Nucleotide-dependent conformational changes direct peptide export by the transporter associated with antigen processing.

The transporter associated with antigen processing (TAP) delivers peptide antigens from the cytoplasm into the endoplasmic reticulum (ER) for loading onto major histocompatibility complex class I (MHC-I) molecules. To examine the mechanisms of peptide transport and release into the ER, we determined cryo-electron microscopy structures of the human TAP heterodimer in multiple functional states along the transport cycle. In the inward-facing conformation, when the peptide translocation cavity within the TAP heterodimer is exposed to the cytosol, ATP binding strengthened intradomain assembly.

Structure of CFTR bound to (R)-BPO-27 unveils a pore-blockage mechanism.

Hyperactivation of the cystic fibrosis transmembrane conductance regulator (CFTR) contributes to secretory diarrhea, a major cause of pediatric mortality worldwide, and autosomal dominant polycystic kidney disease (ADPKD), the most common inherited cause of end-stage renal disease. Selective CFTR inhibition is a potential therapeutic strategy, with (R)-BPO-27 emerging as a promising candidate. Here, we present a cryo-EM structure of CFTR bound to (R)-BPO-27 at an overall resolution of 2.

Protamine-Facilitated Same-Day Discharge Following Distal Transradial Angiography.

Background: Despite growing adoption of distal transradial approach (dTRA), data on same-day discharge with protamine-assisted hemostasis following coronary angiography (CAG) remain limited. This pilot study investigated its safety and feasibility.

Methods: From January 2022 to September 2024, a total of 34 patients who were discharged on the same-day after elective CAG via dTRA in our center were included, as well as 34 matched patients who underwent CAG via standard transradial approach (sTRA) during the same period.

Nucleotide-dependent conformational changes direct peptide export by the transporter associated with antigen processing.

The transporter associated with antigen processing (TAP) is essential for adaptive immunity, delivering peptide antigens from the cytoplasm into the endoplasmic reticulum (ER) for loading onto MHC-I molecules. Previous studies have revealed the mechanism by which TAP selectively binds peptides while allowing for sequence diversity, but how the bound peptides are transported and released into the ER is not yet fully understood. Here, we report cryo-electron microscopy structures of human TAP in multiple functional states along the transport cycle.

A Structural Atlas of TAP Inhibition by Herpesviruses and Poxviruses.

In the host-pathogen arms race, herpesviruses and poxviruses encode proteins that sabotage the transporter associated with antigen processing (TAP), thereby suppressing MHC-I antigen presentation and enabling lifelong infection. Of the five known viral TAP inhibitors, only the herpes simplex virus protein ICP47 has been structurally resolved. We now report cryo-electron microscopy structures of TAP in complex with the remaining four: BNLF2a (Epstein-Barr virus), hUS6 (human cytomegalovirus), bUL49.

Stereoselective Synthesis of High -1,4-Regularity Polyisoprene via Controlled Polymerization with Amidinate Rare-Earth Metal Catalysts.

Synthetic -1,4-polyisoprene is a crystalline thermoplastic with wide applications, but catalysts enable one to achieve high-selectivity and living polymerization remain scarce. In this work, two novel nonsymmetric amidine proligands (2,6-MeCH)NC(Ph)NH(CH-2-OMe) () and (2,6-MeCH)NC(Ph)NH(CHCH-2-OMe) () were prepared. Amine-elimination reactions between and one equivalent of Ln[N(SiHMe)](THF) afforded the amidinate rare-earth metal bis(silylamide) complexes [(2,6-MeCH)NC(CH)N(CH-2-OMe)]Ln[N(SiHMe)](THF) (Ln = Sc, = 0 (); Ln = Y, = 1 (); Ln = Nd, = 1 (); Ln = Sm, = 1 ()) and [(2,6-MeCH)NC(CH)N(CHCH-2-OMe)]Sc[N(SiHMe)] ().

Amine-Bridged Bis(phenolate) Aluminum Complexes as High-Efficiency Catalysts for Controlled Polymerization of Trimethylene Carbonate.

Poly(trimethylene carbonate) (PTMC) is currently attracting increasing attention due to its notable biocompatibility and biodegradability. High-molecular-weight PTMCs would find a wider range of practical applications; however, their preparation methods are still limited. In this work, a series of aluminum complexes supported by amine-bridged bis(phenolate) ligands were synthesized and employed as the catalysts for TMC polymerization.

GABA Receptor: Structure, Biological Functions, and Therapy for Diseases.

