Sensing ceramides by CYSLTR2 and P2RY6 to aggravate atherosclerosis.

Recent evidence shows elevated circulating long-chain ceramide levels predict atherosclerotic cardiovascular disease (ASCVD) independently of cholesterol. Although targeting ceramide signaling may provide therapeutic benefits beyond the treatment of hypercholesterolemia, the underlying mechanism by which circulating ceramides aggravate ASCVD remains elusive. We examined whether circulating long-chain ceramides activate membrane G protein-coupled receptors (GPCRs) to exacerbate atherosclerosis.

Structure-based design of novel 2,4,5-trisubstituted pyrimidine derivatives as potent HIV-1 NNRTIs by exploiting the tolerant regions in NNTRIs binding pocket.

To promote the development of the new generation of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs), a series of novel 2,4,5-trisubstituted pyrimidine derivatives targeting the "tolerant region I″ and "tolerant region II" of NNRTI binding pocket (NNIBP) were designed through multi-site binding strategy. Among them, 13a was demonstrated with an improved potency against wild-type (WT) and a panel of mutant HIV-1 strains with EC values ranging from 0.0062 to 0.

The Global, Regional, and National Burden of Pancreatitis From 1990 to 2021: A Systematic Analysis for the Global Burden of Disease Study 2021.

Background: This study analyzes temporal trends of pancreatitis from 1990 to 2021 across 21 regions and 204 countries based on the Global Burden of Disease (GBD) database to inform prevention and treatment strategies.

Methods: Incidence, death, prevalence, and DALYs estimates for pancreatitis were derived from the GBD 2021, categorized by age, sex, and geographical location for the period 1990-2021. Mortality estimates were generated using the cause of death ensemble model.

Tetrahedral DNA-Enhanced Interparticle Rolling Machine for High-Efficiency Human Neutrophil Elastase SERS Ratiometric Sensing in Serum and Tissue.

The development of DNA rolling machines with high rolling efficiency for ratiometric biosensing is of great significance for the accurate diagnosis and evaluation of diseases. Herein, an interparticle DNA rolling machine constructed by well-oriented and ordered DNA nanorollers guided by tetrahedral DNA was exploited for high-efficiency lung tumor-related human neutrophil elastase (HNE) SERS ratiometric sensing. In this design, tetrahedral DNA with blocked DNAzyme was assembled on AuNPs to engineer well-oriented and ordered walking DNA nanorollers (WDNs) endowed with high collision efficiency and accessibility, significantly improving the reaction kinetics and rolling efficiency.

Application of autologous platelet rich plasma in Sun's procedure for acute type A aortic dissection under moderate hypothermia.

Background: Coagulopathy and inflammatory response are the intractable complication during Sun's procedure for type A aortic dissection (AAD). This study aims to investigate the efficacy of autologous platelet rich plasma (aPRP) on the patients undergoing Sun's procedure under moderate hypothermia.

Methods: A total of 372 AAD patients who underwent Sun's procedure under moderate hypothermia were divided into aPRP group (aPRP was separated before heparinization and transfused after protamine neutralization) and Non-aPRP group (without aPRP apheresis).

Alterations in brain function in patients with post-stroke cognitive impairment: a resting-state functional magnetic resonance imaging study.

Background: Cognitive impairment is a common dysfunction following stroke, significantly affecting patients' quality of life. Studies suggest that post-stroke cognitive impairment (PSCI) may be related to neural activity in specific brain regions. However, the neural mechanisms remain to be further explored.

Ergothioneine attenuates psoriasis symptoms through modulation of M1/M2 macrophage polarisation via the NF-κB/JAK-STAT3 pathway.

Introduction: The underlying cause of psoriasis, a chronic inflammatory skin condition driven by an immune response, remains a topic of active investigation and is not yet fully elucidated. Recent studies have revealed that ergothioneine, a small molecule sulfur-containing histidine derivative that can be ingested from the daily diet and accumulated in the body, exhibits antioxidant capacity that is comparable to that of glutathione. Nevertheless, there is a paucity of empirical data concerning the precise impact of ergothioneine in the context of anti-inflammatory processes, particularly in the context of psoriasis.

Design and biochemical evaluation of 2-cyclopropyl-thioureidobenzamide (CP-TBA) derivatives as potent HBV capsid assembly modulators targeting a novel binding site.

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach in the treatment of chronic HBV infection. In the quest for effective therapeutics against chronic Hepatitis B virus (HBV) infection, we employed a novel binding site occupancy strategy to develop novel 2-cyclopropyl-thioureidobenzamide (CP-TBA) derivatives as potent HBV CAMs. Our diversity modification approach led to the identification of compound 17e, which demonstrated remarkable anti-HBV activity with an EC of 0.

