traumatic epilepsy (PTE) is a debilitating chronic outcome of traumatic brain injury (TBI). Although FTO has been reported as a possible intervention target of TBI, its precise roles in the PTE remain incompletely understood. Here we used mild or serious mice TBI model to probe the role and molecular mechanism of FTO in PTE. The results of electroencephalography showed that frequency of epilepsy in serious TBI model mice was more obvious. Using quantitative PCR (qPCR) and western blot analysis, we demonstrated that FTO and NR4A2 were downregulated, while m6A level of NR4A2 mRNA was upregulated in the hippocampus of serious TBI mice. Functionally, FTO overexpression was found to reduce epilepsy susceptibility, blood-brain barrier (BBB) disruption and neuronal damage in TBI mice, suggested a role for FTO in PTE. In addition, RNA-binding protein immunoprecipitation and dual-luciferase assay experiment showed that NR4A2 was a target of FTO, and FTO upregulated NR4A2 expression through m6A-YTHDF2 manner. Furthermore, the molecular and histological changes caused by FTO overexpression are markedly reversed by NR4A2 knockdown in TBI mice. Collectively, our results demonstrate that FTO alleviates epilepsy susceptibility and brain injury after TBI by mediating epigenetic up-regulation of NR4A2, which implicates it as a potential therapeutic target for PTE.

Prostate cancer (PC) ranks among the most prevalent cancers in males. Recent studies have highlighted intricate connections between long non-coding RNAs (lncRNAs), natural products, and cellular signaling in PC development. LncRNAs, which are RNA transcripts without protein-coding function, influence cell growth, programmed cell death, metastasis, and resistance to treatments through pathways like PI3K/AKT, WNT/β-catenin, and androgen receptor signaling. Certain lncRNAs, including HOTAIR and PCA3, are associated with PC progression, with potential as diagnostic markers. Natural compounds, such as curcumin and resveratrol, demonstrate anticancer effects by targeting these pathways, reducing tumor growth, and modulating lncRNA expression. For instance, curcumin suppresses HOTAIR levels, hindering PC cell proliferation and invasion. The interaction between lncRNAs and natural compounds may open new avenues for therapy, as these substances can simultaneously impact multiple signaling pathways. These complex interactions offer promising directions for developing innovative PC treatments, enhancing diagnostics, and identifying new biomarkers for improved prevention and targeted therapy. This review aims to map the multifaceted relationship among natural products, lncRNAs, and signaling pathways in PC pathogenesis, focusing on key pathways such as AR, PI3K/AKT/mTOR, WNT/β-catenin, and MAPK, which are crucial in PC progression and therapy resistance. Regulation of these pathways by natural products and lncRNAs could lead to new insights into biomarker identification, preventive measures, and targeted PC therapies.

MicroRNAs (miRNA) are categorized as short endogenous non-coding RNAs, which have a significant role in post-transcriptional gene regulation. Identifying new animal precursor miRNA (pre-miRNA) and miRNA is crucial to understand the role of miRNAs in various biological processes including the development of diseases. The present study focuses on the development of a Light Gradient Boost (LGB) based method for the classification of animal pre-miRNAs using various sequence and secondary structural features. In various pre-miRNA families, distinct k-mer repeat signatures with a length of three nucleotides have been identified. Out of nine different classifiers that have been trained and tested in the present study, LGB has an overall better performance with an AUROC of 0.959. In comparison with the existing methods, our method 'pmiRScan' has an overall better performance with accuracy of 0.93, sensitivity of 0.86, specificity of 0.95 and F-score of 0.82. Moreover, pmiRScan effectively classifies pre-miRNAs from four distinct taxonomic groups: mammals, nematodes, molluscs and arthropods. We have used our classifier to predict genome-wide pre-miRNAs in human. We find a total of 313 pre-miRNA candidates using pmiRScan. A total of 180 potential mature miRNAs belonging to 60 distinct miRNA families are extracted from predicted pre-miRNAs; of which 128 were novel and are note reported in miRBase. These discoveries may enhance our current understanding of miRNAs and their targets in human. pmiRScan is freely available at http://www.csb.iitkgp.ac.in/applications/pmiRScan/index.php .