Gamma-aminobutyric acid (GABA) B receptors (GABARs) that acts slowly and maintains the inhibitory tone are versatile regulators in the complex nervous behaviors and their involvement in various neuropsychiatric disorders, such as anxiety, epilepsy, pain, drug addiction, and Alzheimer's disease. Additional study advances have implied the crucial roles of GABARs in regulating feeding-related behaviors, yet their therapeutic potential in addressing the neuropsychiatric disorders, binge eating, and feeding-related disorders remains underutilized. This general review summarized the physiological structure and functions of GABAR, explored the regulation in various psychiatric disorders, feeding behaviors, binge eating, and metabolism disorders, and fully discussed the potential of targeting GABARs and its regulator-binding sites for the treatment of different psychiatric disorders, binge eating and even obesity.

Cross-Cultural Validation and Application of the EDE-Q 6.0 for Screening and Assessment of Eating Disorders in Chinese Females.

Objective: This study aims to evaluate the cross-cultural validity and utility of the Chinese version of the Eating Disorder Examination Questionnaire 6.0 (EDE-Q 6.0) as a screening and assessment tool for eating disorders (EDs) among Chinese females.

[Pharmacokinetics and anti-inflammatory activity of cannabidiol/ γ-polyglutamic acid-g-cholesterol nanomicelles].

In this study, the pharmacokinetic characteristics and tissue distribution of cannabidiol(CBD)/γ-polyglutamic acid-g-cholesterol(γ-PGA-g-CHOL) nanomicelles [CBD/(γ-PGA-g-CHOL)NMs] were investigated by pharmacokinetic experiments, and the effect of CBD/(γ-PGA-g-CHOL)NMs on the lipopolysaccharide(LPS)-induced inflammatory damage of cells was evaluated by cell experiments. CBD/(γ-PGA-g-CHOL)NMs were prepared by dialysis. The CBD concentrations in the plasma samples of male SD rats treated with CBD and CBD/(γ-PGA-g-CHOL)NMs were investigated, and the pharmacokinetic parameters were calculated and compared.

Altered Sensorimotor Striatal Network Connectivity in Women With Anorexia Nervosa.

Objective: Anorexia nervosa (AN) is associated with disturbances in reward processing, cognitive control, and body image perception, implicating striatal dysfunction. Evidence suggests that underweight may modulate brain function in AN. We aimed to investigate whole-brain resting-state functional connectivity (rsFC) of the striatum in patients with AN while controlling for the acute effects of underweight.

Celiac Disease, Gluten-Free Diet, and Eating Disorders: From Bench to Bedside.

Celiac disease (CD) and eating disorders (EDs) are complex chronic conditions in adolescents, sharing symptoms such as weight change, malnutrition, and gastrointestinal symptoms. CD, an autoimmune disorder triggered by gluten ingestion, is managed through a strict gluten-free diet that can unintentionally foster disordered eating behaviors due to dietary restrictions. Conversely, EDs may mask and complicate CD symptoms, leading to diagnostic delays and treatment challenges.

Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2.

Multidrug resistance-associated protein 2 (MRP2) is an ATP-powered exporter important for maintaining liver homeostasis and a potential contributor to chemotherapeutic resistance. Using cryogenic electron microscopy (cryo-EM), we determine the structures of human MRP2 in three conformational states: an autoinhibited state, a substrate-bound pre-translocation state, and an ATP-bound post-translocation state. In the autoinhibited state, the cytosolic regulatory (R) domain plugs into the transmembrane substrate-binding site and extends into the cytosol to form a composite ATP-binding site at the surface of nucleotide-binding domain 2.

Effect of high sensitivity C-reactive protein on uric acid-related cardiometabolic risk in patients with coronary artery disease-a large multicenter prospective study.

Although serum uric acid (SUA) is a risk factor for cardiometabolic outcome, but it remains unclear which patients with coronary artery disease (CAD) benefit the most from SUA lowering therapy (ULT). The association of SUA level, systemic inflammation and cardiometabolic risk is still unclear. The current study is aimed to examine whether SUA-associated cardiometabolic risk is modulated by systemic inflammation in CAD patients.

The structures of protein kinase A in complex with CFTR: Mechanisms of phosphorylation and noncatalytic activation.

Protein kinase A (PKA) is a key regulator of cellular functions by selectively phosphorylating numerous substrates, including ion channels, enzymes, and transcription factors. It has long served as a model system for understanding the eukaryotic kinases. Using cryoelectron microscopy, we present complex structures of the PKA catalytic subunit (PKA-C) bound to a full-length protein substrate, the cystic fibrosis transmembrane conductance regulator (CFTR)-an ion channel vital to human health.