Nanoscale distribution of bioactive ligands on biomaterials regulates cell mechanosensing through translocation of actin into the nucleus.

Cells respond to adhesive ligands such as arginine-glycine-aspartate (RGD) through integrins, which regulates cellular activities via influencing cytoskeleton assembly. Herein, we report that the nanoscale distribution of active ligands on biomaterials regulates cells through not only cytoplasmic tension but also nuclear tension. This is particularly related to translocation of actin into nucleus and highlighted in our interpretation of an "abnormal" phenomenon that large RGD nanospacing (>70 nm) disassembles integrin clusters, inhibits cell adhesion, but promotes osteogenic differentiation of mesenchymal stem cells.

Neutrophils: a new target for postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a prevalent complication affecting the central nervous system after surgery, manifesting as a decline in cognitive abilities, particularly common among elderly patients. Surgical stress and anesthesia can activate systemic inflammation, prompting immune cells, including neutrophils, to infiltrate the brain, thereby triggering neuroinflammation and resulting in cognitive impairment. Neutrophils, as crucial effector cells in innate immunity, have been increasingly recognized in recent years for their significant role in the pathogenesis of POCD due to their vital function in inflammatory responses.

tumor cell engineering reverses immune escape to enhance immunotherapy effect.

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared.

Case Report: Percoronary device occlusion of right coronary artery fistula into left ventricle in an infant.

A 4-month-old male infant (weight 6 kg, height 67 cm) with heart failure was diagnosed with an isolated 8.9 mm right coronary artery fistula draining into the left ventricle (LV), identified via transthoracic echocardiography and computed tomography angiography. The large, tortuous, and aneurysmal fistula was treated using a minimally invasive percoronary approach, avoiding the high risks of surgery and the challenges of percutaneous closure.

Epidermolysis Bullosa with Esophageal Complications and Co-Infection with : A Case Report.

Epidermolysis bullosa (EB) is a group of rare genetic skin disorders that are hereditary and heterogeneous, characterized by skin and mucosal fragility and blister formation, often induced by minimal trauma. Esophageal complications represent a significant extracutaneous manifestation of EB. The lack of standardized diagnostic and therapeutic guidelines of EB with esophageal complications contributes to inconsistent management and a higher susceptibility to recurrence.

Roles of Gut Microbiota Metabolites and Circadian Genes in the Improvement of Glucose and Lipid Metabolism in KKAy Mice by Theabrownin.

Theabrownin (TB), a prominent pigment in fermented dark tea, exhibits beneficial effects on adiposity reduction. Our study revealed that TB derived from Fu brick tea significantly lowered fasting blood glucose levels and insulin resistance in obese/diabetic KKAy mice. Furthermore, TB demonstrated potent anti-inflammatory effects in the liver, adipose tissue, and intestines, as well as enhancing intestinal integrity.

Engineered MXene Biomaterials for Regenerative Medicine.

MXene-based materials have attracted significant interest due to their distinct physical and chemical properties, which are relevant to fields such as energy storage, environmental science, and biomedicine. MXene has shown potential in the area of tissue regenerative medicine. However, research on its applications in tissue regeneration is still in its early stages, with a notable absence of comprehensive reviews.

E3 ubiquitin ligase RNF128 promotes Lys63-linked polyubiquitination on SRB1 in macrophages and aggravates atherosclerosis.

Macrophage-derived foam cell formation is the hallmark of atherosclerotic plaques prominently attributed to excessive lipid uptake and metabolic disorders. As a classic membrane-localized ubiquitin ligase, the role of RNF128 in atherosclerosis remains unknown. We discover that RNF128 is specifically expressed in macrophages of the lipid core based on single-cell RNA sequencing data and persistent hyperlipidemia induces the high expression of RNF128 in macrophages.

Developing a framework for estimating comorbidity burden of inpatient cancer patients based on a case study in China.

Inpatient cancer patients often carry the dual burden of the cancer itself and comorbidities, which were recognized as one of the most urgent global public health issues to be addressed. Based on a case study conducted in a tertiary hospital in Shandong Province, this study developed a framework for the extraction of hospital information system data, identification of basic comorbidity characteristics, estimation of the comorbidity burden, and examination of the associations between comorbidity patterns and outcome measures. In the case study, demographic data, diagnostic data, medication data and cost data were extracted from the hospital information system under a stringent inclusion and exclusion process, and the diagnostic data were coded by trained coders with the 10th revision of the International Classification of Diseases (ICD-10).

Changing epidemiology of leptospirosis in China from 1955 to 2022.

