Sodium oligomannate disrupts the adherence of Rib bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice.

Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer's disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here made advances by pinpointing a Lactobacillus murinus (L.m.

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.

Fruits and vegetables intake and bladder cancer risk: a pooled analysis from 11 case-control studies in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) consortium.

Purpose: High consumption of fruits and vegetables decrease the risk of bladder cancer (BC). The evidence of specific fruits and vegetables and the BC risk is still limited.

Methods: Fruit and vegetable consumptions in relation to BC risk was examined by pooling individual participant data from case-control studies.

The relevance and accuracy of an AI algorithm-based descriptor on 23 facial attributes in a diverse female US population.

Background: The response of AI in situations that mimic real life scenarios is poorly explored in populations of high diversity.

Objective: To assess the accuracy and validate the relevance of an automated, algorithm-based analysis geared toward facial attributes devoted to the adornment routines of women.

Methods: In a cross-sectional study, two diversified groups presenting similar distributions such as age, ancestry, skin phototype, and geographical location was created from the selfie images of 1041 female in a US population.

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.

Implications of the Use of Artificial Intelligence Predictive Models in Health Care Settings : A Simulation Study.

Background: Substantial effort has been directed toward demonstrating uses of predictive models in health care. However, implementation of these models into clinical practice may influence patient outcomes, which in turn are captured in electronic health record data. As a result, deployed models may affect the predictive ability of current and future models.

Late-Onset Anti-GABA Receptor Encephalitis: Clinical Characteristics and Outcomes Differing From Early-Onset Patients.

Background And Objectives: Existing evidence indicates anti-GABA receptor encephalitis (GABAR-E) seems to occur more commonly later in life, yet the age-associated differences in clinical features and outcomes are not well determined. This study aims to explore the demographic, clinical characteristics, and prognostic differences between late-onset and early-onset GABAR-E and identify predictors of favorable long-term outcomes.

Methods: This is an observational retrospective study conducted in 19 centers from China.

[Determination of concentrations and toxicokinetics of triptolide in plasma and liver of mice by UHPLC-MS/MS].

This study aims to establish an ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method for determining the concentrations of triptolide(TP) in plasma and liver, and to explore the toxicokinetics of TP and the relationship between TP exposure and liver injury in C57 BL/6 mice, so as to provide reference for dissecting the toxicity mechanism of TP. The liquid chromatography was conducted with ZORBAX SB-C_(18) column(3.0 mm×100 mm, 3.

Modulation of intracellular kinase signaling to improve TIL stemness and function for adoptive cell therapy.

Introduction: Adoptive cellular therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated promising clinical benefits in several solid tumors, but the efficacy of this therapy might be compromised by the "prone-to-exhaustion" phenotype of TIL and poor persistence in vivo. This calls for a robust expansion process to produce a large number of cells for clinical usage while at the same time maintaining favorable anti-tumor function and memory phenotype. Previous studies showed that the PI3K-AKT signaling pathway plays a key role in the regulation of T cell activation, differentiation and memory formation.

Associations Between Lid Wiper Microvascular Responses, Lens Fit, and Comfort After One Day of Contact Lens Adaptation by Neophytes.

Purpose: To determine associations between lid wiper microvascular responses, lens fit, and comfort after 1 day of contact lens adaptation by neophytes.

Methods: Functional slitlamp biomicroscopy was used to image the microvascular network of the upper tarsal conjunctiva, lid wiper, and bulbar conjunctiva. Fractal dimension was obtained to represent vessel density.

Effect of Food Intake on Pharmacokinetics of Oral Almonertinib: A Randomized Crossover Trial in Healthy Chinese Participants.

The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) almonertinib (HS-10296) targets both EGFR-sensitizing and T790M resistance mutations. This randomized, open-label, two-period crossover trial investigated the effect of food intake on the single-dose pharmacokinetic properties of almonertinib and its metabolite HAS-719. Twenty healthy adults received a single dose of almonertinib tablets (110 mg) on days 1 and 22 under overnight fasting or fed conditions, respectively.

DNA-PK Inhibition and Radiation Promote Antitumoral Immunity through RNA Polymerase III in Pancreatic Cancer.

Unlabelled: Targeting the DNA damage response in combination with radiation enhances type I interferon (T1IFN)-driven innate immune signaling. It is not understood, however, whether DNA-dependent protein kinase (DNA-PK), the kinase critical for repairing the majority of radiation-induced DNA double-strand breaks in cancer cells, is immunomodulatory. We show that combining radiation with DNA-PK inhibition increases cytosolic double-stranded DNA and tumoral T1IFN signaling in a cyclic GMP-AMP synthase (cGAS)- and stimulator of interferon genes (STING)-independent, but an RNA polymerase III (POL III), retinoic acid-inducible gene I (RIG-I), and antiviral-signaling protein (MAVS)-dependent manner.

Establishment of an HPLC Method for Determination of Coumarin-3-Carboxylic Acid Analogues in Rat Plasma and a Preliminary Study on Their Pharmacokinetics.

A simple high performance liquid chromatography (HPLC) method was developed and validated for the determination of coumarin-3-carboxylic acid analogues (C3AA) in rat plasma and a preliminary study on pharmacokinetics. Ferulic acid (FA) was used as the internal standard substance, and coumarin-3-carboxylic acid (C3A) was used as a substitute for quantitative C3AA. After protein precipitation with methanol, the satisfactory separation was achieved on an ODS2 column when the temperature was maintained at 30 ± 2°C.

Preoperative CT for Characterization of Aggressive Macrotrabecular-Massive Subtype and Vessels That Encapsulate Tumor Clusters Pattern in Hepatocellular Carcinoma.

