Excessive accumulation of epicardial adipose tissue promotes microvascular obstruction formation after myocardial ischemia/reperfusion through modulating macrophages polarization.

BACKGROUND: Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship. METHODS: Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation. RESULTS: The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation. CONCLUSIONS: Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

Photocatalytic Sulfonyl Peroxidation of Alkenes via Deamination of N-Sulfonyl Ketimines.

A photocatalytic three-component sulfonyl peroxidation of alkenes with N-sulfonyl ketimines and tert-butyl hydroperoxide is reported. The reaction takes place via the photoinduced EnT process, which allows the efficient synthesis of a variety of ß-peroxyl sulfones under mild reaction conditions in the absence of a transition metal catalyst. The downstream derivatizations of the peroxides were also performed. Furthermore, the utility of this protocol was manifested by the synthesis of 11ß-HSD1 inhibitor and the antiprostate cancer drug bicalutamide.

Trends of underweight, overweight, and obesity among older adults in China from 2008 to 2018: a national observational survey.

OBJECTIVE: This study aims to investigate the 10-year trends and disparities in underweight, overweight, and obesity among older adults aged 65 years and older in China from 2008 to 2018. METHODS: We used four waves (2008, 2011, 2014, and 2018) of data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a national community-based cross-sectional survey conducted every 2-3 years. Body weight and height were measured by trained assessors following standardized procedures. BMI was calculated and divided into underweight (< 18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese (≥ 30.0 kg/m2) according to WHO reference. Multinomial logistic regression models were used to examine factors related with abnormal BMI groups, after adjusting for potential confounders. RESULTS: Among 46,543 older adults in China, the prevalence rates of underweight decreased with each survey year from 2008 to 2018, declining from 20.05 to 7.87% (p < 0.001). In contrast, the prevalence rates of overweight and obesity showed an increasing trend (all p < 0.001). Specifically, the prevalence of overweight rose from 12.82% to 2008 to 28.45% in 2018, and the prevalence of obesity increased from 1.62% to 2008 to 4.95% in 2018. In the multinomial logistic regression model, survey year, gender, residence, marital status, economic status, numbers of chronic diseases, smoking status, sleep quality, and functional disability were factors related with obesity. CONCLUSION: The prevalence rates of overweight and obesity were increasing while the prevalence of underweight and normal weight significantly decreased from 2008 to 2018 among older adults in China, which poses a huge challenge for chronic disease. There is an urgent need for intervention policy planning and early prevention of abnormal body weight for the preparation of an aging society.

Light-controlled scaffold- and serum-free hard palatal-derived mesenchymal stem cell aggregates for bone regeneration.

Cell aggregates that mimic in vivo cell-cell interactions are promising and powerful tools for tissue engineering. This study isolated a new, easily obtained, population of mesenchymal stem cells (MSCs) from rat hard palates named hard palatal-derived mesenchymal stem cells (PMSCs). The PMSCs were positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD146. They exhibited clonogenicity, self-renewal, migration, and multipotent differentiation capacities. Furthermore, this study fabricated scaffold-free 3D aggregates using light-controlled cell sheet technology and a serum-free method. PMSC aggregates were successfully constructed with good viability. Transplantation of the PMSC aggregates and the PMSC aggregate-implant complexes significantly enhanced bone formation and implant osseointegration in vivo, respectively. This new cell resource is easy to obtain and provides an alternative strategy for tissue engineering and regenerative medicine.

DNA damage checkpoint and repair: From the budding yeast Saccharomyces cerevisiae to the pathogenic fungus Candida albicans.

