The safety, tolerability, pharmacokinetics and pharmacodynamics of an optimized dual GLP-1/GIP receptor agonist (BGM0504) in healthy volunteers: A dose-escalation Phase I study.

Objective: Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers.

Methods: A randomized, double-blind, placebo-controlled and dose-escalation Phase I study was conducted as follows: a single dose (2.

A Clinical Drug as the Three-Photon Fluorescence Probe for In Vivo Microscopic Imaging of Mouse Kidney.

Three-photon fluorescence (3PF) microscopy encounters significant challenges in biological research and clinical applications, primarily due to the limited availability of high-performance probes. We took a shortcut by exploring the excellent 3PF property of berberine hydrochloride (BH), a clinically utilized drug derived from the traditional Chinese medicine, Coptis. Capitalizing on its renal metabolism characteristics, we employed BH for in vivo 3PF microscopic imaging of the mouse kidney.

Temporal and Spatial Metabolic Shifts Revealing the Transition from Ulcerative Colitis to Colitis-Associated Colorectal Cancer.

Patients with ulcerative colitis (UC) have a higher risk of developing colorectal cancer (CRC), however, the metabolic shifts during the UC-to-CRC transition remain elusive. In this study, an AOM-DSS-induced three-stage colitis-associated colorectal cancer (CAC) model is constructed and targeted metabolomics analysis and pathway enrichment are performed, uncovering the metabolic changes in this transition. Spatial metabolic trajectories in the "normal-to-normal adjacent tissue (NAT)-to-tumor" transition, and temporal metabolic trajectories in the "colitis-to-dysplasia-to-carcinoma" transition are identified through K-means clustering of 74 spatially and 77 temporally differential metabolites, respectively.

Two-dimensional inverse double sandwich CoB: strain-induced non-magnetic to ferromagnetic transition.

A full-scale structural search was performed using density functional theory calculations and a universal structural prediction evolutionary algorithm. This produced a lowest energy two-dimensional (2D) CoB structure. The CoB-1 global minimum structure has unusual inverse double sandwich features.

Programmed Transformation of Osteogenesis Microenvironment by a Multifunctional Hydrogel to Enhance Repair of Infectious Bone Defects.

Repair of infectious bone defects remains a serious problem in clinical practice owing to the high risk of infection and excessive reactive oxygen species (ROS) during the early stage, and the residual bacteria and delayed Osseo integrated interface in the later stage, which jointly creates a complex and dynamic microenvironment and leads to bone non-union. The melatonin carbon dots (MCDs) possess antibacterial and osteogenesis abilities, greatly simplifying the composition of a multifunctional material. Therefore, a multifunctional hydrogel containing MCDs (GH-MCD) is developed to meet the multi-stage and complex repair needs of infectious bone injury in this study.

Phase Transition Process of Graphite to Diamond Induced by Monodispersed Tantalum Atoms at Ordinary Pressure.

The transformation of graphite into diamond (2-10 nm) at ordinary pressure by monodispersed Ta atoms was recently reported, while the effects of Ta concentration on the transition process remain obscure. Here, by regulating the Ta wire treatment time, as well as the annealing time and temperature, larger diamond grians (5-20 nm) are successfully synthesized, and the transition process of graphite to diamond is revealed to vary with Ta concentration. Specifically, short Ta wire treatments (5-10 min) induce graphite to form a "circle" structure and transforms into diamond directly after annealing.

A Highly Bioactive Organic-Inorganic Nanoparticle for Activating Wnt10b Mediated Osteogenesis by Specifically Anchor CCN3 Protein.

The rapid and efficient bone regeneration is still in unsatisfactory outcomes, demonstrating alternative strategy and molecular mechanism is necessary. Nanoscale biomaterials have shown some promising results in enhancing bone regeneration, however, the detailed interaction mechanism between nanomaterial and cells/tissue formation is not clear. Herein, a molecular-based inorganic-organic nanomaterial poly(citrate-siloxane) (PCS) is reported which can rapidly enhance osteogenic differentiation and bone formation through a special interaction with the cellular surface communication network factor 3 (CCN3), further activating the Wnt10b/β-catenin signaling pathway.

In Situ Anchoring Functional Molecules to Polymer Chains Through Supramolecular Interactions for a Robust and Self-Healing Multifunctional Waterborne Polyurethane.

Nowadays, much attention is paid to the development of high-performance and multifunctional materials, but it is still a great challenge to obtain polymer materials with high mechanical properties, high self-healing properties, and multifunctionality in one. Herein, an innovative strategy is proposed to obtain a satisfactory waterborne polyurethane (PMWPU-Bx) by in situ anchoring 3-aminophenylboronic acid (3-APBA) in a pyrene-capped waterborne polyurethane (PMWPU) via supramolecular interactions. The multiple functional sites inherent in 3-APBA can produce supramolecular interactions with groups on PMWPU, promoting the aggregation of hard domains in the polymer network, which confers the PMWPU-Bx strength (7.