Gamma-aminobutyric acid (GABA) functions as an inhibitory neurotransmitter which blocks the impulses between nerve cells in the brain. Due to the increasing awareness about the health promoting benefits associated with GABA, it is also artificially synthesized and consumed as a nutritional supplement by people in some regions of the world. Though among the fresh vegetables, tomato fruits do contain a comparatively higher amount of GABA (0.07 to 2.01 mg g FW), it needs to be further enhanced to fully impart its potential health benefits. Achieving this feat through classical breeding approaches is time and resource consuming, and is also associated with linkage drag. On the other hand, precise targeting of specific sites in the genome with less off- target effects is mediated by CRISPR/Cas9 genome editing tool and is widely used to overcome the barriers associated with traditional breeding approaches. Combining genome editing with speed breeding techniques can enable the rapid development of GABA-rich tomato cultivars, paving a way to unlock a new era of functional foods, where every bite contributes to cognitive well-being and holistic health. This review highlights the significance of GABA boosted functional foods and explores the potential of CRISPR/Cas9 technology for developing GABA enriched tomatoes.

Long-read sequencing has emerged as a transformative technology in recent years, offering significant potential for the molecular diagnosis of unresolved genetic disorders. Despite its promise, the comprehensive detection and clinical annotation of genomic variants remain intricate and technically demanding. We present SUMMER, an integrated and structured workflow specifically designed to process raw Nanopore sequencing reads. SUMMER facilitates an in-depth analysis of multiple variant types, including SNV, SV, short tandem repeat and mobile element insertion. For clinical applications, SUMMER employs SvAnna to prioritize SV candidates based on phenotype relevance and utilizes Straglr to provide reference distributions of non-pathogenic unit counts for 55 known pathogenic short tandem repeats. By addressing critical challenges in variant detection and annotation, SUMMER seeks to advance the clinical utility of long-read sequencing in diagnostic genomics. SUMMER is available on the web at https://github.com/carolhuaxia/summer .

Clear cell renal cell carcinoma (ccRCC) is a highly malignant tumor characterized by a significant propensity for recurrence and metastasis. DNA methylation has emerged as a critical epigenetic mechanism with substantial utility in cancer diagnosis. In this study, multi-omics data were utilized to investigate the target genes regulated by the transcription factor MYC-associated zinc finger protein (MAZ) in ccRCC, leading to the identification of thymidine phosphorylase (TYMP) as a gene with notably elevated expression in ccRCC. The interaction between MAZ and TYMP was confirmed through chromatin immunoprecipitation (ChIP) assays and bioinformatics analysis. It was found that the binding of MAZ to the TYMP promoter is associated with the methylation status of this promoter region. Furthermore, the methylation of the TYMP promoter appears to be correlated with both the clinicopathological stage and overall survival of ccRCC patients. Further exploration of genes within the "nucleotide metabolism" pathway, identified through Gene Ontology (GO) enrichment analysis, revealed that uridine phosphorylase 1 (UPP1) interacts with TYMP. Interestingly, UPP1 was also shown to be activated by MAZ, suggesting a coordinated regulatory mechanism. Based on these findings, we propose that the TYMP-UPP1 complex, co-regulated by MAZ, plays a pivotal role in nucleotide metabolism in ccRCC. These results suggest that TYMP may contribute to the pathophysiology of ccRCC and that promoter methylation offers potential as a prognostic indicator, providing novel insights into the molecular underpinnings of ccRCC and potential avenues for therapeutic intervention.

Despite years of progress in biotechnology, altering the genetic makeup of many plant species, especially their plastids, remains challenging. The existence of a cell wall poses a significant obstacle to the effectual transportation of biomolecules. Developing efficient methods to introduce genes into plant cells and organelles without causing harm is an ongoing area of research. Traditional approaches like Agrobacterium-mediated transformation, biolistic particle delivery, electroporation and polyethylene glycol (PEG) transformation have shown some success but come with limitations like laborious, time-consuming and causing tissue damage. For instance, the Agrobacterium method can be applied only to the restricted host range, while PEG transformation and biolistic particle delivery are not very efficient. In contrast, nanotechnology made an appearance in the field of genetic engineering. Nanoparticles act as delivery vehicles for many cargos in animals. However, in plants, the application of nanocarriers for the delivery of biomolecules is still in its infant stage. Nonetheless, it holds immense potential for the future of plant biotechnology and genome editing.

