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Background: AGK (acylglycerol kinase) was first identified as a mitochondrial transmembrane protein that exhibits a lipid kinase function. Recent studies have established that AGK promotes cancer growth and metastasis, enhances glycolytic metabolism and function fitness of CD8 + T cells, or regulates megakaryocyte differentiation. However, the role of AGK in platelet activation and arterial thrombosis remains to be elaborated. Methods: We performed hematologic analysis using automated hematology analyzer and investigated platelets morphology by transmission electron microscope. We explored the role of AGK in platelet activation and arterial thrombosis utilizing transgenic mice, platelet functional experiments in vitro, and thrombosis models in vivo. We revealed the regulation effect of AGK on Talin-1 by coimmunoprecipitation, mass spectrometry, immunofluorescence, and Western blot. We tested the role of AGK on lipid synthesis of phosphatidic acid/lysophosphatidic acid and thrombin generation by specific Elisa kits. Results: In this study, we found that AGK depletion or AGK mutation had no effect on the platelet average volumes, the platelet microstructures, or the expression levels of the major platelet membrane receptors. However, AGK deficiency or AGK mutation conspicuously decreased multiple aspects of platelet activation, including agonists-induced platelet aggregation, granules secretion, JON/A binding, spreading on Fg (fibrinogen), and clot retraction. AGK deficiency or AGK mutation also obviously delayed arterial thrombus formation but had no effect on tail bleeding time and platelet procoagulant function. Mechanistic investigation revealed that AGK may promote Talin-1Ser425 phosphorylation and affect the αIIbβ3-mediated bidirectional signaling pathway. However, AGK does not affect lipid synthesis of phosphatidic acid/lysophosphatidic acid in platelets. Conclusions: AGK, through its kinase activity, potentiates platelet activation and arterial thrombosis by promoting Talin-1 Ser425 phosphorylation and affecting the αIIbβ3-mediated bidirectional signaling pathway.

UNSTRUCTURED Language deficits, restricted and repetitive interests, and social difficulties are among the characteristics of autism spectrum disorder (ASD). Machine learning and neuroimaging have also been combined to examine ASD. Utilizing bibliometric analysis, this study examines the current state and hot topics in machine learning for ASD. In 2012 to 2022, the Web of Science Core Collection (WoSCC) was searched for publications relating to machine learning and ASD. Authors, articles, journals, institutions, and countries were characterized using Microsoft Excel 2021 and VOSviewer. Analysis of knowledge networks, collaborative maps, hotspots, and trends was conducted using VOSviewer and CiteSpace. A total of 660 papers were identified between 2012 and 2022. There was a slow growth in publications until 2016; then, between 2017 and 2021, a sharp increase was recorded. Among the most important contributors to this field were the United States, China, and England. Among the top major research institutions with numerous publications were Stanford University, Harvard Medical School, University of Pennsylvania, and King's College London. Wall, Dennis P. was the most productive author. Merico, Daniele, and Scherer, Stephen W. were the highest-cited authors. Scientific Reports, Plos One, and Translational Psychiatry were the three productive journals. "Autism", "machine learning", "Children", "classification" and "adolescent" are the central topics in this period. Cooperation and communication between countries/regions need to be enhanced in future research. A shift is taking place in the research hotspot from “Alzheimer's Disease”, “schizophrenia”, “Mild Cognitive Impairment” and “cortex” to “artificial intelligence”, “deep learning”, “machine learning”, “facial expression”, “functional magnetic resonance”, “young-children”. Machine learning applications for ASD diagnosis should be the future development direction.

A new oxime-modified hierarchical self-assembled polyimide adsorbent with high adsorption capacity, excellent selectivity and recyclability, and the applicability of fixed-bed column adsorption was developed to recycle uranium from wastewater.

The adhesion G protein-coupled receptor GPR56 mediates cell–cell and cell–extracellular matrix interactions. To examine the function of GPR56 in platelet activation and arterial thrombosis, we generated GPR56-knockout mice and evaluated GPR56 expression in human and mouse platelets. The results revealed that the levels of the GPR56 N-terminal fragment were significantly higher on the first day after myocardial infarction than on the seventh day in the plasma of patients with ST-segment-elevation myocardial infarction. Next, we investigated the effects of GPR56 on platelet function in vitro and in vivo. We observed that collagen-induced aggregation and adenosine triphosphate release were reduced in Gpr56 −/− platelets. Furthermore, P-selectin expression on the Gpr56 −/− platelet surface was also reduced, and the spreading area on immobilized collagen was decreased in Gpr56 −/− platelets. Furthermore, collagen-induced platelet activation in human platelets was inhibited by an anti-GPR56 antibody. Gpr56 −/− mice showed an extended time to the first occlusion in models with cremaster arteriole laser injury and FeCl3-induced carotid artery injury. GPR56 activated the G protein 13 signaling pathway following collagen stimulation, which promoted platelet adhesion and thrombus formation at the site of vascular injury. Thus, our study confirmed that GPR56 regulated the formation of arterial thrombosis. Inhibition of the initial response of GPR56 to collagen could significantly inhibit platelet activation and thrombus formation. Our results provide new insights for research into antiplatelet drugs.

