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Sialic acids are predominantly found at the terminal ends of glycoproteins and glycolipids and play key roles in cellular communication and function. The process of sialylation, a form of post-translational modification, involves the covalent attachment of sialic acid to the terminal residues of oligosaccharides and glycoproteins. This modification not only provides a layer of electrostatic repulsion to cells but also serves as a receptor for various biological signaling pathways. Sialylation is involved in several pathophysiological processes. Given its multifaceted involvement in cellular functions, sialylation presents a promising avenue for therapeutic intervention. Current studies are exploring agents that target sialic acid residues on sialoglycans or the sialylation process. These efforts are particularly focused on the fields of cancer therapy, stroke treatment, antiviral strategies, and therapies for central nervous system disorders. In this review, we aimed to summarize the biological functions of sialic acid and the process of sialylation, explore their roles in various pathophysiological contexts, and discuss their potential applications in the development of novel therapeutics.

Background The triglyceride-glucose (TyG) index is a new alternative measure for insulin resistance. This meta-analysis was conducted to assess the associations of the TyG index with the risks of cardiovascular diseases and mortality in the general population. Methods The PubMed, Cochrane Library and Embase databases were searched for randomized controlled trials or observational cohort studies reporting associations of the TyG index with cardiovascular diseases and mortality from inception to April 16, 2022. Effect sizes were pooled using random-effects models. Robust error meta-regression methods were applied to fit nonlinear dose–response associations. Evidence quality levels and recommendations were assessed using the Grading of Recommendations Assessment, Development and Evaluation system (GRADE). Results Twelve cohort studies (6 prospective and 6 retrospective cohorts) involving 6,354,990 participants were included in this meta-analysis. Compared with the lowest TyG index category, the highest TyG index was related to a higher incidence of coronary artery disease (CAD) (3 studies; hazard ratio [HR] = 2.01; 95% confidence interval [CI] 1.68–2.40; I 2  = 0%), myocardial infarction (MI) (2 studies; HR = 1.36; 95% CI 1.18–1.56; I 2  = 35%), and composite cardiovascular disease (CVD) (5 studies; HR = 1.46; 95% CI 1.23–1.74; I 2  = 82%). However, there was no association between the TyG index and mortality (cardiovascular mortality [3 studies; HR = 1.10; 95% CI 0.82–1.47; I 2  = 76%] or all-cause mortality [4 studies; HR = 1.08; 95% CI 0.92–1.27; I 2  = 87%]). In the dose–response analysis, there was a linear association of the TyG index with the risk of CAD (P nonlinear  = 0.3807) or CVD (P nonlinear  = 0.0612). GRADE assessment indicated very low certainty for CVD, MI, cardiovascular mortality and all-cause mortality, and moderate certainty for CAD. Conclusions Based on our current evidence, a higher TyG index may be associated with an increased incidence of CAD (moderate certainty), MI (very low certainty) and CVD (very low certainty) in the general population. There is a potential linear association of the TyG index with CAD and the composite CVD incidence. Further prospective studies (especially in non-Asians) are needed to confirm our findings.

Background This systematic review aims to provide evidence from current observational studies on whether Secondhand smoke (SHS) exposure is associated with increased risk of atrial fibrillation (AF) risk, so to identify potential high-risk subgroup to inform both mechanistic hypotheses and prevention strategies. Methods A systematic screening of the PubMed, EMBASE and Cochrane Central databases was conducted until September 2025 to identify observational studies focused on the association between SHS and AF. Results Six observational studies involving more than 420,000 participants were included. Early-life SHS exposure, including gestational and childhood household exposure, was consistently associated with a higher risk of AF in adulthood. Evidence for adulthood SHS exposure was more heterogeneous; however, studies incorporating objective biomarkers or dose–response assessments demonstrated clearer associations. Several studies reported stronger associations among women, Black individuals, never-smokers, and those with elevated genetic susceptibility. Notably, a large population-based cohort demonstrated a graded relationship between SHS exposure and incident AF, with evidence of gene–environment interaction. Conclusions Available evidence suggests that SHS exposure, particularly during early life, may be associated with an increased risk of AF. The observed heterogeneity by exposure window, assessment method, and population subgroup underscores the importance of life-course and equity-focused approaches to AF prevention. Reducing SHS exposure may represent a modifiable and underrecognized strategy for long-term AF risk reduction.

The optimal timing for initiating direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) following acute ischemic stroke (AIS) remains a critical clinical question. This review evaluates findings from three pivotal randomized controlled trials—TIMING, ELAN, and OPTIMAS—comparing early versus delayed DOAC initiation in AF patients with AIS. Collectively, these trials provide strong evidence supporting the safety and efficacy of early initiation of DOACs in patients with AIS and AF. The TIMING trial demonstrated the non-inferiority of early DOAC initiation (≤4 days) compared to delayed initiation (5-10 days), with numerically lower rates of ischemic stroke and no cases of symptomatic ICH. The ELAN trial further corroborated these findings, showing no significant difference in the composite outcome of recurrent ischemic stroke, systemic embolism, or major hemorrhage between early initiation (≤48 h for minor/moderate strokes; days 6-7 for major strokes) and later initiation (days 3-4 to 12-14). OPTIMAS, the largest trial to date, confirmed the non-inferiority of early initiation (≤4 days) versus delayed initiation (7-14 days), without an increased risk of symptomatic ICH and with comparable rates of recurrent ischemic events.

Clarifying mechanisms underlying the ecological succession of gut microbiota is a central theme of gut ecology. Under experimental manipulations of zebrafish hatching and rearing environments, we test our core hypothesis that the host development will overwhelm environmental dispersal in governing fish gut microbial community succession due to host genetics, immunology, and gut nutrient niches. We find that zebrafish developmental stage substantially explains the gut microbial community succession, whereas the environmental effects do not significantly affect the gut microbiota succession from larvae to adult fish. The gut microbiotas of zebrafish are clearly separated according to fish developmental stages, and the degree of homogeneous selection governing gut microbiota succession is increasing with host development. This study advances our mechanistic understanding of the gut microbiota assembly and succession by integrating the host and environmental effects, which also provides new insights into the gut ecology of other aquatic animals.

Background: Several bleeding risk assessment models have been developed in atrial fibrillation (AF) patients with oral anticoagulants, but the most appropriate tool for predicting bleeding remains uncertain. Therefore, we aimed to assess the diagnostic accuracy of the Hypertension, Abnormal liver/renal function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, Drugs/alcohol concomitantly (HAS-BLED) score compared with other risk scores in anticoagulated patients with AF. Methods: We comprehensively searched the PubMed and Embase databases until July 2021 to identify relevant pieces of literature. The predictive abilities of risk scores were fully assessed by the C-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) values, calibration data, and decision curve analyses. Results: A total of 39 studies met the inclusion criteria. The C-statistic of the HAS-BLED score for predicting major bleeding was 0.63 (0.61–0.65) in anticoagulated patients regardless of vitamin k antagonists [0.63 (0.61–0.65)] and direct oral anticoagulants [0.63 (0.59–0.67)]. The HAS-BLED had the similar C-statistic to the Hepatic or renal disease, Ethanol abuse, Malignancy, Older, Reduced platelet count or function, Re-bleeding risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, Stroke (HEMORR 2 HAGES), the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA), the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT), the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF), or the Age, Biomarkers, Clinical History (ABC) scores, but significantly higher C-statistic than the Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke/transient ischemic attack history (CHADS 2 ) or the Congestive heart failure/left ventricular ejection fraction ≤ 40%, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke/transient ischemic attack/thromboembolism history, Vascular disease, Age 65–74 years, Sex (female) (CHA 2 DS 2 -VASc) scores. NRI and IDI values suggested that the HAS-BLED score performed better than the CHADS 2 or the CHA 2 DS 2 -VASc scores and had similar or superior predictive ability compared with the HEMORR 2 HAGES, the ATRIA, the ORBIT, or the GARFIELD-AF scores. Calibration and decision curve analyses of the HAS-BLED score compared with other scores required further assessment due to the limited evidence. Conclusion: The HAS-BLED score has moderate predictive abilities for bleeding risks in patients with AF regardless of type of oral anticoagulants. Current evidence support that the HAS-BLED score is at least non-inferior to the HEMORR 2 HAGES, the ATRIA, the ORBIT, the GARFIELD-AF, the CHADS 2 , the CHA 2 DS 2 -VASc, or the ABC scores.

Background Venous thromboembolism (VTE) often necessitates extended anticoagulation to reduce the risk of recurrence. While direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists due to their improved safety and convenience, the optimal long-term dosing strategy (reduced vs full dose) remains uncertain. This systematic review assesses the efficacy and safety outcomes of reduced-dose DOACs compared with full-dose therapy for extended VTE treatment. Methods We conducted a systematic review of randomized controlled trials (RCTs) comparing reduced-dose and full-dose DOACs in patients with VTE. Due to heterogeneity in study designs and outcomes, a narrative synthesis was performed. Results Three RCTs were included. In AMPLIFY-EXT, recurrent VTE or death occurred in 1.7% of patients receiving apixaban (both 2.5 mg and 5 mg) versus 8.8% with placebo. In EINSTEIN CHOICE, recurrent VTE occurred in 1.2% and 1.5% of patients receiving rivaroxaban 10 mg and 20 mg, respectively, compared with 4.4% with aspirin. The safety outcomes were comparable between the two DOAC doses in AMPLIFY-EXT and EINSTEIN CHOICE. RENOVE reported 5-year cumulative incidences of recurrent VTE of 2.2% with reduced-dose and 1.8% with full-dose DOACs (hazard ratio 1.32, 95% confidence interval [CI]: 0.67-2.60; P = .23 for non-inferiority). Major or clinically relevant non-major bleeding events occurred in 9.9% patients in the reduced-dose group and 15.2% patients in the full-dose group (HR 0.61; 95% CI 0.48-0.79). Conclusion Current evidence suggest that reduced-dose DOACs provide efficacy comparable to full-dose regimens without a corresponding increase in bleeding events in the extended treatment of VTE.