High-resolution insights into the nucleotide arrangement within an organism's genome are pivotal for deciphering its genetic composition, function, and evolutionary trajectory. Over the years, nucleic acid sequencing has been instrumental in driving significant advancements in genomics and molecular biology. The advent of high-throughput or next-generation sequencing (NGS) technologies has revolutionized whole genome sequencing, revealing novel and intriguing features of genomes, such as single nucleotide polymorphisms and lethal mutations in both coding and non-coding regions. These platforms provide a practical approach to comprehensively identifying and analyzing whole genomes with remarkable throughput, accuracy, and scalability within a short time frame. The resulting data holds immense potential for enhancing healthcare systems, developing novel and personalized therapies, and preparing for future pandemics and outbreaks. Given the wide array of available high-throughput sequencing platforms, selecting the appropriate technology based on specific needs is crucial. However, there is limited information regarding sample preparation, sequencing principles, and output data to facilitate a comparative evaluation of these platforms. This review details various NGS technologies and approaches, examining their advantages, limitations, and future potential. Despite being in their early stages and facing challenges, ongoing advancements in NGS are expected to yield significant future benefits.

One of the outstanding features of chronic hepatitis B infection (CHB) is its strong association with liver fibrosis. CHB induced inflammation and injury trigger multiple biochemical and physical changes that include the promotion of a wide range of cytokines, chemokines and growth factors that activate hepatic stellate cells (HSCs) CHB induced activation of hepatic stellate cells (HSCs) is regarded as a central event in fibrogenesis to directly promote the synthesis of myofibroblasts and the expression of a range of materials to repair injured liver tissue. Fibrogenesis is modulated by the mainstream epigenetic machinery, as well as by non-coding RNA (ncRNA) that are often referred to as an ancillary epigenetic response to fine tune gene expression. Although extensive research has explained the regulatory role of ncRNA in liver fibrogenesis, most of this research relates to non-CHB etiologies. This review paper outlines the complex interactive regulatory role of microRNA (miRNA) and their interaction with long non-coding RNA (lncRNA), circular RNA (circRNA) and the mainstream epigenetic machinery in CHB induced liver fibrosis. The paper also illustrates some of the difficulties involved in translating candidate ncRNA into approved drugs or diagnostic tools. In conclusion, the important regulatory role of ncRNA in CHB induced liver fibrosis warrants further investigation to exploit their undoubted potential as diagnostic and therapeutic agents.

Mitochondria, the cellular powerhouses, are pivotal to neuronal function and health, particularly through their role in regulating synaptic structure and function. Spine reprogramming, which underlies synapse development, depends heavily on mitochondrial dynamics-such as biogenesis, fission, fusion, and mitophagy as well as functions including ATP production, calcium (Ca) regulation, and retrograde signaling. Mitochondria supply the energy necessary for assisting synapse development and plasticity, while also regulating intracellular Ca homeostasis to prevent excitotoxicity and support synaptic neurotransmission. Additionally, the dynamic processes of mitochondria ensure mitochondrial quality and adaptability, which are essential for maintaining effective synaptic activity. Emerging evidence highlights the significant role of epigenetic modifications in regulating mitochondrial dynamics and function. Epigenetic changes influence gene expression, which in turn affects mitochondrial activity, ensuring coordinated responses necessary for synapse development. Furthermore, metabolic changes within mitochondria can impact the epigenetic machinery, thereby modulating gene expression patterns that support synaptic integrity. Altered epigenetic regulation affecting mitochondrial dynamics and functions is linked to several neurological disorders, including Amyotrophic Lateral Sclerosis, Huntington's, Alzheimer's, and Parkinson's diseases, emphasizing its crucial function. The review delves into the molecular machinery involved in mitochondrial dynamics, ATP and Ca regulation, highlighting the role of key proteins that facilitate the processes. Additionally, it also shed light on the emerging epigenetic factors influencing these regulations. It provides a thorough summary on the current understanding of the role of mitochondria in synapse development and emphasizes the importance of both molecular and epigenetic mechanisms in maintaining synaptic integrity.

T cells are involved in every stage of tumor development and significantly influence the tumor microenvironment (TME). Our objective was to assess T-cell marker gene expression profiles, develop a predictive risk model for human papilloma virus (HPV)-negative oral squamous cell carcinoma (OSCC) utilizing these genes, and examine the correlation between the risk score and the immunotherapy response.