Smart Mesoporous Silica Nanoparticles in Cancer: Diagnosis, Treatment, Immunogenicity, and Clinical Translation.

In cancer research and personalized medicine, mesoporous silica nanoparticles (MSNs) have emerged as a significant breakthrough in both cancer treatment and diagnosis. MSNs offer targeted drug delivery, enhancing therapeutic effectiveness while minimizing adverse effects on healthy cells. Due to their unique characteristics, MSNs provide targeted drug delivery, maximizing therapeutic effectiveness with minimal adverse effects on healthy cells.

Side Reaction Turned Positive: Synchronous OER Manipulating the Electrocatalytic Properties of Anodic Electrodeposited Lead Dioxide.

The preparation and modification of porous electrodes are an important component of the new generation electrochemical oxidation technology. Rapid preparation of porous electrodes can be easily achieved by synchronous oxygen bubble electrodeposition. However, according to the reaction mechanism of lead dioxide anodic electrodeposition, there is bound to be a competitive reaction of adsorbed hydroxyl radicals in the oxygen bubble template method, which means that synchronous OER impacts both the surface morphology and potentially the crystalline structure of the metal oxides.

Double-Dynamic-Bond Cross-Linked Hydrogel Adhesive with Cohesion-Adhesion Enhancement for Emergency Tissue Closure and Infected Wound Healing.

The hydrogel adhesives with strong tissue adhesion and biological characteristics adhm202404447are urgently needed for injury sealing and tissue repair. However, the negative correlation between tissue adhesion and the mechanical strength poses a challenge for their practical application. Herein, a bio-inspired cohesive enhancement strategy is developed to prepare the hydrogel adhesive with simultaneously enhanced mechanical strength and tissue adhesion.

Backbone Engineering of Bithiophene Imide Dimer-Based Polymeric Mixed Ionic-Electronic Conductors for High-Performance n-Type Organic Electrochemical Transistors.

Polymeric mixed ionic-electronic conductors (PMIECs) are gaining significant attention due to their potential applications in organic electrochemical transistors (OECTs). However, the performance of n-type OECTs still lags behind that of their p-type counterparts. Here, the structure-performance correlation of fused bithiophene imide dimer (BTI2)-based PMIECs is systematically investigated with the backbone evaluation from acceptor-strong donor (A-SD) to acceptor-donor (A-D), to acceptor-weak donor (A-WD), to acceptor-weak acceptor (A-WA), and finally to A-A structures.

Severe phlebitis and cutaneous necrosis following peripheral administration of high-concentration potassium chloride: A case report and vascular access management implications.

Electrolyte imbalance management is crucial in diverse clinical scenarios, with intravenous potassium repletion often required. High-concentration infusions can pose severe complications if extravasation occurs, leading to phlebitis, local tissue damage, or in severe cases, cutaneous necrosis. This risk is elevated in geriatric patients due to factors like reduced tissue elasticity and sensitivity.

Ahmed glaucoma valve implant for refractory glaucoma in children: A systematic review and meta-analysis.

Purpose: The aim of this study was to evaluate the efficacy and safety of the Ahmed glaucoma valve in pediatric patients with refractory glaucoma.

Methods: A comprehensive literature search was conducted across multiple major databases, including PubMed, Embase, the Cochrane Library of Systematic Reviews, Science Direct, China's National Knowledge Infrastructure, and the Wanfang database. We retrieved studies published before December 2022 that met the inclusion criteria, including clinical controlled trials (randomized controlled trials) and clinical noncontrolled trials (non-randomized controlled trials) on the use of Ahmed glaucoma valve in pediatric patients with refractory glaucoma.

A Baicalin-Based Functional Polymer in Dynamic Reversible Networks Alleviates Osteoarthritis by Cellular Interactions.

Osteoarthritis (OA) is increasingly recognized as a whole-organ disease predominantly affecting the elderly, characterized by typical alterations in subchondral bone and cartilage, along with recurrent synovial inflammation. Despite the availability of various therapeutics and medications, a complete resolution of OA remains elusive. In this study, novel functional hydrogels are developed by integrating natural bioactive molecules for OA treatment.

Stimuli-Responsive Nano Drug Delivery Systems for the Treatment of Neurological Diseases.

Nanomaterials with unparalleled physical and chemical attributes have become a cornerstone in the field of nanomedicine delivery. These materials can be engineered into various functionalized nanocarriers, which have become the focus of research. Stimulus-responsive nanodrug delivery systems (SRDDS) stand out as a sophisticated class of nanocarriers that can release drugs in response to environmental cues.

Evaluation and analysis of the transmission route of sigmoid sinus tinnitus by HRCT of the temporal bone: A retrospective analysis.

Objective: This study aims to analyze anatomical parameters of the transmission route of sigmoid sinus tinnitus (SST) to explore its mechanism and speculate on possible responsible anatomical abnormalities.

