The mechanisms underlying the evolution of lifespan across organisms remain mysterious. This study computes multiple large datasets and reveals that noncoding RNAs (ncRNAs), rather than proteins, drive animal lifespan evolution. Species in the animal kingdom evolutionarily increase their ncRNA length in their genomes, coinciding with trimming of the mitochondrial genome length. This leads to a low energy consumption and longevity. Notably, as species evolve and extend their lifespans, they tend to acquire long-lived ncRNA motifs while simultaneously losing short-lived ones, in contrast to the conservative patterns observed in protein evolution. These longevity-associated ncRNA motifs, such as GGTGCG, are particularly active in crucial tissues including the endometrium, ovaries, testes, and cerebral cortex. The ovary and endometrium carry more activating ncRNAs than the testis, offering insight into why women generally outlive men. Taken together, ncRNAs drive the evolution of the two most important traits of organisms: longevity and reproduction, and they execute many more fundamental functions than those conventionally thought. This discovery provides the foundation for combating longevity and aging.

Glutaric aciduria type-1 (GA-1) is a rare metabolic disorder due to mutation in GCDH gene resulting in varied clinical manifestations. Here we report a case of late-onset GA-1 with acute myelo-neuropathy and chronic renal failure. Institutional ethics committee approval was obtained and genetic analysis was done by clinical exome sequencing. Here we present 19 year-old-adolescent male with chronic renal disease for 2 years presented with 5 months history of sudden onset weakness of proximal and distal lower limbs and bladder retention. This was preceded by recurrent episodes of vomiting. On clinical examination he had features of myeloneuropathy. Laboratory evaluation showed significant elevation of blood glutaryl carnitine with very low free carnitine, while extensive white matter signal changes with diffusion restriction, subependymal nodules and involvement of internal capsule were evidenced on brain magnetic resonance imaging. Diagnosis was confirmed by clinical exome sequencing which showed a pathogenic homozygous missense mutation in exon 11 of GCDH gene (c.120 C>T, p.His403Tyr). This report expands phenotypic spectrum of GA-1 to include late onset acute myelo-neuropathy with chronic renal failure. A high index of suspicion is required since early treatment might decelerate further disease progression.

Kallmann syndrome is a rare genetic disease characterized by the idiopathic hypogonadotropic hypogonadism with hyposmia or anosmia, which exhibits considerable heterogeneity in genotype and phenotype. Herein, we reported a 32-year-old male patient with Kallmann syndrome in a family associated with heterozygous mutations in PROKR2 and SPRY4 genes. The genotyping results indicated PROKR2 mutations and SPRY4 variants of uncertain significance, which might be incompletely penetrant in this family.

Background Duchenne muscular dystrophy (DMD) is a progressive X-linked disorder causing muscle degeneration and multisystem involvement, requiring precise genetic diagnosis for timely intervention and treatment.

Objective To investigate the genetic landscape of DMD using a two-tiered diagnostic approach combining MLPA and WES, and to correlate genetic findings with clinical outcomes for improved management.

Materials and methods A cross-sectional study of 80 male DMD patients was conducted using a sequential genetic approach, combining MLPA and WES, with bioinformatics and statistical analyses to explore genotype-phenotype correlations.

Results Pathogenic variants were identified in 65 cases (81.2 %), with deletions (67.5 %) being the most common, followed by duplications (6.3 %), splice-site (3.8 %), and nonsense variants (3.8 %). WES identified additional pathogenic variants in MLPA-negative cases, including novel mutations, expanding the known genetic spectrum of DMD. The combined MLPA-WES approach significantly improved diagnostic yield (χ² = 12.90, p < 0.001). Functional analysis revealed disruptions in glycogen metabolism (46 %), calcium transport (24 %), and mitochondrial function (12 %), with dystrophin-associated proteins (DAG1, SGCD) critically involved in muscle stability. Out-of-frame deletions were significantly associated with early disease onset (χ² = 49.03, p < 0.001) and severe phenotypes (χ² = 47.04, p < 0.001), supporting exon-skipping therapy. In-frame deletions correlated with milder progression, while nonsense variants posed a 2.5-fold increased risk of early cardiomyopathy (p = 0.002), emphasizing the need for early intervention.

Conclusion Combining MLPA and WES enhances DMD diagnostic accuracy, enabling timely clinical interventions. Integrating functional analysis with genotype-phenotype correlations supports personalized therapeutic strategies, improving patient outcomes.

Introduction Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by the congenital absence of the uterus and vagina in females with 46, XX karyotype. The genetic etiology remains poorly understood.

Case presentation We described a 29-year-old female patient with a main complaint of primary amenorrhea. The MRKHS diagnosis was confirmed, and molecular analysis revealed a 7q11.23 microduplication in the proband that was shown to be inherited from her mother. In the literature, müllerian malformations have been reported in only a few cases of 7q11.23 microduplication. However, the abnormalities observed in our patient have not been described previously. To the best of our knowledge, this is the first documented case of a patient with the coexistence of 7q11.23 microduplication syndrome and MRKHS.

Discussion/conclusion Identification of the 7q11.23 duplication could suggest a new candidate region for MRKHS and add to the already described signs of 7q11.23 microduplication syndrome.

Background The pharmacokinetics (PK) characters of plasma-derived Factor IX (pdFIX) concentrate in Chinese children with Haemophilia B(HB) have not yet been reported.

Aim To assess the PK parameters of pdFIX in children with severe HB and identify factors that influence FIX PK.

Methods This non-randomized, open-label PK study enrolled children with severe HB (FIX≤2 %). Patients received 50 IU± 5 IU/kg pdFIX (Human coagulation Factor IX-CTBB) after at least 96 h wash-out period. Blood samples for PK assessments were collected before infusion (pre-dose) and at 15 min, 30 min, 1 h, 3 h, 6 h, 9 h, 24 h, 48 h, 72 h and 96 h post-infusion. FIX activity was measured by a one-stage assay.

