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The superficial circumflex iliac artery (SCIA) perforator flap is supplied by the SCIA, which consists of superficial and deep branches. In this study, the feasibility of using a flap based solely on the superficial branch of the SCIA for reconstruction surgery in the head and neck region was explored. During flap harvesting, the deep branch of the SCIA was discarded, and the superficial branch was dissected as the vascular pedicle; this technique is referred to as the 'simplified SCIA flap. This simplified SCIA flap was used to repair head and neck defects in 16 patients, all of whom were followed up for at least 3 months postoperatively. The superficial branch of the SCIA was successfully identified in all 16 patients. The mean pedicle length of the superficial branch of the artery was 7.2 cm (range 6.2-8.2 cm). The mean diameter of the superficial branch of the artery was 0.7 mm (range 0.6-0.9 mm), while the mean diameter of the accompanying vein was 1.2 mm (range 1.0-1.3 mm). The reconstruction was successful in 15 of the 16 patients. The remaining patient ultimately underwent reconstruction with a left radial forearm free flap. In this case, the skin paddle of the simplified SCIA flap was used as a full thickness skin graft to repair the defect in the forearm donor site. All patients completed speech and swallowing assessments during postoperative follow-up. Compared with the traditional SCIA flap, the simplified SCIA flap is easier to harvest, offers lower donor site morbidity, and results in a well-concealed scar in the iliac region. This flap warrants clinical promotion.

By positioning phase separation between Kirsten rat sarcoma virus oncogene homolog (KRAS) lipidation and membrane signaling, Wang et al. unify distinct aspects of KRAS biology. They show that farnesylation drives cytoplasmic KRAS condensates that promote processing, trafficking, and signaling, establishing condensat formation as a new mechanism for controlling RAS activity.

Physiological traits related to water status and photosynthesis biophysically link plant performance to environmental conditions like light and water availability. By approaching the concept of species' niches from a trait-based perspective, physiological traits can be used to characterize how trait syndromes diverge to limit direct resource competition and promote resource partitioning in sympatric species. Such traits could also inform broader studies of changing community composition in an era of drastic shifts in climate or disturbance regimes. However, the extent of inter/intraspecies trait variation and how such traits vary along local environmental gradients remains an open question in understanding physiological traits as species-level characteristics. To address this, we quantified hydraulic and gas exchange traits in four co-occurring Viburnum species while also quantifying local canopy coverage and soil conditions. All species displayed significant variation in gas-exchange traits, turgor loss point, and heavy carbon isotope discrimination along gradients of canopy openness. Specifically, plants in shadier environments exhibited higher photosynthetic rates at low light levels while individuals growing in gaps demonstrated higher drought tolerance and stricter stomatal regulation. Soil texture explained little variation in traits assessed. V. acerifolium displayed a more conservative, shade-tolerant trait syndrome, yet little significant difference was found in traits between the congeners, highlighting the potentially limited resolution of physiological traits to differentiate trait syndromes of closely related, co-occurring species.

The incidence of colorectal cancer (CRC) has risen in recent decades, with a disproportionate increase observed among younger individuals in Japan and other countries. The etiological contribution of the gut microbiota to CRC pathogenesis is recognized, yet the mechanisms involved remain to be fully clarified. Here we integrated whole-genome sequencing (WGS) and transcriptome profiling of CRC with whole-genome metagenomic sequencing of fecal samples to interrogate host-microbiome interactions at high resolution. Application of interpretable artificial intelligence enabled the stratification of CRC into four distinct microbiome-informed subtypes. WGS analysis identified mutational signatures SBS88 and ID18, linked to colibactin exposure, as early clonal events detected in 44.8% of non-hypermutated patients. Notably, these signatures were significantly more frequent among patients born after the 1960s. Microbiome-based subclassification revealed subtype-specific clinical and molecular features. Collectively, our findings indicate that colibactin exposure constitutes a prevalent and potentially modifiable risk factor for CRC in the Japanese population.