[Transepithelial transport in vivo and in vitro and anti-inflammatory activity of cannabidiol].

This study used Caco-2 cells and normal rats to investigate the in vitro absorption characteristics and in vivo pharmacokinetic characteristics of cannabidiol(CBD) and explore the anti-inflammatory mechanism of CBD. The safe concentration range of CBD was determined by the CCK-8 assay, and then the effects of time, concentration, temperature, endocytosis inhibitors, and transport inhibitors on the transepithelial absorption and transport of CBD were assessed. The blood drug concentration was measured at different time points after oral administration in rats for pharmacokinetic profiling, and the pharmacokinetic parameters were calculated.

The role of residual inflammatory risk and LDL cholesterol in patients with in-stent restenosis undergoing percutaneous coronary intervention.

Background: To evaluate the relationships between residual inflammatory risk [assessed by high-sensitivity C-reactive protein (hsCRP)], residual cholesterol risk [assessed by low-density lipoprotein cholesterol (LDL-C)] and clinical outcomes among patients who underwent percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) lesions.

Methods: Between January 2017 and December 2018, a total of 2079 patients who underwent PCI for ISR were consecutively enrolled. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization.

Vasculogenic mimicry triggers early recidivation and resistance to adjuvant therapy in esophageal cancer.

Objective: To investigate the impact of vasculogenic mimicry (VM) and postoperative adjuvant therapy on the prognosis and survival of patients with esophageal squamous cell carcinoma (ESCC), as well as to assess whether VM affects the clinical benefit of postoperative adjuvant therapy.

Methods: This single-center retrospective analysis included patients who underwent radical surgery for ESCC, which was documented in the medical record system. The presence or absence of VM in surgical specimens was determined using double staining with PAS/CD31.

Hydroborative Depolymerization of Polyesters and Polycarbonates to Diols Catalyzed by Heterogeneous Lanthanum Materials La(CHCHNMe-)@SBA-15.

Chemical recycling is a promising strategy to establish a circular plastic economy, and it is still in an early stage of development. In this work, the reductive depolymerization of polyesters and polycarbonates into their corresponding borylated alcohols promoted by heterogeneous lanthanum materials was described. Grafting the easily accessible lanthanum tris(aminobenzyl) complex La(CHCHNMe-) () onto the partially dehydroxylated silica support SBA-15 (SBA-15 or SBA-15) gave the inorganic-organic hybrid materials @SBA-15 and @SBA-15.

Practices and outcomes of rotational atherectomy in China: The Rota China registry.

Background: Rotational atherectomy (RA) remains an integral tool for the treatment of severe coronary calcified lesions despite emergence of newer techniques. We aimed to evaluate the contemporary clinical practices and outcomes of RA in China.

Methods: The Rota China Registry (NCT03806621) was an investigator-initiated, prospective, multicenter registry based on China Rota Elite Group.

Preparation, optimisation, and properties of O-carboxymethyl chitosan-g-cholesterol succinic acid monoester polymer nanomicelles.

Polymer nanomicelles have the advantages of small particle size, improved drug solubility, retention effect and enhanced permeability, so they can be used in the treatment of tumour diseases. The aim of this study was to prepare and optimise a nanomicelle which can improve the solubility of insoluble drugs. Firstly, the carboxyl group of cholesterol succinic acid monoester was grafted with the side chain amino group of O-carboxymethyl chitosan-g-cholesterol succinic acid monoester (CCMC), and its structure was characterized by fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (H-NMR).

COE targets EphA2 to inhibit vasculogenic mimicry formation induced by hypoxia in hepatocellular carcinoma.

Background: Vasculogenic Mimicry (VM) can reduce the efficacy of anti-angiogenesis and promote distant metastasis in hepatocellular carcinoma (HCC). Our previous studies have found that extract (COE) can inhibit the VM formation in HCC by reducing EphA2 expression. However the underlying mechanism related to EphA2 in VM formation is unclear.

The influence of service performance in China's sci-tech commissioner system: Using social network analysis and interpretable machine learning.

The Sci-Tech Commissioner System (SCS) is a result of exploratory efforts by the Chinese government to use science and technology to strengthen the agricultural sector. Social network analysis (SNA) and machine learning (ML) techniques make it feasible to assess the service performance in China's SCS by using indicators such as group types and structure features. In this study, SNA and a clustering algorithm were employed to categorize service group types of sci-tech commissioners.