[Ginsenoside Re regulates mitochondrial biogenesis through Nrf2/HO-1/PGC-1α pathway to reduce hypoxia/reoxygenation injury in H9c2 cells].

This article explored the mechanism by which ginsenoside Re reduces hypoxia/reoxygenation(H/R) injury in H9c2 cells by regulating mitochondrial biogenesis through nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/peroxisome prolife-rator-activated receptor gamma coactivator-1α(PGC-1α) pathway. In this study, H9c2 cells were cultured in hypoxia for 4 hours and then reoxygenated for 2 hours to construct a cardiomyocyte H/R injury model. After ginsenoside Re pre-administration intervention, cell activity, superoxide dismutase(SOD) activity, malondialdehyde(MDA) content, intracellular reactive oxygen species(Cyto-ROS), and intramitochondrial reactive oxygen species(Mito-ROS) levels were detected to evaluate the protective effect of ginsenoside Re on H/R injury of H9c2 cells by resisting oxidative stress. Secondly, fluorescent probes were used to detect changes in mitochondrial membrane potential(ΔΨ_m) and mitochondrial membrane permeability open pore(mPTP), and immunofluorescence was used to detect the expression level of TOM20 to study the protective effect of ginsenoside Re on mitochondria. Western blot was further used to detect the protein expression levels of caspase-3, cleaved caspase-3, Cyto C, Nrf2, HO-1, and PGC-1α to explore the specific mechanism by which ginsenoside Re protected mitochondria against oxidative stress and reduced H/R injury. Compared with the model group, ginse-noside Re effectively reduced the H/R injury oxidative stress response of H9c2 cells, increased SOD activity, reduced MDA content, and decreased Cyto-ROS and Mito-ROS levels in cells. Ginsenoside Re showed a good protective effect on mitochondria by increasing ΔΨ_m, reducing mPTP, and increasing TOM20 expression. Further studies showed that ginsenoside Re promoted the expression of Nrf2, HO-1, and PGC-1α proteins, and reduced the activation of the apoptosis-related regulatory factor caspase-3 to cleaved caspase-3 and the expression of Cyto C protein. In summary, ginsenoside Re can significantly reduce I/R injury in H9c2 cells. The specific mechanism is related to the promotion of mitochondrial biogenesis through the Nrf2/HO-1/PGC-1α pathway, thereby increasing the number of mitochondria, improving mitochondrial function, enhancing the ability of cells to resist oxidative stress, and alleviating cell apoptosis.

[Tetrahydropalmatine inhibiting mitophagy through ULK1/FUNDC1 pathway to alleviate hypoxia/reoxygenation injury in H9c2 cells].

This study explored the specific mechanism by which tetrahydropalmatine(THP) inhibited mitophagy through the UNC-51-like kinase 1(ULK1)/FUN14 domain containing 1(FUNDC1) pathway to reduce hypoxia/reoxygenation(H/R) injury in H9c2 cells. This study used H9c2 cells as the research object to construct a cardiomyocyte H/R injury model. First, a cell viability detection kit was used to detect cell viability, and a micro-method was used to detect lactate dehydrogenase(LDH) leakage to evaluate the protective effect of THP on H/R injury of H9c2 cells. In order to evaluate the protective effect of THP on mitochondria, the chemical fluorescence method was used to detect intracellular reactive oxygen species, intramitochondrial reactive oxygen species, mitochondrial membrane potential, and autophagosomes, and the luciferin method was used to detect intracellular adenosine 5'-triphosphate(ATP) content. Western blot was further used to detect the ratio of microtubule-associated protein 1 light chain 3(LC3) membrane type(LC3-Ⅱ) and slurry type(LC3-Ⅰ) and activated cleaved caspase-3 expression level. In addition, ULK1 expression level and its phosphorylation degree at Ser555 site, as well as the FUNDC1 expression level and its phosphorylation degree of Ser17 site were detected to explore its specific mechanism. The results showed that THP effectively reduced mitochondrial damage in H9c2 cells after H/R. THP protected mitochondria by reducing the level of reactive oxygen species in cells and mitochondria, increasing mitochondrial membrane potential, thereby increasing cellular ATP production, enhancing cellular activity, reducing cellular LDH leakage, and finally alleviating H/R damage in H9c2 cells. Further studies have found that THP could reduce the production of autophagosomes, reduce the LC3-Ⅱ/LC3-Ⅰ ratio, and lower the expression of the apoptosis-related protein, namely cleaved caspase-3, indicating that THP could reduce apoptosis by inhibiting autophagy. In-depth studies have found that THP could inhibit the activation of the ULK1/FUNDC1 pathway of mitophagy and the occurrence of mitophagy by reducing the phosphorylation degree of ULK1 at Ser555 and FUNDC1 at Ser17. The application of ULK1 agonist BL-918 reversely verified the effect of THP on reducing the phosphorylation of ULK1 and FUNDC1. In summary, THP inhibited mitophagy through the ULK1/FUNDC1 pathway to reduce H/R injury in H9c2 cells.

[Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction].

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.

Dimensionality-Inhibited Chemical Doping in Two-Dimensional Semiconductors: The Phosphorene and MoS2 from Charge-Correction Method.

Despite the great appeal of two-dimensional semiconductors for electronics and optoelectronics, to achieve the required charge carrier concentrations by means of chemical doping remains a challenge due to large defect ionization energies (IEs). Here, by decomposing the defect IEs into three parts based on ionization process, we propose a conceptual picture that the large defect IEs are caused by two effects of reduced dimensionality. While the quantum confinement effect makes the neutral single-electron point defect levels deep, the reduced screening effect leads to high energy cost for the electronic relaxation. The first-principles calculations for black phosphorus and MoS2 do demonstrate the general trend. Using BP monolayer either embedded into dielectric continuum or encapsulated between two hBN layers, we demonstrate the feasibility of increasing the screening to reduce the defect IEs. Our analysis is expected to help achieve effective carrier doping and open ways toward more extensive applications of 2D semiconductors.

[Effect of Jinzhen Oral Liquid on cough after lipopolysaccharide-induced infection in rats and mechanism].

This study aims to explore the effect of Jinzhen Oral Liquid(JOL) on cough after infection in rats and the mechanism. To be specific, a total of 60 male SD rats were classified into 6 groups: normal group(equivalent volume of distilled water, ig), model group(equivalent volume of distilled water, ig), Dextromethorphan Hydrobromide Oral Solution group(3.67 mL·kg~(-1), ig), high-, medium-, and low-dose JOL groups(11.34, 5.67, and 2.84 mL·kg~(-1), respectively, ig). Lipopolysaccharide(LPS, nasal drip), smoking, and capsaicin(nebulization) were employed to induce cough after infection in rats except the normal group. Administration began on the 19 th day and lasted 7 days. Capsaicin(nebulization) was used to stimulate cough 1 h after the last administration and the cough frequency and cough incubation period in rats were recorded. The pathological morphology of lung tissue was observed based on hematoxylin-eosin(HE) staining. Immunohistochemistry(IHC) was used to detect the specific expression of transient receptor potential vanilloid 1(Trpv1), nerve growth factor(NGF), tropomyosin receptor kinase A(TrkA), and phosphorylated-p38 mitogen-activated protein kinase(p-p38 MAPK) in lung tissue, Western blot the protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue, and real-time fluorescent quantitative polymerase chain reaction(real-time PCR) the mRNA expression of Trpv1, NGF, and TrkA. The results showed that model group demonstrated significantly high cough frequency, obvious proliferation and inflammatory cell infiltration in lung tissue, significantly enhanced positive protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue and significant increase in the mRNA expression of Trpv1, NGF, and TrkA compared with the normal group. Compared with the model group, JOL can significantly reduce the cough frequency, alleviate the pathological changes of lung tissue, and decrease the protein expression of Trpv1, NGF, TrkA, and p-p38 MAPK in lung tissue, and high-dose and medium-dose JOL can significantly lower the mRNA expression of Trpv1, NGF, and TrkA. This study revealed that JOL can effectively inhibit Trpv1 pathway-related proteins and improve cough after infection. The mechanism is that it reduces the expression of NGF, TrkA, and p-p38 MAPK in lung tissue, thereby decreasing the expression of Trpv1 and cough sensitivity.

More Se Vacancies in Sb2 Se3 under Se-Rich Conditions: An Abnormal Behavior Induced by Defect-Correlation in Compensated Compound Semiconductors.

