The therapeutic potential of circular RNAs.

Over the past decade, research into circular RNA (circRNA) has increased rapidly, and over the past few years, circRNA has emerged as a promising therapeutic platform. The regulatory functions of circRNAs, including their roles in templating protein translation and regulating protein and RNA functions, as well as their unique characteristics, such as increased stability and a favourable immunological profile compared with mRNAs, make them attractive candidates for RNA-based therapies. Here, we describe the properties of circRNAs, their therapeutic potential and technologies for their synthesis.

Bilirubin reductase shows host-specific associations in animal large intestines.

Animal gastrointestinal tracts contain diverse metabolites, including various host-derived compounds that gut-associated microbes interact with. Here, we explore the diversity and evolution of bilirubin reductase, a bacterial enzyme that metabolizes the host-derived tetrapyrrole bilirubin, performing a key role in the animal heme degradation pathway. Through an analysis of the bilirubin reductase phylogeny and predicted structures, we found that the enzyme family can be divided into three distinct clades with different structural features.

De novo generation of SARS-CoV-2 antibody CDRH3 with a pre-trained generative large language model.

Artificial Intelligence (AI) techniques have made great advances in assisting antibody design. However, antibody design still heavily relies on isolating antigen-specific antibodies from serum, which is a resource-intensive and time-consuming process. To address this issue, we propose a Pre-trained Antibody generative large Language Model (PALM-H3) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 (CDRH3) with desired antigen-binding specificity, reducing the reliance on natural antibodies.

Conformational Locking Induced Enantioselective Diarylcarbene Insertion into B-H and O-H Bonds Using a Cationic Rh(I)/Diene Catalyst.

Transition-metal-catalyzed enantioselective transformations of aryl/aryl carbene are inherently challenging due to the difficulty in distinguishing between two arene rings in the reaction process thus remain largely less explored. The few successful examples reported so far, without exception, have all been catalyzed by Rh(II)-complexes. Herein, we describe our successful development of a novel cationic Rh(I)/chiral diene catalytic system capable of efficient enantioselective B-H and O-H insertions with diaryl diazomethanes, allowing the access to a broad range of gem-diarylmethine boranes and gem-diarylmethine ethers in good yields with high enantioselectivities.

CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis.

Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being a key component. Yet, the impact of costimulatory domains on the downstream signaling and subsequent functionality of CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated the impact of various costimulatory domains on CAR-NK cell activity, using a CD70-targeting CAR.

Cutaneous pharmacokinetics-based bioequivalence: A clinical dermal open flow microperfusion verification study using lidocaine and prilocaine combination topical products.

Background: Using accurate, sensitive, reproducible and efficient in vivo cutaneous pharmacokinetics (PK)-based bioequivalence (BE) approaches can promote the development of topical generic drug products. A clinical dermal open flow microperfusion (dOFM) study has previously demonstrated the BE of topical drug products containing a hydrophilic drug. However, the utility of dOFM to evaluate the topical BE of drug products containing moderately lipophilic drugs, more representative of most topical drugs, has not yet been established.

SMYD2-Methylated PPARγ Facilitates Hypoxia-Induced Pulmonary Hypertension by Activating Mitophagy.

Background: Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown.

Methods: PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks.

Search for exotic decays of the Higgs boson to a pair of pseudoscalars in the and final states.

A search for exotic decays of the Higgs boson () with a mass of 125 to a pair of light pseudoscalars is performed in final states where one pseudoscalar decays to two quarks and the other to a pair of muons or leptons. A data sample of proton-proton collisions at corresponding to an integrated luminosity of 138 recorded with the CMS detector is analyzed. No statistically significant excess is observed over the standard model backgrounds.

Two-dimensional molybdenum boride coordinating with ruthenium nanoparticles to boost hydrogen generation from hydrolytic dehydrogenation of ammonia borane.

The coordination between carrier and active metal is critical to the catalytic efficiency of ammonia borane (AB) hydrolysis reaction. In the present study, we report a new type of catalytic support based on molybdenum boride (MBene) MoAlB and demonstrate that the effective combination of MoAlB with Ru nanoparticles can realize the significantly enhanced performance for hydrogen generation. Owing to the efficient activation and dissociation of reactants, the optimal Ru/MoAlB catalyst achieves the large turnover frequency of 494 mol mol min, high hydrogen generation rate of 119817 mL min g and favorable apparent activation energy of 39.

Learning Representations from Heart Sound: A Comparative Study on Shallow and Deep Models.

Leveraging the power of artificial intelligence to facilitate an automatic analysis and monitoring of heart sounds has increasingly attracted tremendous efforts in the past decade. Nevertheless, lacking on standard open-access database made it difficult to maintain a sustainable and comparable research before the first release of the PhysioNet CinC Challenge Dataset. However, inconsistent standards on data collection, annotation, and partition are still restraining a fair and efficient comparison between different works.

Dl-3-n-Butylphthalide Alleviates Secondary Brain Damage and Improves Working Memory After Stroke in Cynomolgus Monkeys.

Background: Remote secondary neurodegeneration is associated with poststroke cognitive impairment (PSCI). Dl-3-n-butylphthalide (NBP) improves PSCI clinically. However, whether it ameliorates PSCI by alleviating secondary neurodegeneration remains uncertain.

