Ultraelastic Nanomembrane with Controllable Hotspots and Enhanced Photon Recovery for Single-Molecule Surface-Enhanced Raman Scattering.

The controlled assembly of noble metal nanomaterials at water-oil interfaces holds significant potential for enhancing the sensitivity and stability of surface-enhanced Raman scattering (SERS) technology. However, developing highly efficient nanomaterial assembly techniques to create structures with controllable plasmonic hotspots and easily transferable functionalities remains a critical challenge. Herein, we propose a hydrophobic modification-enhanced float assembly strategy to fabricate an ultraelastic nanomembrane (UE-nanomembrane) by reducing adsorption kinetic barriers.

A Woundplast of Hydrogel Microneedles with ATP-Responsive Therapeutic Logic for Bacteria-Infected Wound Healing.

To reduce the overuse of antibiotics, on-demand antibiotic administration guided by rapid infection assessment is of particular importance. In this study, we present a portable, multifunctional hydrogel microneedle (MN) woundplast capable of real-time monitoring of wound adenosine triphosphate (ATP) levels and simultaneous antibacterial therapy. By leveraging the aggregation-induced emission effect, metal-organic frameworks (MOFs) coencapsulating gold nanoclusters (AuNCs) and vancomycin are integrated into the MN tips, where ATP-Zn interactions enable selective ATP recognition and quantification across 0-5 mM.

A Novel Small Molecule ITK Inhibitor Suppresses Th2/Th17 Differentiation and Attenuates Airway Inflammation in a Mouse Model of HDM-Induced Asthma.

Interleukin (IL)-2-inducible T cell kinase (ITK) is essential for T cell receptor (TCR) signalling and plays a pivotal role in asthma pathogenesis. Thus, ITK inhibitors have therapeutic potential in T cell-derived allergic airway inflammation. Nevertheless, no ITK inhibitors are currently approved for asthma treatment, warranting the need to excavate potent small-molecule ITK inhibitors.

Disrupting bile acid metabolism by suppressing Fxr causes hepatocellular carcinoma induced by YAP activation.

Disruption of bile acid (BA) metabolism causes various liver diseases including hepatocellular carcinoma (HCC). However, the underlying molecular mechanism remains elusive. Here, we report that BA metabolism is directly controlled by a repressor function of YAP, which induces cholestasis by altering BA levels and composition via inhibiting the transcription activity of Fxr, a key physiological BA sensor.

Characteristics and filtering of low-frequency artificial short deletion variations based on nanopore sequencing.

Background: Nanopore sequencing is characterized by high portability and long reads, albeit accompanied by systematic errors causing short deletions. Few tools can filter low-frequency artificial deletions, especially in single samples.

Results: To solve this problem, we first synthesized or purchased 17 DNA/RNA standards for nanopore sequencing with R9 and R10 flowcells to obtain benchmarking datasets.

Low-dose quinine targets KCNH6 to potentiate glucose-induced insulin secretion.

Insulin secretion is mainly regulated by two electrophysiological events, depolarization initiated by the closure of adenosine triphosphate (ATP)-sensitive K+ (KATP) channels and repolarization mediated by K+ efflux. Quinine, a natural component commonly used for the treatment of malaria, has been reported to directly stimulate insulin release and lead to hypoglycemia in patients during treatment through inhibiting KATP channels. In this study, we verified the insulinotropic effect of quinine on the isolated mouse pancreatic islets.

TEC-mediated tRF-31R9J regulates histone lactylation and acetylation by HDAC1 to suppress hepatocyte ferroptosis and improve non-alcoholic steatohepatitis.

Background: Tectorigenin (TEC) is a monomer of anthocyanin, which we found exhibits hepatoprotective effects. tRNA-derived fragments (tRFs) and ferroptosis play important roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). Recent discoveries have revealed that histone lactylation and acetylation play a crucial role in connecting cellular metabolism and epigenetic regulation through post-translational modification of histones.

The association between vitamin D deficiency and childhood obesity and its impact on children's serum calcium, alkaline phosphatase, and bone age.

Objective: The research aimed to investigate the Association between Vitamin D deficiency and childhood obesity and its Impact on children's serum calcium, alkaline Phosphatase, and bone Age.

Methods: The study analyzed clinical data from 159 school-aged children who underwent medical examinations. The children were divided into a 25-(OH)D3 deficiency group and a non-25-(OH)D3 deficiency group based on their serum 25-hydroxy Vitamin D3 levels.

Discovering novel Cathepsin L inhibitors from natural products using artificial intelligence.

Cathepsin L (CTSL) is a promising therapeutic target for metabolic disorders. Current pharmacological interventions targeting CTSL have demonstrated potential in reducing body weight gain, serum insulin levels, and improving glucose tolerance. However, the clinical application of CTSL inhibitors remains limited.