It was believed that the Se-rich synthesis condition can suppress the formation of deep-level donor defect VSe (selenium vacancy) in Sb2 Se3 and is thus critical for fabricating high-efficiency Sb2 Se3 solar cells. However, here it is shown that by first-principles calculations the density of VSe increases unexpectedly to 1016 cm-3 when the Se chemical potential increases, so Se-rich condition promotes rather than suppresses the formation of VSe . Therefore, high density of VSe is thermodynamically inevitable, no matter under Se-poor or Se-rich conditions. This abnormal behavior can be explained by a physical concept "defect-correlation", i.e., when donor and acceptor defects compensate each other, all defects become correlated with each other due to the formation energy dependence on Fermi level which is determined by densities of all ionized defects. In quasi-1D Sb2 Se3 , there are many defects and the complicated defect-correlation can give rise to abnormal behaviors, e.g., lowering Fermi level and thus decreasing the formation energy of ionized donor VSe 2+ in Se-rich Sb2 Se3 . Such behavior exists also in Sb2 S3 . It explains the recent experiments that the extremely Se-rich condition causes the efficiency drop of Sb2 Se3 solar cells, and demonstrates that the common chemical intuition and defect engineering strategies may be invalid in compensated semiconductors.

Hyperdynamics simulations with ab initio forces.

By applying the locally optimal rotation method to deal with the lowest eigenvalue of a Hessian matrix, we have efficiently incorporated the hyperdynamics method into the ab initio scheme. In the present method, we only need to calculate the first derivative of the potential and several more force calls in each molecular dynamics (MD) step, which makes hyperdynamics simulation applicable in ab initio MD simulations. With this implementation, we are able to simulate defect diffusion in silicon with boost factors up to 105. We utilized both direct MD and the hyperdynamics method to investigate diffusion of lithium atoms and silicon vacancies in silicon. We identified the complex diffusion process. The obtained diffusion coefficients of Li atoms and Si vacancies are in good agreement with the direct MD results.

[Network Meta-analysis of clinical efficacy of Chinese herbal injection in adjuvant treatment of unstable angina pectoris].

The present study evaluated the curative efficacy of Chinese herbal injection on unstable angina pectoris( UAP) by network Meta-analysis. The databases,including Pub Med,Cochrane Library,Web of Science,CNKI,CBM,VIP and Wanfang were searched for randomized controlled trial( RCT) of Chinese herbal injection in the treatment of UAP. All researchers independently screened the articles,extracted the data and evaluated the quality. Open BUGS and Stata were employed for the analysis of the trials that met the quality standards. Fifty-eight studies were finally included in this study,involving 20 intervention measures. In terms of the effective rate,16 injections such as Dengzhan Xixin Injection,Xuesaitong Injection and Danshen Injection combined with western medicine exhibited significant efficacy. In terms of ECG,Puerarin Injection,Ginkgo Leaf Extract and Dipyridamole Injection( GDI),Breviscapine Injection combined with western medicine were superior to western medicine. In terms of the reduction of the angina attack times,Sodium Tanshinone ⅡASulfonate Injection,GDI and Dazhu Hongjingtian Injection combined with western medicine showed better effects than western medicine. In terms of shortening the angina duration,Shenmai Injection combined with western medicine was superior to western medicine. As revealed by the results,Dengzhan Xixin Injection,Xuesaitong Injection,Danshen Injection,Breviscapine Injection,Danshen Ligustrazine Injection combined with western medicine displayed prominent curative efficacy,which were recommended for clinical application. Meanwhile,appropriate intervention measures should be selected according to individual conditions. Limited by the quality of the included trials,the conclusions still need to be further verified.

[Salvianolic acid B regulates mitochondrial autophagy mediated by NIX to protect H9c2 cardiomyocytes from hypoxia/reoxygenation injury].

