Peripheral immune characteristics and subset disorder in reproductive females with endometriosis.

Pathogenesis of endometriosis (EN) is still unknown, but growing evidence suggests that immune regulation may be important, and the pattern of peripheral immune changes in reproductive women with EN has yet to be fully explored. In this study, we conducted a comprehensive and systematic analysis of immune cell subsets within T cells, B cells, NK cells, and γδ T cells in peripheral blood (PB) samples from women with EN, women with uterine fibroids (UF) but without EN (UF-alone), and healthy controls using multi-parameter flow cytometry. Our findings revealed that UF, a common comorbidity of EN, exhibited similar peripheral immune features to EN, particularly in T cell and B cell immunity.

ARID1A is a coactivator of STAT5 that contributes to CD8 T cell dysfunction and anti-PD-1 resistance in gastric cancer.

ARID1A deletion mutation contributes to improved treatment of several malignancies with immune checkpoint inhibitors (ICIs). However, its role in modulating of tumor immune microenvironment (TIME) of gastric cancer (GC) remains unclear. Here, we report an increase of CD8 T cells infiltration in GC patients with ARID1A-mutation (MUT), which enhances sensitivity to ICIs.

Simultaneous assessment of cerebral glucose and oxygen metabolism and perfusion in rats using interleaved deuterium (H) and oxygen-17 (O) MRS.

Cerebral glucose and oxygen metabolism and blood perfusion play key roles in neuroenergetics and oxidative phosphorylation to produce adenosine triphosphate (ATP) energy molecules in supporting cellular activity and brain function. Their impairments have been linked to numerous brain disorders. This study aimed to develop an in vivo magnetic resonance spectroscopy (MRS) method capable of simultaneously assessing and quantifying the major cerebral metabolic rates of glucose (CMR) and oxygen (CMRO) consumption, lactate formation (CMR), and tricarboxylic acid (TCA) cycle (V); cerebral blood flow (CBF); and oxygen extraction fraction (OEF) via a single dynamic MRS measurement using an interleaved deuterium (H) and oxygen-17 (O) MRS approach.

Long-term efficacy and safety of stapokibart for moderate-to-severe atopic dermatitis: 52-week results from a phase 3 trial.

Background: Management of moderate-to-severe atopic dermatitis (AD) needs long-term therapy. Stapokibart is a humanized monoclonal antibody targeting interleukin-4 receptor α subunit (IL-4Rα), a shared receptor for IL-4 and IL-13 which are key pathogenic drivers of AD. In a pivotal phase 3 trial (NCT05265923), significant higher proportions of adult AD patients receiving stapokibart than placebo achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75; 66.

[Low-carbon Development Path of Ordos Based on LEAP Model].

To determine the low-carbon development path of Ordos, three scenarios （baseline scenario, low carbon scenario, and enhanced low carbon scenario） were constructed based on the LEAP model to forecast the energy demand and carbon emission in Ordos from 2020 to 2050 and to analyze the contribution of various policy initiatives to reduce carbon emission. The results showed that under the enhanced low carbon scenario, the energy demand in Ordos peaked at 52 million tons of standard coal equivalent in 2025 and decreased to 40 million tons of standard coal equivalent in 2050, and carbon emissions peaked at 163 million tons in 2025 and decreased to 16 million tons in 2050, which was 88% lower than that in 2020. Regarding emission reduction contribution, comparing the baseline scenario and the enhanced low-carbon scenario, the increase in renewable energy power generation installation, the reduction in energy consumption of terminal energy use, and the increase in terminal electrification rate contributed to the emission reductions of 43%, 25%, and 24%, respectively.

Habitual Coffee, Tea, and Caffeine Consumption, Circulating Metabolites, and the Risk of Cardiometabolic Multimorbidity.

Context: Cardiometabolic multimorbidity (CM) is an increasing public health concern. Previous observational studies have suggested inverse associations between coffee, tea, and caffeine intake and risks of individual cardiometabolic diseases; however, their associations with CM and related biological markers are unknown.

Methods: This prospective study involved 172 315 (for caffeine analysis) and 188 091 (tea and coffee analysis) participants free of any cardiometabolic diseases at baseline from the UK Biobank; 168 metabolites were measured among 88 204 and 96 393 participants.

Nurses' acceptance of nursing information systems: A multi-center cross-sectional study in China.

Background: In China, nursing information systems (NIS) implementation can face numerous barriers to acceptance, including the attitudes of potential users. However, few studies have evaluated this acceptance.

Objective: The aim of this study was to explain the acceptance of NIS utilizing a survey based on unified theory of acceptance and use of technology.

A Quantitative Comparison of P Magnetic Resonance Spectroscopy RF Coil Sensitivity and SNR between 7T and 10.5T Human MRI Scanners Using a Loop-Dipole P-H Probe.

In vivo phosphorus-31 (P) magnetic resonance spectroscopy (MRS) imaging (MRSI) is an important non-invasive imaging tool for studying cerebral energy metabolism, intracellular nicotinamide adenine dinucleotide (NAD) and redox ratio, and mitochondrial function. However, it is challenging to achieve high signal-to-noise ratio (SNR) P MRS/MRSI results owing to low phosphorus metabolites concentration and low phosphorous gyromagnetic ratio (γ). Many works have demonstrated that ultrahigh field (UHF) could significantly improve the P-MRS SNR.