Background Macrotrabecular-massive (MTM) subtype and vessels encapsulating tumor clusters (VETC) pattern of hepatocellular carcinoma (HCC) are associated with unfavorable prognosis. Purpose To estimate the potential of preoperative CT in the prediction of MTM subtype and VETC pattern. Materials and Methods Patients who underwent surgical resection or liver transplant and preoperative CT for HCC between January 2015 and June 2018 were retrospectively included in the primary cohort.

Plaque Distribution Correlates With Morphology of Lenticulostriate Arteries in Single Subcortical Infarctions.

Background And Purpose: We aimed to use novel whole-brain vessel-wall magnetic resonance imaging (WB-VWI) to investigate the association between plaque distribution of middle cerebral artery (MCA) and morphological changes of the lenticulostriate arteries (LSAs) in single subcortical infarctions.

Methods: Forty single subcortical infarction patients with no relevant MCA disease on magnetic resonance angiography were prospectively enrolled. Plaque location in the MCA was dichotomized as proximal (located adjacent to the LSA origin) or distal (located distal to the LSA origin) on whole-brain vessel-wall magnetic resonance imaging.

Targeted Ablation of Ventricular Tachycardia Guided by Wavefront Discontinuities During Sinus Rhythm: A New Functional Substrate Mapping Strategy.

Background: Accurate and expedited identification of scar regions most prone to reentry is needed to guide ventricular tachycardia (VT) ablation. We aimed to prospectively assess outcomes of VT ablation guided primarily by the targeting of deceleration zones (DZ) identified by propagational analysis of ventricular activation during sinus rhythm.

Methods: Patients with scar-related VT were prospectively enrolled in the University of Chicago VT Ablation Registry between 2016 and 2018.

High-Resolution Magnetic Resonance Imaging of Cervicocranial Artery Dissection: Imaging Features Associated With Stroke.

Background and Purpose- We aimed to systematically investigate the characteristics of cervicocranial artery dissection (CCAD) on high-resolution magnetic resonance imaging that are associated with acute ischemic stroke. Methods- Patients with CCAD were recruited and divided into stroke and nonstroke groups. The lesion location, the presence of a double lumen, intimal flap, intramural hematoma, pseudoaneurysm, irregular surface, intraluminal thrombus, and other quantitative parameters of each dissected segment were reviewed.

In-Situ Growth of NiAl-Layered Double Hydroxide on AZ31 Mg Alloy towards Enhanced Corrosion Protection.

NiAl-layered double hydroxide (NiAl-LDH) coatings grown in-situ on AZ31 Mg alloy were prepared for the first time utilizing a facile hydrothermal method. The surface morphologies, structures, and compositions of the NiAl-LDH coatings were characterized by scanning electron microscopy (SEM), three dimensional (3D) optical profilometer, X-ray diffractometer (XRD), Fourier transform infrared spectrometer (FT-IR), and X-ray photoelectron spectroscopy (XPS). The results show that NiAl-LDH coating could be successfully deposited on Mg alloy substrate using different nickel salts, i.

Plasma Pharmacokinetic Determination of Canagliflozin and Its Metabolites in a Type 2 Diabetic Rat Model by UPLC-MS/MS.

Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a sensitive and efficient UPLC-MS/MS method for the quantification of canagliflozin and its metabolites in rat plasma was established and applied to pharmacokinetics in a type 2 diabetic rat model. We firstly investigated the pharmacokinetic changes of canagliflozin and its metabolites in type 2 diabetic rats in order to use canagliflozin more safely, reasonably and effectively.

Hyperintense Plaque on Intracranial Vessel Wall Magnetic Resonance Imaging as a Predictor of Artery-to-Artery Embolic Infarction.

Background And Purpose: The aim of the present study was to investigate atherosclerotic plaque characteristics in patients with artery-to-artery (A-to-A) embolic infarction by whole-brain high-resolution magnetic resonance imaging.

Methods: Seventy-four patients (mean age, 54.7±12.

Optogenetic Inhibition of Striatal GABAergic Neuronal Activity Improves Outcomes After Ischemic Brain Injury.

Background And Purpose: Striatal GABAergic neuron is known as a key regulator in adult neurogenesis. However, the specific role of striatal GABAergic neuronal activity in the promotion of neurological recovery after ischemic stroke remains unknown. Here, we used optogenetic approach to investigate these effects and mechanism.

Serum N(1)-Methylnicotinamide Is Associated With Obesity and Diabetes in Chinese.

Context: Nicotinamide N-methyltransferase (NNMT) is a novel histone methylation modulator that regulates energy metabolism, and NNMT knockdown prevents diet-induced obesity in mice. However, whether NNMT plays a role in human obesity and type 2 diabetes (T2DM) remains to be elucidated.

Objective: NNMT catalyzes methylation of nicotinamide to generate N(1)-methylnicotinamide (me-NAM).

lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA.

Rationale: Pathological angiogenesis is a critical component of diseases, such as ocular disorders, cancers, and atherosclerosis. It is usually caused by the abnormal activity of biological processes, such as cell proliferation, cell motility, immune, or inflammation response. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of these biological processes.

Single- and multiple-dose pharmacokinetics of inhaled indacaterol in healthy Chinese volunteers.

Indacaterol is an inhaled, ultra-long-acting β2-agonist that provides 24-h bronchodilation with once-daily dosing in patients with chronic obstructive pulmonary disorder. This study evaluated the pharmacokinetics, safety, and tolerability of multiple daily inhaled doses of indacaterol 150 or 300 μg once daily in healthy Chinese volunteers. This was a single-center, randomized, double-blind, multiple-dose, parallel-group study, placebo-controlled trial including two doses of indacaterol: 150 and 300 μg.