This study aimed to address the risk factors of second decompressive craniectomy (DC) in patients with traumatic brain injury (TBI) who initially underwent mass lesion evacuation, but no primary DC. Patients were enrolled if they had had a hospital visit to Xiangya Hospital, Central South University with acute closed TBI from January 1, 2017 to December 31, 2019 and had undergone craniotomic mass lesion evacuation. Sociodemographic information, computed tomography (CT) information, clinical profiles, and surgical information were obtained from an electronic database. Twenty-four patients who had undergone a second decompressive craniectomy (SDC) and 39 patients who had not (NSO) were included in the analysis. The prevailing lesions differed between the groups (

Diabetic foot ulcer (DFU) is a chronic and non-healing complication of diabetes that leads to high hospital costs and, in extreme cases, to amputation. Recent studies have reported that long non-coding RNAs (lncRNAs) are linked to various diabetes-related symptoms. Thus, we aim to explore the role of lncRNA H19 in the wound healing process following DFU. Fibroblasts were isolated from the ulcer margin tissues of DFU patients, with the expression of lncRNA H19, connective tissue growth factor (CTGF) or serum response factor (SRF) altered by lentivirus infection. Next, rat models of DFU induced by high glucose and lipid diet were established, which was also infected with the corresponding lentivirus. The interaction among lncRNA H19, SRF and CTGF was determined. Afterward, cell proliferation and apoptosis, angiogenesis, ECM remodeling and wound healing in DFU tissues were evaluated to explore the effects of lncRNA H19/SRF/CTGF and MAPK signaling pathway on DFU. CTGF was poorly expressed in ulcer tissues from DFU rats and patients. CTGF overexpression was shown to activate the MAPK signaling pathway to promote cell proliferation, ECM remodeling, angiogenesis and wound healing while inhibiting cell apoptosis. lncRNA H19 was validated to elevate CTGF expression by recruiting SRF to the promoter region of CTGF, thus accelerating cell proliferation, ECM remodeling and wound healing while repressing cell apoptosis. Furthermore, MAPK signaling pathway activation is confirmed to be the underlying mechanism behind lncRNA H19/CTGF/SRF-induced results. Thus, lncRNA H19 accelerated wound healing in DFU through elevation of CTGF and activation of the MAPK signaling pathway.

It has been documented that M2 macrophage polarization plays a suppressive role in atherosclerosis in diabetes mellitus (DM). In addition, prostaglandin E2 (PGE2) is implicated in the development of M2 macrophage polarization. Therefore, the study aimed to investigate the specific mechanism of PGE2 in M2 macrophage polarization in diabetic coronary atherosclerosis (DMAS). Initially, clinical samples were obtained and DMAS mouse model was established. The expression of BDNF was determined, and M1 and M2 macrophage polarizations were evaluated. Then, the levels of BDNF and PGE2 were modified in DMAS mice and the serum indicator, atherosclerotic plaque, lipid uptake by PBMCs, as well as M1 and M2 macrophage polarization were determined. Macrophages were isolated and the effects of PGE2 and the CREB/BDNF/TrkB signaling pathway on M2 macrophage polarization were explored. BDNF was downregulated and macrophages were differentiated into M1 in DMAS patients and mice. BDNF and PGE2 were observed to promote M2 macrophage polarization, where atherosclerotic plaque and lipid uptake by PBMCs were reduced, and DMAS was alleviated in mice. Overexpression of BDNF activated the CREB/BDNF/TrkB signaling pathway and stimulated M2 macrophage polarization in macrophages. PGE2 stimulated M2 macrophage polarization by inducing KLF4 via the activation of the CREB/BDNF/TrkB signaling pathway. This study demonstrates that PGE2 promotes M2 macrophage polarization by activating the CREB/BDNF/TrkB signaling pathway, thus alleviating DMAS.

Atrial fibrillation (AF) is one of the most prevalent arrhythmias. Myocardial sleeves of the pulmonary vein are critical in the occurrence of AF. Our study aims to investigate the effect of synthetic vascular smooth muscle cells (SMCs) on gap junction proteins in cardiomyocytes. (1) Extraction of vascular SMCs from the pulmonary veins of Norway rats. TGF-β1 was used to induce the vascular SMCs switching to the synthetic phenotype and 18-α-GA was used to inhibit gap junctions of SMCs. The contractile and synthetic phenotype vascular SMCs were cocultured with HL-1 cells; (2) Western blotting was used to detect the expression of Cx43, Cx40 and Cx45 in HL-1 cells, and RT-PCR to test microRNA 27b in vascular SMCs or in HL-1 cells; (3) Lucifer yellow dye transfer experiment was used to detect the function of gap junctions. (1) TGF- β1 induced the vascular SMCs switching to synthetic phenotype; (2) Cx43 was significantly increased, and Cx40 and Cx45 were decreased in HL-1 cocultured with synthetic SMCs; (3) The fluorescence intensity of Lucifer yellow was higher in HL-1 cocultured with synthetic SMCs than that in the cells cocultured with contractile SMCs, which was inhibited by18-α-GA; (4) the expression of microRNA 27b was increased in HL-1 cocultured with synthetic SMCs, which was attenuated markedly by 18-α-GA. (5) the expression of ZFHX3 was decreased in HL-1 cocultured with synthetic SMCs, which was reversed by 18-α-GA. The gap junction proteins of HL-1 were regulated by pulmonary venous SMCs undergoing phenotypic transition in this study, accompanied with the up-regulation of microRNA 27b and the down-regulation of ZFHX3 in HL-1 cells, which was associated with heterocellular gap junctions between HL-1 and pulmonary venous SMCs.

Mesenchymal stem cells (MSCs) have been reported to hold promise to accelerate the wound-healing process in diabetic foot ulcer (DFU) due to the multilineage differentiation potential. Hence, this study intended to explore the wound healing role of MSC-derived exosomes containing long noncoding RNA (lncRNA) H19 in DFU. lncRNA H19 was predicated to bind to microRNA-152-3p (miR-152-3p), which targeted phosphatase and tensin homolog (PTEN) deleted on chromosome ten. Fibroblasts in DFU samples exhibited highly expressed miR-152-3p and poorly expressed lncRNA H19 and PTEN, along with an activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt1) signaling pathway. The fibroblasts were cocultured with lncRNA H19-transfected MSCs and MSC-derived exosomes to assess the effect of the lncRNA H19/miR-152-3p/PTEN axis on the biological activities and inflammation in fibroblasts. Mouse models of DFU were developed by streptozotocin, which was injected with MSC-derived exosomes overexpressing lncRNA H19. lncRNA H19 in MSCs was transferred through exosomes to fibroblasts, the mechanism of which improved wound healing in DFU, corresponded to promoted fibroblast proliferation and migration, as well as suppressed apoptosis and inflammation. Wound healing in mice with DFU was facilitated following the injection of MSC-derived exosomes overexpressing lncRNA H19. Taken together, MSC-derived exosomal lncRNA H19 prevented the apoptosis and inflammation of fibroblasts by impairing miR-152-3p-mediated PTEN inhibition, leading to the stimulated wound-healing process in DFU.

Objectives This study aimed to determine the function of Cx43 in the endothelial-to-mesenchymal transition (EndMT) process of endothelial cells (ECs) and to explore the potential signaling pathways underlying these functions. Methods Endothelial cells (ECs) were extracted from rat aorta. ECs was transfected with Cx43 cDNA, Cx43 siRNA and then exposed to 5 or 12 dyne/cm2. Immunofluorescence staining was used to detect the expression of SM22α in ECs, Cx43 and acetylated-α tubulin in ECs. Western Blotting was used to detected the protein expression of α-SMA, CD31, Cx43, H1-caponin, Ift88 and p-smad3 in ECs. Results The expression of αSMA, SM22α and Cx43 was significantly increased and CD31 was markedly decreased in ECs treated with laminar shear stress at 5 dyn/cm2. The Cx43 cDNA transfection could induce the expression of SM22α or H1-caponin, and attenuate CD31 expression in the ECs. Also, Cx43 overexpression harms cilia formation in ECs exposed to 5dyn/cm2, accompanied with the regulated Ift88 and smad signaling. Conclusions This study found that laminar shear stress at 5 dyn/cm2 would increase the expression of Cx43, and interfere with primary cilia formation by inhibiting the expression of Ift88 in ECs.

Glioma is one of the most common malignancies. De novo serine synthesis promotes glioma progression and therapeutic resistance. Therefore, clarifying the regulatory mechanism of serine synthesis is of great significance for glioma therapy. In this study, we found that the expression of TFCP2 was upregulated in glioma and that TFCP2 promoted glioma cell growth and sphere formation. Knockdown of TFCP2 expression inhibited glioma cell growth, sphere formation and tumorigenicity in nude mice. In terms of its molecular mechanism, TFCP2 was found to interact with ATF3 to cooperatively regulate the de novo synthesis of serine. Knockdown of TFCP2 expression significantly inhibited the binding of ATF3 to the promoter of PHGDH (a rate-limiting enzyme in the serine synthesis process). In conclusion, our studies proved that TFCP2 jointly regulates the de novo synthesis of serine through interaction with ATF3, thus promoting glioma progression. This study suggests that TFCP2 is a potential target for glioma therapy.

Traumatic brain injury (TBI) induces a series of epigenetic changes in brain tissue, among which histone modifications are associated with the deterioration of TBI. In this study, we explored the role of histone H3 modifications in a weight-drop model of TBI in rats. Screening for various histone modifications, immunoblot analyses revealed that the phosphorylation of histone H3 serine 10 (p-H3S10) was significantly upregulated after TBI in the brain tissue surrounding the injury site. A similar posttraumatic regulation was observed for phosphorylated extracellular signal-regulated kinase (p-ERK), which is known to phosphorylate H3S10. In support of the hypothesis that ERK-mediated phosphorylation of H3S10 contributes to TBI pathogenesis, double immunofluorescence staining of brain sections showed high levels and colocalization of p-H3S10 and p-ERK predominantly in neurons surrounding the injury site. To test the hypothesis that inhibition of ERK-H3S10 signaling ameliorates TBI pathogenesis, the mitogen-activated protein kinase–extracellular signal-regulated kinase kinase (MEK) 1/2 inhibitor U0126, which inhibits ERK phosphorylation, was administered into the right lateral ventricle of TBI male and female rats via intracerebroventricular cannulation for 7 days post trauma. U0126 administration indeed prevented H3S10 phosphorylation and improved motor function recovery and cognitive function compared to vehicle treatment. In agreement with our findings in the rat model of TBI, immunoblot and double immunofluorescence analyses of brain tissue specimens from patients with TBI demonstrated high levels and colocalization of p-H3S10 and p-ERK as compared to control specimens from non-injured individuals. In conclusion, our findings indicate that phosphorylation-dependent activation of ERK-H3S10 signaling participates in the pathogenesis of TBI and can be targeted by pharmacological approaches.

The electrocatalytic applications of traditional polyimide film and carbon nanomaterials are hindered due to a shortage of three-dimensional hierarchical conductivity and porous structure. Herein, a novel polyimide-based electrode based on a highly efficient palladium nanocatalyst embellished three-dimensional reduced graphene oxide/polyimide foam (Pd/3D RGO@PI foam, signed PRP) toward H2O2 electroreduction was designed and prepared through thermal foaming procedure, followed by facile dip-drying method and electrodeposition. As expected, such a binder-free, 3D hierarchical structure PRP electrode presented high catalytic property, good stability, as well as low activation energy toward H2O2 electroreduction during the electrochemical measurement period. The PRP electrode showed a reduction current density of 810 mA·cm-2 at -0.2 V (vs Ag/AgCl) in 2.0 mol·L-1 H2SO4 and 2.0 mol·L-1 H2O2. Moreover, the PRP electrode also illustrated good reproducibility and repeatability. Reproducibility presented almost 95.8% of the initial current density after 1000 cycles test. Also, the activation energy of H2O2 electroreduction on 3D PRP electrode was 21.624 kJ·mol-1. Benefiting from the 3D hierarchical structure and efficient catalyst, the PRP electrode exhibited excellent electrocatalytic performance and was considered to be a potential candidate material for fuel cells.

Aberrant expression of long noncoding RNA (lncRNA) H19 and microRNA (miR)-29b has been implicated in the complications of diabetes mellitus (DM). As a common and important complication of DM, diabetic foot ulcer (DFU) is characterized by high incidence and poor prognosis. Herein, we explored the role of lncRNA H19 in wound healing of DFU. Differentially expressed DM-related lncRNAs were initially screened by microarray data analysis. DFU models were then induced in DM mouse models. The functional role and interaction of lncRNA H19, miR-29b and FBN1 in DFU were subsequently determined by examining the proliferation, migration, and apoptosis of fibroblasts after silencing H19, inhibiting or overexpressing miR-29b and FBN1. According to microarray-based analysis, lncRNA H19 was upregulated in DM. In the ulcerative edge tissues of DFU, high expression of lncRNA H19 and FBN1 and low expression of miR-29b were observed. FBN1 was identified to be a target gene of miR-29b. LncRNA H19 could competitively bind to miR-29b, and then, inhibited its expression, which consequently upregulating FBN1. Silencing of lncRNA H19 led to inhibited proliferation, migration, and enhanced apoptosis of fibroblasts, accompanied by downregulated FBN1 but upregulated miR-29b, which diminished the expression of TGF-β1, Smad3, FN, and Col-1 and reduced extracellular matrix accumulation. Altogether, upregulation of lncRNA H19 can elevate the expression of FBN1 through competitively binding to miR-29b, which enhances the proliferation, migration, and inhibits apoptosis of fibroblasts, thus facilitating the wound healing of DFU.