Iridium-catalyzed selective arylation of B(6)-H of 3-aryl--carboranes with arylboronic acid direct B-H activation.

This work discloses an iridium-catalyzed selective arylation of B(6)-H of 3-Ar--carboranes with arylboronic acid direct B-H activation for the first time. A series of unsymmetric and symmetric 3,6-diaryl--carboranes decorated with diverse active groups have been synthesized with moderate to excellent yields under mild conditions. This work offers an efficient approach for selective arylation of B(6)-H with arylboronic acid and has important value for selective functionalization of -carboranes.

BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen.

Metabolism of haem by-products such as bilirubin by humans and their gut microbiota is essential to human health, as excess serum bilirubin can cause jaundice and even neurological damage. The bacterial enzymes that reduce bilirubin to urobilinogen, a key step in this pathway, have remained unidentified. Here we used biochemical analyses and comparative genomics to identify BilR as a gut-microbiota-derived bilirubin reductase that reduces bilirubin to urobilinogen.

A search for decays of the Higgs boson to invisible particles in events with a top-antitop quark pair or a vector boson in proton-proton collisions at .

A search for decays to invisible particles of Higgs bosons produced in association with a top-antitop quark pair or a vector boson, which both decay to a fully hadronic final state, has been performed using proton-proton collision data collected at by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138. The 95% confidence level upper limit set on the branching fraction of the 125 Higgs boson to invisible particles, , is 0.54 (0.

A new method for multiancestry polygenic prediction improves performance across diverse populations.

Polygenic risk scores (PRSs) increasingly predict complex traits; however, suboptimal performance in non-European populations raise concerns about clinical applications and health inequities. We developed CT-SLEB, a powerful and scalable method to calculate PRSs, using ancestry-specific genome-wide association study summary statistics from multiancestry training samples, integrating clumping and thresholding, empirical Bayes and superlearning. We evaluated CT-SLEB and nine alternative methods with large-scale simulated genome-wide association studies (~19 million common variants) and datasets from 23andMe, Inc.

Prediction of Drug-Drug Interactions with Ensartinib as a Time-Dependent CYP3A Inhibitor Using Physiologically Based Pharmacokinetic Model.

Ensartinib (X-396) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of ALK-positive patients with locally advanced or metastatic non-small cell lung cancer. Although in vitro experiments and molecular docking suggested its potential as a cytochrome P450 inhibitor, no further investigation or clinical trials have been conducted to assess its drug-drug interaction (DDI) risk. In this study, we conducted a series of in vitro experiments to elucidate the inhibition mechanism of ensartinib.

Efficacy and Interpretability Analysis of Noninvasive Imaging Based on Computed Tomography in Patients with Hepatocellular Carcinoma After Initial Transarterial Chemoembolization.

Rationale And Objectives: The objective of this study is to accurately and timely assess the efficacy of patients with hepatocellular carcinoma (HCC) after the initial transarterial chemoembolization (TACE).

Materials And Methods: This retrospective study consisted of 279 patients with HCC in Center 1, who were split into training and validation cohorts in the ratio of 4:1, and 72 patients in Center 2 as an external testing cohort. Radiomics signatures both in the arterial phase and venous phase of contrast-enhanced computed tomography images were selected by univariate analysis, correlation analysis, and least absolute shrinkage and selection operator regression to build the predicting models.

Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease.

Background And Purpose: The prevalence of cerebral small vessel disease (CSVD) is increasing due to the accelerating global aging process, resulting in a substantial burden on all countries, as cognitive dysfunction associated with CSVD is also on the rise. Clock genes have a significant impact on cognitive decline and dementia. Furthermore, the pattern of DNA methylation in clock genes is strongly associated with cognitive impairment.

Facile construction of robust Ru-CoO Mott-Schottky catalyst enabling efficient dehydrogenation of ammonia borane for hydrogen generation.

Developing efficient catalysts for the dehydrogenation of ammonia borane (AB) is important for the safe storage and controlled release of hydrogen, but it is a challenging task. In this study, we designed a robust Ru-CoO catalyst using the Mott-Schottky effect to induce favorable charge rearrangement. The self-created electron-rich CoO and electron-deficient Ru sites at heterointerfaces are indispensable for the activation of the B-H bond in NHBH and the OH bond in HO, respectively.

Three-wavelength-switchable narrow linewidth thulium-doped fiber laser enabled by a compound-cavity filter and a sampled fiber Bragg grating.

A single-longitudinal-mode (SLM), narrow linewidth thulium-doped fiber laser with a sampled fiber Bragg grating (SFBG), switchable among three wavelengths, with a cascade dual-coupler-ring-based compound cavity (DCR-CC) filter, is proposed and demonstrated. The coupling design, simulation analysis, and characterization of the DCR-CC filter provide the foundation for the experiment. A nonlinear polarization rotation system was injected into the cavity to suppress gain competition and achieve a laser switchable among three wavelengths.

A Case of Successful Treatment of Recurrent Urinary Tract Infection by Extended-Spectrum β-Lactamase Producing Using Oral Lyophilized Fecal Microbiota Transplant.

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing UTIs in a patient with an ileal conduit and urostomy.