Conformational Space Profiling Enhances Generic Molecular Representation for AI-Powered Ligand-Based Drug Discovery.

The molecular representation model is a neural network that converts molecular representations (SMILES, Graph) into feature vectors, and is an essential module applied across a wide range of artificial intelligence-driven drug discovery scenarios. However, current molecular representation models rarely consider the three-dimensional conformational space of molecules, losing sight of the dynamic nature of small molecules as well as the essence of molecular conformational space that covers the heterogeneity of molecule properties, such as the multi-target mechanism of action, recognition of different biomolecules, dynamics in cytoplasm and membrane. In this study, a new model named GeminiMol is proposed to incorporate conformational space profiles into molecular representation learning, which extracts the feature of capturing the complicated interplay between the molecular structure and the conformational space.

Native and engineered extracellular vesicles: novel tools for treating liver disease.

Liver diseases are classified as acute liver damage and chronic liver disease, with recurring liver damage causing liver fibrosis and progression to cirrhosis and hepatoma. Liver transplantation is the only effective treatment for end-stage liver diseases; therefore, novel therapies are required. Extracellular vesicles (EVs) are endogenous nanocarriers involved in cell-to-cell communication that play important roles in immune regulation, tissue repair and regeneration.

Hypercholesterolemia Is Associated With Dysregulation of Lipid Metabolism and Poor Prognosis in Primary Biliary Cholangitis.

Background & Aims: Hypercholesterolemia is frequently diagnosed in patients with primary biliary cholangitis (PBC). However, its association with the prognosis and lipid metabolism is unknown. In this study, we aimed to investigate the prognostic value of baseline total cholesterol (TC) levels in PBC and characterized the associated lipid metabolism.

Identifying optimal candidates for autologous peripheral blood stem cell therapy in patients with decompensated liver cirrhosis: a prognostic scoring system.

Background: Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients.

A multifunctional optoelectronic device based on 2D material with wide bandgap.

Low-dimensional materials exhibit unique quantum confinement effects and morphologies as a result of their nanoscale size in one or more dimensions, making them exhibit distinctive physical properties compared to bulk counterparts. Among all low-dimensional materials, due to their atomic level thickness, two-dimensional materials possess extremely large shape anisotropy and consequently are speculated to have large optically anisotropic absorption. In this work, we demonstrate an optoelectronic device based on the combination of two-dimensional material and carbon dot with wide bandgap.

Integrative bioinformatics analysis and experimental validation of key biomarkers for risk stratification in primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) is an autoimmune liver disease, whose etiology is yet to be fully elucidated. Currently, ursodeoxycholic acid (UDCA) is the only first-line drug. However, 40% of PBC patients respond poorly to it and carry a potential risk of disease progression.

Prognostic significance of liver stiffness in patients with primary biliary cholangitis: validation of Baveno VII criteria.

Background: The role of liver stiffness measurements (LSM) in patients with primary biliary cholangitis (PBC) remains to be further elucidated.

Aims: To clarify the prognostic role of LSM and to validate the "novel concepts" proposed by the Baveno VII Working Group.

Methods: An analysis of the prognostic significance of LSM was performed involving 672 patients.

Construction of Polar Functional Groups on the Surface of a High-Modulus Carbon Fiber and Its Effect on the Interfacial Properties of Composites.

The interfacial bonding between carbon fibers and the resin matrix affects the mechanical properties of carbon fibers, and the increase of modulus brings a challenge to the interfacial properties of carbon fibers. The traditional anodic oxidation with ammonium bicarbonate as an electrolyte has a limited effect on the surface treatment for high-modulus carbon fibers. In this paper, anodic oxidation with an acidic electrolyte is used to treat high-modulus carbon fibers.

N6-methyladenosine RNA methylation in liver diseases: from mechanism to treatment.

Epigenetic modification occurring in RNA has become the hotspot of the field. N6-methyladenosine (m6A) methylation is the most abundant RNA internal modification mainly occurring at the consensus motif DR (m6A) CH (D = A/G/U, R = A/G, H = A/C/U) in the 3'-UTR particularly the region near stop codons. The life cycle of m6A methylation includes "writers," "erasers," and "readers", which are responsible for the addition, removal, and recognition of m6A, respectively.

DeepPROTACs is a deep learning-based targeted degradation predictor for PROTACs.

The rational design of PROTACs is difficult due to their obscure structure-activity relationship. This study introduces a deep neural network model - DeepPROTACs to help design potent PROTACs molecules. It can predict the degradation capacity of a proposed PROTAC molecule based on structures of given target protein and E3 ligase.

Efficacy and safety of fenofibrate add-on therapy in patients with primary biliary cholangitis refractory to ursodeoxycholic acid: A retrospective study and updated meta-analysis.

Ursodeoxycholic acid (UDCA) is currently used for the treatment of primary biliary cholangitis (PBC), but some people do not respond well to UDCA. It reported that the combination of fenofibrate and UDCA can improve the clinical indices in these patients. However, more high-quality evidence is needed to improve guideline recommendations.

Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages.

Background: Despite emerging evidence on the therapeutic potential of mesenchymal stem cells (MSCs) for liver fibrosis, the underlying mechanisms remain unclear. At present, MSC-derived exosomes (MSC-EXOs) are widely accepted as crucial messengers for intercellular communication. This study aimed to explore the therapeutic effects of MSC-EXOs on liver fibrosis and identify the mechanisms underlying the action of MSC-EXOs.

