Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

5'-tRNA halves generated by IRE1α are linked to the ER stress response.

Transfer RNA halves (tRHs) have various biological functions. However, the biogenesis of specific 5'-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNA to produce 5'-tRHs (5'-tRH-Gly) with highly selective target discrimination upon endoplasmic reticulum (ER) stress.

Mesenchymal Stem Cells Injection Is More Effective Than Hyaluronic Acid Injection in the Treatment of Knee Osteoarthritis With Similar Safety: A Systematic Review and Meta-Analysis.

Purpose: To evaluate the efficacy and safety of intra-articular injection of mesenchymal stem cells (MSCs) versus hyaluronic acid (HA) in the treatment of knee osteoarthritis (KOA).

Methods: Eligible randomized controlled trials (RCTs) were identified through a search of PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, and CNKI databases from inception to March 2024. For meta-analysis, data on clinical outcomes were measured using visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and data on cartilage repair were measured using the Whole-Organ Magnetic Resonance Imaging Score (WORMS); data on safety were evaluated by the incidence of adverse events.

Mechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is caused by loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain.

Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs.

Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

Background: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects.

Ultrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device.

The emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a single-step CRISPR-based diagnostic platform, termed SCOPE (Streamlined CRISPR On Pod Evaluation platform), for field-deployable ultrasensitive detection of MPXV in resource-limited settings. The viral nucleic acids are rapidly released from the rash fluid swab, oral swab, saliva, and urine samples in 2 min via a streamlined viral lysis protocol, followed by a 10-min single-step recombinase polymerase amplification (RPA)-CRISPR/Cas13a reaction.

Olgotrelvir, a dual inhibitor of SARS-CoV-2 M and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19.

Background: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance.

Methods: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (M), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells.

Findings: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115.

Evaluating personalized circulating tumor DNA detection for early-stage lung cancer.

Circulating tumor DNA (ctDNA) has been widely used as a minimally invasive biomarker in clinical routine. However, a number of factors such as panel design, sample quality, patients' disease stages are known to influence ctDNA detection sensitivity. In this study, we systematically evaluated common factors associated with the variability of ctDNA detection in plasma and investigated ctDNA abundance in bronchoalveolar lavage (BAL).

Should All Pancreatic Cystic Lesions with Worrisome or High-Risk Features Be Resected? A Clinical and Radiological Machine Learning Model May Help to Answer.

Rationale And Objectives: According to current guidelines, pancreatic cystic lesions (PCLs) with worrisome or high-risk features may have overtreatment. The purpose of this study was to build a clinical and radiological based machine-learning (ML) model to identify malignant PCLs for surgery among preoperative PCLs with worrisome or high-risk features.

Materials And Methods: Clinical and radiological details of 317 pathologically confirmed PCLs with worrisome or high-risk features were retrospectively analyzed and applied to ML models including Support Vector Machine, Logistic Regression (LR), Decision Tree, Bernoulli NB, Gaussian NB, K Nearest Neighbors and Linear Discriminant Analysis.

Phase I study of A166, an antibody‒drug conjugate in advanced HER2-expressing solid tumours.

In this phase I study, the safety, pharmacokinetics, and antitumour activity of the HER2-targeted antibody-drug conjugate A166 were evaluated in patients with HER2-expressing advanced solid tumours. Patients with advanced solid tumours refractory to standard therapies received A166 at doses of 0.1, 0.

Systems-based digital twins to help characterize clinical dose-response and propose predictive biomarkers in a Phase I study of bispecific antibody, mosunetuzumab, in NHL.

Phase I oncology clinical trials often comprise a limited number of patients representing different disease subtypes who are divided into cohorts receiving treatment(s) at different dosing levels and schedules. Here, we leverage a previously developed quantitative systems pharmacology model of the anti-CD20/CD3 T-cell engaging bispecific antibody, mosunetuzumab, to account for different dosing regimens and patient heterogeneity in the phase I study to inform clinical dose/exposure-response relationships and to identify biological determinants of clinical response. We developed a novel workflow to generate digital twins for each patient, which together form a virtual population (VPOP) that represented variability in biological, pharmacological, and tumor-related parameters from the phase I trial.

Young Patients With Colorectal Cancer Have Higher Early Mortality but Better Long-Term Survival.

Introduction: To define the prognosis of colorectal cancer (CRC) in young patients and to compare their postoperative treatment with that of older patients.

Methods: This multicenter study enrolled 5,457 patients with primary CRC who underwent surgical resection. The overall survival (OS), clinicopathologic characteristics, and postoperative treatment of 253 young patients aged 18-44 years and 5,204 older patients aged 44-80 years were analyzed.

Genomic Insight into Sp. Nov. Isolated from Soil and Its Putative Novel Class II Lasso Peptide.

The strain designated as AN120528 was isolated from farmland soil in South Korea. This strain grows well on R2A medium at 28 °C. The cells are an off-white colour and have no hyphae.

Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails.

Retraction Note: Combination therapy with metformin and IL-12 to inhibit the growth of hepatic carcinoma by promoting apoptosis and autophagy in HepG2-bearing mice.

The article "Combination therapy with metformin and IL-12 to inhibit the growth of hepatic carcinoma by promoting apoptosis and autophagy in HepG2-bearing mice, by Z. Jin, B.-X.

Transcription Factor GATA4 Regulates Cell Type-Specific Splicing Through Direct Interaction With RNA in Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitors.

Background: GATA4 (GATA-binding protein 4), a zinc finger-containing, DNA-binding transcription factor, is essential for normal cardiac development and homeostasis in mice and humans, and mutations in this gene have been reported in human heart defects. Defects in alternative splicing are associated with many heart diseases, yet relatively little is known about how cell type- or cell state-specific alternative splicing is achieved in the heart. Here, we show that GATA4 regulates cell type-specific splicing through direct interaction with RNA and the spliceosome in human induced pluripotent stem cell-derived cardiac progenitors.

LAG-3xPD-L1 bispecific antibody potentiates antitumor responses of T cells through dendritic cell activation.

Several preclinical studies demonstrate that antitumor efficacy of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade can be improved by combination with other checkpoint inhibitors. Lymphocyte-activation gene 3 (LAG-3) is an inhibitory checkpoint receptor involved in T cell exhaustion and tumor immune escape. Here, we describe ABL501, a bispecific antibody targeting LAG-3 and PD-L1 in modulating immune cell responses against tumors.

Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation.

Background: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear.

Methods: Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms.

Yellow-b, -c, -d, and -h are required for normal body coloration of Henosepilachna vigintioctopunctata.

The involvement of yellow genes y-b, y-c, y-e, and y-h in cuticle tanning has poorly been clarified. In the present paper, six putative yellow (y-y, y-b, y-c, y-e y-f, and y-h) genes were identified in Henosepilachna vigintioctopunctata. Hvy-b, Hvy-c, Hvy-e, and Hvy-h were abundantly transcribed at early larval and late pupal stages, especially in the epidermis.