Cells are constantly challenged by internal or external genotoxic assaults, which may induce a high frequency of DNA lesions, leading to genome instability. Accumulation of damaged DNA is severe or even lethal to cells and can result in abnormal proliferation that can cause cancer in multicellular organisms, aging or cell death. Eukaryotic cells have evolved a comprehensive defence system termed the DNA damage response (DDR) to monitor and remove lesions in their DNA. The DDR has been extensively studied in the budding yeast Saccharomyces cerevisiae. Emerging evidence indicates that DDR genes in the pathogenic fungus Candida albicans show functional consistency with their orthologs in S. cerevisiae, but may act through distinct mechanisms. In particular, the DDR in C. albicans appears critical for resisting DNA damage stress induced by reactive oxygen species (ROS) produced from immune cells, and this plays a vital role in pathogenicity. Therefore, DDR genes could be considered as potential targets for clinical therapies. This review summarizes the identified DNA damage checkpoint and repair genes in C. albicans based on their orthologs in S. cerevisiae, and discusses their contribution to pathogenicity in C. albicans.

Risk factors for sinus membrane perforation during lateral window maxillary sinus floor elevation surgery: A retrospective study.

PURPOSE: To analyze the sinus membrane perforation (SMP) rate and its potential risk factors during lateral window maxillary sinus floor elevation (LSFE). MATERIALS AND METHODS: For patients with LSFEs at Department of Implantology, Stomatology Hospital, School of Medicine, Zhejiang Universitiy during January 2014 to December 2020, patient-related risk factors (age/sex/smoking habit), surgery-related risk factors (operator experiment/number of tooth units/technique of osteotomy/surgical approach), and maxillary sinus-related risk factors (residual bone height/sinus membrane thickness/lateral wall thickness/maxillary sinus contours/presence of septa/blood vessels at the lateral maxillary sinus wall) were compared between perforated and nonperforated sites and were evaluated for their influence affecting SMP. RESULTS: The study sample comprised 278 LSFE procedures in 278 patients; a total of 47 LSFE procedures (16.91%) presented SMP. Four significant factors were identified: smoking habit (p < 0.001), thin (≤1.5 mm) sinus membrane (p = 0.027), maxillary sinus contours (p < 0.001), and presence of septa (p = 0.001). The SMP rate of irregular, narrow tapered, and tapering sinus contours was significantly higher than that of ovoid and square one (p < 0.05). CONCLUSION: In general, smoking habit, thin sinus membrane, irregular, narrow tapered, and tapering sinus contours, and presence of septa may increase the risk of SMP during LSFE.

1α,25-dihydroxyvitamin D3 promotes early osteogenic differentiation of PDLSCs and a 12-year follow-up case of early-onset vitamin D deficiency periodontitis.

Periodontitis is a chronic periodontal disease that contributes to tooth loss. In recent years, many animal studies have reported that vitamin D (VitD) deficiency results in chronic periodontitis. However, no studies have reported cases of early-onset periodontitis with VitD deficiency. This study reports a 5-year-old male patient with early-onset periodontitis, VitD deficiency and VitD receptor (VDR) mutation. The patient was treated with VitD and calcium, and received systematic periodontal treatment. During the 12-year treatment, the periodontal conditions of this patient were stable. Our in vitro study found that VitD could promote the expression of alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP2), bone gamma-carboxyglutamate protein (BGLAP), and VDR in the early osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Meanwhile, VitD could downregulate mRNA expression levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1ß (IL-1ß) and protein levels of IL-6 in the tumor necrosis factor-α (TNF-α) -induced inflammation of PDLSCs. Therefore, sufficient VitD supply can be a potential treatment for VitD deficiency induced early-onset periodontitis.

A simple organic multi-analyte fluorescent prober: One molecule realizes the detection to DNT, TATP and Sarin substitute gas.

The detections of explosives and chemical warfare agents (CWAs) are always important for global security. In this study, a simple donor (D)- acceptor (A) type small organic fluorescent triazole-based molecule (T1) is reported. T1 is composed of a central 4H-1, 2, 4-triazole (TAZ) "core" and three external triphenylamine (TPA) groups. Its spin-coating films can realize the multi-analyte fluorescent prober to detect DNT (2, 4-dinitrotoluene), hydrogen peroxide (H2O2, the substitute for triacetone triperoxide (TATP)) and diethylchlorophosphate (DCP, the substitute for Sarin) vapors. Additionally, the combination of the triple sensing mechanism in the different channels affords three distinct sets of output-signal responses, these three hazardous compounds could be identified rapidly with high sensitivity and selectivity: fluorescence turn-off response to DNT, fluorescence turn-on response to H2O2 and fluorometric-colorimetric dual-channel response to DCP. T1 fluorescent probe is highly advantageous for concurrently monitoring various hazardous target substances and simultaneously possessing the desirable sensitivity and selectivity, excellent reusability. Hereby, this study provides a prototype method to build novel multifunctional fluorescent probes to explosives and CWAs.

