Complications of diabetes have continued to escalate as a major public health concern worldwide. The situation keenly demands novel treatment strategies alongside the canonical regimen. Underscoring the molecular mechanisms associated with diabetic cellular pathophysiologies is very crucial in terms of therapeutics development. Ras homologue enriched in brain (Rheb) has recently emerged as a key controller for mechanistic (erstwhile mammalian) target of rapamycin complex 1 (mTORC1). The occurrence of different diseases including diabetes is attributed to augmented mTORC1 activation. Thus, investigation of the potential of Rheb as a therapeutic target has gained much interest recently. However, factors like difficulty in in vivo delivery, off-target effects, bioavailability issues, immunosuppressive effects, disruption of mTORC1-independent pathways involving Rheb, and many more, including the complicated nature of the disease diabetes itself, pose significant challenges in the development of Rheb therapeutics. The present article aims to shed light on the existing contribution of Rheb in the regulation of diabetic consequences and to rationalize its feasibility as a therapeutic target, with special emphasis on microRNA-mediated post-transcriptional regulation.
Introduction: Mitochondrial genomes recovered from public sequencing repositories offer cost-effective molecular resources without additional laboratory work. Building on a previously validated targeted Basic Local Alignment Search Tool–Contig Assembly Program version 3 (BLAST–CAP3) workflow for single-gene assembly, the present study demonstrates its extension to complete mitochondrial genome draft assembly using a publicly available whole-genome sequencing (WGS) dataset of Gryllus bimaculatus. Materials and methods: Mitochondrial reads were retrieved using custom National Center for Biotechnology Information (NCBI) nucleotide Basic Local Alignment Search Tool (BLASTN) parameters against the published G. bimaculatus mitochondrial genome reference, followed by CAP3 de novo assembly on Galaxy Europe. Results: Assembly yielded a single complete contig of 15,954 base pairs (bp) with 99.574% nucleotide identity to the reference (E-value = 0.0; bit score = 29,085). Independent read mapping validation confirmed that all 15,954 positions of the assembled contig were covered by at least 2× read depth (mean 44.5×; maximum 92×), with 4731 of the 4749 deduplicated reads (99.6%) successfully mapped. A critical obstacle, failure of standard CAP3 parameters in the A+T-rich control region (~1240 bp) due to the tandem repeat architecture, was resolved by reducing the overlap length cutoff to 10–15 bp. Self-dotplot analysis confirmed that tandem repeats were confined to positions ~14,650–15,450 bp with a repeat unit spacing of ~150–200 bp. Conclusions: This study documents a practical and potentially transferable solution for animal mitochondrial genome draft assembly from public sequencing data. The complete pipeline requires no local software installation and is executable using web-based tools within a single working day.
As a co-transcriptional gene expression regulation process, pre-mRNA polyadenylation is a key co-transcriptional processing step for mRNA maturation. Polyadenylation affects the fate of mRNA by modulating its stability, translation efficiency, and nuclear-to-cytoplasmic translocation. Alternative polyadenylation (APA) is an important regulatory mechanism in the processing of pre-mRNA 3′ ends during transcription, enhancing diversity and plasticity of the transcriptome. A significant amounts of studies have shown that the process of polyadenylation and APA plays an important role in plant growth, development, and their interactions with viruses. In this review, we examined recent progress in the role of polyadenylation and APA in regulating gene expression pathways in response to internal developmental cues as well as external challenges by viruses. APA is also associated with various pathologies, including viral infection, propagation, and release. Viral mRNAs utilize polyadenylation to mimic host transcripts, enhancing their stability and translation efficiency while evading immune recognition. Hosts counteract this through RNA surveillance mechanisms that target polyadenylated viral RNAs for degradation. The infection process also dynamically regulates host APA, reprogramming immune-related gene expression to mediate either antiviral defense or promotion of viral infection. The fact that APA participates in and regulates the intricate relationship during viral–host interaction warrants further research. Future perspectives are provided to aid in the study of the molecular mechanism of APA in development and viral–host interactions.