Catalytic mechanism study of ATP-citrate lyase during citryl-CoA synthesis process.

ATP-citrate lyase (ACLY) is a critical metabolic enzyme and promising target for drug development. The structure determinations of ACLY have revealed its homotetramer states with various subunit symmetries, but catalytic mechanism of ACLY tetramer and the importance of subunit symmetry have not been clarified. Here, we constructed the free energy landscape of ACLY tetramer with arbitrary subunit symmetries and investigated energetic and conformational coupling of subunits during citryl-CoA synthesis process.

Mapping Knowledge Landscapes and Emerging Trends in AI for Dementia Biomarkers: Bibliometric and Visualization Analysis.

Background: With the rise of artificial intelligence (AI) in the field of dementia biomarker research, exploring its current developmental trends and research focuses has become increasingly important. This study, using literature data mining, analyzes and assesses the key contributions and development scale of AI in dementia biomarker research.

Objective: The aim of this study was to comprehensively evaluate the current state, hot topics, and future trends of AI in dementia biomarker research globally.

Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

Background: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials.

Objective: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis.

Methods: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks.

Construction of GSH-responsive polyethyleneimine-based delivery vector for effective gene transfection.

The rise of gene therapy has solved many diseases that cannot be effectively treated by conventional methods. Gene vectors is very important to protect and deliver the therapeutic genes to the target site. Polyethyleneimine (PEI) modified with mannitol could enhance the gene transfection efficiency reported by our group previously.

Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla.

Introduction: Nicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for measurement and imaging.

Development and validation of bioanalytical assays for the quantification of 9MW2821, a nectin-4-targeting antibody-drug conjugate.

We designed and developed 9MW2821, an anti-Nectin-4 antibody-drug conjugate (ADC) with an enzymatically cleavable valine-citrulline linker and monomethyl auristatin E (MMAE) as the payload. Four bioanalytical assays for total antibodies, conjugated antibodies, conjugated payload, and free payload were then developed and validated for the comprehensive evaluation of the multiple drug forms of 9MW2821. Specific sandwich enzyme-linked immunosorbent assays were used to quantify total antibodies and conjugated antibody, showing good drug-to-antibody ratio (DAR) tolerance.

Safety, tolerability, and pharmacokinetic of HY0721 in Chinese healthy subjects: A first-in-human randomized, double-blind, placebo-controlled dose escalation phase I study.

Background: HY0721 is a novel inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) for the treatment of acute ischemic stroke. This study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of single and multiple intravenous administration of HY0721 in Chinese healthy subjects.

Methods: The study enrolled 48 and 30 healthy volunteers in the single-ascending dose (SAD) cohort (20, 60, 120, 240, and 320 mg) and multiple-ascending dose (MAD) cohort (60, 120, and 160 mg/bid), respectively, to receive the corresponding dosage of HY0721 or placebo.

Construction of the pulmonary bio-adhesive delivery system of nintedanib nanocrystalline for effective treatment of pulmonary fibrosis.

Pulmonary fibrosis (PF) is a chronic, progressive, and fatal lung disease with a high mortality rate. Nintedanib, as a multi-tyrosine kinase inhibitor, is widely used as the first line drug for PF patients. However, only nintedanib oral formulations are used currently in clinic and show a low drug selectivity, significant first-pass effect and low bioavailability with 4.

Transgenerational increases in DNA methylation in Arabidopsis plants defective in active DNA demethylation.

Spontaneous gain or loss of DNA methylation occurs in plant and animal genomes, and DNA methylation changes can lead to meiotically stable epialleles that generate heritable phenotypic diversity. However, it is unclear whether transgenerational epigenetic stability may be regulated by any cellular factors. Here, we examined spontaneously occurring variations in DNA methylation in wild-type and mutant Arabidopsis plants that were propagated for ten generations from single-seed descent.

Exploring the activation mechanism of metabotropic glutamate receptor 2.

Homomeric dimerization of metabotropic glutamate receptors (mGlus) is essential for the modulation of their functions and represents a promising avenue for the development of novel therapeutic approaches to address central nervous system diseases. Yet, the scarcity of detailed molecular and energetic data on mGlu2 impedes our in-depth comprehension of their activation process. Here, we employ computational simulation methods to elucidate the activation process and key events associated with the mGlu2, including a detailed analysis of its conformational transitions, the binding of agonists, G protein coupling, and the guanosine diphosphate (GDP) release.

Multi-Responsive Peptide-Based Ultrathin Nanosheets Prepared by a Horizontal Monolayer Assembly.

In this study, peptide-based self-assembled nanosheets with a thickness of approximately 1 nm were prepared using a hierarchical covalent physical fabrication strategy. The covalent alternating polymerization of helical peptide E3 with an azobenzene (AZO) structure yielded copolymers CoP(E3-AZO), which physically self-assembled into ultrathin nanosheets in an unanticipated two-dimensional horizontal monolayer arrangement. This special monolayer arrangement enabled the thickness of the nanosheets to be equal to the cross-sectional diameter of a single linear copolymer, which is a rare phenomenon.