The aim of this paper was to investigate whether the mechanism of salvianolic acid B in protecting H9 c2 cardiomyocytes from hypoxia/reoxygenation injury is related to the regulation of mitochondrial autophagy mediated by NIX. H9 c2 cardiomyocytes were cultured in vitro and divided into normal group, model group and salvianolic acid B group(50 µmol·L~(-1)). Hypoxia/reoxygenation injury model was established by hypoxia for 4 h and reoxygenation for 2 h. In normal group, high glucose DMEM medium was used for culture. Those in model group were cultured with DMEM medium without glucose and oxygen, and no drugs for hypoxia and reoxyge-nation. In salvianolic acid B group, salvianolic acid B prepared by glucose-free DMEM medium was added during hypoxia, and the other process was as same as the model group. The cell viability was evaluated by CCK-8 assay. The leakage of lactate dehydrogenase(LDH) was detected by microplate method. The levels of intracellular reactive oxygen species(ROS) and mitochondrial membrane potential(ΔΨm) were measured by chemical fluorescence method. The level of intracellular adenosine triphosphate(ATP) was mea-sured by fluorescein enzyme method. The autophagy related proteins LC3-Ⅰ, LC3-Ⅱ, apoptosis related protein cleaved caspase-3 and mitochondrial autophagy receptor protein NIX were detected by Western blot. As compared with the normal group, the activity of H9 c2 cardiomyocytes and ATP level were decreased(P<0.05); LDH leakage and ROS production were increased(P<0.01); ΔΨm was decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio, cleaved caspase-3 and NIX protein expression levels were increased(all P<0.05) in the model group. As compared with the model group, the activity of cells and ΔΨm were significantly increased(P<0.01); ATP level was increased(P<0.05); LDH leakage and ROS generation were decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio was decreased(P<0.01); cleaved caspase-3 and NIX expression levels were decreased(P<0.05) in the salvianolic acid B group. The protective effect of salvianolic acid B on hypoxia/reoxygenation injury of H9 c2 cardiomyocytes may be associated with inhibiting mitochondrial auto-phagy. The specific mechanism may be related to inhibiting the activation of mitochondrial autophagy mediated by NIX, increasing ΔΨm, reducing ROS production, reducing the expression of cleaved caspase-3, LC3-Ⅱ, and increasing cell viability.

[Research progress of traditional Chinese medicine in regulating autophagy and ischemic heart disease].

Ischemic heart disease(IHD) is a common and frequently-occurring disease that causes serious harm to human health. Autophagy is a life process that maintains cell homeostasis by degrading macromolecules such as damaged organelles in cells. In the process of ischemic heart disease development, on the one hand, cardiomyocytes degrade macromolecules such as damaged organelles by autophagy to provide material basis for energy synthesis and maintain cell homeostasis; on the other hand, over-activated autophagy can also increase cardiomyocyte death. Ischemic heart disease has a complex pathological mechanism, and the occurrence of autophagy is closely related to the survival or death of myocardial cells, so the regulation of autophagy may be an important therapeutic target for ischemic heart disease. Traditional Chinese medicine(TCM) with obvious effects, unique advantages and great potential has been widely used in the treatment of ischemic heart disease. In recent years, more and more studies have found that TCM can protect myocardium by regulating autophagy of cardiomyocytes. In this review, we summarized recent studies on the regulation of autophagy in myocardial cells by traditional Chinese medicine in ischemic heart disease. The pharmacological mechanism of Chinese medicinein regulating autophagy to protect cardiomyocytes was reviewed through different ways(promoting or inhibiting autophagy) from three levels, i.e. active ingredient, as well as drug pair and compound. The specific mechanism of Chinese medicine in regulating autophagy to protect ischemic heart disease was explored to provide references or new ideas for clinical treatment and drug development of ischemic heart disease.

[Protective effect of safflower yellow injection against rat MIRI by TLR-NF-κB inflammatory pathway].

This study was to investigate the mechanism of safflower yellow injection for regulating inflammatory response against myocardial ischemia-reperfusion injury( MIRI) in rats. Male Wistar rats were randomly divided into sham operation group,model group,Hebeishuang group,safflower yellow injection high,medium and low dose groups. MIRI model was established by ligating left anterior descending coronary artery. Myocardial histopathological changes were observed by HE staining; myocardial infarct size was detected by TTC staining; content and changes of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6),serum creatine kinase( CK),aspartate aminotransferase( AST),and lactate dehydrogenase( LDH) were detected by biochemical method or enzyme-linked immunosorbent assay( ELISA). Western blot assay was used to detect the protein expression of Toll-like receptor 4( TLR4) and nuclear factor-κB( NF-κB p65) in myocardial tissues. The results showed that as compared with the sham operation group,the myocardial arrangement of the model group was disordered,with severe edemain the interstitial,significantly increased area of myocardial infarction,increased activities of AST,CK and LDH in serum,and significantly increased contents of TNF-α and IL-6; the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were also increased. As compared with the model group,the myocardial tissues were arranged neatlyin the Hebeishuang group and safflower yellow injection high,medium and low dose groups; the edema was significantly reduced; the myocardial infarct size was significantly reduced; the serum AST,CK,LDH activity and TNF-α,IL-6 levels were significantly decreased,and the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were decreased. As compared with the Hebeishuang group,the myocardial infarct size was larger in the safflower yellow injection high,medium and low dose groups; the activities of AST,CK and LDH in serum and the contents of TNF-α and IL-6 in serum were higher,but there was no statistically significant difference in the expression levels of TLR4 and NF-κB( p65) protein in tissues. It is suggested that safflower yellow injection has a significant anti-MIRI effect,and its mechanism may be related to the regulation of TLR-NF-κB pathway to inhibit inflammatory response.