Maturity-onset diabetes of the young (MODY) is a group of monogenic diabetes disorders marked by early-onset hyperglycemia and primary pancreatic β-cell dysfunction. MODY is often misclassified as type 1 or type 2 diabetes, which can lead to delayed genetic diagnosis and inappropriate therapy. This review summarizes established MODY mechanisms and organizes them in a clinically oriented way to link major MODY genes with β-cell stimulus–secretion defects and practical treatment choices. In GCK-MODY, reduced glucose phosphorylation shifts the glucose threshold needed to raise ATP, close ATP-sensitive potassium (KATP) channels, open voltage-dependent Ca2+ channels, and trigger insulin granule fusion, which explains stable mild hyperglycemia and limited benefit from routine glucose-lowering drugs outside pregnancy. In HNF1A- and HNF4A-MODY, impaired transcriptional programs weaken glucose-stimulated insulin secretion and often progress over time; sulfonylureas can bypass upstream defects by closing KATP through sulfonylurea receptor-1 (SUR1) binding and restoring depolarization and Ca2+-triggered exocytosis. In KCNJ11- and ABCC8-related diabetes, activating variants keep KATP more open, reduce depolarization, and suppress Ca2+ entry; many responsive variants allow a switch from insulin to sulfonylureas. In HNF1B-, PDX1-, and INS-related disease, reduced β-cell mass or chronic endoplasmic reticulum (ER) stress can limit secretory capacity and increase the need for insulin. The review also discusses advances in genetic testing, variant interpretation, and risk modifiers that shape penetrance and adult misclassification. Together, these established mechanisms provide a clinically useful summary that links molecular diagnosis with treatment selection, variant interpretation, and family counseling.
Minimal residual disease (MRD) is an important prognostic marker in mature B-cell and plasma cell malignancies, providing sensitive assessment of treatment response and risk of relapse. Next-generation sequencing (NGS) enables highly sensitive detection of MRD through identification and tracking of immunoglobulin gene rearrangements associated with malignant clones of B-cell origin. This review outlines the principles of NGS-based MRD assessment and its application in mature B-cell and plasma cell malignancies including several mature B-cell lymphomas, chronic lymphocytic leukaemia (CLL), and multiple myeloma (MM). The advantages of NGS, such as high sensitivity and ability to use a range of sample types, are discussed alongside its limitations, including the requirement for baseline diagnostic samples and cost. Current evidence suggests that NGS is a powerful tool for MRD detection and is increasingly being incorporated into clinical trials as a response endpoint, with potential to guide treatment strategies such as escalation of therapy in routine clinical practice.
Cardiomyopathy is a multifactorial cardiac disorder that results in structural and functional alterations in the heart due to molecular defects in the cardiomyocytes. It can manifest as hypertrophic, dilated, arrhythmogenic, or restrictive cardiomyopathies and affects around 1 in 500 persons globally. These conditions often lead to heart failure or sudden cardiac death. Sarcomeric and non-sarcomeric gene alterations have a well-established genetic foundation, but transcriptional and translational regulatory mechanisms, particularly those involving coding and non-coding RNAs, are becoming important factors in development and course of this disease. With a focus on RNA-mediated regulation and biomarker identification, this review incorporates molecular insights into the pathogenesis of cardiomyopathy. It aims to augment phenotype-based management through biomarker-driven, customized medicine for better diagnosis and targeted therapy, with emphasis on precision-guided approaches.
