Enabling tumor-specific drug delivery by targeting the Warburg effect of cancer.

Metabolic reprogramming of tumor cells is an emerging hallmark of cancer. Among all the changes in cancer metabolism, increased glucose uptake and the accumulation of lactate under normoxic conditions (the "Warburg effect") is a common feature of cancer cells. In this study, we develop a lactate-responsive drug delivery platform by targeting the Warburg effect.

Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials.

The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.

Arthroscopic V-Shaped Double-Pulley Suture-Bridge Repair of Massive Rotator Cuff Tear.

At present, suture bridge is a feasible choice in the treatment of massive rotator cuff tears (MRCTs). However, high tension on the repair site and medial tension during suture tightening and after medial knotting are unavoidable problems in MRCT repair with a suture bridge. Arthroscopic V-shaped double-pulley suture-bridge repair is a pragmatic surgical technique for the repair of MRCTs.

Arthroscopic Suture Anchor Repair and Debridement for Refractory Lateral Epicondylitis Show Significant Clinical Improvement.

Purpose: To retrospectively compare the clinical outcomes of arthroscopic suture anchor repair of the common extensor tendon (CET) and arthroscopic debridement of CET for the treatment of refractory lateral epicondylitis.

Methods: Patients with refractory lateral epicondylitis who underwent arthroscopic surgery between August 2018 and September 2022 with a minimum 1-year follow-up were included. All patients were divided into 2 groups based on whether they underwent suture anchor repair.

ZC3H14 facilitates backsplicing by binding to exon-intron boundary and 3' UTR.

Circular RNAs (circRNAs) are natural outputs of eukaryotic transcription and RNA processing and have emerged as critical regulators in physiology and diseases. Although multiple cis-elements and trans-factors are reported to modulate the backsplicing of circRNA biogenesis, most of these regulations play roles in flanking introns of circRNAs. Here, using a genome-wide CRISPR knockout screen, we have identified an evolutionarily conserved RNA-binding protein ZC3H14 in regulating circRNA biogenesis.

Independent Control Over the H/OH Adsorption: Breaking the Trade-Off Between H/OH-Adsorption and HO-Dissociation of Platinum-Group Metal Electrocatalyst for Hydrogen Evolution Reaction.

Platinum-group metals catalysts (such as Rh, Pd, Ir, Pt) have been the most efficient hydrogen evolution reaction (HER) electrocatalysts due to their moderate H adsorption strength, while the high HO-dissociation barrier in alkaline media restrains the catalytic performance of PGM catalysts. However, the optimization of the HO-dissociation barrier and *H/*OH binding energy toward their individual optima is limited due to the constraints of their scaling relationship on a single active site. Here, a coordinatively unsaturated "M─O─W" (M = Rh, Pd, Ir, Pt) active area is constructed, where H and OH species are anchored on Pt-group metal sites and inactive W sites for individual regulation.

Exploring the charge transfer enhancement mechanism in selective SERS detection with MoWS@AgS nanosheets.

In order to solve the problem of poor sensitivity and selectivity of conventional SERS substrates, we synthesized MoWS@AgS nanosheets in this paper by a two-step hydrothermal method. The structure and morphology of the synthesized MoWS@AgS nanosheets were characterized by XRD and SEM,respectively. The results show that the MoWS@AgS nanosheet has an irregular layered structure.

Search and match across spatial omics samples at single-cell resolution.

Spatial omics technologies characterize tissue molecular properties with spatial information, but integrating and comparing spatial data across different technologies and modalities is challenging. A comparative analysis tool that can search, match and visualize both similarities and differences of molecular features in space across multiple samples is lacking. To address this, we introduce CAST (cross-sample alignment of spatial omics), a deep graph neural network-based method enabling spatial-to-spatial searching and matching at the single-cell level.

Oxysterol Sensing Through GPR183 Triggers Endothelial Senescence in Hypertension.

Background: Despite endothelial dysfunction being an initial step in the development of hypertension and associated cardiovascular/renal injuries, effective therapeutic strategies to prevent endothelial dysfunction are still lacking. GPR183 (G protein-coupled receptor 183), a recently identified G protein-coupled receptor for oxysterols and hydroxylated metabolites of cholesterol, has pleiotropic roles in lipid metabolism and immune responses. However, the role of GPR183 in the regulation of endothelial function remains unknown.

