Visible light-driven photocatalytic sulfonative oxidation of benzyl secondary amines.

A method for the α-oxidation and sulfonation of benzyl secondary amines was developed utilizing Ir(III) or Eosin Y as the photocatalyst in the presence of O2 as a green oxidant. Using commercial substrates, 37 products from cyclic and acyclic benzylamines were achieved with good functional group compatibility in 48-87% yields. Furthermore, tetrahydroisoquinoline protected by an Ac or a Boc group was oxidized under standard conditions.

Post-annealing effect of low temperature atomic layer deposited Al2O3on the top gate IGZO TFT.

Electronical properties of top gate amorphous InGaZnO4thin film transistors (TFTs) could be controlled by post-annealing treatment, which has a great impact on the Al2O3insulator. To investigate the effect of post-annealing on Al2O3, Al/Al2O3/p-Si MOS capacitoras with Al2O3films treated under various post-deposition annealing (PDA) temperature were employed to analysis the change of electrical properties, surface morphology, and chemical components by electrical voltage scanning, atomic force microscope (AFM), and x-ray photoelectron spectroscopy (XPS) technologies. After PDA treatment, the top gate TFTs had a mobility about 7 cm2V-1s-1and the minimum subthreshold swing (SS) about 0.11 V/dec, and the threshold voltage (Vth) shifted from positive direction to negative direction as the post-annealing temperature increased. Electrical properties of MOS capacitors revealed the existence of positive fixed charges and the variation of trap state density with increasing PDA temperature, and further explained the change of negative bias stress (NBS) stability in TFT. AFM results clarified the increased leakage current, degraded SS, and NBS stability in MOS capacitors and TFTs, respectively. XPS results not only illuminated the origin of fixed charges and the trap density variation with PDA temperatures of Al2O3films, but also showed the O and H diffusion from Al2O3into IGZO during post-annealing process, which led to the deviation ofVth, the change of current density, and the negativeVthshift after positive bias stress in TFTs.

Visible-Light-Induced Synthesis of Alkylsulfonated Isoquinolinones from 2-Aryl Indoles/Benzimidazoles through Insertion of Sulfur Dioxide.

A visible-light-induced three-component reaction of 2-aryl indoles/benzimidazoles, Hantzsch esters, and sodium pyrosulfite through a radical cascade cyclization process with the insertion of sulfur dioxide is described. It provides a novel and powerful way for the synthesis of alkylsulfonated isoquinolinones. Hantzsch esters and Na2S2O5 are employed as alkyl radical precursors and SO2 surrogate, respectively. This transformation exhibits good functional group tolerance and substrate applicability under mild conditions.

Serum protein profile analysis via label-free quantitation proteomics in patients with early-onset preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious pregnancy complication, resulting in potentially life-threatening conditions for both mother and foetus. It is worth noting that early-onset PE has become a great challenge for clinicians due to its complex manifestation, rapid progression and serious complications. This study aims to investigate differential serum proteome profiles in patients with early-onset PE. METHODS: Each serum sample was separated using a nanoliter flow rate Easy-nLC chromatography system. Then the samples were analysed by mass spectrometry. Bioinformatics analyses were conducted to analyse the functional categories or signal transduction pathways for differentially abundant proteins. Key proteins identified by mass spectrometry were verified by ELISA. RESULTS: We found 30 and 34 proteins were upregulated and downregulated in early-onset PE patients (n = 3) vs controls (n = 3), respectively. Functional enrichment analysis revealed differentially expressed proteins related to the immune response and regulation of peptidase activity. ELISA confirmed that there were lower CSH1 levels and higher LPA concentrations in the serum samples of early-onset PE patients (n = 22) than in healthy controls (n = 19) (p < 0.05 for CSH1 and p < 0.001 for LPA). CONCLUSIONS: This study revealed the critical features of serum proteins in early-onset PE patients. LPA and CSH1 may serve as biomarkers for early-onset PE diagnosis and therapy.