Background Current guidelines recommend that anticoagulation is reasonable and less robust to prevent stroke among AF patients with an intermediate risk of stroke, suggesting the need for more evidence in this population. Therefore, our current systematic review and meta-analysis aimed to evaluate the effectiveness and safety outcomes of oral anticoagulation (OAC) therapy in AF patients with a single additional stroke risk factor (CHA2DS2-VASc score = 1 in males and 2 in females). Methods We performed the literature searches to identify relevant articles by systematically researching the PubMed and Embase databases. In the pooled analysis by the random-effects model, the comparative treatment indicators to present outcomes of OAC therapy compared with no OAC were adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results A total of 6 studies were finally included. In the pooled analysis by the random-effects model, compared with no OAC therapy, OAC use was associated with increased risks of major bleeding (HR = 1.29, 95%CI: 1.06-1.57) and gastrointestinal bleeding (HR = 1.38, 95%CI: 1.04-1.82). There were no differences in stroke or systemic embolism (SSE) (HR = 0.84, 95%CI: 0.66-1.08), ischemic stroke (HR = 0.79, 95%CI: 0.27-2.33), and intracranial bleeding (HR = 1.17, 95%CI: 0.78-1.76) between the two studied groups Conclusion In patients with AF patients at an intermediate risk of stroke, OAC use was not associated with reductions in thromboembolic events, but might increase the bleeding risks compared with no treatment.

Background The associations between vitamin D and coronavirus disease 2019 (COVID-19) infection and clinical outcomes are controversial. The efficacy of vitamin D supplementation in COVID-19 is also not clear. Methods We identified relevant cohort studies that assessed the relationship between vitamin D, COVID-19 infection and associated death and randomized controlled trials (RCTs) that reported vitamin D supplementation on the outcomes in patients with COVID-19 by searching the PubMed, EMBASE, and medRxiv databases up to June 5th, 2021. Evidence quality levels and recommendations were assessed using the GRADE system. Results Eleven cohort studies with 536,105 patients and two RCTs were identified. Vitamin D deficiency (< 20 ng/ml) or insufficiency (< 30 ng/ml) was not associated with an significant increased risk of COVID-19 infection (OR for < 20 ng/ml: 1.61, 95% CI: 0.92–2.80, I2 = 92%) or in-hospital death (OR for < 20 ng/ml: 2.18, 95% CI: 0.91–5.26, I2 = 72%; OR for < 30 ng/ml: 3.07, 95% CI: 0.64–14.78, I2 = 66%). Each 10 ng/ml increase in serum vitamin D was not associated with a significant decreased risk of COVID-19 infection (OR: 0.92, 95% CI: 0.79–1.08, I2 = 98%) or death (OR: 0.65, 95% CI: 0.40–1.06, I2 = 79%). The overall quality of evidence (GRADE) for COVID-19 infection and associated death was very low. Vitamin D supplements did not significantly decrease death (OR: 0.57, I2 = 64%) or ICU admission (OR: 0.14, I2 = 90%) in patients with COVID-19. The level of evidence as qualified using GRADE was low. Conclusions Current evidence suggested that vitamin D deficiency or insufficiency was not significantly linked to susceptibility to COVID-19 infection or its associated death. Vitamin D supplements did not significantly improve clinical outcomes in patients with COVID-19. The overall GRADE evidence quality was low, we suggest that vitamin D supplementation was not recommended for patients with COVID-19.

Lactate, the end product of glycolysis, plays a crucial role in cellular signaling and metabolism. The discovery of lactylation, a novel post-translational modification, has uncovered the role of lactate in regulating diseases, especially in the brain. Lactylation connects genetic encoding with protein function, thereby influencing key biological processes. Increasing evidence supports lactate-mediated lactylation as a critical modulator in neurological disorders. This review offers an overview of lactate metabolism and lactylation, highlighting recent advances in understanding the regulatory enzymes of lactylation and their role in the central nervous system. We investigate the impact of lactylation on brain dysfunctions, including neurodegenerative diseases, cerebrovascular disorders, neuroinflammation, brain tumors, and psychiatric conditions. Moreover, we highlight the therapeutic potential of targeting lactylation in treating brain disorders and outline key research gaps and future directions needed to advance this promising field.