Introduction: Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative bacterium that poses a significant threat to public health. The virulence factors that enable its colonization and invasion of different anatomical sites, particularly iron acquisition, are critical, as iron limitation within the host environment necessitates specialized uptake mechanisms. In this study, the transcriptional expression of iron acquisition-related virulence genes in K. pneumoniae from environmental interfaces was investigated.Materials and methods: A total of 302 drainage water samples surrounding primary, secondary, and tertiary care hospitals were collected. Phenotypic characterization was done using the string test to assess the hypermucoviscosity. Genotypic characterization was done to detect the presence of iron acquisition-related virulence genes using polymerase chain reaction (PCR). Expression analysis under varying iron conditions and antibiotic stress was conducted through quantitative real-time PCR, and antibiotic susceptibility testing (AST) was done using the Kirby–Bauer disc diffusion method.Results: In total, 76 K. pneumoniae isolates were identified, out of which 18 isolates showed positive results on the string test. Out of them, 15 isolates were found to be hypervirulent and harbored iron acquisition genes such as iroN (PB66, PB77, PB109, PC7, and PC15); iroB (PB60, PB77, PB109, HN72, and PC10); iroC (PB77, PB107, PC29, PC34, and PC40); and iroD (HN21, PC7, PC8, PC39, and PC40). In all the isolates harboring iroB and iroC, expression was upregulated under combined FeCl3 + ethylenediaminetetraacetic acid (EDTA) and imipenem stress, whereas in all the isolates harboring iroN, expression was downregulated. In iroD-harboring isolates, expression was upregulated under FeCl3 and FeCl3 + EDTA but suppressed under EDTA and imipenem. The AST results revealed the highest resistance was to ampicillin (87%), followed by norfloxacin (83%) and ciprofloxacin (76%).Conclusions: This study revealed that iron availability and antibiotic stress significantly influence the transcriptional regulation of key virulence genes in K. pneumoniae. By integrating molecular insights with environmental context, this work contributes to a broader understanding of how hypervirulent K. pneumoniae (hvKp) adapts and persists in environmental interfaces.
Introduction: Follicular condition is reflected in granulosa cells (GCs) and follicular fluid (FF), and miRNAs in GCs and FF play crucial roles in follicular and oocyte development.Materials and methods: In the present study, FF and GCs were collected from 10 cows, and miRNAs in FF and GCs, as well as mRNAs in GCs, were examined by miRNA-seq and RNA-seq.Results: A comparison of the miRNA profiles between the GCs and FF revealed that, although overall miRNA composition in FF reflects that in GCs, the miRNA expression profiles in FF do not fully correspond to those in GCs. The Weighted Gene Co-expression Network Analysis (WGCNA) and motif analysis showed that miRNA clusters in FF differ from those in GCs, and that each miRNA cluster in FF shares several conserved motifs. To examine the relationship between miRNAs and mRNAs in GCs, we developed a Predicted Targeting Efficacy (PTE) index that considers both miRNA abundance and the expression of its target genes. The PTE index showed a negative correlation with the genome-wide expression levels of genes. In addition, the miRNA–mRNA correlation analysis revealed specific clusters of miRNAs and genes with strong correlations. Based on miRNA concentrations in GCs or FF, GC samples were classified into enriched (n = 3) and deficient (n = 3) groups, and differentially expressed genes (DEGs) were identified. Ingenuity Pathway Analysis of the DEGs identified several molecules as activated upstream regulators associated with specific miRNAs.Conclusions: The present study provides a robust foundation for understanding miRNA release from GCs, miRNA–mRNA expression within GCs, and the granulose cellular condition contributing the presence of specific miRNAs in both GCs and FFs.
Quantitative reverse-transcription PCR (qRT-qPCR) remains one of the most precise methods for measuring transcript abundance, yet its application at single-cell resolution poses challenges that differ fundamentally from bulk workflows. As interest in single-cell biology grows, there is a pressing need for methods capable of providing absolute, reproducible, and gene-specific measurements in individual cells. Single-cell qRT-qPCR (scRT-qPCR) holds strong potential to meet this need, offering true molecular quantification that complements the broader but less precise information obtained from single-cell RNA sequencing. However, its practical implementation has been hindered by deep chemical and biochemical conflicts among the reaction phases, by enzyme instability in nanoliter-scale environments, and by the absence of integrated systems that can support lysis, reverse transcription, and amplification within a single unified workflow. This review synthesizes the chemical foundations that distinguish single-cell reactions from bulk qRT-qPCR and explains why conventional protocols cannot simply be miniaturized. By examining the molecular origins of reaction incompatibility and the physical constraints imposed by extremely low input levels, we identify the key factors that limit current methods. We also evaluate the strengths and shortcomings of existing commercial and semi-integrated solutions to highlight where progress has been made and what gaps remain. Finally, we outline future opportunities in enzyme engineering, unified buffer formulation, and microfluidic design that may enable reliable one-pot systems and transform scRT-qPCR into a powerful and widely accessible tool for quantitative single-cell analysis in both research and clinical settings.