The Women's Health Care Committee was established in 2010 to promote women's health. In the fiscal year 2025, the committee advanced research and initiatives with a view toward social implementation, focusing on advancing understanding of disease etiology and improving quality of life (QOL) across the entire female life course, from adolescence to reproductive years, menopause, and older age. This year, nine subcommittees were established, which addressed a broad spectrum of topics, including menopausal disorders and occupational issues, pelvic floor dysfunction during the perinatal period, cancer and sexual education in adolescence, long-term management of Turner syndrome, menstrual disorders, and awareness of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). In addition, emerging areas such as trace elements and supplements, telemedicine, and nutritional assessments have also been explored. Furthermore, cross-cutting discussions were conducted beyond individual diseases and clinical domains, encompassing challenges in healthcare delivery systems, educational frameworks, and the broader social context of women's healthcare. This report is based on the Japanese version of the annual report (Acta Obstetrica et Gynaecologica Japonica 2026; 78(6): 925-930).

Anterior Gradient 2 (AGR2) is an endoplasmic reticulum (ER)-resident protein that belongs to the protein disulphide isomerase (PDI) family, and whose expression and secretion are induced by stress. Extracellular (secreted) AGR2 has been proposed as a marker of ER stress-related proteostasis alterations. Cancer cells frequently overexpress intracellular AGR2 (iAGR2) and secrete extracellular AGR2 (eAGR2). These features are associated with tumour progression and may serve as potential biomarkers in epithelial ovarian cancer (EOC). To investigate the roles of both iAGR2 and eAGR2 in EOC, we first generated EOC cells overexpressing iAGR2 and secreting eAGR2. Antibodies blocking eAGR2 reduced the proliferation and migration of these overexpressing cells. Concurrently, supplementation of parental cells with recombinant eAGR2 partially rescued these properties, further supporting a functional extracellular role for AGR2 in EOC. Quantitative proteomics, complemented by analysis of the TCGA database, revealed that eAGR2 modulated the expression of proteins involved in autophagy. This suggests that eAGR2-induced signalling may enhance catabolic activity under stress conditions, thereby increasing nutrient availability and, in turn, facilitating protein synthesis. This was reflected in the increased translational activity observed in AGR2-overexpressing and eAGR2-stimulated cells. Our results highlight two distinct, compartmentalised roles for AGR2. Specifically, iAGR2 acts as an ER-resident PDI, enhancing protein folding and ER quality control. In a complementary manner, eAGR2 functions as a metabolic regulator that may relieve constraints on tumour cell aggressiveness by maintaining autophagic flux and promoting protein synthesis. Overall, these findings support a dual-compartment model in which iAGR2 couples ER proteostasis with the metabolic and translational stimulation mediated by eAGR2.

Verticillium wilt, caused by Verticillium dahliae, is a devastating vascular disease that severely affects cotton and other dicotyledonous crops worldwide. The fungal effector protein PevD1 promotes disease progression by interacting with the host asparagine-rich protein (NRP) and disrupting cryptochrome 2 (CRY2)-mediated signaling; however, the molecular basis of this interaction remains poorly understood. Here, we combined computational modeling, molecular interaction analysis, mutagenesis, and structural biology approaches to investigate the PevD1-NRP-CRY2 regulatory mechanism in Arabidopsis thaliana. AlphaFold-Multimer prediction and molecular dynamics simulations indicated that both PevD1 and the photolyase homology region of CRY2 interact with the death-associated domain of NRP through highly overlapping interfaces. Surface plasmon resonance and isothermal titration calorimetry analyses showed that PevD1 binds NRP with substantially higher affinity than CRY2 (KD values of 0.19 μM and 4.34 μM, respectively). Site-directed mutagenesis further identified E108 and L111 of PevD1 as critical residues required for NRP recognition. We subsequently determined the crystal structure of PevD1 at 1.35 Å resolution and performed structure-guided virtual screening targeting the predicted interaction interface. This led to the identification of compound A6, which binds PevD1, forms a key interaction with residue E108, and disrupts the PevD1-NRP interaction in biochemical assays. Together, these findings define the molecular mechanism underlying the PevD1-NRP-CRY2 interaction and establish a framework for the development of effector-targeting anti-virulence compounds against V. dahliae.