Scalable spatial single-cell transcriptomics and translatomics in 3D thick tissue blocks.

Characterizing the transcriptional and translational gene expression patterns at the single-cell level within their three-dimensional (3D) tissue context is essential for revealing how genes shape tissue structure and function in health and disease. However, most existing spatial profiling techniques are limited to 5-20 μm thin tissue sections. Here, we developed Deep-STARmap and Deep-RIBOmap, which enable 3D quantification of thousands of gene transcripts and their corresponding translation activities, respectively, within 200-μm thick tissue blocks.

Hospital-Treated Infectious Diseases, Infection Burden, and Risk of Lung Cancer: An Observational and Mendelian Randomization Study.

Background: Although infections play a role in the development of lung cancer, the longitudinal association between infection and the risk of lung cancer is disputed, and data relating to pathogen types and infection sites are sparse.

Research Question: How do infections affect subsequent lung cancer risk, and is the impact limited to specific microbes rather than infection burden?

Study Design And Methods: Data on > 900 infectious diseases were gathered from the UK Biobank study. Short- and long-term effects of infections were assessed by using time-varying Cox proportional hazards models.

Programmable DNA pyrimidine base editing via engineered uracil-DNA glycosylase.

DNA base editing technologies predominantly utilize engineered deaminases, limiting their ability to edit thymine and guanine directly. In this study, we successfully achieve base editing of both cytidine and thymine by leveraging the translesion DNA synthesis pathway through the engineering of uracil-DNA glycosylase (UNG). Employing structure-based rational design, exploration of homologous proteins, and mutation screening, we identify a Deinococcus radiodurans UNG mutant capable of effectively editing thymine.

Effect of Acupuncture for Methadone Reduction : A Randomized Clinical Trial.

Background: Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving.

Objective: To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction.

Design: Multicenter, 2-group, randomized, sham-controlled trial.

High-Entropy Alloy Activating Laves-Phase Network for Multi-Component Metallic Coatings with High Hardness.

The low hardness and poor wear resistance of laser-cladding 316L stainless steel impose significant constraints on its practical applications. In this study, a strategy for strengthening laser-cladding 316L stainless steel with WMoTaNb refractory high-entropy alloy as a reinforcement material is proposed. The results confirm that the coating primarily comprises a body-centered cubic (BCC) Fe-based solid solution, a network-distributed hexagonal FeX (X = W, Mo, Ta, and Nb) Laves phase, and a diffusely distributed face-centered cubic (FCC) (Ta, Nb)C phase.

Estimating Flow Direction of Circle of Willis Using Dynamic Arterial Spin-Labeling MR Angiography.

Background And Purpose: The circle of Willis (COW) is a crucial mechanism for cerebral collateral circulation. This proof-of-concept study aims to develop and assess an analysis method to characterize the hemodynamics of the arterial segments in the COW by using arterial spin-labeling (ASL) based non-contrast-enhanced dynamic MR angiography (dMRA).

Materials And Methods: The developed analysis method uses a graph model, bootstrap strategy, and ensemble learning methodologies to determine the time curve shift from ASL dMRA to estimate the flow direction within the COW.

Modified lentiviral globin gene therapy for pediatric β/β transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial.

β/β thalassemia is the most severe type of transfusion-dependent β-thalassemia (TDT) and is still a challenge facing lentiviral gene therapy. Here, we report the interim analysis of a single-center, single-arm pilot trial (NCT05015920) evaluating the safety and efficacy of a β-globin expression-optimized and insulator-engineered lentivirus-modified cell product (BD211) in β/β TDT. Two female children were enrolled, infused with BD211, and followed up for an average of 25.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

Background: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain.

Methods: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group).

Remodeling ceramide homeostasis promotes functional maturation of human pluripotent stem cell-derived β cells.

Human pluripotent stem cell-derived β cells (hPSC-β cells) show the potential to restore euglycemia. However, the immature functionality of hPSC-β cells has limited their efficacy in application. Here, by deciphering the continuous maturation process of hPSC-β cells post transplantation via single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we show that functional maturation of hPSC-β cells is an orderly multistep process during which cells sequentially undergo metabolic adaption, removal of negative regulators of cell function, and establishment of a more specialized transcriptome and epigenome.