Acute brain reperfusion stress is associated with mitochondrial dysfunction through unknown mechanisms. Accordingly, there is no effective drug to control the development and progression of brain reperfusion stress currently. The aim of our investigation is to verify whether melatonin attenuates acute brain reperfusion stress via affecting mitochondrial function. Our studies demonstrated that melatonin treatment suppressed reperfusion-induced neuron death. At the molecular levels, melatonin treatment modulated mitochondrial homeostasis via activating mitochondrial fusion. At the stage of reperfusion, MFN2 expression was downregulated, contributing to mitochondrial fusion inhibition. Interestingly, MFN2-related mitochondrial fusion was reversed by melatonin. Loss of MFN2-related mitochondrial fusion abrogated the protective actions of melatonin on mitochondrial function. Mechanistically, melatonin sustained MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway. Overexpression of Mst1 attenuated the beneficial effects of melatonin on mitochondrial fusion, evoking mitochondrial damage and neuron death in the setting of brain reperfusion stress. Taken together, our results confirmed the protective effects of melatonin on acute brain reperfusion stress. Melatonin treatment activated MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway, finally sustaining mitochondrial function and reducing reperfusion-mediated cerebral injury.

In this study, a 3D porous Ag+ decorated PCN-222 @ graphene oxide-chitosan foam adsorbent (APGC foam), which is grounded upon the growth of Ag+ decorated zirconium-metalloporphyrin metal–organic framework (PCN-222) on an EDTA-silane modified graphene oxide-chitosan foam substrate (EGC foam) for recovering U(VI) ions out of the seawater, was designed and synthesized with the in-situ growth and solvothermal method. The successfully synthesized APGC foam with excellent antibacterial property not only overcame the difficulty of powder adsorbents in practical application, but also reduced the negative impact of bacteria on the adsorption performance of porous material. The APGC foam showed excellent adsorption capacity (348.8 mg/g), selectivity and reusability of U(VI) adsorption at nearly seawater pH, and this also exhibited excellent adsorption performances in the seawater. The influence factors in the adsorption process were investigated by static and dynamic adsorption in different conditions. Moreover, the U(VI) adsorption mechanism of APGC foam was determined as the comprehensive effect of coordination, electrostatic interaction and intraparticle diffusion. All results indicated that APGC foam was an encouraging adsorbent to recover U(VI) out of the seawater.

In this study, a mesoporous PCN-222/GO-COOH adsorbent, based on the growth of a mesoporous zirconium-metalloporphyrin metal-organic framework (PCN-222) on the carboxylated graphene oxide (GO-COOH) to recover U(VI) from wastewater, was designed and prepared through solvothermal method and ultrasonication assisted stir technique. The U(VI) adsorption performance of the PCN-222/GO-COOH adsorbent was evaluated. The results indicated that the mesoporous PCN-222/GO-COOH adsorbent could effectively recover U(VI) and show an excellent adsorption capacity (426 mg/g), which was superior to those of GO-COOH and PCN-222 probably because the complexation and synergistic effect between GO-COOH and PCN-222 were facilitated by the ultrasonication assisted stir technique. And the PCN-222/GO-COOH adsorbent showed excellent reusability and selectivity for U(VI) adsorption, which also had outstanding adsorption performances in the complex wastewater. Furthermore, the chemical and monolayer adsorption dominated the U(VI) adsorption behavior of PCN-222/GO-COOH adsorbent. The excellent adsorption capacity, selectivity and reusability for U(VI) rendered PCN-222/GO-COOH composites as a promising adsorbent for recovering U(VI) from wastewater.

Nanosilver and nanonickel were first loaded on the surfaces of multiwalled carbon nanotubes (MWCNTs) by liquid-phase reduction method and the multiwalled carbon nanotubes/nanosilver-nickel (MWCNTs/Ag-Ni) composites were formed. The MWCNTs/Ag-Ni were homogeneously dispersed in the epoxy resin (EP), which can form epoxy resin/multiwalled carbon nanotubes/nanosilver-nickel (EP/MWCNTs/Ag-Ni) composites. The results based on X-ray photoelectron spectroscopy show the chemical bonds in the MWCNTs/Ag-Ni. By the scanning electron microscope method, it can be concluded that the enhancement in mechanical properties is due to the strong interaction between MWCNTs and the EP matrix. It is proved that through the comparative tests, the addition of nanosliver-nickel rigid particles can enhance the interaction between MWCNTs and the EP matrix, which can improve the mechanical properties of modified EP. Compared with the pure EP, the tensile strength and impact strength of nanocomposites improve around 81% and 139% by adding 1.3 wt% MWCNTs/Ag-Ni. In addition, the experimental results based on dynamic mechanical analysis (DMA) show that the glass transition temperature of modified EP (1.3 wt% MWCNTs/Ag-Ni in EP matrix) is significantly increased by about 18.6°C. Compared with the pure EP, the conductivity of modified EP (1.3 wt% MWCNTs/Ag-Ni in EP matrix) is also increased by around 63%. Because of the excellent mechanical properties and conductivity of EP/MWCNTs/Ag-Ni nanocomposites, the development of high-performance polymer materials will be greatly achieved.

A novel three-dimensional nickel hydroxide/polyurethane (Ni(OH)2/PU) electrode was prepared by a simple and environmentally friendly method and used for non-enzymatic detection of glucose. The Ni(OH)2/PU electrode was obtained by one-pot hydrothermal method of loading nickel hydroxide on a cheap, easily available and flexible polyurethane sponge, which is facile and energy-saving. The porous structure of the polyurethane sponge provides a large surface area and a rich electrochemical active site for the electrode, which is beneficial to the oxidation reaction of glucose on the surface of the electrode with Ni(OH)2. The Ni(OH)2/PU electrode structure was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The cyclic voltammetry test was used to study the catalytic performance of Ni(OH)2/PU electrode for oxidation of glucose and the chronoamperometry was used to investigate the detection performance of Ni(OH)2/PU electrode on glucose. The results indicate that this non-enzymatic glucose sensor had a high sensitivity of 2845 μA mM−1 cm−2, a low detection limit of 0.32 μM (S/N = 3), a detection range of 0.01–2.06 mM and response time of less than 5 s. In addition, the Ni(OH)2/PU electrode had excellent selectivity, reproducibility and stability and also exhibited effective detection of glucose in fetal bovine serum (FBS). In summary, Ni(OH)2/PU electrode had broad prospects as an excellent candidate for non-enzymatic glucose sensors. The study also opens up a facile and energy-saving approach for preparing three-dimensional (3D) functionalized polymer electrode via hydrothermal method as electrochemical sensors.

Diabetes mellitus-accelerated atherosclerosis (DMAS) is one of the vascular complications of diabetes. Brain-derived neurotrophic factor (BDNF) plays a critical role in diabetes mellitus. However, the mechanism by which BDNF is involved in DMAS remains unknown. This study investigates the effect of BDNF on the progression of DMAS as well as the underlying mechanism of action. The levels of BDNF in serum and peripheral blood mononuclear cells (PBMCs) from patients with DMAS and health controls were measured as well as the expression of inflammatory cytokines (IL-1β, TNF-α, IL-10, TGF-β and IL-13). The effects of BDNF restoration on cytokine release, macrophage differentiation and the formation of atherosclerotic plaques were evaluated both in vitro and in vivo using the DMAS mouse model. Downregulation of BDNF was identified in the serum and PBMCs of patients with DMAS. Elevation of BDNF contributed to a reduction in the AS lesion area in low-density lipoprotein receptor-/- mice, inactivated the STAT3 pathway, decreased pro-inflammatory cytokines IL-1β and TNF-α, and increased IL-10, TGF-β and IL-13. BDNF overexpression also increased the proportion of M2 macrophages and alleviated atherosclerotic lesions. Our findings demonstrate that BDNF overexpression promotes M2 macrophage polarization, which represses the development of DMAS by inactivating the STAT3 pathway.

The present study reports a new approach to improve the adsorption and catalytic properties of hematite nanoparticles (HNPs) synthesized via the chemical precipitation technique as one of the most applicable and preferable synthesis methods. This could be performed through controlling the particles' crystallinity where a facile ultrasonic pathway (UP) modification was introduced as a hybrid replacement for the conventionally-used magnetic stirring pathway (MP) using different precursor concentrations. The X-ray diffraction and Raman spectra define the pristine phase of α-Fe

Acute brain reperfusion stress is associated with mitochondrial dysfunction through unknown mechanisms. Accordingly, there is no effective drug to control the development and progression of brain reperfusion stress currently. The aim of our investigation is to verify whether melatonin attenuates acute brain reperfusion stress via affecting mitochondrial function. Our studies demonstrated that melatonin treatment suppressed reperfusion-induced neuron death. At the molecular levels, melatonin treatment modulated mitochondrial homeostasis via activating mitochondrial fusion. At the stage of reperfusion, MFN2 expression was downregulated, contributing to mitochondrial fusion inhibition. Interestingly, MFN2-related mitochondrial fusion was reversed by melatonin. Loss of MFN2-related mitochondrial fusion abrogated the protective actions of melatonin on mitochondrial function. Mechanistically, melatonin sustained MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway. Overexpression of Mst1 attenuated the beneficial effects of melatonin on mitochondrial fusion, evoking mitochondrial damage and neuron death in the setting of brain reperfusion stress. Taken together, our results confirmed the protective effects of melatonin on acute brain reperfusion stress. Melatonin treatment activated MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway, finally sustaining mitochondrial function and reducing reperfusion-mediated cerebral injury.

This work presents a new green perspective for the synthesis of hematite nanoparticles (HNP) via annealing the plain inorganic ferric sulfate (FS) precursor at (700–900) °C under a caked bed of the treated egg shell wastes as desulfurizer. Morphological and microstructural analyses depict the pristine phase of α-Fe2O3 crystal for the annealed samples along with exhibiting a reduced particles' size of 21 nm for FS annealed at 700 °C compared to the larger sizes of ≈29 and 50 nm for FS annealed at 800 °C and 900 °C, respectively. Moreover, FS annealed at 700 °C exhibited a unique hierarchal structure with various pores system on multi-scales, larger surface area with roughness, lower luminescence, and better uniformity over FS 800 and 900 nanoproducts. FS 700 showed a superior degradation efficiency ≈100% at 10 min with a rate constant of 11.06 × 10−2 min−1 for the pollutant Congo Red dye at room temperature in complete darkness, obeying pseudo-first-order reaction kinetics. Also, FS 700 could catalyze the production rate of biogas yields from the biodegradation of green algae (Enteromorpha) over other products. The photocatalytic study of terephthalic acid hydroxylation revealed that the induced fluorescence intensity is highest for FS 700 and is time dependent, following zero-order reaction kinetics. Accordingly, this contribution can furnish a striking piece of evidence for adopting the present methodology as a novel approach not only for the synthesis of HNP with superior features in good yields for industrial scales but also as a green alternative to the widely-used conventional organic precursors, reducing the greenhouse gases and recycling the environmental egg wastes.

This work explores the promotion effects of employing our proposed mechanical ultrasonic-activated precipitation (MUP) technique on the different features (textural, morphological, thermal, optical, and photo/catalytic) during the synthesis of hematite nanoparticles compared to the conventional chemical precipitation pathway (CPP). X-ray diffraction data revealed the higher amorphicity, microstrains, and lattice defects for the pristine MUP products over CPP. Also, it confirmed the inverse interdependence between the lattice microstrains and the crystallite size. Microstructural and morphological analyses showed a decrease in the average particles' sizes by a factor of 20%, 28% and 39% upon applying MUP at precursor concentrations of 0.05M, 0.15M, and 0.45M, respectively. Moreover, it exhibited higher values of surface area with roughness, mesoporosity and better uniformity over CPP products. A detailed thermal study figured the interdependence correlation between the particle's crystallinity, employed pathway, and the precursor concentration, showing higher crystallinity for CPP within a shorter temperature range over the poorly crystallized MUP products. Besides, it depicted that the proper calcination temperature is

The present study reports a new approach to improve the adsorption and catalytic properties of hematite nanoparticles (HNPs) synthesized via the chemical precipitation technique as one of the most applicable and preferable synthesis methods. This could be performed through controlling the particles' crystallinity where a facile ultrasonic pathway (UP) modification was introduced as a hybrid replacement for the conventionally-used magnetic stirring pathway (MP) using different precursor concentrations. The X-ray diffraction and Raman spectra define the pristine phase of α-Fe2O3 crystal with lower crystallinity and higher degrees of structural disorder for UP products. UP also shows smaller nanosized particles with lower bundles of aggregations and lumps formation in addition to lesser values of polydispersity index compared to the MP products. The catalytic performance supported by the reaction kinetics for the degradation of hazardous Rose Bengal and Congo Red dyes in light and dark, respectively, were examined. It revealed superior efficiencies for all of the UP products within a short span against the conventional MP and previous studies. Moreover, it was confirmed that UP products could catalyze the biodegradation reactions of green algae (Enteromorpha) and induced higher rates of biogas production. In addition to this, decreasing the precursor concentrations was found to be another key factor reducing the produced particles' crystallinity, size, and lumps formation as well as affecting the morphology development. Thus, the synergetic effects of applying the UP at low precursor concentrations could show a practical pathway for the synthesis of low-crystalline HNPs with enhanced properties for green applications over the conventional MP products. Hence, the obtained findings are of vital importance to show the improved catalytic efficiency of HNPs by shedding new light on controlling the crystallinity and developing the surface features in the conventional precipitation process via the proposed modification.

Type 1 diabetes (T1D) is an organ-specific, T-cell-mediated disease resulting from the selective destruction of pancreatic β cells. The signal transducer and activator of transcription 4 (STAT4) gene is one of the most interesting genes for the pathogenesis of autoimmune diseases, including T1D. In this study, a case–control study was conducted in a Han population in northeastern China comparing the genotypes of T1D patients to healthy controls for the presence of two single-nucleotide polymorphisms (SNPs) in the STAT4 gene. The study population comprised of 410 T1D patients and 407 healthy individuals. Two SNPs (rs7574865 and rs3024866) of STAT4 were genotyped with Multiplex SNaPShot method. Data were analyzed with spss 13.0 to determine if a statistical association existed between these genotypes and T1D. One of the two SNPs (rs7574865) was strongly associated with T1D in Northeastern Chinese population compared to healthy controls (P

