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Obesity, which has unknown pathogenesis, can increase the frequency and seriousness of acute myocardial infarction (AMI). This study evaluated effect of Huayu Qutan Recipe (HQR) pretreatment on myocardial apoptosis induced by AMI by regulating mitochondrial function via PI3K/Akt/Bad pathway in rats with obesity. For in vivo experiments, 60 male rats were randomly divided into 6 groups: sham group, AMI group, AMI (obese) group, 4.5, 9.0 and 18.0 g/kg/d HQR groups. The models fed on HQR with different concentrations for 2 weeks before AMI. For in vitro experiments, the cardiomyocytes line (H9c2) was used. Cells were pretreated with palmitic acid (PA) for 24 h, then to build hypoxia model followed by HQR-containing serum for 24 h. Related indicators were also detected. In vivo, HQR can lessen pathohistological damage and apoptosis after AMI. In addition, HQR improves blood fat levels, cardiac function, inflammatory factor, the balance of oxidation and antioxidation, as well as lessen infarction in rats with obesity after AMI. Meanwhile, HQR can diminish myocardial cell death by improving mitochondrial function via PI3K/Akt/Bad pathway activation. In vitro, HQR inhibited H9c2 cells apoptosis, improved mitochondrial function and activated the PI3K/Akt/Bad pathway, but effects can be peripeteiad by LY294002. Myocardial mitochondrial dysfunction occurs following AMI and can lead to myocardial apoptosis, which can be aggravated by obesity. HQR can relieve myocardial apoptosis by improving mitochondrial function via the PI3K/Akt/Bad pathway in rats with obesity.

We aim to establish a simple and easy high-performance liquid chromatography system coupled with an ultraviolet detector suitable for simultaneous determination of 24 antiepileptic drugs in human plasma. Optimized chromatographic separation was performed on a ZORBAX Eclipse Plus-C18 (4.6 × 150 mm

Methionine metabolism has a significant impact on T cells' survival and activation even in comparison to arginine, a well-documented amino acid in metabolic therapy. However, hydrophilic methionine is hardly delivered into TME due to difficult loading and rapid diffusion. Herein, the labeling assembly of methionine into nanoparticle is developed to overcome high hydrophilicity for mild-heat mediated immunometabolic therapy. The strategy is to firstly label methionine with protocatechualdehyde (as the tag) via reversible Schiff-base bond, and then drive nano-assembly of methionine (MPC@Fe) mediated by iron ions. In this fashion, a loading efficiency of 40% and assembly induced photo-thermal characteristics could be achieved. MPC@Fe can accumulate persistently in tumor up to 36 h due to tumor-selective aggregation in acidic TME. A mild heat of 43°C on tumor by light irradiation stimulated the immunogenic cell death and effectively generated CD8

Increasing evidence suggests stem cells from human exfoliated deciduous teeth (SHEDs) serve as desirable sources of dentin regeneration. Photobiomodulation (PBM) has shown great potential in enhancing the proliferation and osteogenesis of human bone marrow mesenchymal stem cells (hBMMSCs). However, the specific role of PBM in odontogenic differentiation of SHEDs is little know, and we further investigated potential mechanism of PBM osteo/odontogenisis. A 980 nm diode laser with different energy densities of (0.5, 5, 10 J cm

Gut microbiota plays a key role in the pathophysiology of type 2 diabetes mellitus (T2D). Mulberry leaf has a hypoglycemic effect, but the potential mechanism is not fully understood. This study aimed to explore the influences and potential mechanisms of mulberry leaf water extract (MLWE) intervention on mice with T2D induced through a high-fat and high-sucrose diet combined with streptozotocin by the combination of fecal metabolomics and gut microbiota analysis. Results showed that MLWE could decrease fasting blood glucose and body weight while ameliorating lipid profiles, insulin resistance, liver inflammation, and the accumulation of lipid droplets in T2D mice. MLWE could reverse the abundances of the phyla Actinobacteria and Bacteroidetes and the ratio of Firmicutes/Bacteroidetes, and increase the abundances of the phyla Cyanobacteria and Epsilonbacteraeota in the feces of T2D mice. The abundances of genera Alloprevotella, Parabacteroides, Muribaculaceae, and Romboutsia in the feces of T2D mice could be reversed, while Oscillatoriales_cyanobacterium and Gastranaerophilales could be reinforced by MLWE supplementation. The levels of nine metabolites in the feces of T2D mice were improved, among which glycine, Phe-Pro, urocanic acid, phylloquinone, and lactate were correlated with Romboutsia and Gastranaerophilales. Taken together, we conclude that MLWE can effectively alleviate T2D by mediating the host-microbial metabolic axis.

Myocardin‐related transcription factor‐A/serum response factor (MRTF‐A/SRF), a well‐known transcriptional programme, has been proposed to play crucial roles in skeletal muscle development and function. However, whether MRTF‐A participates in muscle regeneration and the molecular mechanisms are not completely understood. Here, we show that MRTF‐A levels are highly correlated with myogenic genes using a RNA‐seq assay, which reveal that MRTF‐A knockdown in C2C12 cells significantly reduces PAX7 expression. Subsequent in vitro and in vivo data show that MRTF‐A and PAX7 present identical expression patterns during myoblast differentiation and CTX‐induced muscle injury and repair. Remarkably, MRTF‐A overexpression promotes myoblast proliferation, while inhibiting cell differentiation and the expression of MyoD and MyoG. MRTF‐A loss of function produces the opposite effect. Moreover, mice with lentivirus (MRTF‐A) injection possesses more PAX7+ satellite cells, but less differentiating MyoD+ and MyoG+ cells, leading subsequently to diminished muscle regeneration. Our mechanistic results reveal that MRTF‐A contributes to PAX7‐mediated myoblast self‐renewal, proliferation, and differentiation by binding to its distal CArG box. Overall, we propose that MRTF‐A functions as a novel PAX7 regulator upon myoblast commitment to differentiation, which could provide pathways for dictating muscle stem cell fate and open new avenues to explore stem cell‐based therapy for muscle degenerative diseases.

Fibrosis is a pathological process characterized by abnormal activation of fibroblasts with increased synthesis of extracellular matrix components, including collagens. It may lead to loss of proper tissue architecture and organ function in clinical diseases such as systemic sclerosis and liver fibrosis. Excess accumulation of collagens is considered the primary indicator of fibrosis. Notch signaling has been reported to be involved in the fibrosis of many different organs, including the liver. Our previous study showed that the uterine-specific over-activation of canonical Notch1 signaling in the mouse uterus (Pgrcre/+ Rosa26N1ICD/+ , OEx) results in complete infertility as a consequence of multiple developmental and physiological defects, together with increased collagen accumulation evidenced by Masson's staining. In this study, we further detected expressions of all 44 collagen genes in these Notch1 gain-of-function transgenic mice and found that 18 collagens have been largely affected. In another aspect, using an intrauterine adhesion model (IUA), we mimicked fibrosis in the mouse uterine. The results suggested that Notch receptors were upregulated only 3 days after induction, and most of the fibril-forming collagen began to upregulate 6 days after the surgery. Furthermore, when induced IUA in the N1ICD-OEx mice, the expression of collagens and fibrosis levels were significantly enhanced. At last, as a Notch signaling inhibitor, the γ-secretase inhibitor N-[N-(3,5-difl uorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) pretreatment could alleviate the expression of collagens and the symptoms of fibrosis. These results demonstrate that Notch signaling may play a role in upregulating collagens expression in endometrial fibrosis and might be a potential target of fibrosis therapy in the endometrium.

Adolescents' sleep problems and their association with mental health is an important public health concern. This study aimed to investigate sleep and mental health status and the association of sleep with mental health in Chinese high school students. Data came from a cross-sectional study in Guangdong province which included 42,077 high school students. Sleep quality and sleep duration were obtained through self-report. The Depression Anxiety and Stress Scale (DASS-21) was used to measure mental health. The association between sleep quality, sleep duration, and mental health was analysed using logistic regression. The prevalence of depression, anxiety, and stress symptoms were 35.27%, 42.32%, and 21.87% in high school students, respectively. And only 17.71% and 34.41% of the high school students had very good sleep quality and ≥8 h sleep duration, respectively. Poorer sleep quality and shorter sleep duration were risk factors for mental health problems in high school students. Compared to high school students with very good sleep quality and ≥8 h sleep duration, the high school students with poor or very poor sleep quality and6 h sleep duration had the highest risk of depression symptoms (odds ratio [OR] 5.02, 95% confidence interval [CI] 4.40-5.72), anxiety symptoms (OR 6.02, 95% CI5.25-6.89), and stress symptoms (OR 6.12, 95% CI5.30-7.06). Considering the combined association of sleep quality and sleep duration on mental health, it is important not only to ensure that high school students have sufficient sleep duration, but also to improve their sleep quality.

