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As a canonical non-B DNA secondary structure, the G-quadruplex (G4) dynamically regulates core biological processes, including telomere homeostasis, DNA replication and gene transcription/translation-through its unique four-stranded conformation. The significant enrichment of G4 structures in regulatory regions, particularly promoter regions within mammalian genomes reveals their critical role in transcriptional regulation. In this review, we focus on the dynamic formation mechanisms and transcriptional regulatory functions of endogenous G4 structures, systematically elucidating their three molecular pathways in modulating gene expression: (1) orchestrating spatial assembly of transcription activation complexes; (2) dynamically regulating epigenetic modifications, includinghistone alterations and DNA methylation; (3) remodeling three-dimensional chromatin architecture to establish transcriptionally active microenvironments. By integrating advancements in G4 topological characterization techniques and dynamic equilibrium networks, this work highlights the role of the G4 as a critical cis-regulatory element and provides a theoretical framework for developing G4-targeted therapeutic strategies.

Mitochondria, as crucial organelles within eukaryotic cells, have their proteins and RNAs encoded by both the nuclear genome and the mitochondrial genome. They play vital roles in energy regulation, cellular metabolism, signal transduction, and various other physiological activities. Additionally, mitochondria interact with multiple organelles to collectively maintain cellular homeostasis. Mitochondria can also be transferred between cells and tissues through mechanisms such as migrasomes. Mitochondrial DNA (mtDNA) mutations often cause severe inherited rare diseases, characterized by tissue specificity, heterogeneity, multiple mutation sites, and challenges in achieving a complete cure. Gene editing of mtDNA holds promise for fundamentally curing such diseases. Traditional gene-editing nucleases, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nuclease (TALENs), as well as novel gene editors like DddA-derived cytosine base editors (DdCBEs), have been demonstrated to correct certain mtDNA mutations. However, CRISPR-based technologies-despite their superior programmability and efficiency-are currently limited due to the technical bottleneck of inefficient sgRNA delivery into mitochondria. This article systematically reviews the structure and function of mitochondria, related diseases, and the current state of mtDNA gene-editing therapies. Furthermore, it explores future directions for optimizing therapeutic tools to overcome the challenge of sgRNA delivery, thereby addressing the treatment barriers posed by pathogenic mtDNA mutations in inherited rare diseases.

Given the inherent complexity, hierarchical organization, and dynamic nature of living systems, there is no single best strategy for investigation, and priorities shift with the evolution of the life sciences. In the 1990s, two classic stories, The Salvation of Doug and The Demise of Bill, used automobiles as analogies and satire to contrast two research strategies: dismantling components to uncover underlying mechanisms, or applying functional perturbations to identify critical elements. These heuristic parables stimulated broad discussion on the respective strengths and limitations of different research approaches and continue to be widely used in teaching today. The life sciences have since entered an era integrating high-throughput, high-resolution, and multidimensional approaches, where single-path strategies can no longer provide deep, systematic insights into complex biological processes. We view the intrinsic features of living systems, such as modular organization, regulatory networks, nonlinear responses, and adaptive compensation, as factors that make any single approach likely to capture only local, static aspects, thereby hindering the reconstruction of systems-level, dynamic properties. Against this backdrop, we present a modern continuation of the two parables, reimagined in a contemporary setting and featuring two protagonists with symbolic Chinese names, "Zhiwei" (meaning "decoding hidden mechanisms") and "Sixu" ("reasoning through order"), who personify biochemical and genetic mindsets. In our narrative, the two protagonists transition from working independently to collaborating, integrating high-throughput experimentation, systems-level analysis, and computational modeling to uncover structural and operational principles underlying complex systems. We believe this retelling reflects the growing emphasis on systems-level and dynamic perspectives in biology, highlighting the value of methodological integration and innovation. We hope it will serve as a valuable resource for teaching in genetics and related disciplines, while fostering reflection on the enduring relevance of genetic reasoning in contemporary research.

