Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma.

Objective: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC.

Methods: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively.

Identification of molecular subtypes based on bile acid metabolism in cholangiocarcinoma.

Background: Cholangiocarcinoma is a highly heterogeneous tumor with bile acid metabolism involving in its development. The aim of this study was to characterize bile acid metabolism and identify specific subtypes to better stratify cholangiocarcinoma patients for individualized treatment and prognostic assessment.

Methods: A total of 30 bile acids were quantified using the ultra-performance liquid chromatography tandem mass spectrometry.

The RNF214-TEAD-YAP signaling axis promotes hepatocellular carcinoma progression via TEAD ubiquitylation.

RNF214 is an understudied ubiquitin ligase with little knowledge of its biological functions or protein substrates. Here we show that the TEAD transcription factors in the Hippo pathway are substrates of RNF214. RNF214 induces non-proteolytic ubiquitylation at a conserved lysine residue of TEADs, enhances interactions between TEADs and YAP, and promotes transactivation of the downstream genes of the Hippo signaling.

Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19.

Background: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., M) and human cathepsin L.

Corticosteroid in non-COVID-19 induced community-acquired pneumonia, a meta-analysis.

Background: Corticosteroid treatment in non-COVID-19 induced Community-acquired pneumonia (CAP) remains inconclusive.

Objectives: We aimed to assess the role of corticosteroid treatment in CAP.

Methods: We conducted a comprehensive search of online databases, including PubMed, Embase, and Cochrane, to identify articles published from January 1, 2000, to May 5, 2023.

Clinical Timing-Sequence Warning Models for Serious Bacterial Infections in Adults Based on Machine Learning: Retrospective Study.

Background: Serious bacterial infections (SBIs) are linked to unplanned hospital admissions and a high mortality rate. The early identification of SBIs is crucial in clinical practice.

Objective: This study aims to establish and validate clinically applicable models designed to identify SBIs in patients with infective fever.

TheMarker: a comprehensive database of therapeutic biomarkers.

Distinct from the traditional diagnostic/prognostic biomarker (adopted as the indicator of disease state/process), the therapeutic biomarker (ThMAR) has emerged to be very crucial in the clinical development and clinical practice of all therapies. There are five types of ThMAR that have been found to play indispensable roles in various stages of drug discovery, such as: Pharmacodynamic Biomarker essential for guaranteeing the pharmacological effects of a therapy, Safety Biomarker critical for assessing the extent or likelihood of therapy-induced toxicity, Monitoring Biomarker indispensable for guiding clinical management by serially measuring patients' status, Predictive Biomarker crucial for maximizing the clinical outcome of a therapy for specific individuals, and Surrogate Endpoint fundamental for accelerating the approval of a therapy. However, these data of ThMARs has not been comprehensively described by any of the existing databases.

Effect of Food on the Pharmacokinetics of Tenofovir Amibufenamide: A Phase I, Randomized, Open-Label, Two-Period Crossover Trial in Healthy Adult Subjects.

Purpose: Tenofovir amibufenamide (TMF) is a novel nucleotide reverse transcriptase inhibitor. The aim of this study was to investigate the effect of food on the single-dose pharmacokinetic properties of TMF.

Patients And Methods: In this open-label, randomized, crossover study, after an overnight fast, eligible subjects received a single 25 mg dose of TMF tablet, either under fasted conditions or following consumption of a high-fat, high-calorie meal, followed by a two-week washout period.

TTD: Therapeutic Target Database describing target druggability information.

Target discovery is one of the essential steps in modern drug development, and the identification of promising targets is fundamental for developing first-in-class drug. A variety of methods have emerged for target assessment based on druggability analysis, which refers to the likelihood of a target being effectively modulated by drug-like agents. In the therapeutic target database (TTD), nine categories of established druggability characteristics were thus collected for 426 successful, 1014 clinical trial, 212 preclinical/patented, and 1479 literature-reported targets via systematic review.

Molecular subtypes and scoring tools related to Foxo signaling pathway for assessing hepatocellular carcinoma prognosis and treatment responsiveness.

Transcription factors in Foxo signaling pathway influence hepatocellular carcinoma metastasis through epithelial mesenchymal transition-related pathways. Prognostic factors in the Foxo signaling pathway are feasible for HCC prognosis and therapeutic management. Based on the differentially expressed genes and Foxo signaling pathway genes in HCC, the ConsensusClusterPlus package was conducted to identify Foxo signaling pathway-related molecular subtypes in HCC.

Integrating Medical Domain Knowledge for Early Diagnosis of Fever of Unknown Origin: An Interpretable Hierarchical Multimodal Neural Network Approach.

Accurate and interpretable differential diagnostic technologies are crucial for supporting clinicians in decision-making and treatment-planning for patients with fever of unknown origin (FUO). Existing solutions commonly address the diagnosis of FUO by transforming it into a multi-classification task. However, after the emergence of COVID-19 pandemic, clinicians have recognized the heightened significance of early diagnosis in patients with FUO, particularly for practical needs such as early triage.

RNAenrich: a web server for non-coding RNA enrichment.

Motivation: With the rapid advances of RNA sequencing and microarray technologies in non-coding RNA (ncRNA) research, functional tools that perform enrichment analysis for ncRNAs are needed. On the one hand, because of the rapidly growing interest in circRNAs, snoRNAs, and piRNAs, it is essential to develop tools for enrichment analysis for these newly emerged ncRNAs. On the other hand, due to the key role of ncRNAs' interacting target in the determination of their function, the interactions between ncRNA and its corresponding target should be fully considered in functional enrichment.

SISPRO: Signature Identification for Spatial Proteomics.

Spatial proteomics aims for a global description of organelle-specific protein distribution and dynamics, which is essential for understanding the molecular functions and cellular processes in health and disease. However, the application of this technique is seriously restricted by the neglect of robustness among proteomic signatures identified using standard statistical frameworks. Moreover, it is still a major bottleneck to automatically interpretate the identified proteomic signatures due to lack of integration of subcellular information.

Serum Ribonucleotide Reductase Subunit M2 in Patients with Chronic Liver Diseases and Hepatocellular Carcinoma.

Background: Ribonucleotide reductase subunit M2 (RRM2) plays a key role in cell and hepatitis B virus (HBV) replication. Nevertheless, its clinical implications for managing liver diseases have been inadequately studied.

Methods: A total of 412 participants were enrolled, including 60 healthy control individuals, 55 patients with chronic hepatitis B (CHB), 173 patients with cirrhosis, and 124 patients with hepatocellular carcinoma (HCC).

MecDDI: Clarified Drug-Drug Interaction Mechanism Facilitating Rational Drug Use and Potential Drug-Drug Interaction Prediction.

Drug-drug interactions (DDIs) are a major concern in clinical practice and have been recognized as one of the key threats to public health. To address such a critical threat, many studies have been conducted to clarify the mechanism underlying each DDI, based on which alternative therapeutic strategies are successfully proposed. Moreover, artificial intelligence-based models for predicting DDIs, especially multilabel classification models, are highly dependent on a reliable DDI data set with clear mechanistic information.

Enterococcus faecalis promotes the progression of colorectal cancer via its metabolite: biliverdin.

Background: Enterococcus faecalis (Efa) has been shown to be a "driver bacteria" in the occurrence and development of colorectal cancer (CRC). This study aims to explore the effect of specific metabolites of Efa on CRC.

Methods: The pro-tumor effects of Efa were assessed in colonic epithelial cells.

Diagnostic accuracy of metagenomic next-generation sequencing in diagnosing infectious diseases: a meta-analysis.

Many common pathogens are difficult or impossible to detect using conventional microbiological tests. However, the rapid and untargeted nature of metagenomic next-generation sequencing (mNGS) appears to be a promising alternative. To perform a systematic review and meta-analysis of evidence regarding the diagnostic accuracy of mNGS in patients with infectious diseases.

Structural and biochemical characteristics of mRNA nanoparticles determine anti-SARS-CoV-2 humoral and cellular immune responses.

The coronavirus disease 2019 (COVID-19) pandemic underlines the urgent need for effective mRNA vaccines. However, current understanding of the immunological outcomes of mRNA vaccines formulated under different nanoplatforms is insufficient. Here, severe acute respiratory syndrome coronavirus 2 receptor binding domain mRNA delivered via lipid nanoparticle (LNP), cationic nanoemulsion (CNE), and cationic liposome (Lipo) was constructed.

DRESIS: the first comprehensive landscape of drug resistance information.

Widespread drug resistance has become the key issue in global healthcare. Extensive efforts have been made to reveal not only diverse diseases experiencing drug resistance, but also the six distinct types of molecular mechanisms underlying this resistance. A database that describes a comprehensive list of diseases with drug resistance (not just cancers/infections) and all types of resistance mechanisms is now urgently needed.

CovInter: interaction data between coronavirus RNAs and host proteins.

Coronavirus has brought about three massive outbreaks in the past two decades. Each step of its life cycle invariably depends on the interactions among virus and host molecules. The interaction between virus RNA and host protein (IVRHP) is unique compared to other virus-host molecular interactions and represents not only an attempt by viruses to promote their translation/replication, but also the host's endeavor to combat viral pathogenicity.

M6AREG: m6A-centered regulation of disease development and drug response.

As the most prevalent internal modification in eukaryotic RNAs, N6-methyladenosine (m6A) has been discovered to play an essential role in cellular proliferation, metabolic homeostasis, embryonic development, etc. With the rapid accumulation of research interest in m6A, its crucial roles in the regulations of disease development and drug response are gaining more and more attention. Thus, a database offering such valuable data on m6A-centered regulation is greatly needed; however, no such database is as yet available.