Tectorigenin improves metabolic dysfunction-associated steatohepatitis by down-regulating tRF-3040b and promoting mitophagy to inhibit pyroptosis pathway.

Tectorigenin (TEC) as a plant extract has the advantage of low side effects on metabolic dysfunction-associated steatohepatitis (MASH) treatment. Our previous study have shown that tRNA-derived RNA fragments (tRFs) associated with autophagy and pyroptosis in MASH, but whether TEC can mitigate MASH through tRFs-mediated mitophagy is not fully understood. This study aims to investigate whether TEC relies on tRFs to adjust the crosstalk of hepatocyte mitophagy with pyroptosis in MASH.

Generation and characterization of mature hepatocyte organoids for liver metabolic studies.

Hepatocyte organoids (HOs) generated in vitro are powerful tools for liver regeneration. However, previously reported HOs have mostly been fetal in nature with low expression levels of metabolic genes characteristic of adult liver functions, hampering their application in studies of metabolic regulation and therapeutic testing for liver disorders. Here, we report development of novel culture conditions that combine optimized levels of triiodothyronine (T3) with the removal of growth factors to enable successful generation of mature hepatocyte organoids (MHOs) of both mouse and human origin with metabolic functions characteristic of adult livers.

Establishment and application of a reverse dot blot assay for 13 mutations of hearing-loss genes in primary hospitals in China.

Background: Hearing loss is a common sensorineural dysfunction with a high incidence in China. Although genetic factors are important causes of hearing loss, hearing-related gene detection has not been widely adopted in China.

Objective: Establishing a rapid and efficient method to simultaneously detect hotspot hearing loss gene mutations.

Risk factors of post-operative diarrhoea in patients with pancreatic cancer after neoadjuvant chemotherapy: A retrospective cohort study.

Background: Post-operative diarrhoea is a common adverse event after pancreatic surgery. While the risk factors for this condition have been identified, the increasing trend of administering chemotherapy before surgery might change these factors. This study aimed to identify the risk factors of post-operative diarrhoea in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent neoadjuvant chemotherapy.

HERC5-catalyzed ISGylation potentiates cGAS-mediated innate immunity.

The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) is essential to elicit type I interferon cascade response; thus, the activity of cGAS must be strictly regulated to boost the antiviral innate immunity. Here, we report that cGAS is responsible for the DNA-induced ISG15 conjugation system. The E3 HERC5 catalyzes the ISGylation of cytoplasmic cGAS at lysine 21, 187, 219, and 458, whereas Ubl carboxy-terminal hydrolase 18 removes the ISGylation of cGAS.

KCNH6 is essential for insulin secretion by regulating intracellular ER Ca store.

Appropriate Ca concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca signal, serves significant roles in physiological function of pancreatic β cells. To maintaining ER homeostasis, Ca movement across the ER membrane is always accompanied by a simultaneous K flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca influx.

All-potassium channel CRISPR screening reveals a lysine-specific pathway of insulin secretion.

Objective: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of K depolarization and K repolarization.

Effects of Hawthorn Flavonoids on Intestinal Microbial Community and Metabolic Phenotype in Obese Rats.

Obesity (OB) is a prevalent metabolic disorder. With the advancement of the economy, the prevention and treatment of obesity is a big problem for the global community. The methods to lose weight include exercise, diet, medicine, and surgery.

DNMT1 mediates the disturbed flow-induced endothelial to mesenchymal transition through disrupting β-alanine and carnosine homeostasis.

Increasing evidence suggests that hemodynamic disturbed flow induces endothelial dysfunction via a complex biological process so-called endothelial to mesenchymal transition (EndoMT). Recently, DNA methyltransferases (DNMTs) was reported as a key molecular mediator to promote EndoMT. Our understanding of how DNMTs, particularly the maintenance DNMTs, DNMT1, coordinate EndoMT is still lacking.

Risk factors and nomogram predictive model of surgical site infection in closed pilon fractures.

Objectives: In this study, we try to investigate the risk factors of postoperative surgical site infection (SSI) in closed pilon fractures and establish a nomogram prediction model.

Methods: From January 2012 to June 2021, 516 closed pilon fracture patients were included in this study. Of these, 387 patients were randomly assigned to the training group and 129 patients were assigned to the validation group (3:1).

Depressive symptom trajectories and new-onset arthritis in a middle-aged and elderly Chinese population.

Objective: Previous studies reported that depression was associated with a high risk of arthritis. However, the effect of different long-term depressive symptom trajectory patterns on the risk of arthritis has not been evaluated. Our study aimed to explore the association between depressive symptom trajectories and the risk of arthritis.