The medicinal preparation of Chilobrachys jingzhao possesses various therapeutic properties, including anti-inflammatory, detoxifying, analgesic, and anti-edema effects. However, research on its genetic background and toxin mechanisms is held back by the lack of chromosome karyotype and genome data. In this study, we analyzed the karyotype of C. jingzhao using chromosome preparation techniques, estimated the genome size using flow cytometry and K-mer analysis, and performed genome sequencing and assembly using second- and third-generation single molecule real-time sequencing technologies. The results showed that C. jingzhao has a diploid chromosome number of 2n=68, with a karyotype formula of 2n=46m+18sm+4st and a chromosomal complement of 2n=10L+18M2+38M1+2S. Using Solanum lycopersicum and Trichonephila clavata as references, flow cytometry estimates the genome size at 7,775.49 Mb and 7,680.26 Mb, respectively. The 19-mer analysis also estimated the genome size to be 7,626.00 Mb, consistent with the flow cytometry results. Further analysis indicated that the genome of C. jingzhao has a high level of heterozygosity (8.45%) and a high proportion of repetitive sequences (67.10%), classifying it as an ultra-high heterozygous and high-repeat genome. The initial genome assembly of C. jingzhao was 8,804.93 Mb in size, with a contig N50 of 55.55 Mb and a BUSCO completeness score of 95.9%, indicating high assembly quality. This study first reveals the karyotype and genome information of C. jingzhao, offering crucial data for future research on its whole genome, toxin mechanisms, genetics, origin, evolution, and taxonomy.

Significant body size variations exist among different primate species. To investigate the genes influencing primate body size evolution, this study employed evolutionary genetics approaches to analyze functional differences and natural selection patterns of genes across species with distinct body sizes. Six primate species representing significant size variations were selected. Through comparative analysis of genome, molecular evolution and RNA-seq, Bcl-2 gene was detected and it has a significant impact on primate body size. Results demonstrated a positive correlation between Bcl-2 gene expression levels with body size, with differential natural selection observed among species of varying sizes. Population genetic analysis identified specific Bcl-2 SNP loci associated with body size evolution, and cellular experiments confirmed that this gene regulates osteoblast proliferation through pathways such as Wnt/β-catenin and BMP signaling. Multi-omics analysis further revealed that Bcl-2 expression increases with body size and exhibits significant selection signals and physicochemical property differences between species with substantial size variations. Functional studies indicated that Bcl-2 plays a crucial role in body size evolution by regulating skeletal development-related pathways. This study systematically reveals Bcl-2 as a key regulatory factor influencing primate adaptive body size evolution through processes such as apoptosis, skeletal development, and metabolism. From an evolutionary genetics perspective, it elucidates the molecular mechanisms underlying body size differences, providing new insights into primate body size evolution.

Short tandem repeat (STR) is a significant genetic marker for the identification of forensic DNA. DNA databases worldwide, including those in China, are established based on STR markers. Length- and sequence-based polymorphism are two features of STR markers. Sequence-based polymorphism includes polymorphisms in both repeat and flanking regions. Traditional capillary electrophoresis-based STR genotyping method can only profile length-based genotypes. However, a deep understanding of the sequence polymorphism of core STR loci is crucial for primer design and DNA identification. Firstly, single nucleotide polymorphisms and insertions/deletions in STR primer binding regions may reduce the affinity between primers and DNA templates, leading to allele dropout or poor interlocus balance, thereby impacting the accuracy of DNA identification. Secondly, sequence-based polymorphism can be unveiled by next-generation sequencing technology, which could significantly enhance the detectable polymorphic information of core STR loci and improve the efficiency of individual identification and kinship analysis. Thirdly, different populations exhibit distinct STR sequence characteristics. Over the past decade, studies on sequence-based polymorphisms of STR loci have increased alongside the application of next-generation sequencing technology, and sequence-based polymorphisms from multiple populations were reported. However, previously studied populations and data were scattered, and different formats of repeat region sequences were used in various studies. These limitations result in the absence of a systematic summary and analysis of sequence polymorphism for core STR loci, hindering its further application in forensic practices. A comprehensive understanding of core STR loci sequence characteristics is crucial for individual identification from trace DNA, deconvolution of mixed samples, and determination of mutation origins in paternity testing. In this review, we focus on 19 autosomal core STRs and systematically review the sequence polymorphisms of these loci based on population data reported in the literature. We summarize variations in repeat regions, analyze variation patterns, present high-frequency variations in flanking regions within the Chinese population, and discuss potential challenges encountered in STR sequence analyses, with the aim to provide a reference for the analyses and application of STR sequence, the identification of rare alleles in criminal case testing, and the development of STR genotyping panel.