Background: Leptospirosis, a zoonotic disease caused by pathogenic species of the genus Leptospira, is an important public health concern globally. Leptospirosis has been notifiable under statute in China since 1955, and its epidemiological characteristics have evolved during near 70 years. This study aimed to describe the spatial and temporal patterns and demographic characteristics of leptospirosis from 1955 to 2022 in China, and explore the possible factors that influence leptospirosis transmission risk.

Dexmedetomidine exerts a neuroprotective effect by inhibiting Th1 cells and actuating Tregs in postoperative inflammation: Molecular structure and mechanism of action of STAT1 protein.

Dexmedetomidine, an α2-adrenergic receptor agonist, has received attention in recent years for its role in reducing perioperative inflammatory response and neuroprotection. The aim of this study was to investigate how dexmedetomidine exerts neuroprotective effects by inhibiting Th1 cells and activating regulatory T cells (Tregs), and to analyze the molecular structure of STAT1 protein and its mechanism in this process. The number and function of Th1 cells and Tregs in peripheral blood and spleen were analyzed following treatment with dexmedetomidine.

Prevalence and distribution of cervical facet joint degeneration in patients with cervical spondylotic myelopathy without/with instability and ossification of the posterior longitudinal ligament-a comparative study.

Objectives: To compare the prevalence and distribution characteristics of the grade of cervical facet joint degeneration (FJD) among patients with cervical spondylotic myelopathy without/with instability (CSM/CSMI), and ossification of the posterior longitudinal ligament (OPLL). Furthermore, to compare the differences in sagittal parameters and preoperative clinical symptoms between patients with mild and severe FJD.

Methods: The study enrolled 253 patients who underwent surgical treatment at our institution (90 CSM, 79 CSMI, 84 OPLL).

Frequency-dependent changes in the amplitude of low-frequency fluctuations in post stroke apathy: a resting-state fMRI study.

Background: Apathy is a prevalent psychiatric condition after stroke, affecting approximately 30% of stroke survivors. It is associated with slower recovery and an increased risk of depression. Understanding the pathophysiological mechanisms of post stroke apathy (PSA) is crucial for developing targeted rehabilitation strategies.

Gut microbiota in treating inflammatory digestive diseases: Current challenges and therapeutic opportunities.

Accumulating evidence indicates that the gut microbiota is intricately involved in the initiation and progression of human diseases, forming a multidirectional regulatory axis centered on intestinal microbiota. This article illustrates the challenges in exploring the role of the gut microbiota in inflammatory digestive diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and inflammatory bowel disease (IBD), and summarizes the existing microbiome-focused treatment strategies (probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and bacteriophages therapy), emerging technologies (gut microbiome-on-a-chip and artificial intelligence), as well as possible future research directions. Taken together, these therapeutic strategies and technologies present both opportunities and challenges, which require researchers and clinicians to test the rationality and feasibility of various therapeutic modalities in continuous practice.

Synergistic restoration of spinal cord injury through hyaluronic acid conjugated hydrogel-polydopamine nanoparticles combined with human mesenchymal stem cell transplantation.

Spinal cord injury (SCI) is a devastating disease with limited treatment options due to the restricted regenerative capacity of the central nervous system. The accumulation of reactive oxygen species (ROS) and inadequate endogenous neural stem progenitor cells (eNSPCs) in the lesion site exacerbates neurologic deficits and impedes motor function recovery. We have developed a temperature-responsive hyaluronic acid conjugated hydrogel-polydopamine nanoparticles (PDA NPs) combined with human mesenchymal stem cell (hMSCs) transplantation, denoted as H-P-M hydrogel.

A Semi-Interpenetrating Network Hydrogel with Excellent Photothermal Antibacterial and ROS Scavenging Activities for MRSA-Infected Wounds.

The prolonged infection of bacteria at the wound site may lead to serious physical problems. Herein, a multifunctional macroporous hydrogel with superior photothermal antibacterial and ROS scavenging activity (denoted as M-XG gel) was designed for the treatment of MRSA-infected wounds. The M-XG gels are composed of embedding Prussian blue nanoparticles (PBNPs) as photothermal converters and chelating ferric ions with xanthan gum (XG) and dopamine (DA) to form a semipermeable network.

Genomic diversity of mcr-carrying plasmids and the role of type IV secretion systems in IncI2 plasmids conjugation.

The rapid dissemination of colistin resistance via mcr-carrying plasmids (pMCRs) poses a significant public health challenge. This study examined the genomic diversity and conjugation mechanisms of pMCRs, with a particular focus on the role of type IV secretion systems (T4SS) in IncI2 plasmids. The 868 complete plasmid sequences revealed various replicon types of pMCRs, with IncI2 as the primary epidemic type, and the co-transfer risk of multidrug resistance genes associated with IncHI2.