Early on-treatment LSM reliably predicts liver-related events in CHB patients with significant fibrosis and cirrhosis.

Background: Evidence comparing longitudinal liver stiffness measurements (LSM) dynamics to on-treatment LSM for predicting clinical outcomes in patients receiving etiology therapy is limited.

Objective: This study aimed to assess the prognostic value of on-treatment LSM in patients with chronic hepatitis B (CHB) receiving antiviral therapy.

Design: Patients with CHB and significant fibrosis or cirrhosis were included in this prospective cohort.

Semi-elemental versus polymeric formula for enteral nutrition in critically ill patients: a secondary analysis of a multicenter cluster-randomized controlled trial.

Objectives: Semi-elemental enteral nutrition (EN) might theoretically improve gastrointestinal tolerance in critically ill patients; however, it is associated with an increased risk of diarrhea when delivered postpylorically. This study aimed to assess whether the use of semi-elemental formula compared to polymeric formula may provide benefits in patients receiving gastric tube feeding.

Methods: This is a analysis of data from a multicenter, cluster-randomized, controlled, investigator-initiated trial (NEED trial).

De novo design of protein condensation inhibitors by targeting an allosteric site of cGAS.

Cyclic GMP-AMP synthase (cGAS), a key mediator of the cGAS-STING DNA sensing pathway that triggers type-I interferon responses, plays a crucial role in innate immunity and has been implicated in the pathogenesis of various disease. Despite advances in the development of cGAS inhibitors, none have reached the market and there remains an unmet need for divergent chemical scaffolds with high selectivity, potency across species, and target-adaptive mechanisms of action to explore cGAS's potential as a therapeutic target. Here we report the structural, biochemical, cellular, and mechanistic characterization of the XL series of allosteric inhibitors, designed to engage an innovative allosteric site near the activation loop of cGAS.

Effect of letrozole doses on clinical pregnancy rates in polycystic ovary syndrome: a systematic review and network meta-analysis.

Letrozole, an aromatase inhibitor, is commonly used for ovulation induction in patients with polycystic ovary syndrome (PCOS). However, the effect of different doses of letrozole on pregnancy outcomes remains controversial. This systematic review and network meta‑analysis aims to compare the effects of different doses of letrozole on pregnancy outcomes in PCOS patients.

Integrated analysis of transcriptome and metabolome revealed clomazone biodegradation in maize seedlings.

Clomazone (CMZ) is a pesticide widely used for weed control in soybean fields. However, its persistence in the environment, including soil, surface water, and groundwater, poses potential risks to subsequent crops and human health. To evaluate the ecotoxicological impacts of CMZ residues on maize growth, a comprehensive study was conducted using integrated transcriptomic and metabolomic analyses of maize seedlings.

Structure-based design of potent and selective inhibitors targeting RIPK3 for eliminating on-target toxicity in vitro.

The essential role of RIPK3 in necroptosis makes its inhibition a promising therapeutic strategy. However, the development of RIPK3 inhibitors has been hampered by on-target apoptosis and limited kinase selectivity. Inspired by the R69H mutation, which prevents on-target apoptosis by disrupting RIPK3 dimerization, we design LK-series inhibitors that effectively inhibit RIPK3 in biochemical assays and block TNF-α-induced necroptosis in both mouse L929 and human HT29 cells without inducing apoptosis.

Tetramethylpyrazine mitigates lipopolysaccharide-induced acute lung injury by inhibiting the HMGB1/TLR4/NF-κB signaling pathway in mice.

Background: Tetramethylpyrazine (TMP) possesses anti-inflammatory and antioxidant properties and plays a crucial role in mitigating acute lung injury (ALI). However, the specific underlying mechanisms remain elusive. High mobility group box 1 (HMGB1), a pro-inflammatory factor, can bind to Toll-like receptor 4 (TLR4), activating downstream signaling pathways, which in turn activate nuclear factor kappa-B (NF-κB).

Metabonomic and transcriptomic profiling reveals amino acid metabolism affects the quality of premium japonica rice varieties in Northeast China.

Rice consumption and demand for premium rice are increasing worldwide. However, the characterizations and how to identify the premium rice are still unclear. Small molecular metabolites have a great advantage in distinguishing subtle differences among similar agricultural products.

Synthesis and Characterization of Asymmetric Azatwistarenes with Chiroptical Property.

Three novel azatwistarenes , , and have been synthesized via the Povarov reaction and fully characterized. All of the enantiomers were separated using chiral high-performance liquid chromatography, and their optical properties were investigated through circular dichroism and circularly polarized luminescence spectra. In addition, such desired azatwistarenes have a positive response to acid in dichloromethane.

Research Progress on the Quality, Extraction Technology, Food Application, and Physiological Function of Rice Bran Oil.

Rice bran oil is recommended by the World Health Organization as one of the three major healthy edible oils (along with corn and sesame oils), owing to its unique fatty acid composition and functional components. This study screened, organized, and analyzed a large number of studies retrieved through keyword searches, and investigated the nutritional value and safety of rice bran oil. It reviews the stability of raw rice bran materials and the extraction and refining process of rice bran oil and discusses food applications and sub-health regulations.

Tetramethylpyrazine ameliorates LPS-induced acute lung injury via the miR-369-3p/DSTN axis.

Acute lung injury (ALI) is a severe clinical respiratory condition characterized by high rates of mortality and morbidity, for which effective treatments are currently lacking. In this study, lipopolysaccharide (LPS) was used to induce ALI mice, demonstrating the efficacy of tetramethylpyrazine (TMP) in ameliorating ALI. Subsequent we perfored high-throughput sequencing analysis and used Targetscan 8.

Predictive modeling of lower extreme deep vein thrombosis following radical gastrectomy for gastric cancer: based on multiple machine learning methods.

Postoperative venous thromboembolic events (VTEs), such as lower extremity deep vein thrombosis (DVT), are major risk factors for gastric cancer (GC) patients following radical gastrectomy. Accurately predicting and managing these risks is crucial for optimal patient care. This retrospective case‒control study involved 693 GC patients from our hospital who underwent radical gastrectomy.

Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer.

Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic "face-off" mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism.

Pre-Operative Immunonutrition Enhances Postoperative Outcomes and Elevates Tumor-Infiltrating Lymphocyte Counts in Colorectal Cancer Patients: A Meta-Analysis of Randomized Controlled Trials.

Objective: This study (CRD42023464989) aimed to explore the effects of pre-operation immunonutrition on safety and immune related factors in colorectal cancer patients undergoing surgery.

Methods: We systematically searched PubMed, Embase, and Wanfang databases to collect all clinical randomized controlled trials of the application of pre-operation immunonutrition for patients with colorectal cancer, published until July 2023. The primary outcomes were safety and immune related factors.

A novel AML1-ETO/FTO positive feedback loop promotes leukemogenesis and Ara-C resistance via stabilizing IGFBP2 in t(8;21) acute myeloid leukemia.

Background: t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities in acute myeloid leukemia (AML), leading to the generation of the fusion protein AML1-ETO. Despite t(8;21) AML being considered as a subtype with a favorable prognosis, approximately 30-50% of patients experience drug resistance and subsequent relapse. N-methyladenosine (mA) is demonstrated to be involved in the development of AML.

Allogeneic Hematopoietic Stem Cell Transplantation Can Improve Prognosis of Extramedullary Infiltration Positive t(8;21) Acute Myeloid Leukemia.

BACKGROUND In t(8;21) acute myeloid leukemia (AML), patients with extramedullary infiltration (EMI) tend to have worse survival outcomes than those without EMI. However, it is still unclear whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefits EMI-positive t(8;21) AML patients. MATERIAL AND METHODS This study retrospectively enrolled 651 t(8;21) AML patients, and analyzed 51 patients with EMI at diagnosis.

Structure-based design of potent FABP4 inhibitors with high selectivity against FABP3.

Fatty-acid binding protein 4 (FABP4) presents an attractive target for therapeutic intervention in metabolic and inflammatory diseases in recent years. However, highly similar three-dimensional structures and fatty acid binding ability of multiple FABP family members pose a significant challenge in design of FABP4-selective inhibitors. Particularly, inhibition of FABP3 raises safety concerns such as cardiac dysfunction and exercise intolerance.

Drug repurposing and structure-based discovery of new PDE4 and PDE5 inhibitors.

Phosphodiesterase-4 (PDE4) and PDE5 responsible for the hydrolysis of intracellular cAMP and cGMP, respectively, are promising targets for therapeutic intervention in a wide variety of diseases. Here, we report the discovery of novel, drug-like PDE4 inhibitors by performing a high-throughput drug repurposing screening of 2560 approved drugs and drug candidates in clinical trial studies. It allowed us to identify eight potent PDE4 inhibitors with IC values ranging from 0.

The effects of treating GERD on the outcomes of otitis media with effusion: A systematic review and meta-analysis.

Objective: Gastroesophageal reflux disease (GERD) may cause otitis media with effusion (OME). However, whether treating GERD can benefit patients with OME has not been well studied.

Methods: We systematically searched PubMed, Embase, Cochrane Library, and Wanfang databases.