TLR7/8/9 agonists and low-dose cisplatin synergistically promotes tertiary lymphatic structure formation and antitumor immunity.

In situ vaccination (ISV) triggers antitumor immune responses using the patient's own cancer antigens, yet limited neoantigen release hampers its efficacy. Our novel combination therapy involves low-dose local cisplatin followed by ISV with a TLR7/8/9 agonist formulation (CR108), in which CR108 boosts and sustains the antitumor responses induced by the cisplatin-released neoantigens. In mouse models, the cisplatin+CR108 combination significantly outperformed cisplatin or CR108 alone in abrogating established 4T1 and B16 tumors.

Comparison of two in vitro methods progressed in a computer-controlled simulated digestion system to determine amino acid digestibility of feed ingredients for yellow-feathered roosters.

This experiment compared amino acid (AA) digestibility assessed by 2 in vitro methods using a computer-controlled simulated digestion system and in vivo assay for corn, soybean meal, casein, corn gluten meal, cottonseed meal, rapeseed meal and a corn-soybean meal diet. In vitro method 1 simulated gizzard digestion at pH 2.0, followed by small intestinal digestion, and the subsequent clearance of the digested product from dialysis tubing.

DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.

DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2.

Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database.

Background: CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Objective: Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database.

Methods: Eligible CVAEs were extracted from the ClinicalTrials.

Covalent DNA-Encoded Library Workflow Drives Discovery of SARS-CoV-2 Nonstructural Protein Inhibitors.

The COVID-19 pandemic, exacerbated by persistent viral mutations, underscored the urgent need for diverse inhibitors targeting multiple viral proteins. In this study, we utilized covalent DNA-encoded libraries to discover innovative triazine-based covalent inhibitors for the 3-chymotrypsin-like protease (3CL, Nsp5) and the papain-like protease (PL) domains of Nsp3, as well as novel non-nucleoside covalent inhibitors for the nonstructural protein 12 (Nsp12, RdRp). Optimization through molecular docking and medicinal chemistry led to the development of , a nonpeptide 3CL inhibitor with an IC of 0.

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma.

Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.

Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.

CT Radiomics Features of Abdominal Adipose and Muscle Tissues Can Predict the Postoperative Early Recurrence of Hepatocellular Carcinoma.

Rationale And Objectives: To investigate the potential of computed tomography radiomics features extracted from abdominal adipose and muscle in predicting early recurrence (ER) of hepatocellular carcinoma (HCC) after surgery.

Materials And Methods: This retrospective study enrolled 252 patients with HCC who underwent curative resection from two independent institutions. In the training cohort of 178 patients from institution A, radiomics signatures extracted from abdominal visceral adipose, subcutaneous adipose, and muscle were applied to establish the radiomics score using the least absolute shrinkage and selection operator regression.

The Formation Criteria of LPSO Phase in Type I LPSO Mg-Y-X Alloy from the Perspective of Liquid-Solid Correlation.

The formation criteria of the LPSO phase are important for the design of long-period stacking-ordered (LPSO) Mg alloys. This work focuses on Type I LPSO Mg-Y-X alloys and attempts to explore the formation criteria of the LPSO phase from the perspective of liquid-solid correlation. With the aid of molecular dynamics simulation, liquid Mg-Y-X alloys are investigated to obtain the common liquid characteristics from the reported Type I LPSO Mg-Y-X alloys.

Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection.

Background: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection.

Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection.

Evolutionary Pathways of T-Phase Transition Metal Dichalcogenides: A Comprehensive Study of PtSe Clusters.

Understanding the transition from nonplanar to planar clusters is crucial for the controllable synthesis of transition metal dichalcogenide (TMDC) monolayers. Using PtSe as a model, we investigate how the chemical environment influences the nucleation and growth stages of monolayer PtSe through structure searching and first-principles calculations. We established a comprehensive database of platinum selenide clusters (PtSe, = 1-10), analyzing 2095 unique clusters and identifying 191 stable isomers and 63 structures with the lowest formation energy on the convex hull.

Leveraging cfDNA fragmentomic features in a stacked ensemble model for early detection of esophageal squamous cell carcinoma.

In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness.

The conditional recurrence-free survival after R0 hepatectomy for locally advanced intrahepatic cholangiocarcinoma: A competing risk analysis based on inflammation-nutritional status.

Background: Conditional survival analysis can serve as a dynamic prognostic metric, which helps to estimate the real-time survival probability over time. The present study conducted a conditional recurrence-free survival (CRFS) analysis for locally advanced intrahepatic cholangiocarcinoma (ICC) after R0 hepatectomy from an inflammatory-nutritional perspective using the competing risk method.

Methods: We extracted the medical data of 164 locally advanced ICC patients after R0 resection from Sun Yat-sen University Cancer Center.

Effect of Activated Charcoal on Mavacamten Pharmacokinetics in Healthy Participants.

Objective: To assess the effect of activated charcoal on the single-dose pharmacokinetics of mavacamten when administered 2 h or 6 h after mavacamten dosing.

Methods: In this open-label, randomized, parallel-group study, healthy adults were randomized into three groups to receive mavacamten 15 mg alone or mavacamten 15 mg plus activated charcoal 50 g administered either 2 h or 6 h after mavacamten dosing. Pharmacokinetic parameters were derived from plasma concentration-time data using noncompartmental methods.

PD-1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer.

Background: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies).

Tauroursodeoxycholic Acid Reverses Dextran Sulfate Sodium-Induced Colitis in Mice via Modulation of Intestinal Barrier Dysfunction and Microbiome Dysregulation.

Ulcerative colitis (UC) is an immune-mediated inflammatory disease that can lead to persistent damage and even cancer without any intervention. Conventional treatments can alleviate UC symptoms but are costly and cause various side effects. Tauroursodeoxycholic acid (TUDCA), a secondary bile acid derivative, possesses anti-inflammatory and cytoprotective properties for various diseases, but its potential therapeutic benefits in UC have not been fully explored.

Hsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation.

Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane.

Plaque Ruptures Are Related to High Plaque Stress and Strain Conditions: Direct Verification by Using In Vivo OCT Rupture Data and FSI Models.

Background: While it has been hypothesized that high plaque stress and strain may be related to plaque rupture, its direct verification using in vivo coronary plaque rupture data and full 3-dimensional fluid-structure interaction models is lacking in the current literature due to difficulty in obtaining in vivo plaque rupture imaging data from patients with acute coronary syndrome. This case-control study aims to use high-resolution optical coherence tomography-verified in vivo plaque rupture data and 3-dimensional fluid-structure interaction models to seek direct evidence for the high plaque stress/strain hypothesis.

Methods: In vivo coronary plaque optical coherence tomography data (5 ruptured plaques, 5 no-rupture plaques) were acquired from patients using a protocol approved by the local institutional review board with informed consent obtained.

Influence and Clinical Significance of Knee Flexion Angle on the Anatomic Course of the Common Peroneal Nerve in the Posterolateral Corner of the Knee Joint.

Background: Detailed knowledge of the anatomic course of the common peroneal nerve (CPN) is crucial for the surgical treatment of the posterolateral corner (PLC) of the knee.

Purpose: To investigate the relationship of the CPN to the PLC of the knee at different flexion angles.

Study Design: Descriptive laboratory study.