Diabetic calcific tendinopathy is the leading cause of chronic pain, mobility restriction, and tendon rupture in patients with diabetes. Tendon stem/progenitor cells (TSPCs) have been implicated in the development of diabetic calcified tendinopathy, but the molecular mechanisms remain unclear. This study found that diabetic tendons have a hyperoxic environment, characterized by increased oxygen delivery channels and carriers.
View Article and Find Full Text PDFBone aging, a major global health concern, is the natural decline in bone mass and strength. Concurrently, extracellular vesicles (EVs), tiny membrane-bound particles produced by cells, have gained recognition for their roles in various physiological processes and age-related diseases. The interaction between EVs and bone aging is of growing interest, particularly their effects on bone metabolism, which become increasingly critical with advancing age.
View Article and Find Full Text PDFThe healing of large skin defects remains a significant challenge in clinical settings. The lack of epidermal sources, such as autologous skin grafting, limits full-thickness skin defect repair and leads to excessive scar formation. Skin organoids have the potential to generate a complete skin layer, supporting in-situ skin regeneration in the defect area.
View Article and Find Full Text PDFThe airborne fungus Aspergillus fumigatus is a major pathogen that poses a serious health threat to humans by causing aspergillosis. Azole antifungals inhibit sterol 14-demethylase (encoded by cyp51A), an enzyme crucial for fungal cell survival. However, the most common mechanism of azole resistance in A.
View Article and Find Full Text PDFPneumocandin B (PB) is a lipopeptide produced by the fungus Glarea lozoyensis. The existing challenges with the low-yield and the extended-fermentation cycle emphasize necessity for strain improvement. In this study, we optimized conditions to obtain high-quality protoplasts and screened effective selection markers, leading to the construction of three CRISPR/Cas9 gene editing systems.
View Article and Find Full Text PDFPatients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model.
View Article and Find Full Text PDFThe issue of polyiodide crossover at an iodine cathode significantly diminishes the efficiency and practicality of aqueous zinc-iodine flow batteries (ZIFBs). To address this challenge, we have introduced a localized high iodine concentration (LHIC) coating layer onto a porous polyolefin membrane, which featured strong chemical adsorption by exploiting adduct chemistry between the iodine species and a series of low-cost oxides, , MgO, CeO, ZrO, TiO, and AlO. Leveraging the LHIC based on the potent iodine adsorption capability, the as-fabricated MgO-LHIC composite membrane effectively mitigates iodine crossover Donnan repulsion and concentration gradient effects.
View Article and Find Full Text PDFDisorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy. Patients often suffer chronic pain and might eventually have to undergo end-stage surgery. Therefore, future treatments should focus on early detection and intervention of regional lesions.
View Article and Find Full Text PDFPurpose: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures.
Methods: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18-65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center.
Early cyanobacterial blooms studies observed that exposure to blue-green algae led to fish gills impairment. The objective of this work was to evaluate the toxic mechanisms of exudates of Microcystis aeruginosa (MaE) on fish gills. In this study, the toxic mechanism of MaE (2×10 cells/mL) and one of its main components phytosphingosine (PHS) with two concentrations 2.
View Article and Find Full Text PDFThe integration of functional nanomaterials with tissue engineering scaffolds has emerged as a promising solution for simultaneously treating malignant bone tumors and repairing resected bone defects. However, achieving a uniform bioactive interface on 3D-printing polymer scaffolds with minimized microstructural heterogeneity remains a challenge. In this study, we report a facile metal-coordination self-assembly strategy for the surface engineering of 3D-printed polycaprolactone (PCL) scaffolds with nanostructured two-dimensional conjugated metal-organic frameworks (cMOFs) consisting of Cu ions and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP).
View Article and Find Full Text PDFMale infertility is a worldwide health issue, affecting 8%-12% of the global population. Oligoasthenoteratozoospermia (OAT) represents a severe type of male infertility, characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology. Using whole-exome sequencing, this study identified a novel missense mutation (c.
View Article and Find Full Text PDFCombination therapy is a highly successful way to address the limitations of using a single treatment method and improve therapy's overall efficacy. In this study, we developed a unique hollow mesoporous silica nanoparticle (HMSN) coated with folic acid (FA)-modified bovine serum albumin (FA-BSA). This nanoparticle, referred to as HFB, was designed to target cancer cells and release dual therapeutic drugs, Indocyanine green (ICG) and Paclitaxel (PTX), in response to specific stimuli termed as HFB@IP.
View Article and Find Full Text PDFIn recent years, cationic polymer vectors have been viewed as a promising method for delivering nucleic acids. With the advancement of synthetic polymer chemistry, we can control chemical structures and properties to enhance the efficacy of gene delivery. Herein, a facile, cost-effective, and scalable method was developed to synthesize PEGylated PDMAEMA polymers (PEO-PDMAEMA-PEO), where PEGylation could enable prolonged polyplexes circulation time in the blood stream.
View Article and Find Full Text PDFBackground: The degree of postoperative pain and defecation function in colorectal cancer will affect patients' prognosis. Therefore, exploring the correlation between postoperative pain and defecation function, and analyzing the related factors, will help to improve the quality of patients' prognosis.
Methods: A total of 94 patients with colorectal cancer admitted to our hospital from March 2022 to June 2023 were retrospectively selected for study.
Proc Natl Acad Sci U S A
April 2024
Clearance of serotonin (5-hydroxytryptamine, 5-HT) from the synaptic cleft after neuronal signaling is mediated by serotonin transporter (SERT), which couples this process to the movement of a Na ion down its chemical gradient. After release of 5-HT and Na into the cytoplasm, the transporter faces a rate-limiting challenge of resetting its conformation to be primed again for 5-HT and Na binding. Early studies of vesicles containing native SERT revealed that K gradients can provide an additional driving force, via K antiport.
View Article and Find Full Text PDFThe monoamine transporters, including the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET), are the therapeutic targets for the treatment of many neuropsychiatric disorders. Despite significant progress in characterizing the structures and transport mechanisms of these transporters, the regulation of their transport functions through dimerization or oligomerization remains to be understood. In the present study, we identified a conserved intramolecular ion-pair at the third extracellular loop (EL3) connecting TM5 and TM6 that plays a critical but divergent role in the modulation of dimerization and transport functions among the monoamine transporters.
View Article and Find Full Text PDFSquamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common.
View Article and Find Full Text PDFUnlabelled: Histone acetyltransferase (HAT)-mediated epigenetic modification is essential for diverse cellular processes in eukaryotes. However, the functions of HATs in the human pathogen remain poorly understood. In this study, we characterized the functions of OZ, bf2/as3, Sas2, and ip60 (MYST)-family histone acetyltransferase something about silencing (Sas3) in .
View Article and Find Full Text PDFUnlabelled: Azoles are the primary antifungal drugs used to treat infections caused by . However, the emergence of azole resistance in has become a global health concern despite the low proportion of resistant isolates in natural populations. In bacteria, antibiotic resistance incurs a fitness cost that renders strains less competitive in the absence of antibiotics.
View Article and Find Full Text PDFThere is an inseparable link between bone metabolism and gut microbiota, and the supplementation of probiotics exhibits a significant role in maintaining the homeostasis of gut microbiota and inhibiting bone loss. This study aims to explore the preventive and therapeutic potentials and the specific mechanisms of on osteoporosis. The mice models of osteoporosis induced by ovariectomy (OVX) were built, and the regular (once a day) and quantitative (200 μL/d) gavage of was performed for 8 weeks starting from 1 week after OVX.
View Article and Find Full Text PDFOrganoid culture systems are very powerful models that recapitulate in vivo organ development and disease pathogenesis, offering great promise in basic research, drug screening and precision medicine. However, the application of organoids derived from patients with cancer to immunotherapeutic research is a relatively untapped area. Esophageal cancer is one of the most lethal malignancies worldwide, including two major pathological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma.
View Article and Find Full Text PDFGeological events can strongly affect the genetic structures and differentiation of fish populations. Especially, as an endemic fish of the genus in the Yunnan-Guizhou Plateau, the effects of key geological events on the distributions and genetic structures remain poorly understood. Examining the phylogeographic patterns of fishes can be useful for elucidating the spatio-temporal dynamics of their population size, dispersal history and extent of geographical isolation, thereby providing a theoretical basis for their protection.
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