Introduction: Multidrug-resistant Klebsiella pneumoniae (Kpn) poses a growing global health threat due to its role in severe hospital-acquired infections and increasing resistance to antibiotics. The objective of this study was to isolate, characterize, and evaluate the therapeutic potential of two novel lytic bacteriophages targeting multidrug-resistant K. pneumoniae, aiming for the development of alternatives to conventional antibiotics. Materials and methods: Phages KpnS01BRG and KpnS02SCE were analyzed using transmission electron microscopy (TEM) and whole-genome sequencing (WGS). Replication kinetics were determined through single-step growth curves (latency period and burst size). Antibacterial efficacy was tested in vitro using a phage cocktail at a multiplicity of infection (MOI) of 10,000 over 12 h. Additionally, a genome mechanics analysis was conducted to evaluate viral DNA cyclizability and flexibility. Results: TEM revealed that both phages belong to the class Caudoviricetes with a siphovirus-like morphology, and WGS classified them within the genus Webervirus (family Drexlerviridae). Phage KpnS01BRG exhibited a latency period of 60 min and a burst size of 17.7 virions/cell, while KpnS02SCE showed a latency of 5.8 min and a burst size of 18.6 virions/cell. The phage cocktail reduced the bacterial load by approximately 97.2% after 12 h, relative to the untreated control. Genomic analysis indicated that the higher DNA flexibility in KpnS02SCE correlated with a slightly higher virion production, corroborating previous findings on genome mechanics. Conclusions: The novel phages demonstrated potent antibacterial activity (i.e., strongly reduced bacterial counts after 6 h) and favorable genomic characteristics, establishing themselves as promising candidates for phage-based therapeutic strategies against multidrug-resistant K. pneumoniae infections.
The past two decades have witnessed a revolution in high-throughput omics technologies, which now offer unprecedented views of the molecular complexity underlying Alzheimer’s Disease (AD) and associated biomarkers. By leveraging nonlinear models and pattern recognition, artificial intelligence (AI) can integrate omics data to transcend the limitations of individual modalities, improving early detection and molecular subtype identification, expediting the identification of possible therapies via the inference of molecular pathways, and tracking disease progression. Yet, despite these breakthroughs, most AI-omics applications remain confined to research settings. From this perspective, we focus on three critical translational challenges: algorithmic bias, interpretability and trust, and the implementation of AI-driven omics into clinical practice. This perspective advocates for inclusive data infrastructures, improving interpretability and trust by providing greater mechanistic insight, and improving clinical translation by increasing reproducibility and cost-effectiveness. Such lessons from AD will seek to inform translational medicine across diverse diseases, beyond AD.
Introduction: One of the first steps in analyzing viral nucleotide/protein sequences is multiple sequence alignment (MSA). Due to the global effort of rapid diagnosis and advancement of sequencing technologies, more than three million SARS-CoV-2 genomes have been sequenced. This has given us an unprecedented opportunity to examine the capabilities of the MSA tools in handling datasets of various sizes.Materials and methods: In this study, we evaluated the speed, capacity, and user-friendliness of four frequently used MSA tools [MAFFT (Multiple Alignment using Fast Fourier Transform), Clustal Omega, MUSCLE (Multiple Sequence Comparison by Log-Expectation), and T-Coffee] on three laptops (ProArt Studiobook 16 OLED, ASUS Vivobook 17X, and ASUS Vivobook 14) using the Windows and Linux operating systems to align SARS-CoV-2 genomes and S protein sequences, which involved up to 2000 and 1,280,000 sequences, respectively. Results: Generally, runtime performance was similar across the laptops; however, only ProArt Studiobook 16 OLED could handle larger datasets and run Clustal Omega on Linux. Through using MSA tools to analyze S protein sequences with downloaded versions for the small dataset (≤2000), no significant difference in runtime was found for Clustal Omega, MUSCLE-super5 and MAFFT on Windows, whereas on Linux, MAFFT was the fastest. For the medium dataset (4000–64,000), MUSCLE-super5 (Windows) had the shortest runtime, while Clustal Omega took longer on both operating systems. For the large dataset (≥128,000), MUSCLE-super5 (Windows) was the fastest. As for SARS-CoV-2 genome sequences, T-Coffee failed to process them, whereas MAFFT consistently had the shortest runtime, irrespective of dataset size.Conclusions: Overall, the downloaded versions of MAFFT and MUSCLE were the most efficient for analyzing SARS-CoV-2 genome and S protein sequences, respectively.
