Proteasomal processing of the viral replicase ORF1 facilitates HEV-induced liver fibrosis.

Chronic infections with hepatitis E virus (HEV), especially those of genotype 3 (G3), frequently lead to liver fibrosis and cirrhosis in patients. However, the causation and mechanism of liver fibrosis triggered by chronic HEV infection remain poorly understood. Here, we found that the viral multiple-domain replicase (ORF1) undergoes unique ubiquitin-proteasomal processing leading to formation of the EV-erived MAD ctivator (HDSA), a viral polypeptide lacking putative helicase and RNA polymerase domains.

Optimizing drug sensitivity assays in patient-derived tumor organoids: a comparison of IC50 estimation methods and experimental parameters.

Patient-derived tumor organoids (PDOs) hold immense potential for personalized drug sensitivity testing, but accurate efficacy determination is crucial for clinical translation. This study investigated factors influencing the accuracy and reproducibility of drug sensitivity measurements in PDOs, focusing on half-maximal-inhibitory-concentration (IC50) calculation methods, drug concentration numbers, and plate types. PDOs were established from six primary cancer tissues, including two cervical resections, one lung biopsy, one lung pleural effusion, one breast biopsy, and one gastric resection.

Selective Area Growth of Josephson Junctions in Ladder-Like Structures of Bismuth Islands.

A distinguishing characteristic of Josephson junctions (JJs) is their nonlinear current-voltage response, which fulfills the requirements for superconducting quantum computing. Achieving atomically sharp interfaces between superconductors and weak links in JJs can realize the superconductivity proximity effect, advancing the investigation of intrinsic properties in unconventional superconductors and their potential applications. Here, a contamination-free approach to fabricating planar JJs using molecular beam epitaxy (MBE) is presented.

High-throughput screening of new psychoactive substances and related compounds in food by UHPLC-Q/Orbitrap.

Currently, there is concern about food products to which new psychoactive substances (NPS) have been added illegally. However, rapid, high-sensitivity, and high-throughput screening methods for such harmful substances have not been reported yet. In this study, a high-throughput non-targeted screening strategy was developed based on UHPLC-Q/Orbitrap.

Clinical features and outcomes of unresectable locally advanced lung adenocarcinoma with uncommon mutations: a retrospective multi-center Chinese study.

Background: Uncommon epidermal growth factor receptor () gene mutant locally advanced non-small cell lung cancer (NSCLC) has been poorly documented in the literature. Our study aimed to investigate the clinical features and outcomes associated with these mutations.

Methods: A multi-center retrospective study was conducted to review 511 patients with mutant unresectable stage III lung adenocarcinoma, treated between 2012 and 2018 across 12 Chinese institutions.

Polysaccharide alleviates neurodegeneration and behavioral deficit by enhancing mitochondrial autophagy in chronic methamphetamine mice.

Methamphetamine (METH) is a psychostimulant drug widely abused because of its addictive properties.Its impact on the central nervous system is a major area of interest due to its unique ability to cross the blood-brain barrier, facilitated by its dual water and lipid solubility. Studies have indicated that oxidative stress, neuroinflammation, neuronal apoptosis, and mitochondrial dysfunction are primary mechanisms of METH-induced neurotoxicity.

Apigenin Ameliorates Insulin Resistance in 3T3-L1 Adipocytes: Establishment of a New Insulin Resistance Model Induced by Combined Treatments.

Adipose tissue dysfunction due to insulin resistance (IR) plays a central role in the development of metabolic diseases. Obesity-associated IR greatly attributes to low-grade inflammation and high circulating levels of FFAs and sugar. 3T3-L1 adipocytes exposed to a mixture of TNF-α, fructose, and palmitate acid for 24 h were validated as a model to simulate the pathogenesis of IR in obese people under a high-fat-fructose diet.

Early one-stage posterior-only surgery for congenital cervicothoracic scoliosis in children: medium- and long-term follow-up.

Objective: The purpose of this study is to investigate the medium- and long-term correction outcomes and complications of early one-stage posterior-only surgery for congenital cervicothoracic scoliosis in children.

Methods: From March 2006 to March 2022, we retrospectively investigated 33 consecutive cases of congenital cervicothoracic scoliosis treated by one-stage posterior-only surgery, including 15 males and 18 females, with a mean age of 3.2 years.

Development and Application of a Comprehensive Non-targeted Screening Strategy for Fentanyl Analogues.

The growing abuse of fentanyl and its analogues (FTNs) presents a substantial public health threat, prompting the introduction of regulatory controls by government authorities. Nevertheless, existing screening strategies for FTNs are primarily based on targeted or non-targeted approaches that utilize a limited set of mass spectrometry fragmentation data, which are far from meeting the needs of class scheduling. In this study, a comprehensive non-targeted screening strategy for FTNs was developed.

Metabolic Reprogramming of Neural Stem Cells by Chiral Nanofiber for Spinal Cord Injury.

Exogenous neural stem cells (NSCs) have great potential to reconstitute damage spinal neural circuitry. However, regulating the metabolic reprogramming of NSCs for reliable nerve regeneration has been challenging. This report discusses the biomimetic dextral hydrogel (DH) with right-handed nanofibers that specifically reprograms the lipid metabolism of NSCs, promoting their neural differentiation and rapid regeneration of damaged axons.

Engineered Extracellular Vesicles from Antler Blastema Progenitor Cells: A Therapeutic Choice for Spinal Cord Injury.

Deer antler blastema progenitor cells (ABPCs) are promising for regenerative medicine due to their role in annual antler regeneration, the only case of complete organ regeneration in mammals. ABPC-derived signals show great potential for promoting regeneration in tissues with limited natural regenerative ability. Our findings demonstrate the capability of extracellular vesicles from ABPCs (EVs) to repair spinal cord injury (SCI), a condition with low regenerative capacity.

Stevioside mitigates metabolic dysregulation in offspring induced by maternal high-fat diet: the role of gut microbiota-driven thermogenesis.

Maternal obesity poses a significant threat to the metabolic profiles of offspring. Microorganisms acquired from the mother early in life critically affect the host's metabolic functions. Natural non-nutritive sweeteners, particularly stevioside (STV), play a crucial role in reducing obesity and affecting gut microbiota composition.

USP18 Promotes Cholesterol Efflux and Mitigates Atherosclerosis by Deubiquitinating ABCG1.

Deubiquitinating enzymes (DUBs) are integral regulators of protein stability. Among these, Ubiquitin-specific protease 18 (USP18) has emerged as a potential therapeutic target for heart failure. However, its precise role in atherosclerosis remains to be comprehensively understood.

Epidemiological Characteristics and Diagnostic Outcomes of Suspected Occupational Noise-Induced Deafness - Guangdong Province, China, 2014-2023.

Introduction: Suspected occupational noise-induced deafness (ONID) represents the most prevalent suspected occupational disease in Guangdong Province and is among the most frequently reported nationwide. Given its public health significance, we conducted a systematic investigation of suspected ONID cases in Guangdong from 2014 to 2023, analyzing their epidemiological characteristics and diagnostic outcomes to inform evidence-based policies for ONID prevention and management.

Methods: Data on suspected ONID cases reported in Guangdong Province from 2014 to 2023 were extracted from the "Occupational Diseases and Health Hazard Factors Monitoring Information System.

Construction of Double-layered DNA Tiles and Arrays from Double Crossover Motifs.

DNA double crossover (DX) motifs including DAE (double crossover, antiparallel, even spacing) and DAO (double crossover, antiparallel, odd spacing) are well-known monolayered DNA building blocks for construction of 2D DNA arrays and tubes in nanoscale and microscale. Compared to the 3D architectures of DNA origami and single-stranded DNA bricks to build nanoscale 3D bundles, tessellations, gears, castles, etc., designs of double- and multi-layers of DX motifs for 3D architectures are still limited.

Galactin-8 DNA methylation mediates macrophage autophagy through the MAPK/mTOR pathway to alleviate atherosclerosis.

DNA methylation modifications are an important mechanism affecting the process of atherosclerosis (AS). Previous studies have shown that Galectin-8 (GAL8) DNA methylation level is associated with sudden death of coronary heart disease or acute events of coronary heart disease. However, the mechanism of GAL8 DNA methylation and gene expression in AS has not been elucidated, prompting us to carry out further research on it.

Effect of biopolymers on morphology and functionality of low-sodium condiments containing Maillard reaction products.

The impact of various biopolymers on low-sodium condiments composed of salt, potassium chloride, sodium glutamate and Maillard reaction products with chicken flavor were evaluated in order to generate uniformly distributed low-sodium condiments. The addition of biopolymers reduced the sodium and potassium content of low sodium condiments, as well as improved the particle size, changed the particle morphology. The addition of different biopolymers had different effects on the color, flow characteristics, solubility, hygroscopicity and thermal stability of low sodium condiments.

A Novel Deer Antler-Inspired Bone Graft Triggers Rapid Bone Regeneration.

Adult mammals are unable to regenerate bulky bone tissues, making large bone defects clinically challenging. Deer antler represents an exception to this rule, exhibiting the fastest bony growth in mammals, offering a unique opportunity to explore novel strategies for rapid bone regeneration. Here, a bone graft exploiting the biochemical, biophysical, and structural characteristics of antlers is constructed.

Precise evaluation of the nutritional value of yeast culture and its effect on pigs fed low-protein diets.

The purpose of the present study was to assess the nutritional value of yeast culture (YC) and to explore the effect of YC on growth performance and health of piglets fed low-protein diets. In Exp. 1, 12 growing barrows were allocated into control diet and YC diet treatments to determine the available energy of YC.

Tuning architectural organization of eukaryotic P450 system to boost bioproduction in Escherichia coli.

Eukaryotic cytochrome P450 enzymes, generally colocalizing with their redox partner cytochrome P450 reductase (CPR) on the cytoplasmic surface of organelle membranes, often perform poorly in prokaryotic cells, whether expressed with CPR as a tandem chimera or free-floating individuals, causing a low titer of heterologous chemicals. To improve their biosynthetic performance in Escherichia coli, here, we architecturally design self-assembled alternatives of eukaryotic P450 system using reconstructed P450 and CPR, and create a set of N-termini-bridged P450-CPR heterodimers as the counterparts of eukaryotic P450 system with N-terminus-guided colocalization. The covalent counterparts show superior and robust biosynthetic performance, and the N-termini-bridged architecture is validated to improve the biosynthetic performance of both plant and human P450 systems.

hUC-MSCs mitigate atherosclerosis induced by a high-fat diet in ApoE mice by regulating the intestinal microbiota.

Background: The mechanism underlying human umbilical cord mesenchymal stem cells (hUC-MSCs) regulating the stability of atherosclerotic plaque was explored by establishing mice models of atherosclerosis induced by a high-fat diet and hUC-MSCs intervention.

Methods: The ApoE mice atherosclerosis model was constructed using a high-fat diet, and mice were divided into a normal diet group (ND), high-fat diet group (HFD), hUC-MSCs treatment group (HFDM), while the blank control (BC) consisted of C57BL/6J mice. After successful establishment of the model, the feces, hearts, and aorta of mice were collected.

Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer: The Phase 3 EXTENTORCH Randomized Clinical Trial.

Importance: Patients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs.

Objective: To evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC.

Design, Setting, And Participants: This multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China.

Postoperative tumor bed radiation versus T-shaped field radiation in the treatment of locally advanced thoracic esophageal squamous cell carcinoma: a phase IIb multicenter randomized controlled trial.

Background: Postoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients.