Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.

The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology.

Longitudinal CT Radiomics to Predict Progression-free Survival in Patients with Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy.

Rationale And Objectives: To develop and validate a radiomics signature, utilizing baseline and restaging CT, for preoperatively predicting progression-free survival (PFS) after neoadjuvant chemotherapy (NAC) in locally advanced gastric cancer (LAGC).

Methods: A total of 316 patients with LAGC who received NAC followed by gastrectomy were retrospectively included in this single-center study; these patients were split into two cohorts, one for training (n = 243) and the other for validation (n = 73), based on the different districts of our hospital. A total of 1316 radiomics features were extracted from the volume of interest of the gastric-cancer lesion on venous phase CT images.

Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer.

The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2- MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.

Development and Characterisation of an Immortal Cell Line From Largemouth Bass (Micropterus salmoides) for Viral Studies.

Largemouth bass (Micropterus salmoides), a freshwater fish species, is cultivated widely across China. The industry has been greatly affected by various viral diseases. We generated a new immortal cell line from the fin of M.

Patient-Derived Xenografts of Triple-Negative Breast Cancer Enable Deconvolution and Prediction of Chemotherapy Responses.

Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to individual agents cannot be easily delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination.

Heteroaryl Glutarimides and Dihydrouracils as Cereblon Ligand Scaffolds for Molecular Glue Degrader Discovery.

Stabilization of cereblon (CRBN)/neosubstrate complexes with molecular glues followed by degradation of those neosubstrates is an emerging strategy in drug discovery with compelling potential to target certain proteins that were previously considered to be undruggable. In this context, the discovery of novel CRBN ligands is an important area of ongoing research that holds promise to expand the scope of proteins that can be targeted through this mode of action. Herein, we describe the synthesis and evaluation of CRBN ligands featuring heteroaryl glutarimide and dihydrouracil scaffolds.

Femtosecond Laser Introduced Cantilever Beam on Optical Fiber for Vibration Sensing.

An all-fiber vibration sensor based on the Fabry-Perot interferometer (FPI) is proposed and experimentally evaluated in this study. The sensor is fabricated by introducing a Fabry-Perot cavity to the single-mode fiber using femtosecond laser ablation. The cavity and the tail act together as a cantilever beam, which can be used as a vibration receiver.

Metagenomics and metatranscriptomics insights into microbial enhancement of HS removal and CO assimilation.

This study focuses on the coupled process of bio-enhanced absorption and biodesulfurization for the toxic gas HS and the greenhouse gas CO. The results show that on the basis of stabilized absorption of HS and CO by alkaline solution (Stage I), the addition of air-lift bioreactor process solution in the absorption column enhanced their absorption (Stage II). Specifically, at constant inlet concentrations of H₂S and CO₂ of 3% (30,000 ppmv) and 30% (300,000 ppmv), respectively, the outlet gases were primarily H₂S, CO₂, and N₂.

Endothelial FUNDC1 Deficiency Drives Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is associated with endothelial dysfunction. However, the cause of endothelial dysfunction and its impact on PH remain incompletely understood. We aimed to investigate whether the hypoxia-inducible FUNDC1 (FUN14 domain-containing 1)-dependent mitophagy pathway underlies PH pathogenesis and progression.

A new species of (Amphibia, Anura, Strabomantidae) from a montane forest of the Pui Pui Protected Forest in central Peru.

Herpetological inventories conducted in the Pui Pui Protected Forest in the central Peruvian Andes between 2012 and 2014 revealed unusually high local anuran richness and endemism. Herein, we describe a new species of discovered in the buffer zone of the protected area between 1550 and 1730 m a.s.

Mapping fetal brain development of 10 weeks gestational age with 9.4T postmortem MRI and histological sections.

Background And Purpose: The 10th week of gestational age (GA) is a critical period for evaluating brain development, but there is limited knowledge regarding the specific characteristics at this GA. This study is to map the brain structures at 10 weeks GA using 9.4T MRI and histological sections.

SGK1-Mediated Vascular Smooth Muscle Cell Phenotypic Transformation Promotes Thoracic Aortic Dissection Progression.

Background: The occurrence of thoracic aortic dissection (TAD) is closely related to the transformation of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. The role of SGK1 (serum- and glucocorticoid-regulated kinase 1) in VSMC phenotypic transformation and TAD occurrence is unclear.

Methods: Four-week-old male Sgk1 ( floxed) and Sgk1;Tagln (smooth muscle cell-specific knockout) mice were administered β-aminopropionitrile monofumarate for 4 weeks to model TAD.

Buprenorphine Salivary Gland Accumulation Sustaining High Oral Fluid Exposure and Increasing the Risk of Streptococcus mutans Biofilm Formation.

Objectives: The US Food and Drug Administration (FDA) issued a warning about buprenorphine-induced dental caries of unknown mechanism in 2022. To investigate the potential mechanism, the association between local buprenorphine exposure and dental biofilm formation will be explored in this study.

Methods: Female F344 rats were dosed with sublingual buprenorphine film or intravenous injection to explore the oral cavity exposure of the buprenorphine.

Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients.

Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies.

Patients And Methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed.

Pharmacokinetics of infigratinib and its active metabolites in Chinese patients with advanced gastric cancer harboring FGFR2 gene amplification.

Infigratinib, an FGFR1-3 selective oral tyrosine kinase inhibitor, has shown clinical activity in cancers with FGFR alterations. The pharmacokinetics (PK) of infigratinib and its major metabolites have been characterized in global populations. This study examined the PK profile of infigratinib and its metabolites in Chinese patients.

Efficacy and tolerability of celastrol and edaravone in the multiple-hit rat model of infantile spasms.

Objective: To test whether anti-inflammatory and antioxidant drugs that inhibit the nuclear factor kappa light chain enhancer of activated B cells (NF-kB), celastrol and edaravone, suppress spasms and improve developmental outcomes in the multiple-hit rat model of refractory infantile spasms (IS) due to structural lesions.

Methods: Postnatal day 3 (PN3) Sprague-Dawley rats were treated according to the multiple-hit IS model protocol. Using a randomized, blinded, vehicle-controlled, dose- and time-response study design, we tested the effects of single celastrol [1, 2, or 4 mg/kg intraperitoneally (i.

Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at F-SynVesT-1 Brain PET Imaging.

Background Synaptic loss is an important factor in Alzheimer disease (AD); however, blood assays that conveniently and rapidly reflect changes in synaptic density are lacking. Purpose To correlate multiple potential synaptic blood markers with synaptic density measured using F-SynVesT-1, a fluorine 18 (F)-labeled radiotracer, brain PET and to explore the independent associations between these markers and synaptic density. Materials and Methods This prospective study included 50 cognitively unimpaired (mean age, 65.

Three-chamber electrochemical reactor for selective lithium extraction from brine.

Efficient lithium recovery from geothermal brines is crucial for the battery industry. Current electrochemical separation methods struggle with the simultaneous presence of Na, K, Mg, and Ca because these cations are similar to Li, making it challenging to separate effectively. We address these challenges with a three-chamber reactor featuring a polymer porous solid electrolyte in the middle layer.