Introduction: Dystrophic epidermolysis bullosa (DEB) is a severe genodermatosis caused by mutations in COL7A1, leading to deficient type VII collagen (C7). RNA-based therapeutics offer promising, mutation-specific alternatives. We aimed to map the preclinical and early translational research landscape of RNA-based therapies for DEB.Materials and methods: A scoping review was conducted per PRISMA-ScR guidelines (January 2005 to July 2025). Studies investigating antisense oligonucleotides (ASOs), RNA interference (RNAi), RNA trans-splicing (RTMs), or related strategies for DEB were included. Data were systematically charted and synthesized.Results: Twenty-three studies were included. Most were preclinical (95.7%), focusing on recessive DEB (RDEB). Dominant strategies were RTMs (43.5%) and ASOs (39.1%); RNAi comprised 13.0% of approaches. Efficacy assessments confirmed partial C7 restoration in vitro and in vivo, with levels reaching up to 36–56% in some ASO studies. Delivery was predominantly nonviral, yet reliance on simple models was common. Critical translational assessments, including long-term safety, immunogenicity, and delivery to intact skin, were largely absent. The sole Phase 1/2 clinical trial (NCT03605069) was terminated early, underscoring the translational gap.Conclusions: RNA-based strategies show robust preclinical proof-of-concept for partial C7 restoration. However, a significant gap persists due to delivery challenges, reliance on early-stage models, and lack of clinical validation. Future development must prioritize advanced delivery systems, rigorous safety profiling, and innovative trial designs to realize the therapeutic potential for DEB.
Introduction: Clustered regularly interspaced short palindromic repeats (CRISPR)-associated genes (CRISPR-Cas) is an acquired immune system that confers resistance in prokaryotes against invading extrachromosomal elements such as viruses and plasmids, and CRISPR editing technology is an important tool in bacterial genetic engineering. Recently, some bacteriophages have been found to harbor CRISPR system elements, suggesting an unexpected reservoir for antiviral genetic elements.Materials and methods: This study examined 325 genomes of Streptomyces bacteriophages for CRISPR elements using CRISPRCasFinder to search for CRISPR arrays and associated cas genes. Putative CRISPR elements were found in 30 genomes, including 11 containing genes identified as coding for Cas4 proteins. These gene products were compared with Clustal Omega (version 1.2.4) and phylogenetic analysis through the neighbor-joining method. Protein homology modeling was carried out using ProMod3, and the phage proteins were aligned to the Cas4 protein from Pyrobaculum calidifontis using the Matchmaker function of UCSF Chimera.Results: The Cas4-like proteins from three groups of Streptomyces phages mapped to the same node as AdnA proteins from Mycolicibacterium smegmatis and Streptomyces coelicolor in the phylogenetic tree analysis. We also found five representative phage protein sequences that contained conserved residues corresponding to functional domains of Cas4 proteins. The modeled protein from Streptomyces phage Circinus showed a moderate to strong alignment and high structural conservation in the core domain to P. calidifontis Cas4 crystal structure.Conclusions: This study utilized bioinformatic and modeling tools to identify likely CRISPR elements in several Streptomyces bacteriophages. These results provide a first step toward understanding how prevalent CRISPR elements are in these bacteriophages and will assist in future experimental studies of possible roles for these elements in phage biology or for use as potential new genetic tools.
