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Background: There is a lack of precision in the immunotherapy strategy tailored for patients exhibiting diverse clinical characteristics. This study aims to employ a rigorous network meta-analysis (NMA) approach to systematically evaluate the effectiveness of immune-combination therapies among patients with advanced hepatocellular carcinoma, taking into account their varying clinico-characteristics. Methods: Studies were retrieved from PubMed, Embase, Cochrane Library, and Web of Science databases. The included first-line phase III studies were categorized into three types: immunotherapy combined with anti-angiogenetic agents, immunotherapy combined with tyrosine kinase inhibitors, and dual immunotherapy, with sorafenib serving as the control group. The primary endpoint used to assess efficacy was overall survival (OS), facilitating a comparative analysis among the three treatment modalities. Furthermore, subgroup analyses were conducted to evaluate the varying effectiveness for patients with diverse clinico-characteristics. Secondary outcome measures included progression-free survival, objective response rate, and toxicity assessment. Results: A total of 6 studies were included in the NMA, encompassing a cohort of 3840 patients. The results revealed that immunotherapy combined with anti-angiogenetic agents exhibited a significantly enhanced therapeutic effect in terms of improving OS compared to sorafenib (HR = 0.61, 95% CrI, 0.42–0.90). Furthermore, based on various clinicopathological features, this combination therapy demonstrated superior OS responses in specific patient subgroups: BCLC C (HR = 0.63, 95% CrI, 0.42–0.93), ECOG 1 (HR = 0.57, 95% CrI, 0.36–0.91), with extrahepatic spread (EHS) (HR = 0.59, 95% CrI, 0.37–0.92), alpha fetoprotein (AFP)<400ng/ml (HR = 0.56, 95% CrI, 0.33–0.94) and viral hepatitis positivity (HR = 0.56, 95% CrI, 0.39–0.77) (especially HBV (HR = 0.58, 95% CrI, 0.40–0.85)). Importantly, the advantage of this combination therapy was even more pronounced in patients with viral hepatitis positivity. Also, the adverse events associated with immunotherapy combined with antiangiogenic drugs were moderate. Conclusions: Immunotherapy combined with anti-angiogenetic agents could represent the most effective first-line intervention for achieving improved OS, particularly in patients with viral hepatitis positivity. [ABSTRACT FROM AUTHOR]

The complexity of surface characteristics in rural areas poses challenges for accurate extraction of built-up areas from remote sensing images. The Artificial Surface Index (ASI) emerged as a novel and accurate built-up land index. However, the absence of short-wave infrared (SWIR) bands in most high-resolution (HR) images restricts the application of index-based methods in rural built-up land extraction. This paper presents a rapid extraction method for high-resolution built-up land in rural areas based on ASI. Through the downscaling techniques of random forest (RF) regression, high-resolution SWIR bands were generated. They were then combined with visible and near-infrared (VNIR) bands to compute ASI on GaoFen-2 (GF-2) images (called A S I G F ). Furthermore, a red roof index (RRI) was designed to reduce the probability of misclassifying built-up land with bare soil. The results demonstrated that SWIR downscaling effectively compensates for multispectral information absence in HR imagery and expands the applicability of index-based methods to HR remote sensing data. Compared with five other indices (UI, BFLEI, NDBI, BCI, and PISI), the combination of ASI and RRI achieved the optimal performance in built-up land enhancement and bare land suppression, particularly showcasing superior performance in rural built-up land extraction. [ABSTRACT FROM AUTHOR]

Protein–protein interactions (PPIs) between the B-cell lymphoma 2 (Bcl-2) family are considered a major driving force in cell cycle regulation and signaling. However, how this interfacial noncovalent interaction is achieved molecularly remains poorly understood. Herein, anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (BAX) were used as models and their PPIs were explored for the first time using atomic force microscopy-based single-molecule force spectroscopy (SMFS) and in silico approaches. In addition, we used advanced analytical models, including multiple kinetic models, thermodynamic models, Poisson distributions, and contact angle molecular recognition to fully reveal the complexity of the BAX/Bcl-2 interaction interfaces. We propose that the binding kinetics between BAX/Bcl-2 are mainly mediated by specific (hydrogen bonding) and non-specific forces (hydrophobic interactions and electrostatic interactions) and show that the complicated multivalent binding interaction induces stable BAX/Bcl-2 complexes. This study enriches our understanding of the molecular mechanisms by which BAX interacts with Bcl-2. It provides valuable insights into the physical factors that need to be considered when designing PPI inhibitors. [ABSTRACT FROM AUTHOR]