Narciclasine (Ncs) was effective in sepsis management due to its antioxidant properties. The present study dissected the protective effects of Ncs against sepsis-associated acute kidney injury (SA-AKI) and the molecular mechanisms. The SA-AKI mice were developed using cecum ligation and puncture and pretreated with Ncs and adenoviruses. Human renal microvascular endothelial cells (RMECs) were induced with LPS and treated with Ncs. Ncs alleviated proximal tubular dilatation, interstitial widening, and necrosis in renal tissues and reduced the renal injury marker and pro-inflammatory cytokine levels in the serum of SA-AKI mice. Ncs promoted the expression of ZO-1, VE-cadherin, and CD31 and the activities of SOD, GSH-Px, and CAT, and inhibited the levels of pro-inflammatory cytokines, and apoptosis rate in LPS-treated RMECs. Estrogen receptor 1 (ESR1) was a target protein of Ncs, and S100 calcium-binding protein A11 (S100A11) was a target of the transcription factor ESR1. Ncs blocked transcription of S100A11 by inhibiting ESR1. Silencing of S100A11 overturned the deteriorating effects of ESR1 overexpression on SA-AKI progression in vivo and RMEC injury in vitro. These findings suggest that Ncs may ameliorate SA-AKI by repressing the ESR1/S100A11 signaling, providing a novel perspective for research on SA-AKI.

Rice (Oryza sativa L.), Poaceae family, forms staple diet of half of world's population, and brinjal (Solanum melongena L.), an important solanaceous crop, are consumed worldwide. Rhizosphere research is gaining importance towards application of knowledge for improving productivity, sustainable agricultural practice, and rhizoremediation for nature restoration. While there are reports on rhizobacteriome of rice, studies comparing structural, functional and metabolomic traits of microbial communities in rhizospheres of rice and brinjal are not yet available. We demonstrated, in Oryza sativa (1144-Hybrid, Dhiren, Local Saran cultivars) and Solanum melongena (Jhiloria, Chandtara, Jotshna cultivars) rhizospheres from Malda, India, using integrated approach of 16 S ribosomal sequencing, shotgun metagenomics, and microbial metabolomics to decipher microbial diversity, association with soil physicochemical characteristics, key genes and pathways. Ectoine biosynthesis was significantly expressed in brinjal (Jhiloria), but not in rice rhizosphere. The dominant brinjal rhizobacteriome-specific bacteria comprised Thermus sp., Petrobacter succinatimandens, Thermoanaerobacter sp., and Diaphorobacter sp., that were involved in house-keeping functions including pentose phosphate pathway, biosynthesis of amino acids, lipopolysaccharide, and photosynthesis. The dominant bacteria unique to rice rhizobacteriome (Local Saran) consisted of Aeromonas sp., associated with catechol meta-cleavage, while Clostridium sp., Faecalibacterium prausnitzii, and Roseburia sp. were involved with lysine biosysnthesis in rice (1144-Hybrid). Our results imply novel information for improved breeding of brinjal specific cultivar with enhanced ectoine production associated with osmotic stress tolerance, rice specific cultivars with enhanced lysine production significant to human nutrition and catechol removal for the maintenance of environmental quality.