Early-onset preeclampsia (PE) is still lacking definitive diagnostic or therapeutic strategies. Thus, we tried to identify effective and specific biomarkers for early-onset PE. In this study, we explored the serum protein profiles through the approach of label-free quantitation proteomics between early-onset PE patients and healthy controls. We identified 64 differentially expressed proteins in early-onset PE patients' serum samples. These differentially expressed proteins are associated with the immune response and regulation of peptidase activity. In addition, our findings suggest that LPA and CSH1 may serve as candidate biomarkers for early-onset PE diagnosis and therapy. These results may help physicians to diagnose early-onset PE clinically. What's more, our findings provide new insights into the onset and progression of early-onset PE disease.

Three important short-chain fatty acids (SCFAs) attenuate the inflammatory response induced by 5-FU and maintain the integrity of intestinal mucosal tight junction.

BACKGROUND: 5-Fluorouracil (5-FU) is a used chemotherapy drug for cancer, and its main side effect is intestinal mucositis which causes chemotherapy to fail. It was known that short-chain fatty acids (SCFAs) can inhibit immune cell release of various proinflammatory factors and inhibit excessive intestinal inflammation. However, the inhibitory effect of SCFAs on 5-FU-induced intestinal mucositis is still unclear. RESULTS: To simulate the effects of SCFAs on immune and intestinal epithelial cells, the cells (THP-1 cells and Caco-2 cells) were pretreated with sodium acetate (NaAc), sodium propionate (NaPc) and sodium butyrate (NaB), then inflammation was induced by 5-FU. The expressions of reactive oxygen species (ROS), Beclin-1, LC3-II, NF-κB p65, NLRP3 inflammasome, proinflammatory/anti-inflammatory cytokines and mucosal tight junction proteins were determined. In our results, the three SCFAs could inhibit ROS expressions, NLRP3, Caspase-1, IL-1ß, IL-6, IL-18, Beclin-1 and LC3-II, when induced by 5-FU. In a 5-FU-induced chemoentermuctis mouse model, Lactobacillus rhamnoides can increase the concentrations of three SCFAs in faeces and increase the concentrations of IL-1ß, IL-6 and IgA in serum, and decrease the expressions of NLRP3 and IL-17 in spleen cells. The expressions of ZO-1 and Occludin in intestinal mucosa were significantly increased. CONCLUSIONS: These results indicated that the three SCFAs can effectively suppress the inflammation of THP-1 cells and Caco-2 cells and maintain tight junction integrity in intestinal mucosal epithelial cells.

Genetic susceptibility analysis of FGF5 polymorphism to preeclampsia in Chinese Han population.

Fibroblast growth factor 5 (FGF5), which is a well-established causative factor for blood pressure, has been identified as a susceptibility gene for preeclampsia (PE) in European and Central Asian women. Here, we examined whether polymorphism rs16998073 in FGF5 confer a significant risk to PE in Chinese Han population by case-control association analysis. FGF5 rs16998073 was genotyped by Sanger sequencing in women with preeclampsia (n = 187) and healthy controls (n = 229) of Han Chinese. We found the frequency of rs16998073T allele was significantly higher in PE patients than that in controls. Next, we utilized dual-luciferase reporter assays and electrophoretic mobility shift assay (EMSA) reactions to investigate whether rs16998073 different alleles could affect the transcriptional activity of FGF5. The dual luciferase reporter assay showed that T allele increased the transcriptional efficiency by 1.5-fold compared with the G allele. Similarly, EMSA revealed that the T allele had a strong transcription factor binding strength compared with the G allele. We then examined the mRNA and protein expression levels of FGF5 in placental tissues by real-time PCR and Western blot assays. We found FGF5 were significantly upregulated in placental tissues from PE patients or PE mouse model than their corresponding controls. In addition, in vitro cell experiments confirmed that FGF5 could promote cell apoptosis of HTR8/SVneo and inhibit cell invasion. Taken together, our data provide evidence implicating rs16998073 of FGF5 as a functional genetic risk variant for PE disease and FGF5 might participate in development of PE disease.

Self-powered UV photodetectors and imaging arrays based on NiO/IGZO heterojunctions fabricated at room temperature.

Self-powered UV photodetectors and imaging arrays based on p-type NiO/n-type InGaZnO (IGZO) heterojunctions are fabricated at room temperature by using ratio-frequency magnetron sputtering. The p-n heterojunction exhibits typical rectifying characteristics with a rectification ratio of 7.4×104 at a ±4 V applied bias. A high photo-responsivity of 28.8 mA/W is observed under zero bias at a wavelength of 365 nm. The photodetector possesses a fast response time of 15 ms which is among the best in reported oxide-based p-n junction-based UV photodetectors. Finally, recognition of an "H" pattern is demonstrated by a 10×10 photodetector array at zero bias. The results indicate that the NiO/IGZO based photodetectors may have a great potential in constructing large-scale self-powered UV imaging systems.

Interfacial thermal transport of graphene/ß-Ga2O3 heterojunctions: a molecular dynamics study with a self-consistent interatomic potential.

Graphene/ß-Ga2O3 heterojunctions are widely used in high-power and high-frequency devices, for which thermal management is vital to the device operation and life. Here we apply molecular dynamics simulation to calculate the interfacial thermal resistance (ITR) between graphene and ß-Ga2O3. Based on the rigid ion model, a self-consistent interatomic potential with a set of parameters that can well reproduce the basic physical properties of crystal ß-Ga2O3 is fitted. Using this potential, the effects of model size, interface type, temperature, vacancy defects and graphene hydrogenation on the ITR of graphene/ß-Ga2O3 heterojunctions are evaluated. The results show that there is no obvious dependence of ITR on the size of graphene and ß-Ga2O3. It is reported that the ITR values of the (100), (010) and (001) interfaces are 7.28 ± 0.35 × 10-8 K m2 W-1, 6.69 ± 0.44 × 10-8 K m2 W-1 and 5.22 ± 0.35 × 10-8 K m2 W-1 at 300 K, respectively. Both temperature increase and vacancy defect increase can prompt the energy propagation across graphene/ß-Ga2O3 interfaces due to the enhancement of phonon coupling. In addition, graphene hydrogenation provides new channels for in-plane and out-of-plane phonon coupling, and thus reduces the ITR between graphene and ß-Ga2O3. This study provides basic strategies for the thermal design and management of graphene/ß-Ga2O3 based photoelectric devices.

An IgD-Fc-Ig fusion protein restrains the activation of T and B cells by inhibiting IgD-IgDR-Lck signaling in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis and the destruction of small joints. Emerging evidence shows that immunoglobulin D (IgD) stimulation induces T-cell activation, which may contribute to diseases pathogenesis in RA. In this study, we investigated the downstream signaling pathways by which IgD activated T cells as well as the possible role of IgD in the T-B interaction. Peripheral blood mononuclear cells were isolated from peripheral blood of healthy controls and RA patients. We demonstrated that IgD activated T cells through IgD receptor (IgDR)-lymphocyte-specific protein tyrosine kinase (Lck)-zeta-associated protein 70 (ZAP70)/phosphatidylinositol 3-kinase (PI3K)/nuclear factor kappa-B (NF-κB) signaling pathways; IgD-induced CD4+ T cells promoted the proliferation of CD19+ B cells in RA patients. A novel fusion protein IgD-Fc-Ig (composed of human IgD-Fc domain and IgG1 Fc domain, which specifically blocked the IgD-IgDR binding) inhibited the coexpression of IgDR and phosphorylated Lck (p-Lck) and the expression levels of p-Lck, p-ZAP70, p-PI3K on CD4+ T cells, and decreased NF-κB nuclear translocation in Jurkat cells. Meanwhile, IgD-Fc-Ig downregulated the expression levels of CD40L on CD4+ T cells as well as CD40, CD86 on CD19+ B cells in RA patients and healthy controls. It also decreased the expression levels of CD40L on CD4+ T cells and CD40 on CD19+ B cells from spleens of collagen-induced arthritis (CIA) mice and reduced IL-17A level in mouse serum. Moreover, administration of IgD-Fc-Ig (1.625-13 mg/kg, iv, twice a week for 4 weeks) in CIA mice dose-dependently decreased the protein expression levels of CD40, CD40L, and IgD in spleens. IgD-Fc-Ig restrains T-cell activation through inhibiting IgD-IgDR-Lck-ZAP70-PI3K-NF-κB signaling, thus inhibiting B-cell activation. Our data provide experimental evidences for application of IgD-Fc-Ig as a highly selective T cell-targeting treatment for RA.

Extremely high-gain source-gated transistors.

Despite being a fundamental electronic component for over 70 years, it is still possible to develop different transistor designs, including the addition of a diode-like Schottky source electrode to thin-film transistors. The discovery of a dependence of the source barrier height on the semiconductor thickness and derivation of an analytical theory allow us to propose a design rule to achieve extremely high voltage gain, one of the most important figures of merit for a transistor. Using an oxide semiconductor, an intrinsic gain of 29,000 was obtained, which is orders of magnitude higher than a conventional Si transistor. These same devices demonstrate almost total immunity to negative bias illumination temperature stress, the foremost bottleneck to using oxide semiconductors in major applications, such as display drivers. Furthermore, devices fabricated with channel lengths down to 360 nm display no obvious short-channel effects, another critical factor for high-density integrated circuits and display applications. Finally, although the channel material of conventional transistors must be a semiconductor, by demonstrating a high-performance transistor with a semimetal-like indium tin oxide channel, the range and versatility of materials have been significantly broadened.

A review of BMP and Wnt signaling pathway in the pathogenesis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease.Bone morphogenetic proteins (BMPs) and their receptors were required for PAH-induced right ventricular hypertrophy. Emerging data suggest that restoration of BMP type II receptor (BMPR2) signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. BMPR2 mutations have been identified in >70% of familial and roughly 15% of sporadic PAH cases. Wingless (Wnt) are a family of secreted glycoproteins with varying expression patterns and a range of functions, Wnt signaling pathway is divided into canonical signaling pathway and non-canonical signaling pathway. A recent study reports that interaction between BMP and Wnt closely associated with lung development, those cascade coordination regulation stem cell fate which determine lung branching morphogenes. The promoting effect of BMPR2 on proliferation, survival, and motility of endothelial cells was through recruiting Wnts signaling pathway, the interaction between BMP and Wnt closely associated with lung development.Therefore, in this review, we outline the latest advances of BMP and Wnt signaling pathway in the pathogenesis of PAH and disease progression.

Oxidative dehydrogenation of light alkanes to olefins on metal-free catalysts.

Metal-free boron- and carbon-based catalysts have shown both great fundamental and practical value in oxidative dehydrogenation (ODH) of light alkanes. In particular, boron-based catalysts show a superior selectivity toward olefins, excellent stability and atom-economy to valuable carbon-based products by minimizing CO2 emission, which are highly promising in future industrialization. The carbonaceous catalysts also exhibited impressive behavior in the ODH of light alkanes helped along by surface oxygen-containing functional groups. This review surveyed and compared the preparation methods of the boron- and carbon-based catalysts and their characterization, their performance in the ODH of light alkanes, and the mechanistic issues of the ODH including the identification of the possible active sites and the exploration of the underlying mechanisms. We discussed different boron-based materials and established versatile methodologies for the investigation of active sites and reaction mechanisms. We also elaborated on the similarities and differences in catalytic and kinetic behaviors, and reaction mechanisms between boron- and carbon-based metal-free materials. A perspective of the potential issues of metal-free ODH catalytic systems in terms of their rational design and their synergy with reactor engineering was sketched.

Garcinia Biflavonoid 1 Improves Lipid Metabolism in HepG2 Cells via Regulating PPARα.

Garcinia biflavonoid 1 (GB1) is one of the active chemical components of Garcinia kola and is reported to be capable of reducing the intracellular lipid deposition, which is the most significant characteristic of non-alcoholic fatty liver disease. However, its bioactive mechanism remains elusive. In the current study, the lipid deposition was induced in HepG2 cells by exposure to oleic acid and palmitic acid (OA&PA), then the effect of GB1 on lipid metabolism and oxidative stress and the role of regulating PPARα in these cells was investigated. We found that GB1 could ameliorate the lipid deposition by reducing triglycerides (TGs) and upregulate the expression of PPARα and SIRT6, suppressing the cell apoptosis by reducing the oxidative stress and the inflammatory factors of ROS, IL10, and TNFα. The mechanism study showed that GB1 had bioactivity in a PPARα-dependent manner based on its failing to improve the lipid deposition and oxidative stress in PPARα-deficient cells. The result revealed that GB1 had significant bioactivity on improving the lipid metabolism, and its potential primary action mechanism suggested that GB1 could be a potential candidate for management of non-alcoholic fatty liver disease.

The protective effects of MSC-EXO against pulmonary hypertension through regulating Wnt5a/BMP signalling pathway.

The aim of the study was to explore the mechanism of mesenchymal stem cell-derived exosomes (MSC-EXO) to protect against experimentally induced pulmonary hypertension (PH). Monocrotaline (MCT)-induced rat model of PH was successfully established by a single intraperitoneal injection of 50 mg/kg MCT, 3 weeks later the animals were treated with MSC-EXO via tail vein injection. Post-operation, our results showed that MSC-EXO could significantly reduce right ventricular systolic pressure (RVSP) and the right ventricular hypertrophy index, attenuate pulmonary vascular remodelling and lung fibrosis in vivo. In vitro experiment, the hypoxia models of pulmonary artery endothelial cell (PAEC) and pulmonary vascular smooth muscle cell (PASMC) were used. We found that the expression levels of Wnt5a, Wnt11, BMPR2, BMP4 and BMP9 were increased, but ß-catenin, cyclin D1 and TGF-ß1 were decreased in MSC-EXO group as compared with MCT or hypoxia group in vivo or vitro. However, these increased could be blocked when cells were transfected with Wnt5a siRNA in vitro. Taken together, these results suggested that the mechanism of MSC-EXO to prevent PH vascular remodelling may be via regulation of Wnt5a/BMP signalling pathway.

Mesenchymal stromal cell-derived exosomes improve pulmonary hypertension through inhibition of pulmonary vascular remodeling.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, right ventricular hypertrophy and failure. So far no effective treatment exists for this disease; hence, novel approaches are urgently needed. The aim of the present research was to observe the treatment effect of mesenchymal stromal cell derived exosomes and reveal the mechanism. METHODS: Monocrotaline (MCT)-induced PH in rats and hypoxia-induced cell damage model were established, respectively. Exosomes derived from the supernatant of human umbilical cord mesenchymal stem cells (MSC-exo) were injected into MCT-PH model rat or added into the cells cultured medium. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods were used in vivo and vitro. RESULTS: The results showed that MSC-exo could significantly attenuate right ventricular (RV) hypertrophy and pulmonary vascular remodelling in MCT-PH rats. In the cell culture experiments, we found that MSC-exo could significantly inhibit hypoxia-induced pulmonary arterial endothelial cell (PAEC) apoptosis and pulmonary arterial smooth muscle cells (PASMC) proliferation. Furthermore, the pulmonary arterioles endothelial-to-mesenchymal transition (EndMT) was obviously suppressed. Moreover, the present study suggest that MSC-exo can significantly upregulate the expression of Wnt5a in MCT-PH rats and hypoxic pulmonary vascular cells. Furthermore, with Wnt5a gene silencing, the therapeutic effect of MSC-exo against hypoxia injury was restrained. CONCLUSIONS: Synthetically, our data provide a strong evidence for the therapeutic of MSC-exo on PH, more importantly, we confirmed that the mechanism was associated with up-regulation of the expression of Wnt5a. These results offer a theoretical basis for clinical prevention and treatment of PH.

Molecular dynamic simulation of thermal transport in monolayer C3B x N1-x alloy.