Topological Dirac States beyond π-Orbitals for Silicene on SiC(0001) Surface.

The discovery of intriguing properties related to the Dirac states in graphene has spurred huge interest in exploring its two-dimensional group-IV counterparts, such as silicene, germanene, and stanene. However, these materials have to be obtained via synthesizing on substrates with strong interfacial interactions, which usually destroy their intrinsic π(pz)-orbital Dirac states. Here we report a theoretical study on the existence of Dirac states arising from the px,y orbitals instead of pz orbitals in silicene on 4H-SiC(0001), which survive in spite of the strong interfacial interactions. We also show that the exchange field together with the spin-orbital coupling give rise to a detectable band gap of 1.3 meV. Berry curvature calculations demonstrate the nontrivial topological nature of such Dirac states with a Chern number C = 2, presenting the potential of realizing quantum anomalous Hall effect for silicene on SiC(0001). Finally, we construct a minimal effective model to capture the low-energy physics of this system. This finding is expected to be also applicable to germanene and stanene and imply great application potentials in nanoelectronics.

[Cas9 protein variant VQR recognizes NGAC protospacer adjacent motif in rice].

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system is the third-generation genome editing tools that was developed and widely used in recent years. However, Streptococcus pyogenes Cas9 (SpCas9) in this system could only recognize NGG PAM (protospacer adjacent motif), which largely restricts the range of genome editing. The VQR (D1135V/R1335Q/T1337R) variant of SpCas9 could recognize NGAA, NGAG and NGAT PAMs in rice. However, whether VQR variant could recognize NGAC PAM remains unclear. In this study, three low editing efficiency sites of the VQR variant, NAL1-Q1, NAL1-Q2 and LPA1-Q, were selected for genome editing using the improved CRISPR/VQR system. The improved CRISPR/VQR system effectively edited these target sites, and the gene editing efficiency was 9.75%, 43.90% and 29.26% respectively. To ensure the recognition of NGAC PAM by the improved CRISPR/VQR system, two NGAC PAM containing sites (NAL-C and GL1-C) in the NARROW LEAF 1 (NAL1) for leaf length and GLOSSY1 (GL1) genes for wax biosynthesis were selected for genome editing in rice in this study, and 57 transgenic plants were obtained. The PCR amplification and sequencing results showed that 27 plants (47.36%) had mutation in the NAL1-C site, 44 plants (77.19%) had mutation in the GL1 gene, and 26 plants (45.61%) had mutation in the NAL-C and GL1-C sites. Further analysis revealed that there were four types of mutations caused by the CRISPR/VQR system, respectively for the hybrid mutation, biallelic mutation, chimeric mutation and homozygous mutations. Among them, heterozygous mutation and biallelic mutation were dominant changes. These results indicated that the improved CRISPR/VQR system could efficiently edit the NGAC PAM sites of the rice and produce abundant mutant types. This study provides a theoretical basis for NGAC PAM editing in rice and other related plants.

Novel Gas Sensor Based on ZnO Nanorod Circular Arrays for C2H5OH Gas Detection.

Novel side-heating gas sensor based on ZnO nanorod circular arrays was firstly fabricated by hydrothermal treatment assisted with a kind of simple dip-coating technique. The structure and morphologies of ZnO nanorods were characterized by X-ray diffraction (XRD), Scanning Electron Microscope (SEM), respectively. XRD result indicates that the obtained ZnO nanorods have good crystalline with the hexagonal wurtzite structure. SEM result indicates that ZnO nanorod arrays are vertically growth on the surface of ceramic tube of side-heating sensor with controlled diameter and length, narrow size distribution and high orientation. The gas sensing properties of ZnO nanorod circular arrays are also evaluated. Comparative to the sensor based on scattered ZnO nanorods responding to 25 ppm H2, CO, C6H5CH3 and C2H5OH gas, respectively, the sensing values of high orientation gas sensor are generally increased by 5%. This novel sensor has good application promising for the fabrication of cost effective and high performance gas sensors.

