Glecirasib in KRAS-mutated nonsmall-cell lung cancer: a phase 2b trial.

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).

Preventing Site-Specific Calpain Proteolysis of Junctophilin-2 Protects Against Stress-Induced Excitation-Contraction Uncoupling and Heart Failure Development.

Background: Excitation-contraction (E-C) coupling processes become disrupted in heart failure (HF), resulting in abnormal Ca homeostasis, maladaptive structural and transcriptional remodeling, and cardiac dysfunction. Junctophilin-2 (JP2) is an essential component of the E-C coupling apparatus but becomes site-specifically cleaved by calpain, leading to disruption of E-C coupling, plasmalemmal transverse tubule degeneration, abnormal Ca homeostasis, and HF. However, it is not clear whether preventing site-specific calpain cleavage of JP2 is sufficient to protect the heart against stress-induced pathological cardiac remodeling in vivo.

Search for Narrow Trijet Resonances in Proton-Proton Collisions at sqrt[s]=13 TeV.

The first search for singly produced narrow resonances decaying to three well-separated hadronic jets is presented. The search uses proton-proton collision data corresponding to an integrated luminosity of 138  fb^{-1} at sqrt[s]=13  TeV, collected at the CERN LHC. No significant deviations from the background predictions are observed between 1.

The Toxoplasma Effector GRA4 Hijacks Host TBK1 to Oppositely Regulate Anti-T. Gondii Immunity and Tumor Immunotherapy.

Toxoplasma gondii (T. gondii)-associated polymorphic effector proteins are crucial in parasite development and regulating host anti-T. gondii immune responses.

Observation of Type-II Topological Nodal-Line Fermions in ZrSiSe.

Recently, there has been significant interest in topological nodal-line semimetals due to their linear energy dispersion with one-dimensional nodal lines or loops. These materials exhibit fascinating physical properties, such as drumhead surface states and 3D anisotropic nodal-line structures. Similar to Weyl semimetals, type-II nodal-line semimetals have two crossing bands that are both electron-like or hole-like along a certain direction.

Pharmacology of Hydrogen Sulfide and Its Donors in Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (HS) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of HS in regulating proteins via persulfidation, a well known modification intricately associated with the pathogenesis of CMDs.

US-based Sequential Algorithm Integrating an AI Model for Advanced Liver Fibrosis Screening.

Background Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B-mode US of the liver between January 2014 and September 2022 at three health care facilities.

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.

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses.

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production.

Collaborative Enhancement of Consistency and Accuracy in US Diagnosis of Thyroid Nodules Using Large Language Models.

Background Large language models (LLMs) hold substantial promise for medical imaging interpretation. However, there is a lack of studies on their feasibility in handling reasoning questions associated with medical diagnosis. Purpose To investigate the viability of leveraging three publicly available LLMs to enhance consistency and diagnostic accuracy in medical imaging based on standardized reporting, with pathology as the reference standard.

Comparative study on chain conformations, physicochemical and rheological properties of three acidic polysaccharides from Opuntia dillenii Haw. fruits.

In this study, three acidic polysaccharides (OFPP-1, OFPP-2 and OFPP-3) were isolated from the pulps of Opuntia dillenii Haw. fruits, and their chain conformations, physicochemical and rheological properties were investigated. The molecular weight and conformational parameters (M, M, M, R and R) of OFPPs in 0.

Global analysis of HLA-A2 restricted MAGE-A3 tumor antigen epitopes and corresponding TCRs in non-small cell lung cancer.

Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. Adoptive cell therapy using engineered T-cell receptors (TCRs) targeting cancer-testis antigens, such as Melanoma-associated antigen 3 (MAGE-A3), is a potential approach for the treatment of NSCLC. However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking.

Glycopeptide database search and de novo sequencing with PEAKS GlycanFinder enable highly sensitive glycoproteomics.

Here we present GlycanFinder, a database search and de novo sequencing tool for the analysis of intact glycopeptides from mass spectrometry data. GlycanFinder integrates peptide-based and glycan-based search strategies to address the challenge of complex fragmentation of glycopeptides. A deep learning model is designed to capture glycan tree structures and their fragment ions for de novo sequencing of glycans that do not exist in the database.

Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection.

The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.

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.

Endothelial HDAC1-ZEB2-NuRD Complex Drives Aortic Aneurysm and Dissection Through Regulation of Protein S-Sulfhydration.

Background: Aortic aneurysm and aortic dissection (AAD) are life-threatening vascular diseases, with endothelium being the primary target for AAD treatment. Protein S-sulfhydration is a newly discovered posttranslational modification whose role in AAD has not yet been defined. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates AAD and its underlying mechanism.

Population-based heteropolymer design to mimic protein mixtures.

Biological fluids, the most complex blends, have compositions that constantly vary and cannot be molecularly defined. Despite these uncertainties, proteins fluctuate, fold, function and evolve as programmed. We propose that in addition to the known monomeric sequence requirements, protein sequences encode multi-pair interactions at the segmental level to navigate random encounters; synthetic heteropolymers capable of emulating such interactions can replicate how proteins behave in biological fluids individually and collectively.

Comparison of crop productivity, economic benefit and environmental footprints among diversified multi-cropping systems in South China.

Diversified multi-cropping system with high productivity and low environmental costs is crucial for the development of sustainable agriculture in different regions. However, the information on this practice has still been limited in the South China. This study compared different diversified multi-cropping systems including peanut-rice-fallow (P-R-F), peanut-rice-ryegrass (P-R-R), soybean-rice-ryegrass (S-R-R), feed corn-rice-milk vetch (FC-R-M), sweet corn-rice-milk vetch (SC-R-M) and zucchini -rice-milk vetch (Z-R-M), with the conventional double-rice system (CK).

Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

Background: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations.

Methods: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone.

A comparative study on the three calculation methods for reproduction numbers of COVID-19.

Objective: This study uses four COVID-19 outbreaks as examples to calculate and compare merits and demerits, as well as applicational scenarios, of three methods for calculating reproduction numbers.

Method: The epidemiological characteristics of the COVID-19 outbreaks are described. Through the definition method, the next-generation matrix-based method, and the epidemic curve and serial interval ()-based method, corresponding reproduction numbers were obtained and compared.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.

Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.

Reassembled saturation transfer (REST) MR images at 2 B values for in vivo exchange-dependent imaging of amide and nuclear Overhauser enhancement.

Purpose: Design an efficient CEST scheme for exchange-dependent images with high contrast-to-noise ratio.

Theory: Reassembled saturation transfer (REST) signals were defined as r.Z = r.