Although the Turing structures, or stationary reaction-diffusion patterns, have received increasing attention in biology and chemistry, making such unusual patterns on inorganic solids is fundamentally challenging. We report a simple cation exchange approach to produce Turing-type Ag2 Se on CoSe2 nanobelts relied on diffusion-driven instability. The resultant Turing-type Ag2 Se-CoSe2 material is highly effective to catalyze the oxygen evolution reaction (OER) in alkaline electrolytes with an 84.5 % anodic energy efficiency. Electrochemical measurements show that the intrinsic OER activity correlates linearly with the length of Ag2 Se-CoSe2 interfaces, determining that such Turing-type interfaces are more active sites for OER. Combing X-ray absorption and computational simulations, we ascribe the excellent OER performance to the optimized adsorption energies for critical oxygen-containing intermediates at the unconventional interfaces.

Accompanying with diabetes mellitus-induced osteoporosis (DM-OS), diabetic patients show poor peri-implant osteogenesis after implantation for dentition defect. Berberine (BBR), a candidate oral hypoglycemic agent, is a promising agent for treating DM-OS. In this study, BBR was applied on DM rats and high-glucose-cultured bone mesenchymal stem cells (BMSCs) to investigate its therapeutic mechanism on DM-OS, thus laying a theoretical basis for the future application of BBR in implant restoration. Phenotypes were assessed in the DM rats after 4 w of gavage with BBR. Furthermore, BMSCs were cultured with high glucose and BBR. Cell Counting Kit-8, 2',7'-dichlorofluorescin diacetate (H2 DCF-DA), quantitative real-time PCR (qRT-PCR), and western blot were performed to estimate the cell proliferation, oxidative stress, and osteogenic differentiation. Moreover, the DM rats treated with BBR and insulin receptor substrate-1 anti-sense oligonucleotide (IRS-1-ASO) underwent a 4-w implant-healing period and then micro computed tomography (Micro-CT) and histology were performed to verify the mechanism. Results showed that the 4-w administration of BBR markedly improved the glucose metabolism and bone metabolism in the DM rats. in vitro experiments revealed that BBR alleviated high-glucose-inhibited osteogenesis of the BMSCs by upregulating reactive oxygen species (ROS)-mediated IRS-1 signaling. Besides, injection of IRS-1-ASO abolished the BBR promotion of implant osseointegration in the DM rats. In conclusion, targeting ROS-mediated IRS-1 signaling, BBR acted as an efficient agent to advance osseointegration in DM, which indicated that BBR use is a good strategy for future implants restoration in diabetic patients.

The integration of silver nanoparticles (Ag NPs) with mesoporous silica nanoparticles (MSNs) protects the former from aggregation and promotes the controlled release of silver ions, resulting in therapeutic significance on cancer and infection. The unique size, shape, pore structure and silver distribution of silver mesoporous silica nanoparticles (Ag-MSNs) embellish them with the potential to perform combined imaging and therapeutic actions via modulating optical and drug release properties. Here, we comprehensively review the recent progress in the fabrication and application of Ag-MSNs for combination therapies for cancer and infection. We first elaborate on the fabrication of star-shaped structure, core-shell structure, and Janus structure Ag-MSNs. We then highlight Ag-MSNs as a multifunctional nanoplatform to surface-enhanced Raman scattering-based detection, non-photo-based cancer theranostics and photo-based cancer theranostics. In addition, we detail Ag-MSNs for combined antibacterial therapy via drug delivery and phototherapy. Overall, we summarize the challenges and future perspectives of Ag-MSNs that make them promising for diagnosis and therapy of cancer and infection.

The clinical use of FDA-approved bone morphogenetic proteins (BMPs) are impeded by high costs, super-high dosage requirement, short half-life, and other undesirable side effects. Therefore, designing a biomaterial that can promote new bone formation without using exogenous BMPs is highly desirable in clinical applications. In the present work, a new kind of nanofibrous scaffold composed of gelatin and 45S5 bioglass (GF/45S5 BG) was prepared through thermally induced phase separation method together with the particle leach technique (TIPS&P). In addition to the significantly higher mechanical strength, the composite scaffolds (GF/45S5 BG) significantly increased osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro compared with the neat scaffold (GF) without adding other biological agents, for example, BMPs or hormones. Most importantly, our in vivo studies also indicated that GF/45S5 BG scaffolds could directly promote ectopic bone regeneration in SD rats without exogenous BMP2. In summary, both in vitro and in vivo results indicated that the novel 45S5 bioglass functionalized GF nanofibrous scaffold is a promising alternative for bone tissue engineering.

A considerable challenge in the conversion of carbon dioxide into useful fuels comes from the activation of CO2 to CO2 .- or other intermediates, which often requires precious-metal catalysts, high overpotentials, and/or electrolyte additives (e.g., ionic liquids). We report a microwave heating strategy for synthesizing a transition-metal chalcogenide nanostructure that efficiently catalyzes CO2 electroreduction to carbon monoxide (CO). We found that the cadmium sulfide (CdS) nanoneedle arrays exhibit an unprecedented current density of 212 mA cm-2 with 95.5±4.0 % CO Faraday efficiency at -1.2 V versus a reversible hydrogen electrode (RHE; without iR correction). Experimental and computational studies show that the high-curvature CdS nanostructured catalyst has a pronounced proximity effect which gives rise to large electric field enhancement, which can concentrate alkali-metal cations resulting in the enhanced CO2 electroreduction efficiency.

Acute myeloid leukemia (AML) is a highly aggressive disease that causes high mortality. Long noncoding RNA (lncRNA) have studied in recent years that could be a potential biomarker and therapeutic target. Therefore, it is urgently necessary to explore the novel lncRNAs in AML. Microarray analysis was performed to determine the differentially expressed lncRNAs between mononuclear cells of AML and normal samples. The biological function of lncRNA on cell proliferation and migration was measured in vitro. The predicted downstream target of lncRNA was validated by dual-luciferase reporter assay, RNA immunoprecipitation, RNA pull-down, and rescue experiments. The tumor formation and metastasis study were conducted in vivo. The expression of lncRNA in clinical samples was determined by a quantitative reverse transcription-polymerase chain reaction. LINC00449 was one of the most differentially expressed lncRNA which is mainly located in the cytoplasm. We found that overexpression of LINC00449 could inhibit the cell proliferation and invasion of AML cells in vitro and in vivo. Besides, miR-150 was identified as the downstream target gene that was negatively regulated by LINC00449 and FOXD3 was targeted by miR-150. The results were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, RNA pull-down, rescue experiments, and in vivo assays. Patients with AML with high expression of LINC0049 may characterize a favorable survival. All the above-mentioned findings indicated that the LINC00449/miR-150/FOXD3 signaling pathway might represent a novel prognostic biomarker or therapeutic target for the treatment of AML.

The anode oxygen evolution reaction (OER) is known to largely limit the efficiency of electrolyzers owing to its sluggish kinetics. While crystalline metal oxides are promising as OER catalysts, their amorphous phases also show high activities. Efforts to produce amorphous metal oxides have progressed slowly, and how an amorphous structure benefits the catalytic performances remains elusive. Now the first scalable synthesis of amorphous NiFeMo oxide (up to 515 g in one batch) is presented with homogeneous elemental distribution via a facile supersaturated co-precipitation method. In contrast to its crystalline counterpart, amorphous NiFeMo oxide undergoes a faster surface self-reconstruction process during OER, forming a metal oxy(hydroxide) active layer with rich oxygen vacancies, leading to superior OER activity (280 mV overpotential at 10 mA cm-2 in 0.1 m KOH). This opens up the potential of fast, facile, and scale-up production of amorphous metal oxides for high-performance OER catalysts.