BYSL gene encodes the bystin-like (BYSL) protein, a nucleolar protein involved in eukaryotic ribosome biogenesis and essential for 40S ribosomal subunit synthesis. Although BYSL upregulation has been implicated in hepatocellular carcinoma, its mechanistic contribution to tumor progression remains undefined. We observed that BYSL is consistently upregulated across multiple cancer types and is associated with adverse clinicopathological features and poor prognosis, with the strongest clinical relevance observed in hepatocellular carcinoma through the integrative transcriptomic and proteomic analyses. BYSL-knockout suppresses malignant phenotypes, including proliferation, migration, and invasion, and induced G1/S arrest and apoptosis. Mechanistically, loss of BYSL disrupts nucleolar homeostasis and reduces global protein synthesis, thereby activating the RPL5/RPL11-MDM2-p53 axis, leading to p53 stabilization and tumor suppression. Importantly, MYC directly bound to the BYSL promoter and transcriptionally activated its expression, whereas co-targeting BYSL and MYC produced more synergistic antitumor effects than either intervention alone. Collectively, our study reveals that BYSL acts as a pivotal downstream mediator of MYC-regulated ribosome biogenesis and promotes hepatocellular carcinoma progression. Our findings suggest that BYSL may represent a potential therapeutic target for hepatocellular carcinoma; nevertheless, additional in vivo preclinical studies are warranted to validate its translational prospects.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe conditions lacking specific pharmacological treatments. Endoplasmic reticulum (ER) stress plays a pivotal role in their pathophysiology, yet the precise regulatory mechanisms remain elusive. In this study, we identify the E3 ubiquitin ligase ring finger protein 5 (RNF5) as a critical driver of ALI/ARDS. RNF5 is markedly upregulated in response to ALI and significantly exacerbates lung injury by stabilizing HSPA5 (heat shock protein family A member 5), a master regulator of the unfolded protein response (UPR). Notably, in vivo Rnf5 ablation effectively attenuated pulmonary edema, inflammatory cell infiltration, and apoptosis, whereas lung-specific Rnf5 overexpression worsened inflammation and cell death in mice. Mechanistically, RNF5 interacts with HSPA5 and competitively blocks its binding to PERK, facilitating PERK release. Furthermore, RNF5 promotes the retro-translocation of HSPA5 from the ER lumen to the cytosol. In the cytosol, RNF5 mediates the K6- and K63-linked polyubiquitination of HSPA5, enhancing its thermal stability and preventing its re-entry into the ER. This spatial sequestration sustains the persistent dissociation of the PERK-HSPA5 complex, leading to the hyperactivation of the pro-apoptotic and pro-inflammatory PERK-eIF2α-CHOP signaling cascade. The ability of RNF5 to promote ALI is strictly dependent on its E3 ligase activity. In conclusion, our findings uncover a compartment-specific regulatory mechanism of HSPA5, suggesting that the RNF5-HSPA5-PERK axis represents a promising therapeutic target for ALI/ARDS.