Results Twenty patients were enrolled with a median age of 8.3 (range 1.8-15.4) years. The peak plasma levels of FIX: C in all patients were observed within 15 min. Their median terminal half-life (t_1/2) was 32.6 (range 23.3-52.0) hours. The median values of in vivo recovery (IVR) at 15 min, clearance (CL), volume of distribution at state (Vss) and area under the curve (AUC) were 1.0 (0.9, 1.2) IU/dL per IU/kg, 5.2 (IQR 4.8, 6.4) mL/h/kg, 207.9 (IQR 183.5, 301.4) mL/kg, 9.77 (IQR 7.76, 11.23) U*h/mL respectively. The t_1/2, Vss and mean residence time after intravenous injection (MRT) decreased with increasing age and body weight. Changes in CL with body weight were similar to t_1/2, but no significant correlation exists with age.

Conclusions There is a significant inter-individual variability in PK profiles among Chinese children with severe HB, which is related to age and body weight changes, indicating the necessity of individualized prophylaxis driven by PK.

Preeclampsia(PE) is the most prevalent complication during pregnancy and constitutes a significant cause of morbidity and mortality among pregnant women and their fetuses. Recent studies have demonstrated elevated levels of angiotensin II type 1 receptor autoantibodies (AT1-AA) in patients diagnosed with PE. These autoantibodies can mimic the physiological effects of angiotensin II by engaging with the AT1 receptor, thereby instigating inflammatory responses and vasoconstriction, which contribute to the clinical manifestations of PE. Although the precise pathogenesis of PE remains unclear, it is influenced by a multitude of factors. This paper aims to provide a comprehensive overview of the relationship between PE and AT1-AA, along with an analysis of the pathophysiological effects and signaling pathways related to these autoantibodies.

Antibiotic resistance in bacteria is a critical global health challenge, driven by molecular mechanisms such as genetic mutations, efflux pumps, enzymatic degradation of antibiotics, target site modifications, and biofilm formation. Horizontal gene transfer (HGT) further accelerates the spread of resistance genes across bacterial populations. These mechanisms contribute to the emergence of multidrug-resistant (MDR) strains, rendering conventional antibiotics ineffective. Recent advancements in CRISPR/Cas9-based genome editing offer innovative solutions to combat drug resistance. CRISPR/Cas9 enables precise targeting of resistance genes, facilitating their deletion or inactivation, and provides a potential method to eliminate resistance-carrying plasmids. Furthermore, phage-delivered CRISPR systems show promise in selectively killing resistant bacteria while leaving susceptible strains unaffected. Despite challenges such as efficient delivery, off-target effects, and potential bacterial resistance to CRISPR itself, ongoing research and technological innovations hold promise for using CRISPR-based antimicrobials to reverse bacterial drug resistance and develop more effective therapies. These abstract highlights the molecular mechanisms underlying bacterial drug resistance and explores how CRISPR/Cas9 technology could revolutionize treatment strategies against resistant pathogens.

The stability and satisfaction of sexual relationships are critical determinants of individual well-being and societal cohesion. While much is known about the psychological and social factors influencing these outcomes, the genetic underpinnings remain an emerging field of inquiry. This literature review synthesizes findings from 42 peer-reviewed studies published between 2003 and 2023, exploring the genetic contributions to relationship stability and satisfaction. Key findings indicate that neuroticism, with an estimated heritability of ∼40 %, is a strong predictor of relationship instability, while agreeableness and extraversion are associated with greater relationship satisfaction. The review examines the genetic foundations of personality traits, attachment styles, emotional regulation, hormonal influences, sexual compatibility, communication styles, and mental health predispositions. Additionally, it highlights the interplay between genetic and environmental factors, presenting case studies and empirical evidence that elucidate the complex interactions at play. Ethical considerations and future research directions are discussed to provide a comprehensive understanding of how genetics can shape successful sexual relationships. By bridging the gap between genetic research and relationship science, this review offers data-driven insights to guide future investigations in this interdisciplinary domain.

Objective This study aimed to investigate the prognostic factors for the treatment efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR exon 21 L858R mutation.

Methods The study enrolled patients with advanced EGFR L858R-mutant NSCLC who received first-line EGFR-TKI treatment between January 2019 and April 2024. Cox regression analyses were performed to identify the prognostic factors from clinical characteristics and concomitant genetic alterations that influenced progression-free survival (PFS) and overall survival (OS).

Results According to the study of a cohort of 120 patients, we found that more metastatic organs (≥3 organs), specific metastatic patterns (liver and bone involvement), concurrent TP53 mutations, and worse Eastern Cooperative Oncology Group Performance Status (ECOG PS) were associated with shorter PFS. And ECOG PS was an independent predictive factor for PFS. Similarly, metastatic organs ≥ 3 (HR, 2.719; 95 % CI, 1.386-5.333; p = 0.004), ECOG PS of 2 (HR, 10.756; 95 % CI, 4.002-28.906; p < 0.001), and body mass index (BMI)>24 kg/m² (HR, 0.335; 95 % CI, 0.147-0.760; p = 0.009) were associated with worse OS. We also observed that patients harboring TP53 co-mutations demonstrated significantly inferior PFS compared with their TP53 wild-type counterparts (13.7 months vs. 18.8 months; p = 0.006).

Conclusions This study identified several factors significantly associated with worse response to EGFR-TKIs in NSCLC patients with EGFR L858R mutation and respective independent predictive factors for PFS and OS. These findings could enable personalized therapeutic efficacy assessment to facilitate clinical decision-making for EGFR L858R-mutant NSCLC patients treated with EGFR-TKIs.