Introduction: Metatranscriptomic analyses provide critical insights into differentially expressed genes (DEGs) and their clinical implications. By leveraging wastewater-based epidemiology (WBE) and high-throughput sequencing, we can monitor viral pathogens cost-effectively, offering a robust approach to public health surveillance.Materials and methods: Our study utilized short-read Illumina whole transcriptome shotgun sequencing (WTSS) and long-read Oxford Nanopore Technologies (ONT) to identify DEGs associated with SARS-CoV-2 pathogenesis and viral–host interactions. We processed 10 samples via an Illumina metatranscriptomic approach and 48 samples using the ONT midnight protocol, followed by downstream statistical and pathway analyses.Results: The merged assembly between Illumina and ONT yielded 381,524 transcripts mapped to 340,439 unigenes, with a total transcript length of 287,252,541 and an average unigene length of 752.9 bases. Our research reveals distinct transcriptional and microbial diversity patterns across sample types, likely reflecting both environmental and host-specific factors. We identified distinct alpha diversity clades between WBE and clinical microbiomes, suggesting concurrent infections.Conclusions: Host transcriptional signatures, such as methyl-accepting chemotaxis proteins (MCP) signals and ATP-binding cassette (ABC) transporters, clarify the role of DEGs in the infectious cycle. This analysis advances our understanding of the molecular basis of SARS-CoV-2 and underscores the importance of WBE in combating infectious diseases.
Sexual reproduction arose at the dawn of the evolution of living beings and is a defining moment for Darwinian evolution and fitness. Its primary significance lies in the mixing of genes in a population and the creation of new genomic complexes in each new generation. From this perspective, the separation of individuals in a population by sex and the control of this separation are important attributes of sexual reproduction. Despite extensive research on the determination and control of sex expression in plants, this field of research remains relevant and less studied than in animals. This review discusses the current research and views on genetic and non-genetic sex determination in plants; the presence and role of sex chromosomes in dioecious species; sex-determining genes and downstream regulators; hormonal and epigenetic factors regulating sex expression; the influence of external and environmental factors; plasticity of plant sex expression and the transition from bisexual individuals to female and male and vice versa. The influence of sex-determining genes on the conserved floral meristem identity genes A, B, C, D and E, which ultimately express sex, is also considered.
The origin of life may have emerged through physical mechanisms that enable molecular organization and self-assembly. Building on Alexander Oparin’s concept of coacervate droplets, liquid–liquid phase separation (LLPS) offers a plausible route for prebiotic molecules to concentrate and interact, supporting the transition from chemistry to biology. LLPS provides a dynamic, membrane-free environment that could enhance RNA function and facilitate the evolution of regulatory and signaling networks that are foundational to the creation of life. By linking molecular interactions and emergent behaviors, LLPS bridges the gap between simple biochemical interactions and collective cellular organization. Deoxyribonucleic acid (DNA), ribonucleic acid (RNA), peptides, ions, and other organics can be incorporated into coacervates that concentrate molecules, accelerate reactions, and compartmentalize specific chemicals, which effectively organize primitive environments and produce an arena for “natural selection” to ignite. This framework suggests that RNA, DNA, and proteins each possess intrinsic agency (molecular behavior), which is defined as possessing the ability to sense, respond, and self-organize. When coupled through LLPS, a novel and enhanced agency arises to provide higher-order properties and coordinated function. Emerging theories may explain how such networks achieve coherence and suggest that the boundary conditions created by LLPS provide the architecture by which abiogenesis, evolution, and cognition are possible.