Recently, two-dimensional (2D) monolayers C3B and C3N attract growing research interest due to the excellent physical properties. In this work, the thermal conductivities (k) of the monolayer C3B x N1-x alloy and the special C3B0.5N0.5 superlattice (C3B0.5N0.5-SL) alloy are systematically evaluated by using molecular dynamic simulation. First, the k of monolayer C3B x N1-x alloy presents a U-shaped profile with the increasing random doping ratio (x), in which the lowest k exists in x = 0.5. Second, we further calculate the thermal conductivity of C3B0.5N0.5-SL. The result shows an initial decreasing and then rising trend, and the coherent length is 5.11 nm which occupies the minimum thermal conductivity. Furthermore, to uncover the phonon thermal transport mechanism, we calculate the spatiotemporal thermal transport, phonon density of states, phonon group velocity, participation ratio and the phonon wave packet simulations in monolayer alloy system. We note that on account of the random doping atoms, the enhancive phonon-impurity scattering and phonon localization reduce the thermal conductivity in monolayer C3B x N1-x alloy. In C3B0.5N0.5-SL, when the period length is smaller than the coherent length, coherent phonon modes emerge because of the phonon interference, in which the superlattice can be regarded as a 'newly generated material'. However, when the period length is larger than the coherent length, the decreasing number of the interface in superlattice lessens phonon-interface scattering and cause the increasing thermal conductivity. This work contributes the fundamental knowledge for thermal management in 2D monolayer C3B x N1-x alloy based nanoelectronics.

Percutaneous ultrasound-guided 'three-step' radiofrequency ablation for giant hepatic hemangioma (5-15 cm): a safe and effective new technique.

Purpose: To evaluate the safety and efficacy of percutaneous ultrasound-guided 'three-step' radiofrequency ablation (RFA) for the treatment of giant hepatic hemangioma.Materials and methods: Patients with giant hepatic hemangioma who underwent percutaneous ultrasound-guided 'three-step' RFA (n = 52) and conventional RFA (n = 54) at our center from June 2013 to December 2017 were retrospectively analyzed. The 'three-step' RFA proceeds as follows. Step 1: Ablate the feeding artery of the hemangioma. Step 2: Aspirate blood from the tumor. Step 3: Ablation the lesion. Intraoperative information, postoperative recovery, therapeutic effects, and complications were compared between the two groups.Results: The duration of RFA was significantly shorter (19.2 ± 0.8 min versus 44.5 ± 2.8 min, p < 0.001), the number of punctures was significantly lower (3.2 ± 0.1 versus 4.7 ± 0.3, p = 0.002), and the duration of hospital stay was significantly shorter (9.0 ± 0.5 versus 11.5 ± 0.7, p = 0.013) in the TS-RFA group than in the C-RFA group. The complete ablation rate (86.5% versus 40.7%), the maximum postoperative pain score (2.5 ± 1.3 versus 4.1 ± 2.0) and symptom relief were also significantly better in the TS-RFA group than in the C-RFA group (p < 0.05). No postoperative death occurred in either group. There were no grade III or higher complications in the TS-RFA group, but one patient in the C-RFA group developed the grade III complication of postoperative abdominal bleeding.Conclusions: 'Three-step' RFA is a safe and effective minimally invasive treatment for giant hepatic hemangioma. It is worthy of further promotion and application.

Baicalin attenuates myocardial ischemia-reperfusion injury through Akt/NF-κB pathway.