Vitamin K was discovered during the 1930s when a strange haemorrhagic disorder was observed in chickens fed a cholesterol-free diet. A fat-soluble agent, present in green leafy vegetables and hog liver, was able to restore haemostasis in the chickens. The chemical structure and the physiological role of vitamin K were uncovered resulting in the Nobel Prize being awarded to Henrik Dam and Edward Doisy in 1943. The discovery of vitamin K led to a breakthrough in our understanding of the human coagulation system, where vitamin K plays a pivotal role in activating prothrombin and other coagulation factors. The prevention of vitamin K-dependent bleeding in newborns by vitamin K prophylaxis was introduced in the 1940s and is today a strong recommendation by the World Health Organization. Vitamin K also became crucial to the management of diseases with high risk of vitamin K deficiency due to malabsorption of fat. Later a new type of drug was developed, vitamin K antagonists, counteracting the physiologic effects of vitamin K for the prevention of thrombotic events. Recent research has indicated that vitamin K may have important functions beyond coagulation in extra-hepatic tissues by promoting healthy bone mineralization and preventing vascular calcification. Vitamin K was first discovered in the 1930s when scientists noticed bleeding problems in chickens lacking it. This breakthrough revealed its key role in blood clotting and led to life‐saving practices like giving newborns vitamin K to prevent bleeding. It also became essential for treating people with fat absorption issues and for developing drugs that reduce clotting risks. Today, research shows vitamin K may do more than help blood clot—it could support strong bones and protect blood vessels from harmful calcium buildup, making it important for overall health.

This study examined how state and local parks and recreation funding relates to county-level access to exercise opportunities, physical inactivity, and obesity, and how these associations differed in metropolitan versus nonmetropolitan areas. A cross-sectional analysis of all US counties (n = 3142) linked 2021 Census expenditure data with 2021 County Health Rankings measures. Generalized estimating equations assessed associations between expenditures and each outcome. Results showed that parks and recreation spending accounted for an average of 1.1% of state-local budgets (range: 0.4%-2.5%). Each 1% increase in expenditures was associated with significantly greater access to exercise opportunities and lower rates of physical inactivity and obesity. Such associations were strongest in metropolitan counties. In conclusion, increased investment in parks and recreation may improve community access to active environments and reduce physical inactivity and obesity. Future research should explore parks and recreation funding allocations in more detail and across a broader range of health outcomes.

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Gestational diabetes mellitus (GDM) may increase offspring susceptibility to neurodevelopmental stressors. Sevoflurane is widely used in pediatric anesthesia but carries potential neurotoxicity risks. This study investigated whether maternal GDM exacerbates sevoflurane-induced developmental neurotoxicity in offspring, and explored the underlying mechanisms related to neuroinflammation, microglial activation and mitochondrial dysfunction. A mouse model of maternal GDM was established, and offspring received sevoflurane exposure during brain development. Cognitive function was assessed by behavioral tests. Neuronal apoptosis and dendritic spine morphology were detected by TUNEL and Golgi-Cox staining. Microglial activation and inflammatory profiles were analyzed using immunofluorescence and multiplex liquid-chip assays. Transcriptomic and proteomic analyses were integrated to identify dysregulated molecular pathways, and key proteins were verified by Western Blot. Compared with control and single-treatment groups, combined GDM and sevoflurane exposure significantly worsened long-term cognitive impairment, promoted neuronal apoptosis, and reduced dendritic spine density in the hippocampus. The dual-hit induced robust microglial overactivation and disrupted inflammatory cytokine homeostasis. Multi-omics analyses revealed significant enrichment of pathways governing synaptic vesicle cycling, glutamatergic synaptic function, and immune-inflammatory responses. Mechanistically, the dual-hit caused severe mitochondrial dynamic imbalance characterized by downregulation of the fusion protein Mfn2, together with abnormal expression of the microglial receptor CX3CR1. Maternal GDM exposure is associated with aggravated sevoflurane-induced developmental neurotoxicity in offspring. Our correlative findings suggest potential underlying links involving altered mitochondrial homeostasis and excessive microglial activation. This study provides potential targets for preventing anesthesia-related neurotoxicity in high-risk children.