Chromatin-associated RNAs (caRNAs), closely related to chromatin structure and functions, are a class of RNAs that interact with chromatin in cis, trans, or cis-trans cooperation modes, regulating gene expression and maintaining the orderly progression of cellular processes. N⁶-methyladenosine (m⁶A) is a ubiquitous and dynamically reversible epigenetic modification in eukaryotic RNAs, playing an important regulatory role in a variety of biological processes. m⁶A modification of chromatin-associated RNAs can regulate chromatin accessibility and gene expression at the transcriptional level, maintaining the normal functions of organisms. In this review, we summarize the mechanisms of m⁶A-modified caRNAs-chromatin interactions and their role in gene expression, with the aim of providing scientific basis and ideas for the analysis of the molecular mechanisms of gene transcriptional regulation.

In the field of forensic science, mixed DNA evidence obtained from crime scenes often contains genetic information from multiple individuals, and its accurate interpretation is crucial for case investigation and judicial decision-making. With the advancement of forensic genetic technologies, although detection capabilities have significantly improved, there are still substantial bottlenecks in the interpretation of multi-contributor DNA profiles. Traditional methods are often unable to simultaneously and precisely infer both the genotypes of suspects and their respective contribution proportions, which makes them insufficient to meet the stringent requirements of complex mixture analysis. To address these challenges, we propose a continuous gamma distribution model algorithm based on probabilistic residual optimization in this study. By constructing a two-step probabilistic evaluation framework, the algorithm first generates candidate genotype combinations through allelic permutations and estimates preliminary contributor proportions. It then introduces the gamma distribution hypothesis to build a probability density function, dynamically optimizes the shape parameter (α) and the scale parameter (β) to calculate residual probability weights, and employs an iterative maximum likelihood estimation process to simultaneously optimize genotype combinations and contributor proportion parameters. The final results are derived by integrating population allele frequency databases to output the maximum likelihood solution. This algorithm provides a reliable and quantifiable analytical tool for forensic identification, significantly improving the accuracy of complex mixture interpretation and enhancing the practical utility of mixed DNA in criminal investigations. It holds substantial significance in advancing forensic science technologies and safeguarding judicial fairness.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with multi-organ involvement. The FAM167A-BLK locus at 8p23 has been identified as a genetic susceptibility locus for SLE by previous genome-wide association studies (GWAS). To explore the role of functional single-nucleotide polymorphisms (SNPs) within this locus on the regulation of BLK and FAM167A genes, we perform comprehensive functional annotation using GCTA and fnGWAS approaches to identify candidate functional SNPs，and verify them through dual-luciferase reporter assays, shRNA knockdown experiments, and CRISPR/dCas9 knockdown experiments. The results show that four functional SNPs exhibit allele-specific enhancing effect on BLK expression, while showing no discernible regulatory influence on FAM167A expression. Importantly, BLK is shown to regulate the expression of FAM167A. These findings highlight FAM167A as a potential pathogenic gene contributing to SLE. This study expands the mechanistic understanding of genetic regulation at the FAM167A-BLK locus and provides new insights into SLE development.

Extracellular vesicles (EVs) are membrane-bound particles released by cells into the extracellular microenvironment. In the nervous system, EVs serve as critical mediators of biomolecule trafficking and intercellular communication. These vesicles are deeply involved in orchestrating physiological homeostasis and pathological cascades, while demonstrating significant potential for therapeutic and diagnostic applications. In this review, we systematically summarize the functional heterogeneity and research advances in neuron- and glial cell-derived EVs, aiming to provide a theoretical basis for understanding the diverse roles of EVs in the nervous system.