// Lili Du 1, * , Mingli Wang 1, * , Yingying Kang 1, * , Bo Li 1 , Min Guo 1 , Zhifeng Cheng 1 , Changlong Bi 1 1 Department of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China * These authors have contributed equally to this work Correspondence to: Changlong Bi, email: bcl_63@163.com Zhifeng Cheng, email: zhifc55@126.com Keywords: metformin, anti-diabetic drug, colorectal cancer, prognosis, diabetes mellitus Received: October 29, 2016 Accepted: December 29, 2016 Published: January 17, 2017 ABSTRACT Several observational studies have shown that metformin can modify the risk and survival of colorectal cancer (CRC) in patients with diabetes mellitus, although the magnitude of this relationship has not been determined. We conducted an updated systematic review and meta-analysis to analyze the association between metformin and CRC mortality and searched relevant databases up to July 2016. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CS) and disease-free survival (DFS). Summary hazard ratios (HRs) were calculated using a random-effects model. Seventeen studies enrolling 269,417 participants were eligible for inclusion. Comparing with non-metformin users in diabetic CRC patients, the summary HRs for OS in metformin users were 0.69 (95% CI, 0.61-0.77). Subgroup analyses stratified by the study characteristics and sensitivity analysis by the trim-and-fill method (adjusted HR 0.77, 95% CI, 0.67-0.87) confirmed the robustness of the results. However, significant OS benefit was noted in patients with stage II and III disease. Five studies reported the CRC prognosis for CS and three for DFS; metformin intake was significantly associated with patient CS (HR 0.75, 95% CI, 0.59-0.94), but not DFS (HR 0.38, 95% CI, 0.13-1.17). Our findings suggest that metformin intake is associated with improved survival outcomes in terms of OS and CS in CRC patients with diabetes, particular for OS in stage II and stage III patients. Further studies should be conducted to determine CRC survival between metformin use and patient specific clinical and molecular profiles.

OBJECTIVE: To explore the endocrine mechanisms of aldosterone-producing adenoma (APA) by using the microarray expression profiles of normal and APA samples. METHODS: The gene expression profile GSE8514 was downloaded from Gene Expression Omnibus database, including samples from normal adrenals (n = 5) and APAs (n = 10). The differentially expressed genes (DEGs) were identified by samr package and endocrine DEGs were obtained according to Clinical Genome Database. Then, functional enrichment analysis of screened DEGs was performed by DAVID (Database for Annotation, Visualization and Integrated Discovery). Finally, a regulatory network was constructed to screen endocrine genes related with adrenal dysfunction and pathway enrichment analysis for the constructed network was performed. RESULTS: A total of 2149 DEGs were identified including 379 up- and 1770 down-regulated genes. And 26 endocrine genes were filtered from the DEGs. Furthermore, the down-regulated DEGs are mainly related to protein kinase cascade, response to molecule of bacterial origin, response to lipopolysaccharide, cellular macromolecule catabolic process and macromolecule catabolic process, while the up-regulated DEGs are related with regulation of ion transport. The target genes of VDR (vitamin D receptor), one of the three endocrine genes differentially expressed in the regulatory network, were endocrine genes including CYP24A1 (25-hydroxyvitamin D-24-hydroxylase) and PTH (parathyroid hormone). Three pathways may be associated with APA pathogenesis including cytokine-cytokine receptor interaction, pathways in cancer and autoimmune thyroid disease. CONCLUSION: The VDR is the most significant transcription factor and related endocrine genes might play important roles in the endocrine mechanisms of APA.

To explore the microneurosurgical technique and prevention of postoperative complications for the fourth ventricle tumors in adults.We retrospectively analyzed the clinical data of 68 patients with the fourth ventricle tumors between August 2005 and August 2007 in Xiangya Hospital after microsurgical operation. Tumors were excised by inferior vermis cerebellar approach or cerebellomedullary fissure approach. The extent of tumor removal should take into consideration the possible injury of brain stem respiratory center, especially tumors adherent to the brain stem. Cerebral aqueduct obstructions were removed in all patients, suspending dura on the neck muscles during closing skull to eliminate scalp hydrops.There were 58 total tumor excisions and 10 subtotal tumor excisions. No patient died and no suboccipital hydrops took place before discharge in this study. Postoperative symptomatic hydrocephalus was found in 10 patients, but it was cured by ventricle-abdomen shunt. Hemorrhage in tumor lumen happened in 4 patients, who received second microsurgery. Drugs were given to 8 patients with intracranial pneumatocele, 10 with intracranial infection, and 18 with upper gastrointestinal hemorrhage. Five patients out of the 16 tracheotomies recovered well by mechanical ventilation.Protecting the life center of brain stem and dredging the aqueduct outlet completely were the key to surgical success. Therapeutic effect could be improved by adept microneurosurgical techniques after operation. The prognosis of patients may be improved by preventing complications actively and combined therapy after the operation.