Association of apolipoprotein E (ApoE) polymorphisms with risk of primary hyperuricemia in Uygur men, Xinjiang, China.

BACKGROUND: Apolipoprotein E (ApoE) participates in lipoprotein metabolism and immune regulation. This study assessed association between ApoE polymorphisms with hyperuricemia and uric acid metabolism in Uygur men, Xinjiang, China. METHODS: A total of 474 hyperuricemia patients and 518 healthy male controls were recruited from the Health Screening Center, Uygur region of Xinjiang, China and subjected to ApoE genotyping using a multiplex amplification refractory mutation system PCR. RESULTS: Apolipoprotein E3/3 genotype was the predominant type with a frequency of 67.7%, while E2/2 was lower than E4/4 in Uygur males. The frequencies of ApoE2, E3, and E4 alleles were 8.5%, 80.1% and 11.4%, respectively. Distribution of ApoE genotypes was significantly different in hyperuricemia patients from the healthy controls (p<0.001). Particularly, the frequency of ApoE E3/3 was 71.7%, E2/3 9.3%, E3/4 9.3%, E4/4 3.2%, E2/4 2.3%, and E2/2 0.2% in patients vs. 68.1%, 4.6%, 2.9%, 12%, 0.6%, and 4.6% in controls, respectively. Moreover, frequency of ApoE E2 allele was greater in the healthy controls than in patients (p<0.001) and the highest level of uric acid occurred in those with ApoE2/4 and E3/4 genotypes, whereas the lowest uric acid level occurred in those with ApoE E2/2 genotype. In addition, the subjects with the ApoE2 allele had a lower uric acid and LDL-C level than those with the ApoE3 allele and ApoE4 allele (p<0.05). The risk of developing hyperuricemia in subjects without the ApoE2 allele was 1.7 fold higher than those subjects with the ApoE2 allele. CONCLUSIONS: This study revealed frequencies and distributions of ApoE alleles and genotypes in Uygur males, which are different from Han Chinese. ApoE E4 was associated with a slightly higher risk of primary hyperuricemia, whereas ApoE E2 was associated with reduced risk of primary hyperuricemia and LDL-C level.

Low-dose ketamine pretreatment reduces oxidative damage and inflammatory response following CO2 pneumoperitoneum in rats.

PURPOSE: The duration of pneumoperitoneum during laparoscopic procedures may contribute to post-surgical oxidative stress. Previous studies have shown that low-dose ketamine, an anesthetic with anti-inflammatory properties, protects various organs from ischemia-reperfusion injury. This study investigated the effects of low-dose ketamine on the overproduction of oxidants and the tissue damage caused by intra-abdominal pressure during CO2 pneumoperitoneum. METHODS: Male Sprague Dawley rats received a CO2 pneumoperitoneum of 15 mmHg and preceded by either low-dose ketamine (KP1, 5 mg/kg; KP2, 10 mg/kg) or 0.9% saline (PR, 3 ml). General anethesia was provided by pentobarbital and sevoflurane. The control group (CR) received an intraperitoneal saline injection and sham surgery. Three hours after pneumoperitoneum, serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and intestinal fatty acid binding protein (iFABP) were measured and liver, kidney, lung, and intestine were evaluated for tissue damage. RESULTS: The highest plasma MDA, TNF-α, IL-6 and iFABP values were observed at T1 (after 3 hours of pneumoperitoneum) in the PR group, followed by the KP1, KP2, and CR groups (P < 0.01). SOD concentrations showed an opposite trend and were highest in the CR group, followed by the KP2, KP1, and PR groups (P < 0.01). TNF-α concentration was significantly lower in the KP2 than the KP1 group (P < 0.05). Histopathologic scoring of organ sections demonstrated the lowest scores in the KP2 group, followed by the KP1 and PR groups, in an increasing order (P < 0.05). CONCLUSION: Pretreatment with low-dose ketamine before general anaesthesia protects against potential oxidative damage and inflammatory response caused by CO2 pneumoperitoneum.

Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway.

OBJECTIVE: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 ß, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. RESULTS: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 ß, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). CONCLUSIONS: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

Preparation of water storage ceramsite via dredged silt and biomass waste: Pore formation, water purification and application.

Natural water pollution and eutrophication are environmental problems that urgently need to be solved. Porous ceramsite could be applied for both water storage and water purification. This research used biomass and dredged silt to prepare water storage ceramsite (WSC), and investigated the adsorption and removal effects of WSC on phosphorus (P), nitrogen ((NH4+)N) and chemical oxygen demand (COD). The results showed that the biomass was mostly burned and partially carbonized during the high-temperature sintering process to form a rich pore structure inside the material. The rich pore structure effectively improved the water absorption to 105.58 %. The abundant specific surface area could provide many attachment sites, which is conducive to the adsorption of target ions by WSC. Further testing showed that WSC could adsorb ions with different charges in different pH solutions. Therefore, this study provides a sustainable solution for the co-utilization of biomass waste and dredged silt, and the application of WSC could reduce the damage caused by extreme rainfall and water pollution.

Natalizumab Treatment of Relapsing Remitting Multiple Sclerosis Has No Long-Term Effects on the Proportion of Circulating Regulatory T Cells.

INTRODUCTION: Natalizumab (NTZ), a monoclonal antibody against the integrin α4ß1 (VLA-4) found on activated T cells and B cells, blocks the interaction of this integrin with adhesion molecules of central nervous system (CNS) endothelial cells and lymphocyte migration through the blood-brain barrier, effectively preventing new lesion formation and relapses in multiple sclerosis (MS). Whether NTZ treatment has additional effects on the peripheral immune system cells, and how its actions compare with other MS disease-modifying treatments, have not been extensively investigated. In particular, its effect on the proportions of circulating regulatory T cells (Treg) is unclear. METHODS: In this study, we investigated the effect of NTZ treatment in 12 patients with relapsing MS, at 6 and 12 months after the start of treatment. We evaluated the proportions of regulatory T cells (Treg), defined by flow cytometry as CD4+ CD25++ FoxP3+ cells and CD4+ CD25++ CD127- cells at these intervals. As an exploratory study, we also investigated the NTZ effects on the proportions of bulk T and B lymphocyte populations, and of those expressing novel the markers CD195 (CCR5), CD196 (CCR6), or CD161 (KLRB1), which are involved in MS pathogenesis but have been studied less in the context of MS treatment. The effects of NTZ were compared to those obtained with 11 patients under interferon-beta-1a (IFN-ß1a) treatment, and against 9 healthy volunteers. RESULTS: We observed a transient increment in the proportion of Treg cells at 6 months, which was not sustained at 12 months. We observed a reduction in the proportion of T cells expressing CD195 (CCR5) and CD161 (KLRB1) subsets of T cells. CONCLUSION: We conclude that NTZ does not have an effect on the proportion of Treg cells over 1 year, but it may affect the expression of molecules important for some aspects MS pathogenesis, in a manner that is not shared with IFN-ß1a.

Semiconductor-to-metal transition from monolayer to bilayer blue phosphorous induced by extremely strong interlayer coupling: a first-principles study.

Monolayer blue phosphorous has a large band gap of 2.76 eV but counterintuitively the most stable bilayer blue phosphorous has a negative band gap of -0.51 eV. Such a large band gap reduction from just monolayer to bilayer has not been revealed before, the underlying mechanism behind which is important for understanding interlayer interactions. In this work, we reveal the origin of the semiconductor-to-metal transition using first-principles calculations and tight-binding models. We find that the interlayer interactions are extremely strong, which can be attributed to the short layer distance and strong π-like atomic orbital couplings. Therefore, the upshift of the valence band maximum (VBM) from monolayer to bilayer blue-P is so large that the VBM in the bilayer gets higher than the conduction band minimum, leading to a negative band gap and an energy gain. Besides, the interlayer atomic misplacements weaken the couplings of out-of-plane orbitals. Therefore, the energy gain due to the semiconductor-to-metal transition is larger than the energy cost due to interlayer repulsions, thus stabilizing the metallic phase. The large band gap reduction with layer number increasing is expected to exist in other similar layered systems.