The escalating incidence of autoimmune diseases cannot be fully explained by genetics alone. It is increasingly linked to the exposome-the cumulative burden of lifelong environmental exposures. This review examines how pollutants (particulate matter, microplastics, agrochemicals, heavy metals) reshape the gut microbiota-immune axis and disrupt intestinal homeostasis. This triggers profound dysbiosis, characterized by reduced commensal diversity and expanded pathobionts. We highlight three mechanisms driving pollution-induced immune reprogramming: (i) barrier compromise facilitating metabolic endotoxemia; (ii) toxic Aryl Hydrocarbon Receptor (AhR) overactivation skewing the Th17/Treg balance; and (iii) epigenetic modifications like aberrant DNA methylation. Chronic environmental exposure accelerates telomere attrition, inducing premature immunosenescence and inflammaging. This promotes the pathological accumulation of senescent T cells and Age-associated B Cells (ABCs), linking environmental stress to tissue damage and autoantibody generation. However, a major limitation of the current literature is that many in vivo and in vitro models employ supraphysiological concentrations of pollutants that do not reflect actual human exposure scenarios. Without evaluating these specific exposure scenarios against realistic human gut concentrations, it is difficult to determine under which exact conditions the postulated dysbiotic effects occur. Ultimately, mitigating environmental risks and employing microbiota-targeted therapeutics are vital to restore barrier integrity.

Replacing high-performance synthetic fibers with sustainable bio-derived alternatives is critical for mitigating microplastic pollution but remains limited by the inferior mechanical performance of biomass-derived fibers. Here, we present bioinspired cellulose metafibers (Meta-CFs) enabled by a scalable hydrodynamic twisting strategy, wherein an asymmetric microfluidic field precisely guides the formation of continuously twisted architectures within a chemically cross-linked network, thereby locking in the ordered configuration and markedly suppressing defect accumulation. Multiscale experiments and simulations reveal that this strategy promotes efficient stress delocalization and cooperative load transfer. The resulting Meta-CFs achieve an unprecedented maximum tensile strength of 3.29 GPa (average 3.06 ± 0.23 GPa) and a toughness of 349.5 MJ m-3, simultaneously rivaling the strength of high-performance synthetic fibers and the toughness of natural spider silk. Furthermore, encapsulating multiple individual Meta-CFs with calcium alginate effectively scales up the bundle diameter while preserving GPa-level strength and full biodegradability. This upscaling strategy enables large-diameter structural applications, as demonstrated by durable trimmer lines that avoid the generation of persistent agricultural microplastic residues, thereby establishing a viable pathway toward high-performance, sustainable material alternatives.

The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor that plays a critical role in regulating cell proliferation, survival, and differentiation. Aberrant activation or overexpression of EGFR has been observed in several cancers, including prostate cancer (PCa), and is associated with aggressive tumor behavior and poor prognosis. The development and progression of PCa largely depend on the involvement of androgen receptor (AR) pathways, which are directly related to EGFR signaling. Research indicates that EGFR can affect AR activity, increasing transcriptional activity or promoting ligand-independent activation, which may lead to castration-resistant prostate cancer (CRPC). Furthermore, emerging evidence suggests that estrogen receptors (ERs) may also interact with EGFR signaling in prostate tissue. These may influence tumor growth, interactions with cellular plasticity, and therapy resistance, but their exact mechanisms require further investigation. Identifying and improving treatment strategies for advanced and treatment-resistant PCa requires understanding the interplay between the EGFR, AR, and ER pathways. However, clinical trials have shown limited success in targeting EGFR alone, possibly through compensatory mechanisms via steroid hormone receptors. Therefore, therapies that simultaneously target EGFR and AR/ER activity may be more effective. Continued research into the molecular interplay between these pathways will broaden our understanding of prostate cancer biology and support the development of more personalized and effective treatments. In this review will focus on EGFR/HER1 and its putative role in prostate cancer. Furthermore, we discuss the potential interaction between EGFR, androgen receptor (AR), and estrogen receptor (ER) signaling pathways.

