A B7H3-targeting antibody-drug conjugate in advanced solid tumors: a phase 1/1b trial.

Antibody-drug conjugates (ADCs) have emerged as a transformative modality in the treatment of solid tumors. YL201, a novel B7H3-targeting ADC, leverages a tumor microenvironment activable linker-payload platform, coupled with a novel topoisomerase 1 inhibitor via a protease-cleavable linker. Here we report the findings from a large-scale, global, multicenter, phase 1 trial evaluating the safety, pharmacokinetics and preliminary efficacy of YL201 in patients with advanced solid tumors refractory to standard therapies.

miRNA-328-3p regulates ZO-1 expression and inhibits PEDV proliferation via the PLC-β1-PKC pathway.

Porcine epidemic diarrhea virus (PEDV) is a significant pathogen affecting swine, causing severe economic losses worldwide. This study explores the regulatory role of miRNA-328-3p to ZO-1 expression and its impact on PEDV proliferation via the PLC-β1-PKC pathway in IPEC-J2 cells. We found that miRNA-328-3p can target ZO-1, influencing its expression and subsequently affecting the integrity of tight junctions in the cells.

Photoredox-Catalyzed Aminolactonization of 2-Styrylbenzoic Acids with -Aminopyridinium Salts to Access 4-Sulfonamino-3,4-dihydroisocoumarins.

A photoredox-catalyzed aminolactonization of unsaturated carboxylic acids was achieved using -aminopyridinium salts as the amino radical precursor. The transformation features mild conditions and a remarkably broad substrate scope, offering an efficient approach to construct a wide range of 4-sulfonamino 3,4-dihydroisocoumarins. Mechanistic studies indicate that the reaction proceeds via a distinctive -aminopyridinium salt-promoted electrophilic amination of 2-styrylbenzoic acids.

Interplay of chain dynamics and ion transport on mechanical behavior and conductivity in ionogels.

Understanding the interplay among the mechanical behavior, ionic conductivity and chain dynamics of ionogels is essential for designing flexible conductors that exhibit both high conductivity and excellent mechanical properties. In this study, ionogels were synthesized the radical polymerization of ,'-dimethylacrylamide (DMAA) and methacrylic acid (MAAc) monomers in the presence of ionic liquid 1-ethyl-3-methylimidazolium trifluoromethane sulfonate ([EMIM][OTf]). By varying the mass content of ionic liquid within ionogels, we investigated the mechanical behavior and ionic conductivity at the macroscopic scale using tensile, rheological testing and electrochemical impedance spectroscopy, as well as the dynamic behavior of chain segments and ions within the network at the microscopic scale using broadband dielectric relaxation spectroscopy (BDS) over a broad temperature range.

The broad-spectrum deubiquitinating enzyme inhibitor PR-619 protects retinal ganglion cell and augments parkin-mediated mitophagy in experimental glaucoma.

Glaucoma is a leading cause of irreversible visual impairment worldwide, characterized by the progressive death of retinal ganglion cells (RGCs). Deubiquitinating enzyme (DUB) inhibitors have shown promise as pharmacological interventions for neurodegenerative disorders. Our study focuses on the pan-DUB inhibitor PR-619 and its potential neuroprotective effects on RGCs through modulation of parkin-mediated mitophagy in experimental glaucoma models.

Risk prediction of diabetic retinopathy based on visit-to-visit fasting blood glucose indices.

Objective: The long-term glucose monitoring is essential to the risk assessment of diabetic retinopathy (DR), the aim of this study was to investigate the predictive ability of visit-to-visit fasting blood glucose (FBG) indices on the risk of DR.

Methods: This was a community-based, cohort study conducted from 2013 to 2021. DR was diagnosed by digital fundus photography.

Quantitative Study on the Anticollapse Ability of Casing in Shale Gas Wells under Complex Load Conditions.

Implementing novel technologies, including the "well factory" model and zipper fracturing techniques, has become prevalent in shale gas development. During completion operations such as lowering casing and multistage fracturing, the casing is subjected to many complex loads, reducing its strength and increasing the risk of casing deformation. By establishing a casing wear model and conducting multistage cyclic loading experiments and numerical simulations, we analyzed the change rule of casing anticollapse strength under complex loads, developed a calculation method for casing comprehensive anticollapse ability under complex loads, and applied the method to an illustrative calculation.

Network pharmacology and experimental verification revealing valnemulin alleviates DSS-induced ulcerative colitis by inhibiting intestinal senescence.

Ulcerative colitis (UC) is a chronic inflammatory disease that is increasing in prevalence globally. Senescence is characterized by a specific chronic, low-grade, "sterile" inflammatory state known as inflammaging, suggesting that senescence may exacerbate the severity of UC. However, the link between UC and senescence remains unclear.

