Metabolic syndrome (MetS) has long been used as a pragmatic tool for population-level cardiometabolic risk stratification, rather than as a mechanistically defined disease entity. However, mounting evidence suggests the existence of marked biological heterogeneity among individuals meeting identical MetS criteria, encompassing diverse metabolic phenotypes, disease trajectories, and responses to interventions. Such heterogeneity helps explain the limited and inconsistent effectiveness of uniform dietary strategies. In parallel, dietary research has shifted from a nutrient-centric approach to a food-based dietary pattern, emphasizing higher intakes of whole foods and reduced consumption of ultra-processed foods. In the context of metabolic heterogeneity, these shared food-level characteristics may confer relatively consistent metabolic benefits across diverse phenotypes. Future research may shift from uniform dietary recommendations to stratified strategies, grounded in dietary principles and informed by mechanistic insights, to better address metabolic heterogeneity.

Upon infection, bacteria form polysaccharides barriers, such as capsular polysaccharide (CPS), exopolysaccharide (EPS) and lipopolysaccharide (LPS). The barrier hinders antibiotic penetration and host immune clearance, exacerbating antimicrobial resistance crisis. Bacteriophages (phages), natural viruses that can specifically infect and kill bacteria, have evolved depolymerase to degrade the polysaccharides. This review evaluates the primary therapeutic value of depolymerases as synergists to existing therapies, systematically detailing their potential to enhance antibiotic efficacy, improve phage therapy, and augment host immunity. We further integrate an evolutionary perspective to analyze likely adaptive responses and potential strategies to eradicate resistance. Finally, the discussion addresses formulation challenges and future prospects for the clinical translation of depolymerase-based synergistic therapies.

Mitochondria are organelles that play a crucial role in various physiological processes. They are particularly important during embryonic development, as their proper function is required for essential processes such as fertilization, implantation, and embryonic growth. In addition to their well-known role in adenosine triphosphate (ATP) synthesis and energy production, mitochondria serve multiple other functions during embryonic development. These include the synthesis of important metabolites, involvement in cell signaling pathways, regulation of reactive oxygen species, and facilitation of interactions between organelles. The mitochondrial genome, known as mitochondrial DNA (mtDNA), also plays a unique role in embryonic development. Dysfunction in mitochondria can lead to failures in fertilization, suboptimal embryo development, post-implantation failures, and mitochondrial-related diseases in adults. Advances in sequencing technology and experimental techniques have greatly improved our understanding of mitochondrial function. This paper reviews the roles of mitochondrial functions in embryonic development and the influence of mitochondrial technologies and it highlights the potential impact of understanding mitochondria's unique genetic and functional characteristics on embryonic development and offspring health.

Inflammatory bowel disease (IBD) and physiological gut aging present with overlapping clinical features, including impaired barrier functioning, decreased nutrient absorption, and intestinal frailty. Emerging evidence indicates that even young IBD patients can exhibit gut phenotypes akin to those seen with aging. However, the two processes differ substantially in their underlying mechanisms. Gut aging is characterized by low-grade, chronic inflammation and gradual cellular senescence, whereas IBD involves persistent immune activation, cyclical tissue damage, and accelerated degenerative changes. This review systematically contrasts physiological gut aging and IBD-associated accelerated gut aging across several dimensions: cellular senescence and programmed cell death, immune cell remodeling, alterations in gut microbiota, changes in mesenteric adipose tissue, and the evolving role of the appendix. By integrating current advances in basic and translational research, this article highlights both the shared and distinct pathways driving gut dysfunction in aging and IBD, and underscores the importance of early recognition and targeted intervention for premature gut aging in clinical practice.

Pancreatic cancer, and especially pancreatic ductal adenocarcinoma (PDAC), is extremely difficult to treat due to early asymptomatic stage, molecular heterogeneity, and resistance to conventional treatments, with a 5-year survival rate of less than 10%. Antibody-drug conjugates (ADCs), as an emerging precision therapy, show the potential to treat PDAC through the synergy of antibody targeting and cytotoxic drugs. Multiple targets (such as uPAR, Mesothelin, CLDN18.2, and TROP2) are highly expressed in PDAC, which has become the key direction of ADC development. However, the matrix barrier restricts drug delivery, heterogeneous expression leads to efficacy differentiation, and drug resistance mechanisms further limit the role of ADCs. To overcome these challenges, researchers are exploring high-stability single domain antibodies, more potent payloads and linkers, bystander effect mechanisms, and combined treatment strategies with immune, autophagy, DNA damage repair, and other pathways. Bispecific ADC, conditionally activated ADC, and penetration enhancement design have also been used to improve efficacy. On the whole, ADCs offer hope for the treatment of PDAC. Future research and development should focus on improving delivery efficiency, alleviating drug resistance, and individualized design.

Metabolic syndrome (MetS), characterized by the clustering of metabolic risk factors, substantially increases the risk of cardiovascular disease and type 2 diabetes. Although dietary patterns (DPs) are known to influence MetS, evidence remains limited regarding the applicability of established dietary principles in populations living at a high altitude in an environment with a halal diet. This study examined the associations between both a priori and locally derived DPs and MetS and its components, with particular emphasis on low high-density lipoprotein cholesterol (HDL-C). A cross-sectional analysis was performed among 1,133 adults ages 18–80 using data from an ongoing pilot cohort study (2024–2025). DPs were identified using a modified Dietary Approaches to Stop Hypertension (DASH) score and factor analysis. Associations with MetS and its components were assessed using inverse probability of exposure-weighted logistic regression. Subgroup and interaction analyses evaluated effect modification, and mediation analysis examined the mediating role of being overweight. The prevalence of MetS was 54.81%. Three major DPs were identified: the Sugary Drinks and Fast-Food Pattern, the Halal Protein-Rich Pattern, and the Traditional Grain and Tonic Pattern. The DASH score was moderately correlated with the Halal Protein-Rich Pattern (Spearman's r = 0.37). Participants in the highest tertile of the Halal Protein-Rich Pattern had a significantly lower risk of MetS compared to those in the lowest tertile (OR = 0.64, 95% CI: 0.45–0.92; p for trend < 0.05), as well as a 35% lower risk of low HDL-C. In contrast, higher adherence to the Sugary Drinks and Fast-Food Pattern was associated with an increased risk of low HDL-C. Similar protective associations were observed for higher DASH scores. Subgroup analyses showed that the Halal Protein-Rich Pattern was inversely associated with MetS among overweight participants (OR = 0.80, 95% CI: 0.66–0.96). Mediation analysis indicated that being overweight mediated 19.84% of the association between the Halal Protein-Rich Pattern and MetS. In conclusion, in a high-altitude environment with a halal diet, both DASH and a culturally adapted Halal Protein-Rich Pattern were inversely associated with MetS and low HDL-C in particular. DASH offers an evidence-based guideline, while the Halal Protein-Rich Pattern reflects a culturally appropriate and locally practical diet. Longitudinal studies are warranted to confirm these findings.

Closely associated with metabolic disorders, non-alcoholic fatty liver disease (NAFLD) substantially increases the risk of hepatocellular carcinoma. This study aimed to apply machine learning (ML) algorithms to a community-based cohort in southern Taiwan to identify key risk factors for NAFLD and to develop predictive models with clinical applicability. Data were derived from community health examinations, and eighteen clinical and demographic features were analyzed. Five ML algorithms were evaluated: logistic regression (LR), random forest (RF), K-nearest neighbors (KNN), adaptive boosting (AdaBoost), and extreme gradient boosting (XGBoost). Model performance was assessed using accuracy, precision, recall, F1 score, and area under the receiver operating characteristic curve (AUROC). A total of 7,510 participants were included (38.8% male; mean age 50.9 ± 15.0 years). The dataset was randomly divided into training (80%) and testing (20%) subsets, with no significant differences observed between groups in most independent variables. The Synthetic Minority Over-sampling Technique (SMOTE) was employed to balance NAFLD and non-NAFLD groups in the training dataset. Among all models, XGBoost achieved the highest performance, with an accuracy of 83.48%, precision of 84.31%, recall of 81.21%, F1 score of 82.72%, and AUROC of 92.85%. Feature importance analysis identified low-density lipoprotein cholesterol (LDL-C), body mass index (BMI), waist circumference, fasting plasma glucose (FPG), and triglycerides (TG) as the most influential predictors of NAFLD. ML algorithms, particularly XGBoost, demonstrated high accuracy in predicting NAFLD and effectively identified key clinical predictors. These findings may enhance early diagnosis and facilitate the development of targeted intervention strategies in the management of NAFLD.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options. Transient receptor potential ankyrin 1 (TRPA1) has been implicated in inflammation and pain, but its role in UC remains a subject of debate. The current study investigated the effects of TRPA1 inhibition in both acute and subacute murine models of dextran sulfate sodium (DSS)-induced colitis. Genetic knockout of Trpa1 or pharmacological inhibition with A967079 significantly ameliorated inflammation in the acute model, reducing the disease activity index (DAI), colon shortening, histopathological damage, and TNF-α secretion from macrophages. In contrast, TRPA1 suppression exacerbated subacute colitis and worsened weight loss, DAI, colon shortening, and histopathology. Mechanistically, Trpa1 deletion promoted CD4+ T cell polarization toward the Th1 subtype in subacute colitis, increasing IFN-γ levels. These findings reveal a dual role for TRPA1 in colonic inflammation: it mediates pro-inflammatory effects primarily via innate immune cells in the acute phase but has anti-inflammatory effects by modulating adaptive immunity in the subacute phase. These findings provide new insights into the context-dependent roles of TRPA1 and suggest that TRPA1 may represent a context-specific and stage-dependent therapeutic target in UC.

This study investigates the prognostic significance of alpha-fetoprotein (AFP) in hepatitis B virus-related intrahepatic cholangiocarcinoma (HBV-ICC), given that AFP — though commonly used for hepatocellular carcinoma — is sometimes elevated in HBV-ICC, yet its clinical relevance remains unclear. The research retrospectively analyzed 839 HBV-ICC patients who underwent curative hepatectomy, categorizing them into AFP-positive (≥ 20 ng/mL) and AFP-negative groups. Using propensity score matching and inverse probability of treatment weighting to reduce bias, the study compared overall survival (OS) and time to recurrence (TTR). Results showed that AFP-positive patients had poorer liver function and more aggressive tumor characteristics, including higher rates of cirrhosis, microvascular invasion, and satellite nodules. Across both unadjusted and adjusted cohorts, elevated AFP was significantly associated with worse OS and earlier recurrence. Multivariate Cox analysis identified AFP as an independent predictor of poor prognosis. While CA19-9 alone demonstrated limited predictive value, its combination with AFP improved prognostic accuracy. The study concludes that elevated serum AFP independently predicts adverse survival and recurrence outcomes in HBV-ICC patients after curative resection, and combining AFP with CA19-9 enhances prognostic stratification, supporting AFP as a practical biomarker for postoperative risk assessment.

Optimal post-remission therapy is crucial for long-term survival in patients with acute myeloid leukemia (AML). Multidisciplinary team (MDT) conferences address this challenge by providing comprehensive, patient-centered consultations that support individualized treatment decision-making. We evaluated the effectiveness of MDT conferences in guiding post-remission treatment decisions in adults with de novo AML. We enrolled 653 adult patients with de novo AML who were treated at our center between January 2017 and December 2022. Of the 591 eligible patients (90.5%), 501 (84.8%) attended a scheduled MDT evaluation. Allogeneic hematopoietic cell transplantation (allo-HCT) was recommended for 315 patients (62.9%), of whom 251 (79.7%) subsequently underwent transplantation. Survival analyses showed that MDT attendees had superior 3-year overall survival (68.9% vs. 53.5%, p < 0.0001) and a lower 3-year cumulative incidence of relapse (30.7% vs. 44.9%; p < 0.0001) compared with patients who did not attend MDT conferences. Patients most likely to benefit from allo-HCT following MDT recommendations included those with intermediate- or adverse-risk disease according to the European LeukemiaNet 2017 classification, and those with favorable-risk disease who showed a suboptimal response to induction therapy. The main barriers to allo-HCT were persistent or relapsed disease and patient preference. Overall, MDT conferences effectively identified patients who were most likely to benefit from allo-HCT and were associated with higher transplantation rates within a modern healthcare system.