Stem-cell-derived ECM sheet-implant complexes for enhancing osseointegration.

Numerous treatment methods have been developed to modify the surface of dental implants to improve cell migration and proliferation, removal torque, and osseointegration. Recent studies have constructed cell sheet-implant complexes with enhanced osteogenic capabilities. However, these complexes have some limitations, such as requirements for complex preparation processes, cell vitality maintenance, strict preservation conditions, and the induction of immunogenicity. Extracellular matrix (ECM) sheets without cells may be a more desirable material. To date, the effect of ECM sheets on implant osseointegration has not been reported. In this study, we fabricated ECM sheet-implant complexes through the combination of rat bone marrow mesenchymal stem cell (BMSC)-derived ECM sheets with sandblasted, large-grit, acid-etched (SLA) implants. These complexes were characterized by light microscopy, scanning electron microscopy (SEM), and immunofluorescence (IF) assays. The adhesion, proliferation, and osteogenic differentiation of BMSCs cultured on ECM sheets were detected in vitro. Then, the ECM sheet-implant complexes were transplanted into the metaphysis of the tibias of rats to evaluate the implant osseointegration in vivo. The results showed that ECM sheets were successfully constructed and showed significantly improved adhesion and proliferation. BMSCs cultured on ECM sheets upregulated the expression levels of the osteogenic-related genes alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (Runx2) compared to controls. In vivo, ECM sheet-implant complexes demonstrated superior new bone formation. Our findings proved that the BMSC-derived ECM sheets promoted osseointegration in vitro and in vivo. The current study indicated that the ECM sheet could be an ideal tissue engineering material, and ECM sheet-implant complexes could provide a strategy with low immunogenicity and easy storage and transportation. This research provides a novel strategy for the development of implant surface modification approaches.

Light-Controlled BMSC Sheet-Implant Complexes with Improved Osteogenesis via an LRP5/ß-Catenin/Runx2 Regulatory Loop.

The combination of bone marrow mesenchymal stem cell (BMSC) sheets and titanium implants (BMSC sheet-implant complexes) can accelerate osseointegration. However, methods of fabricating BMSC sheet-implant complexes are quite limited, and the survival of BMSC sheet-implant complexes is one of the key barriers. Here, we show that a light-controlled fabricating system can generate less injured BMSC sheet-implant complexes with improved viability and osteogenesis and that noninvasive monitoring of the viability of BMSC sheet-implant complexes using a lentiviral delivery system is feasible. Enhanced green fluorescent protein- and luciferase-expressing BMSC sheets were used to track the viability of BMSC sheet-implant complexes in vivo. The experiments of micro-computed tomography analysis and hard tissue slices were performed to evaluate the osteogenic ability of BMSC sheet-implant complexes in vivo. The results showed that BMSC sheet-implant complexes survived for almost 1 month after implantation. Notably, BMSC sheet-implant complexes fabricated by the light-controlled fabricating system had upregulating expression levels of low-density lipoprotein-receptor-related protein 5 (LRP5), ß-catenin, and runt-related transcription factor 2 (Runx2) compared to the complexes fabricated by mechanical scraping. Furthermore, we found that Runx2 directly bound to the rat LRP5 promoter and the LRP5/ß-catenin/Runx2 regulatory loop contributed to the enhancement of the osseointegrating potentials. In this study, we successfully fabricated BMSC sheet-implant complexes with improved viability and osteogenesis and established a feasible, noninvasive, and continuous method for tracking BMSC sheet-implant complexes in vivo. Our findings lay the foundation for the application of BMSC sheet-implant complexes in vivo and open new avenues for engineered BMSC sheet-implant complexes.