Long Non-Coding RNA PVT1 Facilitates Radiation-Induced Vascular Endothelial Cell Injury through Sponging MicroRNA-9-5p.

Radiotherapy is a common therapeutic strategy for various solid tumors, with vascular endothelial injury being a common side effect. The study aimed to examine the effect of long non-coding RNA PVT1 on radiation-induced vascular endothelial cell injury, and explore the possible underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were exposed to different doses of X ray to mimic radiation.

The key point of transsphenoidal surgery for infradiaphragmatic craniopharyngioma：Better sellar diaphragm resection.

Background: Craniopharyngiomas have a high recurrence rate and a poor prognosis, and the key methods for reducing recurrences are unknown. The aim of this study was to explore the key points of microscopic or endoscopic transsphenoidal surgery used to treat infradiaphragmatic craniopharyngiomas.

Methods: We reviewed the medical records of patients with infradiaphragmatic craniopharyngiomas who were admitted to Peking Union Medical College Hospital between 2011 and 2018.

CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.

Recently, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor-modified T cells (CAR-Ts) have been shown to have high therapeutic efficacy in hematological tumors. CD87 is highly expressed in solid tumors with an oncogenic function. To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas (iNFPAs), we first examined CD87 expression and its effects on the metabolism of iNFPA cells.

Probabilistic sunspot predictions with a gated recurrent units-based combined model guided by pinball loss.

Sunspots play a crucial role in both weather forecasting and the monitoring of solar storms. In this work, we propose a novel combined model for sunspot prediction using improved gated recurrent units (GRU) guided by pinball loss for probabilistic forecasts. Specifically, we optimize the GRU parameters using the slime mould algorithm and employ a seasonal-trend decomposition procedure based on loess to tackle challenges related to sequence prediction, such as self-correlations and non-stationarity.

The impact of skeletal muscle index at the third lumbar spine on nosocomial deterioration and short-term prognosis in acute pancreatitis: a retrospective observational study.

Objective: To investigate the impact of the third lumbar skeletal muscle index (L3-SMI) assessed by CT on the in-hospital severity and short-term prognosis of acute pancreatitis.

Methods: A total of 224 patients with severe acute pancreatitis admitted to Yantaishan Hospital from January 2021 to June 2022 were selected as the subjects. Based on the in-hospital treatment outcomes, they were divided into a mortality group of 59 cases as well as a survival group of 165 cases.

Biomechanical comparative study on external fixators of new configurations in the treatment of Tile C pelvic injury.

To compare the biomechanical properties of several anterior pelvic ring external fixators with two new configurations in the treatment of Tile C pelvic fractures, in order to evaluate the effectiveness of the new configurations and provide a reference for their clinical application. A finite element model of a Tile C pelvic ring injury (unilateral longitudinal sacral fracture and ipsilateral pubic fracture) was constructed. The pelvis was fixed with iliac crest external fixator (IC), anterior inferior iliac spine external fixator (AIIS), combination of IC and AIIS, combination of anterior superior iliac spine external fixator (ASIS) and AIIS, and S1 sacroiliac screw in 5 types of models.

Visible-Light-Promoted Deoxygenative Alkylation of Quinoxalin-2(1)-ones with Activated Alcohols.

A one-pot strategy for deoxygenative alkylation of alcohols with quinoxalin-2(1)-ones was developed by using xanthate salts as alcohol-activating groups for radical generation in the presence of tricyclohexylphosphine under visible-light-promoted conditions. The remarkable features of this reaction include a broad substrate scope, excellent functional group tolerance, mild conditions, and simple operation. Moreover, the synthetic utility of this reaction was validated by the success of two-step one-pot reactions, scale-up synthesis, and chemoselective radical monodeoxygenation of diols.

QsvR and OpaR coordinately regulate the transcription of and in .

, the leading cause of seafood-associated gastroenteritis, has a strong capacity to form biofilms on surfaces, which is strictly regulated by the CpsS-CpsR-CpsQ regulatory cascade. OpaR, a master regulator of quorum sensing, is a global regulator that controls multiple cellular pathways including biofilm formation and virulence. QsvR is an AraC-type regulator that works coordinately with OpaR to control biofilm formation and virulence gene expression of .

Reliability Prediction of Near-Isothermal Rolling of TiAl Alloy Based on Five Neural Network Models.

The near-isothermal rolling process has the characteristics of multi-variable and strong coupling, and the industrial conditions change constantly during the actual rolling process. It is difficult to consider the influence of various factors in industrial sites using theoretical derivation, and the compensation coefficient is difficult to accurately determine. The neural network model compensates for the difficulty in determining the compensation coefficient of the theoretical model.

Preoperative and postoperative blood testosterone levels in patients with acromegaly: a prospective study.

Purpose: To investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients.

Methods: A retrospective, single-center study focused on 252 male acromegaly patients aged 18 years-60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed.