Design, Modeling, and Experimental Validation of an Active Microcatheter Driven by Shape Memory Effects.

Microcatheters capable of active guidance have been proven to be effective and efficient solutions to interventional surgeries for cardiovascular and cerebrovascular diseases. Herein, a novel microcatheter made of two biocompatible materials, shape memory alloy (SMA) and polyethylene (PE), is proposed. It consists of a reconfigurable distal actuator and a separate polyethylene catheter. The distal actuator is created via embedding U-shape SMA wires into the PE base, and its reconfigurability is mainly dominated by the shape memory effect (SME) of SMA wires, as well as the effect of thermal mismatch between the SMA and PE base. A mathematical model was established to predict the distal actuator's deformation, and the analytical solutions show great agreement with the finite element results. Structural optimization of such microcatheters was carried out using the verified analytical model, followed by fabrication of some typical prototypes. Experimental testing of their mechanical behaviors demonstrates the feasibility of the structural designs, and the reliability and accuracy of the mathematical model. The active microcatheter, together with the prediction model, will lay a solid foundation for rapid development and optimization of active navigation strategies for vascular interventions.

Injectable thermosensitive selenium-containing hydrogel as mesenchymal stem cell carrier to improve treatment efficiency in limb ischemia.

Limb ischemia is a refractory disease characterized by persistent inflammation, insufficient angiogenesis, and tissue necrosis. Although mesenchymal stem cells (MSCs) have shown potential for treating limb ischemia, their therapeutic effects are limited by low engraftment rates. Therefore, developing an optimal MSC delivery system that enhances cell viability is imperative. Selenium, known for its cytoprotective properties in various cell types, offers a potential strategy to enhance therapeutic effect of MSCs. In this study, we evaluated the cytoprotective effects of selenium on MSCs, and developed an injectable thermosensitive selenium-containing hydrogel based on PLGA-PEG-PLGA triblock copolymer, as a cell carrier to improve MSC viability after engraftment. The biocompatibility, biodegradability, and cytoprotective capabilities of selenium-containing hydrogels were assessed. Furthermore, the therapeutic potential of MSCs encapsulated within a thermosensitive selenium-containing hydrogel in limb ischemia was evaluated using cellular and animal experiments. Selenium protects MSCs from oxidative damage by upregulating GPX4 through a transcriptional mechanism. The injectable thermosensitive selenium-containing hydrogel exhibited favorable biocompatibility, biodegradability, and antioxidant properties. It can be easily injected into the target area in liquid form at room temperature and undergoes gelation at body temperature, thereby preventing the diffusion of selenium and promoting the cytoprotection of MSCs. Furthermore, MSCs encapsulated within the selenium-containing hydrogel effectively inhibited macrophage M1 polarization while promoting macrophage M2 polarization, thus accelerating angiogenesis and restoring blood perfusion in ischemic limbs. This study demonstrated the potential of an injectable thermosensitive selenium-containing hydrogel as a promising method for MSC delivery. By addressing the challenge of low retention rate, which is a major obstacle in MSC application, this strategy effectively improves limb ischemia.

Multi-functional composite dressings with sustained release of MSC-SLP and anti-adhesion property for accelerating wound healing.

Exudate management is of significant clinical value for the treatment of acute wound. Various wound dressings have been developed to restore the function of injured tissues and promote wound healing, but proper exploiting the healing factors inside exudate and achieving anti-adhesion wound care remains a challenge. Herein, we present a novel multi-functional composite dressing (MCD) by coupling supernatant lyophilized powder of mesenchymal stem cells (MSC-SLP) with a sandwich-structured wound dressing (SWD). The developed MCDs demonstrated unique unidirectional drainage capability, stable anti-adhesion characteristics, and improved wound healing performance. The designed SWD with both superhydrophobic inner surface and liquid-absorption ability of mid layer enables the dressings exhibit desired anti-adhesion property to neoformative granulation tissues, favorable shielding effect to exogenous bacteria, as well as appropriate exudate-retaining capability and unidirectional exudate-absorption property. The introduction of MSC-SLP in SWD was demonstrated to further improve wound healing quality. Compared to medical gauze, the synergic effect of SWD and MSC-SLP significantly accelerates wound healing rate by over 30%, avoids tissue avulsion when changing dressings, and produces a flat-smooth closure surface. More importantly, the wound treated with MCDs presents more skin accessory organs and blood vessels in regenerated tissues than other groups. In vivo/vitro biocompatibility evaluations indicated little toxicity, demonstrating the biosecurity of the developed dressings. The proposed method offers great potential in clinical applications particularly for chronic wound treatments.

Decreased miR-329-3p upregulates Adamts4 and Dnajb1 in mouse hepatic I/R injury in an age-independent manner.

Introduction: Hepatic ischemia/reperfusion (I/R) injury is common after liver surgery, particularly in patients of older age. However, an understanding of the mechanism of injury remains incomplete. In this study, we explored the molecular mechanisms underlying hepatic I/R injury and associations with age in a murine model. Methods: Gene expression profiling datasets (GSE72315 and GSE10654) and a microRNA (miRNA) expression profiling dataset (GSE72315) were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) and miRNAs (DEMiRs) were identified using online GEO2R or R before and after hepatic I/R injury in mice. Significant Gene Ontology (GO) terms were analyzed with the DAVID functional annotation tool. The DEMiR-miRNA target gene (miRTG) networks were constructed with miRTarBase, and the differentially expressed miRNAs and genes were analyzed with real-time quantitative polymerase chain reaction and immunofluorescence staining. Results: Through bioinformatic analysis, seven novel candidate miRNAs were identified that may regulate the expression of nine genes in hepatic I/R injury. Before and after hepatic I/R injury, mmu-miR-9-5p, mmu-miR-329-3p, and mmu-miR-290a-5p showed significant differential expression both in young (1 month old) and old (1 year old) mice. miR-329-3p had the most significant differential expression, and its predicted target genes Adamts4 and Dnajb1 were also significantly upregulated. Conclusions: The decrease in miR-329-3p expression upregulated Adamts4 and Dnajb1 expression in mouse hepatic I/R injury in an age-independent manner. This finding contributes to our understanding of hepatic I/R injury, and highlights novel molecular targets for future therapeutic development.

Electrothermally Driven Reconfiguration of Microrobotic Beam Structures for the ChipSail System.

Solar sailing enables efficient propellant-free attitude adjustment and orbital maneuvers of solar sail spacecraft with high area-to-mass ratios. However, the heavy supporting mass for large solar sails inevitably leads to low area-to-mass ratios. Inspired by chip-scale satellites, a chip-scale solar sail system named ChipSail, consisting of microrobotic solar sails and a chip-scale satellite, was proposed in this work. The structural design and reconfigurable mechanisms of an electrothermally driven microrobotic solar sail made of Al\Ni50Ti50 bilayer beams were introduced, and the theoretical model of its electro-thermo-mechanical behaviors was established. The analytical solutions to the out-of-plane deformation of the solar sail structure appeared to be in good agreement with the finite element analysis (FEA) results. A representative prototype of such solar sail structures was fabricated on silicon wafers using surface and bulk microfabrication, followed by an in-situ experiment of its reconfigurable property under controlled electrothermal actuation. The experimental results demonstrated significant electro-thermo-mechanical deformation of such microrobotic bilayer solar sails, showing great potential in the development of the ChipSail system. Analytical solutions to the electro-thermo-mechanical model, as well as the fabrication process and characterization techniques, provided a rapid performance evaluation and optimization of such microrobotic bilayer solar sails for the ChipSail.

Metformin increases bone marrow adipose tissue by promoting mesenchymal stromal cells apoptosis.

Bone marrow adipose tissue (MAT) has the potential to exert both local and systemic effects on metabolic homeostasis. As a first-line drug used to treat type 2 diabetes mellitus, metformin has conflicting effects on MAT and bone marrow mesenchymal stem cell (BM-MSC) differentiation. Through a series of experiments in vivo and in vitro, we found that except improving the glucose and lipid metabolism disorder in ob/ob mice, 200 mg/kg metformin increased MAT in mice tibia, and prompted osteogenic genes (RunX2, OPN, OCN) and lipogenic genes (Ppar-γ, Cebpα, Scd1) expression in mice bone marrow. However, metformin promoted osteogenesis and inhibited lipogenesis of MSC in vitro, which is inconsistent with the results in vivo. Given MAT being considered the "filler" of the space after the apoptosis of bone marrow stroma, the effect of metformin on MSC apoptosis was examined. We discovered that metformin induces MSC apoptosis in vivo and in vitro. Therefore, we speculated that the increased MAT in mice tibia may be attributed to the filling of adipose tissue after apoptosis of bone marrow stromal cells induced by metformin. The increased MAT may be involved in the regulation of metformin on glucose, lipid, and bone metabolism in diabetic mice, providing a new way to understand the metabolic regulation of metformin. While increased MAT-associated insulin resistance and metabolic disorders may account for the poorer clinical benefits in patients with intensive glucose control.

Engineered Sandwich-Structured Composite Wound Dressings with Unidirectional Drainage and Anti-Adhesion Supporting Accelerated Wound Healing.

Proper management of exudate is of great clinical value for reducing wound infection and promoting wound healing, thus various dressings have been studied to address this widespread medical challenge. Herein, a novel sandwich-structured composite wound dressing (SCWD), integrating of a superlyophobic (SLO) polydimethylsiloxane (PDMS) layer, a superlyophilic gauze layer, and a lyophobic PDMS layer is presented, with particular unidirectional droplet drainage and stable anti-adhesion capabilities, which realizes effective management of wound exudate and provides a favorable environment for wound healing. Thanks to the stable SLO property on the PDMS surface with hierarchical micro/nanostructures, the continuously accumulated wound exudate at the interface between dressing and wound surface is gradually deformed, eventually passing through SLO PDMS layer through milli-scale channels and being absorbed by gauze layer. Experimental results show that the application of SCWD can significantly reduce the occurrence of wound infection, avoid the tearing of wound tissues when replacing dressings, and accelerate wound healing by ≈20%. The combination of SCWD and lyophilized powders of stem cells supernatant (LPSCS) is verified to better accelerate the healing process. The proposed method offers great potential in clinical applications, particularly for acute trauma wound treatments.

An Integrated Digital Magnetic Resonance Imaging Spectrometer / 中国医疗器械杂志

An integrated digital magnetic resonance imaging spectrometer was proposed in this study. By using the FPGA chip Artix7 200T, timing control, data processing, digital frequency conversion and phase control were implemented into a single-chip, thus effectively improved timing accuracy and phase accuracy, while avoided the structural design complexity caused by multi-board connection and improved system integration and imaging quality.

Genome-Wide Analysis of the Fatty Acid Desaturase Gene Family Reveals the Key Role of PfFAD3 in α-Linolenic Acid Biosynthesis in Perilla Seeds.

Perilla (Perilla frutescens), a traditional medicinal and oilseed crop in Asia, contains extremely high levels of polyunsaturated α-linolenic acid (ALA) (up to 60.9%) in its seeds. ALA biosynthesis is a multistep process catalyzed by fatty acid desaturases (FADs), but the FAD gene family in perilla has not been systematically characterized. Here, we identified 42 PfFADs in the perilla genome and classified them into five subfamilies. Subfamily members of PfFADs had similar exon/intron structures, conserved domain sequences, subcellular localizations, and cis-regulatory elements in their promoter regions. PfFADs also possessed various expression patterns. PfFAD3.1 was highly expressed in the middle stage of seed development, whereas PfFAD7/8.3 and PfFAD7/8.5 were highly expressed in leaf and later stages of seed development, respectively. Phylogenetic analysis revealed that the evolutionary features coincided with the functionalization of different subfamilies of PUFA desaturase. Heterologous overexpression of PfFAD3.1 in Arabidopsis thaliana seeds increased ALA content by 17.68%-37.03%. These findings provided insights into the characteristics and functions of PfFAD genes in perilla.

Unveiling the dimension-dependence of femtosecond nonlinear optical properties of tellurium nanostructures.

Low dimensional tellurium is currently of great interest for potential electronic applications due to the experimentally observed Weyl fermions and the excellent carrier mobility, on/off ratios and current-carrying capacity in devices. However, the optical properties of Te nanostructures are not well explored, especially in the field of nonlinear optics. Here, we prepared a series of Te nanostructures by electrochemical exfoliation and liquid phase exfoliation methods, including one-dimensional (1D) Te nanowires (NWs), quasi-1D Te nanorods (NRs), zero-dimensional (0D) Te nanodots (NDs) and two-dimensional (2D) Te nanosheets (NSs). Femtosecond Z-scan measurements reveal unique dimension-dependent nonlinear optical (NLO) properties. 1D Te NWs and quasi-1D Te NRs exhibited higher saturable absorption behavior than 0D Te nanostructures, while the 2D Te NSs are a high performance optical limiting material. Ultrafast transient absorption spectroscopy revealed the dimension-dependent exciton dynamics. The reverse saturable absorption of 2D Te NSs is derived from faster exciton relaxation and stronger excited state absorption. This work paves the way for the design of saturable absorbers with high performance and broadens the application of 2D Te in the field of laser protection and other novel ultrafast photonics.

Molecular epidemiologic study of citrin deficiency by screening for four reported pathogenic SLC25A13 variants in the Shaanxi and Guangdong provinces, China.

BACKGROUND: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China. METHODS: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG_012247.2 (NM_014251.3): c.852_855del, c.1638_1660dup, c.615+5G>A, and c.1751-5_1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests. RESULTS: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ2=8.570, P=0.003) in general, with higher c.852_855del (54/6,818 vs. 13/5,492, χ2=17.328, P=0.000) but lower c.1751-5_1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638_1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly. CONCLUSIONS: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China.

Characteristics and Risk Factors of Pulmonary Hypertension in Patients With Hyperthyroidism.

OBJECTIVE: This study aimed to comprehensively assess the characteristics and risk factors of hyperthyroidism with pulmonary hypertension (PH). METHODS: This was a retrospective cross-sectional analysis of 315 consecutive patients with hyperthyroidism admitted to the endocrinology department of Tongji Hospital from February 2016 to December 2017. PH was defined as a pulmonary arterial systolic pressure above 35 mm Hg measured by echocardiography. RESULTS: Among the 315 patients, 208 were females, the median age was 42 (30-51) years, and the median disease duration was 12 (3-48) months. Thirty-five percent (111/315) of patients were identified with PH. Patients with hyperthyroidism and PH showed significantly higher serum concentrations of free thyroxine (FT4), free triiodothyronine, thyroid receptor antibodies, total bilirubin (TB), direct and indirect bilirubin, lower serum levels of hemoglobin and creatinine, and more severe cardiac load (P < .05 for each) compared with patients without PH. Levels of serum FT4, free triiodothyronine, thyroid receptor antibodies, and thyroid peroxidase antibody were different among groups of patients with different levels of pulmonary arterial systolic pressure (P < .05 for each). Multivariate logistic regression analysis indicated that serum FT4 (odds ratio, 1.02; 95% CI, 1.01-1.04; P = .004) and TB (OR, 1.03; 95% CI, 1.00-1.06; P = .030) were independent risk factors for PH in patients with hyperthyroidism. CONCLUSION: Elevated serum FT4 and TB levels may be independent risk factors for PH in patients with hyperthyroidism and valuable indicators for the identification and treatment of patients with PH and hyperthyroidism.

Association between weight cycling and risk of developing diabetes in adults: A systematic review and meta-analysis.

AIMS/INTRODUCTION: In this meta-analysis, we aimed to explore the association between bodyweight cycling (weight fluctuation) and the risk of developing diabetes. MATERIALS AND METHODS: We analyzed data from eligible cohort studies that assessed the association between weight cycling in adults and the risk of developing diabetes from online databases PubMed, Cochrane Library and EMBASE databases (1966 to April 2020). We pooled data using relative risks (RRs) with a random effects model. RESULTS: A total of 14 studies involving 253,766 participants, including 8,904 diabetes events, were included. One study included eight independent reports, resulting in 21 reports in 14 studies. Summary analysis showed that individuals who suffered weight cycling had a higher risk of diabetes (RR 1.23. 95% confidence interval 1.07-1.41; P = 0.003). However, the association between weight cycling and the risk of developing diabetes was not observed in obese participants (body mass index ≥30 kg/m2 ; P = 0.08). CONCLUSIONS: The present meta-analysis showed that weight cycling was a strong independent predictor of new-onset diabetes. Future studies are required to detect the causal links between weight cycling and the risk of developing diabetes.

The circulating ANGPTL8 levels show differences among novel subgroups of adult patients with diabetes and are associated with mortality in the subsequent 5 years.

ANGPTL8, an important regulator of glucose and lipid metabolism, is associated with diabetes, but the role of ANGPTL8 in the outcomes of novel subgroups of diabetes remains unclear. To assess the circulating ANGPTL8 levels in novel subgroups of diabetes and their association with health outcomes, we performed a data-driven cluster analysis (k-means) of patients with newly diagnosed diabetes (741 patients enrolled from 2011 through 2016) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study. The primary outcomes were mortality from all causes and cardiovascular diseases (CVD), and the secondary outcome was any cardiovascular event. Comparisons among groups were performed using the Kruskal-Wallis test, and the correlations between variables were assessed using the Pearson correlation test. Logistic regression was used to detect associations between the risk of outcomes and the ANGPTL8 levels. We identified four replicable clusters of patients with diabetes that exhibited significantly different patient characteristics and risks of all-cause mortality. The serum ANGPTL8 levels in the cluster of mild age-related diabetes (MARD), severe insulin-resistant diabetes (SIRD), and severe insulin-deficient diabetes (SIDD) were significantly higher than those in the mild obesity-related diabetes (MOD) cluster (685.01 ± 24.50 vs. 533.5 ± 18.39, p < 0.001; 649.69 ± 55.83 vs. 533.5 ± 18.39, = 0.040; 643.29 ± 30.89 vs. 533.5 ± 18.39, p = 0.001). High circulating ANGPTL8 levels were more highly associated with a greater hazard of all-cause mortality (quartile 4 vs 1: risk ratio [RR] 3.23, 95% CI 1.13-9.22; per unit increase in the Z score: RR 1.53, 95% CI 1.17-2.01) than low circulating ANGPTL8 levels. In conclusion, this 5-year follow-up REACTION study revealed that the circulating ANGPTL8 levels show differences among novel subgroups of adult patients with diabetes and are associated with all-cause mortality in the subsequent 5 years.

Attenuating ischemia/reperfusion injury in rat cardiac transplantation by intracoronary infusion with siRNA cocktail solution.

Tumor necrosis factor-α (TNF-α), caspase-8, and complement component 5a receptor (C5aR) are known to play a crucial role in the myocardial ischemia/reperfusion (I/R) injury in cardiac transplantation. We hypothesized that the intracoronary infusion of TNF-α, caspase-8, and C5aR small interfering RNAs (siRNA) would protect cardiac allograft function and improve graft survival from I/R injury-induced organ failure. I/R injury of cardiac allograft was induced by syngeneic rat cardiac transplantation, in which the transplanted hearts were infused with saline or different amounts of siRNA cocktail solution targeting TNF-α, caspase-8, and C5aR via coronary arteries, and subsequently subjected to 18 h of preservation at 4°C in histidine-tryptophan-ketoglutarate (HTK) solution. The effects of siRNA cocktail solution on prolonged cold I/R injury were determined by assessing graft survival, histopathological changes, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) concentration. The perfused siRNA cocktail solution successfully knocked down the expression of TNF-α, caspase-8, and C5aR in vitro and in vivo. Approximately 91.7% of control hearts that underwent 18 h of cold ischemia ceased their function after transplantation; however, 87.5% of cardiac allografts from the highest dose siRNA cocktail solution-pretreated hearts survived >14 days and exhibited minimal histological changes, with minimal cellular infiltration, interstitial edema, and inflammation and maximal reduced MPO activity and MDA concentration in the cardiac allograft. We demonstrated the feasibility and efficiency of infusion of TNF-α, caspase-8, and C5aR siRNA via the intracoronary route as a promising strategy for gene silencing against I/R injury in cardiac transplantation.

Hydrogen Sulfide, Adipose Tissue and Diabetes Mellitus.

Hydrogen sulfide (H2S) is now increasingly considered to be the third gasotransmitter alongside other gaseous signaling molecules, nitric oxide (NO) and carbon monoxide (CO). H2S is produced by a variety of endogenous enzymatic and non-enzymatic pathways and acts as a modulator of the physiological and pathological events of the body. Adipocytes express the cystathionine γ lyase (CSE)/H2S system, which modulates a variety of biological activities in adipose tissue (AT), including inflammation, apoptosis, insulin resistance, adipokine secretion and adipocyte differentiation. Abnormalities in the physiological functions of AT play an important role in the process of diabetes mellitus. Therefore, this review provides an overview of the general aspects of H2S biochemistry, the effect of H2S on AT function and diabetes mellitus and its molecular signalling mechanisms as well as the potential application of H2S in pharmacotherapy.

Bone Marrow Mesenchymal Stem Cell-Derived Hepatocyte-Like Cell Exosomes Reduce Hepatic Ischemia/Reperfusion Injury by Enhancing Autophagy.

Ischemia/reperfusion (I/R) injury remains a major problem in liver transplantation. I/R causes inflammatory cytokine release, apoptosis, and necrosis. Bone marrow-mesenchymal stem cells (BM-MSCs) can differentiate into hepatocytes in vivo, and differentiation further increases when hepatocytes are damaged. Exosomes are important mediators of cellular connections. Recently, exosomes of hepatocytes have been shown to play a pivotal role in inhibiting hepatocyte apoptosis and promoting hepatocyte regeneration. Therefore, we induced MSCs to differentiate into hepatocyte-like cells and extracted their exosomes; we then injected the exosomes into a mouse hepatic I/R model through the tail vein. Simultaneously, CoCl2 was used to mimic I/R in vitro. Our data indicated that in vivo, mesenchymal stem cell-derived hepatocyte-like cell exosomes (MSC-Heps-Exo) effectively relieve hepatic I/R damage, reduce hepatocyte apoptosis, and decrease liver enzyme levels. Consistent with the in vivo results, the in vitro experiments confirmed that exosomes effectively increased hepatocyte tolerance to ischemia and reduced hepatocyte apoptosis. We thus found that autophagy enhancement may be the mechanism by which exosomes protect the liver from I/R injury. These results indicate that exosomes play a protective role in hepatic I/R, and that the use of BM-MSCs for hepatocyte induction and exosome extraction may provide a new clinical treatment method through bioengineering.

Protective effect of hydrogen sulfide on endothelial cells through Sirt1-FoxO1-mediated autophagy.

BACKGROUND: As a new member of the vasculoprotective gasotransmitter family, hydrogen sulfide (H2S) functions similar to nitric oxide (NO) and carbon monoxide (CO). Endothelial cell (EC) death and autophagy enable cells to cope with the progression of cardiovascular diseases. However, the impacts and underlying mechanisms of H2S in the autophagic process in ECs are not completely understood. Here, we investigated the effects of H2S on autophagy in human vascular ECs. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations (0, 50, 100, 200, 500 and 1,000 µmol/L) GYY4137 (H2S donor) for indicated times (0, 0.5, 1, 2, 4 and 8 h), with or without pre-treatment with the autophagy inhibitor 3-methyladenine (3-MA) or bafilomycin A1. HUVECs were transfected with sirtuin 1 (Sirt1) overexpression plasmids (PIRES-Sirt1), Sirt1-siRNAs or forkhead box O1 (FoxO1)-siRNA using Lipofectamine 2000. Cell autophagy was evaluated via Western blotting and fluorescence microscopy. Co-immunoprecipitation assay was used to measure acetylation level of FoxO1. The distribution of FoxO1 in the cytoplasm and nucleus was observed using Western blotting and immunofluorescence. Western blotting, flow cytometric analysis, and cell count kit-8 assay were conducted to evaluate the effect of H2S on the oxidized low-density lipoprotein (Ox-LDL) induced apoptosis of HUVECs. RESULTS: Using both gain- and loss-of-function experiments, we showed that Sirt1-dependent activation of FoxO1, including its nuclear translocation and deacetylation, was critical for mediating H2S-induced autophagy in ECs. Furthermore, H2S-induced autophagy protected ECs from Ox-LDL-induced apoptosis by activating Sirt1. CONCLUSIONS: These results suggest that Sirt1-mediated autophagy in ECs is a novel mechanism by which H2S exerts vascular-protective actions.

Disentangling the Luminescent Mechanism of Cs4PbBr6 Single Crystals from an Ultrafast Dynamics Perspective.

New all-inorganic perovskites like Cs4PbBr6 provide rich luminescent tools and particularly novel physical insights, including their zero-dimensional structure and controversial emitting mechanism. The ensuing debate over the origin of the luminescence of Cs4PbBr6 inspired us to tackle the issue through fabricating high-quality Cs4PbBr6 single crystals and employing ultrafast dynamics study. Upon photoexcitation, Cs4PbBr6 underwent dynamics steps distinct from that of CsPbBr3, including exciton migration to the defect level on a time scale of several hundred femtoseconds, exciton relaxation within the defect states on the picosecond time scale, and exciton recombination from the subnanosecond to nanosecond time scale. The observation disclosed that crystal defects of Cs4PbBr6 induced green emission while CsPbBr3 mainly relied on quantum confinement to emit at room temperature. The study provides an in-depth understanding of the photoinduced multistep dynamics steps of Cs4PbBr6 associated with display and photovoltaic applications, establishing Cs4PbBr6 as a new candidate for uses associated with the perovskite family of materials.

Metformin mitigates autoimmune insulitis by inhibiting Th1 and Th17 responses while promoting Treg production.

Type 1 diabetes mellitus (T1DM) is still one of the major threats on global public health. This autoimmune condition is mainly caused by the imbalance of auto-reactive inflammatory effector T cells (Teffs) and protective regulatory T cells (Tregs). Therefore, inhibiting the development of Teffs and/or promoting Tregs provides a therapeutic strategy for preventing the development of T1DM. Pathways of energy metabolism have been shown to play a pivotal role in dictating the activation, differentiation and immune function of T cells. Studies have shown that inhibition of glycolysis suppresses the development of Th1 and Th17 cells, but promotes Treg production. AMP-activated protein kinase (AMPK) is a master sensor and regulator of cellular energy metabolism in mammals, which has also been demonstrated to interfere with T cell differentiation and effector function through inhibiting mammalian target of rapamycin (mTOR) and subsequent inhibition of glycolysis, and enhancement of lipid oxidation. In this study, we found that AMPK activator metformin suppresses T cell proliferation and inhibits the differentiation of Th1 and Th17 cells while promoting the development of Tregs in vitro in a dose-dependent manner. Treatment of NOD mice with metformin significantly mitigated autoimmune insulitis and substantially decreased the number of pro-inflammatory IFN-γ+ as well as IL17+ CD4 T cells in the spleens of NOD mice. However, a significantly increased percentage of regulatory IL-10+ and Foxp3+ CD4 T cells were seen. We provided a novel potential therapeutic method--by regulating T cell metabolism through targeting AMPK, to reduce the severity of autoimmune insulitis.