Accurate assessment of the critical view of safety (CVS) is essential for preventing bile duct injuries during laparoscopic cholecystectomy. Existing artificial intelligence approaches primarily rely on static frame-level analysis and often fail to capture the temporal evolution of surgical scenes, limiting their ability to provide reliable and context-aware safety assessment. To address this challenge, we propose TempoSafe-CVS, a temporal multi-scale framework for automated CVS assessment in surgical videos. The proposed architecture integrates complementary visual representations through a Swin Transformer-based global context encoder, a ResNet-based local feature extractor, and a structure-aware convolutional module. These multi-scale features are combined and processed using temporal sequence modelling and spatio-temporal reasoning to capture both visual and temporal dependencies across surgical sequences. Furthermore, a unified multi-task prediction framework jointly estimates CVS safety status, procedural progression, anatomical structure visibility, and clinically relevant C1/C2/C3 criteria. Experiments conducted on the Endoscapes benchmark dataset demonstrate the effectiveness of the proposed approach, achieving 79.6% AUC-ROC for safety assessment, 81.5% average balanced accuracy for C1/C2/C3 criteria classification, and a mean absolute error of 0.187 for progression estimation. Comparative evaluations show consistent improvements over existing CVS assessment methods, highlighting the benefits of temporal reasoning and multi-scale visual representation learning. Qualitative analyses further demonstrate the interpretability of the framework through temporally consistent and anatomically grounded predictions. The proposed framework advances intelligent surgical video understanding by combining temporal sequence reasoning with multi-scale visual analysis, offering a potential solution for explainable and context-aware decision support in safety-critical surgical environments.

PIF1 family helicases promote genome stability during DNA replication and repair, yet the biochemical activity of human PIF1 (hPIF1) remains poorly understood. Here, we directly compare full-length hPIF1 and budding yeast Pif1 (yPif1) and show that the two enzymes operate differently. In bulk assays, hPIF1 displays weak net DNA unwinding because its robust intrinsic single-stranded DNA (ssDNA) annealing activity rapidly reforms duplex DNA behind the helicase motor. Single-molecule magnetic tweezers experiments reveal that hPIF1 is only modestly slower than yPif1 and similarly processive, indicating that poor apparent unwinding primarily reflects rapid reannealing rather than impaired motor activity. Mutagenesis and structural modeling indicate that this functional divergence depends on a yeast-specific insertion within the catalytic domain. Unlike yPif1, hPIF1 fails to stimulate Polδ-dependent displacement-loop (D-loop) extension, arguing that it does not promote DNA unwinding ahead of the migrating bubble. However, similarly to yPif1, hPIF1 likely unwinds newly synthesized DNA coupled with DNA reannealing behind the migrating D-loop. hPIF1 efficiently remodels intramolecular G-quadruplex DNA into fully base-paired dsDNA, whereas yPif1 generates ssDNA products. Together, our data support a model in which hPIF1 acts primarily as a DNA translocase that couples local unwinding with rapid rewinding to clear secondary DNA structures without generating extensive ssDNA.

Rapid maxillary expansion (RME) is a widely used orthodontic intervention for correcting transverse maxillary deficiencies. By mechanically separating the midpalatal suture, RME improves occlusal relationships and induces tissue repair processes similar to fracture healing. Inflammation and bone regeneration following fracture are regulated by epigenetic mechanisms, such as DNA methylation. However, the effects of RME-induced mechanical stimulation on epigenetic dynamics in humans remain unclear. We evaluated genome-wide DNA methylation changes in saliva associated with RME treatment. Twenty patients undergoing orthodontic treatment with RME and four untreated controls were enrolled. Saliva samples were collected before (T0) and after treatment (T1), and genome-wide DNA methylation profiling was performed using the Illumina Infinium HumanMethylationEPIC v2.0 BeadChip. Differential methylation analysis was conducted using linear models accounting for within-subject correlations. In the RME group, 164 CpG sites were differentially methylated between T0 and T1 (false discovery rate&#x2009;<&#x2009;0.05), whereas no significant changes were observed in controls. The differentially methylated CpG sites were annotated to genes associated with biological responses to RME, including inflammatory pathways and metabolic processes. RME may be associated with measurable changes in salivary DNA methylation, suggesting epigenetic responses detectable in saliva and providing a basis for future mechanistic investigations.