Introduction: The three-amino-acid-loop-extension (TALE) transcription factor family is widely present in plants and plays an important role in plant growth and development processes as well as responses to abiotic stresses. However, studies on the gene family are limited in Rosa persica. Materials and Methods: Taking the genome of Rosa persica as the research object, we systematically performed genome-wide identification of members, structural analysis, evolutionary analysis, cis-acting element analysis, and secondary and tertiary structure prediction of the TALE gene family in Rosa persica. Combined with transcriptome data, we analyzed the expression profiles of these genes across different tissues, as well as under varying levels of drought stress and low-temperature stress conditions. Results: Twenty-five TALE genes were identified in the R. persica genome and classified into two subfamilies—BELL and KNOX—based on the phylogenetic tree. Genes within the same subfamily exhibited similar structural features and conserved motifs. Collinearity analysis revealed four pairs of segmental duplication genes and three pairs of tandem duplication genes. The promoter regions of R. persica TALE genes contain numerous hormone-responsive and abiotic stress response elements. The predominant secondary structures are α-helices and random coils, while the tertiary structures all feature helix-turn-helix motifs. Expression pattern analysis indicates that RpTALE genes are predominantly expressed in roots, stems, leaves, and fruits, with lower expression levels in flowers. RpTALE genes exhibit gene-specific expression patterns under abiotic stress conditions. Conclusions: Identified 25 RpTALE genes, RpTALE2, RpTALE8, RpTALE15, and RpTALE25 show positive responses to drought stress, while RpTALE2 responds positively to cold stress. These findings provide theoretical support for elucidating the functions and regulatory mechanisms of TALE genes in R. persica.
Introduction: The growing demand for stress-resistant industrial microorganisms in green biomanufacturing has intensified research into the stress tolerance mechanisms of Saccharomyces cerevisiae. As the central organelle for energy metabolism and redox homeostasis, mitochondrial function is critical for enhancing yeast adaptability under stress conditions. Materials and methods: This study investigates the molecular mechanism by which Q0130 (ATP9, subunit C of Φ0-ATP synthase) improves stress tolerance in S. cerevisiae through the regulation of mitochondrial energy metabolism. A yeast strain overexpressing Q0130 was constructed, and its growth performance and mitochondrial function were evaluated under high-temperature and high-ethanol conditions. Results: The results revealed that Q0130 overexpression helped maintain mitochondrial homeostasis under thermal stress (40 °C), significantly enhanced yeast growth (by 58%), and mitigated the excessive accumulation of reactive oxygen species (ROS). Conclusions: This study, for the first time, links ATP9 to adaptive energy metabolism across different stress types, providing a theoretical foundation for mitochondrial-targeted engineering of highly stress-tolerant yeast strains and advancing the performance of yeast chassis cells in green biomanufacturing.
Epigenetic marks such as DNA methylation, histone modifications, and non-coding RNAs play a central role in regulating gene expression without altering the DNA sequence. These dynamic and reversible modifications contribute to cellular differentiation, genomic stability, and the fine-tuning of transcriptional activity in response to environmental and metabolic cues. Beyond genetic variation alone, epigenetic mechanisms provide a critical regulatory layer linking environmental factors, cellular context, and disease susceptibility. Alterations in epigenetic marks can disrupt normal gene expression patterns, contributing to a wide range of pathological conditions, including cancer, neurodegenerative, metabolic, and immune-mediated diseases. This review places particular emphasis on cancer, cardiovascular diseases, and autoimmune disorders, where epigenetic dysregulation has been most extensively characterized and therapeutically explored. Because epigenetic modifications are reversible and influenced by environmental and lifestyle factors, they represent highly promising targets for therapeutic intervention. In recent years, epigenetic-based drugs—such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and agents targeting non-coding RNAs—have demonstrated significant potential in preclinical and clinical studies. However, their clinical application remains limited by challenges including non-selectivity, systemic toxicity, and limited tissue specificity. Emerging technologies such as CRISPR/dCas9-mediated epigenome editing offer opportunities for precise regulation of disease-associated genes without permanent genomic alterations. This review summarizes current knowledge on major epigenetic mechanisms and highlights recent advances in epigenetic therapies, including FDA-approved agents, combinatorial strategies, and next-generation epigenetic editing approaches. A deeper understanding of these mechanisms is expected to enable targeted, reversible, and patient-specific therapeutic strategies within the framework of precision medicine.