Methods: Clinical data were retrospectively collected from SST and sigmoid sinus wall dehiscence (SSWD) patients suggested by temporal bone high resolution computed tomography (HRCT), with and without tinnitus, at the First Affiliated Hospital of Chongqing Medical University from January 2015 to August 2022. Patients were divided into SSWD tinnitus ( = 61), and non-tinnitus ( = 60) groups based on HRCT features.

Diverse Care Needs Assessment for Older Adults in China: A Latent Profile Analysis Study.

Background: Grasping the nuanced needs of older adults is paramount for the efficacious provision of day-care services. Our study sought to identify the demand patterns for day-care services in China and to explore the underlying factors. This study aims to offer useful evidence that can refine nursing care strategies and guide policy development within day-care settings.

An on-Demand Oxygen Nano-vehicle Sensitizing Protein and Nucleic Acid Drug Augment Immunotherapy.

Hypoxia severely limits the antitumor immunotherapy for breast cancer. Although efforts to alleviate tumor hypoxia and drug delivery using diverse nanostructures achieve promising results, the creation of a versatile controllable oxygen-releasing nano-platform for co-delivery with immunostimulatory molecules remains a persistent challenge. To address this problem, a versatile oxygen controllable releasing vehicle PFOB@F127@PDA (PFPNPs) is developed, which effectively co-delivered either protein drug lactate oxidase (LOX) or nucleic acids drug unmethylated cytosine-phosphate-guanine oligonucleotide (CpG ODNs).

Disentangling Effects of Vegetation Structure and Physiology on Land-Atmosphere Coupling.

Terrestrial vegetation is a key component of the Earth system, regulating the exchange of carbon, water, and energy between land and atmosphere. Vegetation affects soil moisture dynamics by absorbing and transpiring soil water, thus modulating land-atmosphere interactions. Moreover, changes in vegetation structure (e.

Gut Microbiota Metabolites Sensed by Host GPR41/43 Protect Against Hypertension.

Background: Fermentation of dietary fiber by the gut microbiota leads to the production of metabolites called short-chain fatty acids, which lower blood pressure and exert cardioprotective effects. Short-chain fatty acids activate host signaling responses via the functionally redundant receptors GPR41 and GPR43, which are highly expressed by immune cells. Whether and how these receptors protect against hypertension or mediate the cardioprotective effects of dietary fiber remains unknown.

Therapeutic Black Phosphorus Nanosheets Elicit Neutrophil Response for Enhanced Tumor Suppression.

Black phosphorus (BP) has demonstrated potential as a drug carrier and photothermal agent in cancer therapy; however, its intrinsic functions in cancer treatment remain underexplored. This study investigates the immunomodulatory effects of polyethylene glycol-functionalized BP (BP-PEG) nanosheets in breast cancer models. Using immunocompetent mouse models-including 4T1 orthotopic BALB/c mice and MMTV-PyMT transgenic mice, it is found that BP-PEG significantly inhibits tumor growth and metastasis without directly inducing cytotoxicity in tumor cells.

Association between weight-adjusted waist index and obstructive sleep apnea among adults in the United States: data from NHANES (2005-2008 and 2015-2018).

Objective: We aimed to examine the relationship between the weight-adjusted waist index (WWI) and obstructive sleep apnea (OSA), a condition often caused by obesity, which remains unclear.

Methods: In this cross-sectional study, we analyzed data from the National Health and Nutrition Examination Survey among adults in the United States (US) aged 20 to 65 years, covering the periods 2005 to 2008 and 2015 to 2018. The study included 8278 participants; we used multivariate logistic regression, restricted cubic splines, and subgroup analyses to explore the relationship between WWI and OSA.

Intermittent Fasting Ameliorates β-Amyloid Deposition and Cognitive Impairment Accompanied by Decreased Lipid Droplet Aggregation Within Microglia in an Alzheimer's Disease Model.

Scope: Alzheimer's disease (AD) is the most prevalent form of dementia, lack of effective therapeutic interventions. In this study, we investigate the impact of intermittent fasting (IF), an alternative strategy of calorie restriction, on cognitive functions and AD-like pathology in a transgenic mouse model of AD.

Methods And Results: APP/PS1 mice at 6 months were randomly allocated to two dietary groups: one receiving ad libitum (AL) feeding and the other undergoing IF for 1 month.

Gaseous Synergistic Self-Assembly and Arraying to Develop Bio-Organic Photocapacitors for Neural Photostimulation.

Bioinspired supramolecular architectonics is attracting increasing interest due to their flexible organization and multifunctionality. However, state-of-the-art bioinspired architectonics generally take place in solvent-based circumstance, thus leading to achieving precise control over the self-assembly remains challenging. Moreover, the intrinsic difficulty of ordering the bio-organic self-assemblies into stable large-scale arrays in the liquid environment for engineering devices severely restricts their extensive applications.