Hepatocellular carcinoma (HCC) remains a malignant and life-threatening tumor with an extremely poor prognosis, posing a significant global health challenge. Despite the continuous emergence of novel therapeutic agents, patients exhibit substantial heterogeneity in their responses to anti-tumor drugs and overall prognosis. The pentose phosphate pathway (PPP) is highly activated in various tumor cells and plays a pivotal role in tumor metabolic reprogramming. This study aimed to construct a model based on PPP-related Genes for risk assessment and prognosis prediction in HCC patients. We integrated RNA-seq and microarray data from TCGA, GEO, and ICGC databases, along with single-cell RNA sequencing (scRNA-seq) data obtained from HCC patients via GEO. Based on the "Seurat" R package, we identified distinct gene clusters related to the PPP within the scRNA-seq data. Using a penalized Cox regression model with least absolute shrinkage and selection operator (LASSO) penalties, we constructed a risk prognosis model. The validity of our risk prognosis model was further confirmed in external cohorts. Additionally, we developed a nomogram capable of accurately predicting overall survival in HCC patients. Furthermore, we explored the predictive potential of our risk model within the immune microenvironment and assessed its relevance to biological function, particularly in the context of immunotherapy. Subsequently, we performed in vitro functional validation of the key genes (ATAD2 and SPP1) in our model. A ten-gene signature associated with the PPP was formulated to enhance the prediction of HCC prognosis and anti-tumor treatment response. Following this, the ROC curve, nomogram, and calibration curve outcomes corroborated the model's robust clinical predictive capability. Functional enrichment analysis unveiled the engagement of the immune system and notable variances in the immune infiltration landscape across the high and low-risk groups. Additionally, tumor mutation frequencies were observed to be elevated in the high-risk group. Based on our analyses, the IC50 values of most identified anticancer agents demonstrated a correlation with the RiskScore. Additionally, the high-risk and low-risk groups exhibited differential sensitivity to various drugs. Cytological experiments revealed that silencing ATAD2 or SPP1 suppresses malignant phenotypes, including viability and migration, in liver cancer cells. In this study, a novel gene signature related to the PPP was developed, demonstrating favorable predictive performance. This signature holds significant guiding value for assessing the prognosis of HCC patients and directing individualized treatment strategies.

Waxy maize is highly preferred diet in developing countries due to its high amylopectin content. Enriching amylopectin in biofortified maize meets food security and fulfils the demand of rising industrial applications, especially bioethanol. The mutant waxy1 (wx1) gene is responsible for increased amylopectin in maize starch, with a wide range of food and industrial applications. Conventional maize has a modest amount of amylopectin (70-75% of starch), but waxy maize, with favourable wx1 allele, has ~ 95-100% amylopectin. In this study, the wx1 allele was introgressed into the multi-nutrient-rich maize parental inbreds (PMI-PV9 and PMI-PV5) of APQH8, a multi-nutrient rich maize hybrid having high lysine, tryptophan, and provitamin-A nutritionally superior over the traditional hybrids. Gene-specific markers specific for o2 and crtRB1 were employed to select desirable gene segregants from BCF, BCF, and BCF. Background selection was employed with > 90 SSR markers. Selected backcross progenies showed high recovery of recurrent parent genomes (RPG: 94.8-96.8%). The reconstituted waxy hybrids exhibited an increase in amylopectin (mean: 98.4%) compared to the original hybrid (mean: 72.7%). The reconstituted hybrids also recorded enhanced lysine (mean: 0.382%), tryptophan (mean: 0.092%), and provitamin-A (mean: 10.36 ppm), respectively, than normal maize, however similar to the original hybrid with high lysine: 0.330%, tryptophan: 0.079% and provitamin-A: 10.42 ppm. Furthermore, MAS-derived genotypes showed similar agro-morphological traits and grain yield. These biofortified waxy maize hybrids, rich in provitamin-A, lysine, and tryptophan with enhanced amylopectin hold great potential in diverse industrial applications and nutritional security.

The agronomical interest of hybrid wheat has long been a matter of debate. Compared to maize where hybrids have been successfully grown for decades, the mixed results obtained in wheat have been attributed at least partially to the lack of heterotic groups. The wheat genome is known to be strongly partitioned and characterized by numerous presence/absence variations and alien introgressions which have not been thoroughly considered in hybrid breeding. The objective was to investigate the relationships between hybrid performance and genomic diversity. For this, we characterized a set of 124 hybrids as well as their 19 female and 16 male parents. Phenotyping for yield and yield components was conducted during two years in three locations. Parental lines were genotyped using a 410 K SNP array as well as through sequence capture of roughly 200,000 loci. This led to the identification of 180 structural variations including presence-absence variations and alien introgressions. Twenty-six of them were associated to hybrid performance through either additivity or dominance effects. While no correlation was observed at the whole genome level, the genetic distance for 25 genomic regions resulting from the structural and functional partitioning of the chromosomes shown positive or negative correlation with agronomic traits including yield. Large introgressions, like the Aegilops ventricosa 2NS-2AS translocation, can correspond to entire chromosomal regions, such as the R1 region, with an impact on yield. Our results suggest hybrid breeding should consider both structural variations and chromosome partitioning rather than maximizing whole-genome genetic distance, and according to genomic regions to combine homozygosity and heterozygosity.

