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Protein structure underpins functional roles in all biological processes; therefore, improved understanding of protein structures is of fundamental importance in nearly all biological and biomedical research areas. Traditional techniques such as X‐ray crystallography and more recently, cryo‐EM, can reveal structural features on isolated proteins/protein complexes at atomic resolution level and have become indispensable tools for structural biology. Crosslinking mass spectrometry (XL‐MS), on the other hand, is an emerging technique capable of capturing transient and dynamic information on protein interactions and assemblies in their native environment. The combination of XL‐MS with traditional techniques holds potential for bridging the gap between structural biology and systems biology approaches. Such a combination will enable visualization of protein structures and interactions within the crowded macromolecular environment in living systems that can dramatically increase understanding of biological functions. In this review, we first discuss general strategies of XL‐MS and then survey recent examples to show how qualitative and quantitative XL‐MS studies can be integrated with available protein structural data to better understand biological function at systems level. [ABSTRACT FROM AUTHOR]

Background and Aim: Tri‐typing of acute‐on‐chronic liver failure (ACLF), as proposed by the World Gastroenterology Organization (WGO), has not been validated in patients infected with hepatitis B virus (HBV). We aim to compare the three types of ACLF patients in clinic characteristics. Methods: Hospitalized ACLF patients with chronic hepatitis B from five hepatology centers were retrospectively selected and grouped according to the WGO classification. For each group, we investigated laboratory tests, precipitating events, organ failure, and clinical outcome. Results: Compared with type‐B (n = 262, compensated cirrhosis) and type‐C (n = 129, decompensated cirrhosis) ACLF, type‐A patients (n = 195, non‐cirrhosis) were associated with a younger age, the highest platelet counts, the highest aminotransferase levels, and the most active HBV replications. HBV reactivation were more predominant in type‐A, while bacterial infections in type‐B and type‐C ACLF cases. Liver failure (97.4%) and coagulation failure (86.7%) were most common in type‐A compared with type‐B or type‐C ACLF patients. Kidney failure was predominantly identified in type‐C subjects (41.9%) and was highest (23/38, 60.5%) in grade 1 ACLF patients. Furthermore, type‐C ACLF showed the highest 28‐day (65.2%) and 90‐day (75.3%) mortalities, compared with type‐A (48.7% and 54.4%, respectively) and type‐B (48.4% and 62.8%, respectively) ACLF cases. Compared with type‐A (11.7%) ACLF patients, the increased mortality from 28 to 90 days was higher in type‐B (31.6%) and type‐C (37.5%). Conclusion: Tri‐typing of HBV‐related ACLF in accordance with the WGO definition was able to distinguish clinical characteristics, including precipitating events, organ failure, and short‐term prognosis in ACLF patients. [ABSTRACT FROM AUTHOR]

Background & Aims: The role of cigarette smoking in the development of chronic hepatitis B (CHB) remains poorly understood. We assessed the potential contributions of cigarette smoking to liver fibrosis and its regression after starting antiviral therapy in CHB patients. Methods: In this cohort study, 2144 consecutive male CHB patients under no antiviral therapy were evaluated and 206 patients with significant liver fibrosis (≥F2) initiating antiviral therapy had longitudinal follow‐up. Liver fibrosis was measured by liver stiffness measurement using transient elastography. To adjust for imbalances between smoking history and never smoking groups, propensity score (PS) matching model with 1:1 ratios were performed. Cigarette smoking history and intensity (pack‐years) were collected and documented using a standardized questionnaire. Results: Before PS matching, 432/2144 patients had advanced fibrosis in prevalence cohort. Patients with smoking history (n = 1002) had a greater prevalence of advanced fibrosis than those without (n = 1142) (24.4% vs 16.5%, P = 0.001). Multivariate logistic regression analysis demonstrated that smoking contributed to advanced fibrosis (OR, 1.458; 95% CI, 1.114‐1.908). In longitudinal cohort, multivariate logistic regression analysis demonstrated retarded fibrosis regression in patients with history of smoking ≥10 pack‐years (OR, 0.288; 95% CI, 0.1‐0.825). After PS matching, patients with smoking history had higher prevalence of advanced fibrosis (22.8% vs 18%, P = 0.024) than those non‐smokers. In post‐PS‐matching logistic regression, the effect of smoking on advanced fibrosis persisted (OR, 1.415; 95% CI, 1.047‐1.912; P = 0.024). Conclusions: Cigarette smoking in male CHB patients aggravated liver fibrosis prior to and delayed fibrosis regression under antiviral therapy. [ABSTRACT FROM AUTHOR]