BACKGROUND: Baicalin can attenuate myocardial ischemia-reperfusion (I/R) on damage. However, the mechanisms are still not fully understood. The study aimed to investigate the antiapoptosis and anti-inflammatory effects of baicalin on myocardial I/R-induced injury. METHODS: We established male rats I/R model, and baicalin was intragastric administration after ischemia onset. All experimental animals were randomly divided into five groups: group I, sham; group II, I/R; group III, 50 mg/kg; group IV, 100 mg/kg; and group V, 200 mg/kg baicalin. Postoperation, left ventricular (LV) function was recorded by transthoracic echocardiography. Myocardial infarct size, number of vessels and apoptosis were detected by histology and immunohistochemistry. Furthermore, the messenger RNA (mRNA) and protein levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), IL-6, IL-8, IL-10, Bcl2, Bax, caspase-3, phosphatidylinositol 3-kinase (PI3K), Akt, p-Akt, and nuclear factor-κB (NF-κB) p65 in myocardial tissues were measured by quantitative real-time polymerase chain reaction and Western blot analysis assays. RESULT: When compared with I/R groups, baicalin could significantly improve LV hemodynamic parameters. Myocardial infarct size and apoptosis were significantly decreased, but the vessel density was increased. The mRNA levels of TNF-α, IL-1ß, IL-6, and IL-8 were downregulated, but the levels of IL-10, proapoptotic genes caspase-3, and the ratio of Bax/Bcl2 were upregulated. Moreover, the protein expression of PI3K, p-Akt, and Akt were upregulated but NF-κB p65 was downregulated in the groups III, IV, and V than in group II. CONCLUSION: Our current study suggested that baicalin attenuated myocardial I/R-induced damage, inhibited myocardial apoptosis, and inflammation by activating PI3K/Akt but suppressing NF-κB signaling.

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α-Endoplasmic Reticulum Stress-Beclin1 Autophagy Regulatory Pathway.

The genetic association of orosomucoid-like 3 (ORMDL3) with an array of immunoinflammatory disorders has been recently unraveled in multiple ethnic groups, and functional exploration has received attention of the particular relevance of this gene in endoplasmic reticulum stress, lipid metabolism, and inflammatory response. In this study, we demonstrated the upregulation of ORMDL3 in both patients with systemic lupus erythematosus and lupus mice compared with controls. By establishing ORMDL3 knockout mice (Ormdl3-/-), we showed that silencing Ormdl3 in vivo significantly decreased the proportions of mature B lymphocytes and transitional 2B cells in spleen and B1a cells from abdominal cavity perfusion fluid, the secretion of IgG and IgM, and the expression of Baff. Additionally, knockdown of Ormdl3 augmented the apoptosis of total splenic cells and splenic CD19+ B cells but did not affect B cell proliferation and cell cycle. Subsequently, we in vitro and in vivo demonstrated that ORMDL3 potentially mediates the autophagy via the ATF 6-Beclin1 autophagy pathway, and it facilitates the survival of splenic B cells via promoting autophagy and suppressing apoptosis. Taken together, we uncovered a role of ORMDL3 in fine-tuning B cell development and survival, besides highlighting a potential mechanism by which ORMDL3 regulates autophagy via ATF6 pathway.

Association Between Single Nucleotide Polymorphisms in the Vitamin D Receptor and Incidence of Dry Eye Disease in Chinese Han Population.

BACKGROUND Dry eye disease (DED) is a chronic dysfunction of the ocular surface and has become an important public problem. Vitamin D receptor (VDR) gene polymorphism has been found to be associated with different kinds of diseases. The relationship between single nucleotide polymorphisms (SNPs) in the VDR gene should be studied. MATERIAL AND METHODS In the present case-control study, we investigated the association of VDR gene polymorphism with DED risk. Clinical data including age, gender, body mass index (BMI, kg/m²), smoking history, diabetes, and blood pressure were recorded. Serum 25-hydroxy vitamin D (25[OH]D) was chosen as the main parameter that reflected the level of vitamin D. We identified SNPs of VDR gene Apa-1, Bsm-1, Fok-1, and Taq-1 in both DED cases and healthy controls. RESULTS A total of 124 DED cases and 135 healthy controls were included in this study. It was reported that aa in Apa-1 (OR=2.803, 95% CI, 1.350-5.820) and tt in Taq-1 (OR=0.362, 95% CI, 0.141-0.930) were associated with increased the risk of DED. Analysis of the allele frequencies of VDR gene polymorphisms among DED patients and healthy controls showed that allele differences in Apa-1 were significantly associated with higher risk. CONCLUSIONS SNPs of VDR gene (Apa-1 and Taq-1) were associated with the risk of DED. No significant association of Bsm-1 and Fok-1 in VDR gene demonstrated significant effect in the incidence of DED. Thus, we found that several SNPs of VDR gene could provide significant pathogenic effects in the risk of DED.