A novel immune checkpoint-related gene signature for predicting overall survival and immune status in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype and only some of patients could benefit from the immunotherapy. The present study aims to investigate the expression pattern and prognostic value of immune checkpoint genes (ICGs) in TNBC and develop a novel ICGs-signature to predict the prognosis and immune status in TNBC.

Methods: ICGs expression profiles and clinical characteristics of TNBC samples were obtained from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database.

Immunoglobulin M: A Neglected Serum Biomarker in Treatment-Naive Primary Biliary Cholangitis With Normal Alkaline Phosphatase.

The diagnosis of primary biliary cholangitis (PBC) in patients with seropositive anti-mitochondrial antibody (AMA) but normal alkaline phosphatase (ALP) depends on a liver biopsy. We aimed to reveal potential serum biomarkers that could suggest the necessity of a liver biopsy in such patients. Retrospective analysis was performed.

Symptoms Burden and Health-related Quality of Life in Chinese Patients with Primary Biliary Cholangitis.

Background And Aims: Primary biliary cholangitis (PBC) is a chronic liver disease that negatively affects the health-related quality of life (HRQoL) of patients. Furthermore, the HRQoL of Chinese patients has been neglected for a long time. The present study aimed to assess the HRQoL of Chinese patients with PBC and explore the clinical variables correlating to the improvement of itch and fatigue.

Systematic Construction and Validation of a Prognostic Model for Hepatocellular Carcinoma Based on Immune-Related Genes.

Hepatocellular carcinoma (HCC), a highly aggressive tumor, has high incidence and mortality rates. Recently, immunotherapies have been shown to be a promising treatment in HCC. The results of either the CheckMate-040 or IMbrave 150 trials demonstrate the importance of immunotherapy in the systemic treatment of liver cancer.

Systematic Construction and Validation of an RNA-Binding Protein-Associated Model for Prognosis Prediction in Hepatocellular Carcinoma.

Background: Evidence from prevailing studies show that hepatocellular carcinoma (HCC) is among the top cancers with high mortality globally. Gene regulation at post-transcriptional level orchestrated by RNA-binding proteins (RBPs) is an important mechanism that modifies various biological behaviors of HCC. Currently, it is not fully understood how RBPs affects the prognosis of HCC.

An enhanced level of LAMP-2A participates in CD4T cell hyperactivity in patients with primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) is an immune-mediated chronic cholestasis, in which T cell homeostasis plays an important role. Lysosomal-associated membrane protein 2 isoform A (LAMP-2A) has been implicated in the regulation of CD4T cell responses.

Methods: We comprehensively evaluated the immunobiology of CD4T cells in patients with PBC (PBC, n=42), chronic hepatitis B (CHB, n=20), and healthy control subjects (HC, n=20) by flow cytometry including activation status and LAMP-2A expression.

NEK9, a novel effector of IL-6/STAT3, regulates metastasis of gastric cancer by targeting ARHGEF2 phosphorylation.

Inflammatory stimuli from the tumor microenvironment play important roles in cancer progression. However, the mechanism of promotion of cancer metastasis by inflammation in gastric cancer (GC) is poorly understood. The roles of NEK9 were validated loss-of-function and gain-of-function experiments in vitro and in an animal model of metastasis.

A nomogram based on pretreatment clinical parameters for the prediction of inadequate biochemical response in primary biliary cholangitis.

Background: Ursodeoxycholic acid (UDCA) has been widely recommended as the first-line drug for primary biliary cholangitis (PBC) in the current guidelines. However, its therapeutic effects are poor in nearly one-third of patients. The early identification and intervention of these patients is crucial for delaying disease progression.

Expression Level and Clinical Significance of NKILA in Human Cancers: A Systematic Review and Meta-Analysis.

Background: A number of researches focused on the study of tumors have concluded that the expression level of lncRNA was decreased in different tumors. This is an indication that might influence the start and growth of a cancer. In addition, studies have fatalities and worsening health of cancer patients is associated with a reduced level of .

Forecasting dryland vegetation condition months in advance through satellite data assimilation.

Dryland ecosystems are characterised by rainfall variability and strong vegetation response to changes in water availability over a range of timescales. Forecasting dryland vegetation condition can be of great value in planning agricultural decisions, drought relief, land management and fire preparedness. At monthly to seasonal time scales, knowledge of water stored in the system contributes more to predictability than knowledge of the climate system state.

Hydration of phenylacetylene on sulfonated carbon materials: active site and intrinsic catalytic activity.

A series of sulfonated carbon materials (sulfonated glucose-derived carbon, carbon nanotubes, activated carbon and ordered mesoporous carbon, denoted as Sglu, SCNT, SAC and SCMK, respectively) were synthesized and applied as acid catalysts in phenylacetylene (PA) hydration reactions. The sulfonic acid groups (-SOH) were identified to be the only kind of active sites and were quantified with XPS and a cation exchange process. Mechanistic studies revealed that the catalytic PA hydration reaction follows pseudo first order reaction kinetics.

A survey of run-to-run control for batch processes.

Run-to-run (R2R) control is widely used in semiconductor manufacturing systems to minimize the process drift, shift and variability. The R2R controller adjusts control actions or recipes in a supervisory manner after each batch. This paper provides a comprehensive literature review of R2R control methods for the batch process.