Dwarfism is a major trait for developing lodging-resistant rice cultivars. Gamma irradiation-induced mutagenesis has proven to be an effective method for generating dwarf rice mutants. In this research, we isolated a dwarf mutant from Anna R (4) in the M generation and subsequently stabilized the trait through successive selfing of progeny across the M-M generations. We then employed whole-genome re-sequencing (WGRS) and RNA sequencing (RNA-seq) analyses of Anna R (4) and the mutant (designated as ACM-20001) to elucidate the underlying mechanisms and identify candidate genes associated with dwarfness. Numerous genetic variations were identified between Anna (R) 4 and ACM-20001 through WGRS. In total, 2049 genetic variants, including 343 InDels and 1706 nonsynonymous SNPs, were identified across 697 genes. Additionally, RNA-seq analysis revealed 2,881 differentially expressed genes between the wild-type Anna (R) 4 and the mutant ACM-20001, with 1,451 genes up-regulated and 1,430 genes down-regulated in ACM-20001 compared to Anna (R) 4. By integrating WGRS and RNA-seq data with functional annotation analysis, we identified the most likely candidate genes (i.e., Os02g0506400, Os05g0515200, Os06g0154200 and Os08g0250900) related to dwarfness. Quantitative real-time PCR analysis verified the expression of these genes. Collectively, our study provides valuable insights in to the genes and mechanisms underlying dwarfness in rice. Further studies are required to elucidate the roles of these candidate genes in dwarfness, which contribute to advancements rice breeding programs.

Gene‒gene interactions play pivotal roles in disease pathogenesis and are fundamental in the development of targeted therapeutics, particularly through the elucidation of oncogenic gene drivers in cancer. The systematic analysis of pathways and gene interactions is critical in the drug discovery process for various cancer subtypes. SPAG5, known for its role in spindle formation during cell division, has been identified as an oncogene in several cancers, although its specific impact on AML remains underexplored. This study leverages a high-throughput swarm-based deep neural network (SDNN) and transcriptomic data-an approach that enhances predictive accuracy and robustness through collective intelligence-to augment, model, and enhance the understanding of the TP53 pathway in AML cohorts. Our integrative systems biology approach identified SPAG5 as a uniquely downregulated driver in adult AML, underscoring its potential as a novel therapeutic target. The interaction of SPAG5 with key hub genes such as MDM2 and CDK1 not only reinforces its role in tumour suppression through negative regulation but also highlights its potential in moderating the phenotypic and genomic alterations associated with AML progression. This study of the role and interaction dynamics of SPAG5 sets the stage for future research aimed at developing targeted and personalized treatment approaches for AML, utilizing the capabilities of genetic interventions.

Metabolic reprogramming, the shifting from fatty acid oxidation to glucose utilization, improves cardiac function as heart failure (HF) progresses. Leptin plays an essential role in regulating glucose metabolism. However, the crosstalk between leptin and metabolic reprogramming is poorly understood. We tested the hypothesis that leptin improves cardiac function after myocardial infarction via enhancing glucose metabolism. In the isoproterenol (ISO)-induced heart failure model in vitro, H9c2 cell apoptosis was assessed by the TUNEL and Annexin V/PI staining assay. Leptin-mediated mitochondrial fusion was performed via TEM, and glucose oxidation was explored, as well as the ECAR, OCR, and protein expression of the vital metabolic enzymes. By blocking OPA1 expression or HDAC5 inhibition, the mitochondrial dynamic and glucose metabolic were detected to evaluate the role of OPA1 and HDAC5 in leptin-stimulated glucose metabolism. In the mouse model of HF in vivo, intraperitoneal leptin administration appreciably increased glucose oxidation and preserved cardiac function 56 days after coronary artery ligation. In vitro, we identified the OPA1-dependent HDAC5 nucleus export as a crucial process in boosting glucose utilization by activating MEF2 to upregulate Glut4 expression using the RNA interference technique in H9c2 cells. In vivo, leptin promotes glucose utilization and confers heart functional and survival benefits in chronic ischemic HF. The current study provided a novel insight into the role of leptin in metabolic reprogramming and revealed potential therapeutic targets for chronic HF.