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The development of cost-effective bifunctional catalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is critical to realize the commercialization of electrocatalytic water splitting. Herein, an effective defect engineering strategy, Ar plasma treatment, was adopted to promote both the HER and OER activity of pre-synthesized Fe-doped Ni3S2 nano-pyramid arrays on nickel foam. The abundant sulfur vacancies endow the Fe-doped Ni3S2 nano-pyramid arrays with a low overpotential of 171 mV at 10 mA cm−2 and a small Tafel slope of 49 mV dec−1 to drive the OER in 1.0 M KOH. Density functional theory (DFT) calculations reveal that sulfur vacancies together with Fe doping can effectively regulate the electronic structure of Ni3S2, resulting in increased electrical conductivity and a reduced energy barrier, as well as enhanced reaction kinetics through weakening the binding strength between active sites and intermediates. Such defect-rich hetero-metal doped catalyst also delivers enhanced HER activity. As a result, a cell assembled using defect-rich Fe-Ni3S2 nano-pyramid arrays as both the anode and cathode needs a low applied voltage of 1.63 V to reach a current density of 10 mA cm−2, and exhibits outstanding long-term stability up to 60 h.

It is important to explore novel therapeutic targets and develop an effective strategy for the treatment of anorexia nervosa. In this work, serum samples were analyzed using ultra-performance liquid chromatography coupled with quadrupole time-of flight mass spectrometry (UPLC/Q-TOF MS) coupled with chemometric analysis and multivariate analysis to obtain the metabolites and their corresponding pathways. In addition, knock-in and knock-down of the key enzyme in vivo was performed to verify the reliability of the obtained metabolic pathway, which is closely associated with the anorexia nervosa pathomechanism and the potential targets. There were significant differences in the biochemical parameters between the model group and the control group. A total of 26 potential biomarkers were identified to resolve the difference between the control and model rats, which were closely related to amino acid metabolism, sphingolipid metabolism, arachidonic acid metabolism, the citrate cycle, and so forth. According to the ingenuity pathway analysis, we further elucidated the relationship between the gene, protein, and metabolite alteration in anorexia nervosa, which are involved in cellular compromise, lipid metabolism, small molecule biochemistry, cell signaling, molecular transport, nucleic acid metabolism, cell morphology, cellular function and maintenance. Arginosuccinate synthetase (ASS) deficiency was accompanied by a significant downregulation of the β-endorphin and ghrelin in the animal models. The metabolites and pathways obtained using the metabolomics strategy may provide valuable information for the early treatment for anorexia nervosa.

Chronic inflammation plays an important role in the progression of vascular calcification (VC). This study was designed to explore the effects and underlying mechanisms of inflammation on VC in the radial arteries of patients with end-stage renal disease (ESRD) with arteriovenostomy. Forty-eight ESRD patients were divided into control (n = 25) and inflammation groups (n = 23) according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in this study. Alizarin Red S staining was used to examine calcium deposition. The expression of inflammation markers, bone structure-associated proteins and mammalian target of rapamycin complex1 (mTORC1) pathway-related proteins was assessed by immunohistochemical staining. The expression of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) was increased in the radial arteries of the inflammation group. Additionally, Alizarin Red S staining revealed a marked increase in calcium deposition in the inflammation group compared to controls. Further analysis by immunohistochemical staining demonstrated that the deposition was correlated with the increased expression of bone-associated proteins such as bone morphogenetic proteins-2 (BMP-2) and osteocalcin and collagen I, which suggested that inflammation induces osteogenic differentiation in vascular tissues and that osteogenic cells are the main cellular components involved in VC. Interestingly, there was a parallel increase in the expression of phosphorylated mTOR (p-mTOR) and pribosomal protein S6 kinase 1 (p-S6K1) in the inflammation group. Furthermore, mTORC1 pathway-related proteins were significantly associated with the enhanced expression of bone formation biomarkers. Inflammation contributed to VC in the radial arteries of ESRD patients via the induction of osteogenic differentiation in vessel walls, which could be regulated by the activation of the mTORC1 pathway.

Idiopathic pulmonary fibrosis (IPF) and tumor are highly similar to abnormal cell proliferation that damages the body. This malignant cell evolution in a stressful environment closely resembles that of epithelial-mesenchymal transition (EMT). As a popular EMT-inducing factor, TGFβ plays an important role in the progression of multiple diseases. However, the drugs that target TGFB1 are limited. In this study, we found that triptolide (TPL), a Chinese medicine extract, exerts an anti-lung fibrosis effect by inhibiting the EMT of lung epithelial cells. In addition, triptolide directly binds to TGFβ and subsequently increase E-cadherin expression and decrease vimentin expression. In in vivo studies, TPL improves the survival state and inhibits lung fibrosis in mice. In summary, this study revealed the potential therapeutic effect of paraquat induced TPL in lung fibrosis by regulating TGFβ-dependent EMT progression.

In the present study, the levels of neuron-specific enolase (NSE), interleukin-1β (IL-1β), and erythropoietin (EPO) in cerebrospinal fluid (CSF) in children with idiopathic epilepsy were measured to illuminate the relationships between these markers with idiopathic epilepsy. Eighty-five children from 6 months to 12.5 years of age with single, previously undiagnosed, and untreated idiopathic epilepsy were participated in this study. The concentrations of CSF NSE, 1L-1β, and EPO were measured by specific ELISA methods. The mean concentrations of CSF NSE, IL-1β, and EPO in the epileptic groups showed a significant increase (P < 0.01) compared with those in the control groups. Besides, the mutual correlations of NSE, 1L-1β, and EPO were also analyzed. Results showed that there were positive correlations between the levels of IL-1β, NSE, and EPO. The changes of NSE, 1L-1β, and EPO level in CSF may be beneficial for the pathophysiology study of epileptic seizures and the identification and diagnosis of a seizure clinically.

BACKGROUND Oral fluconazole is used to treat vulvovaginal candidiasis during pregnancy. However, there are concerns regarding the pregnancy outcomes following exposure to fluconazole. OBJECTIVES To evaluate the pregnancy outcomes associated with exposure to oral fluconazole during the first trimester of pregnancy. SEARCH STRATEGY A systematic literature search was conducted to identify relevant studies published from inception until April 2019. SELECTION CRITERIA Relevant English-language citations using the terms oral fluconazole and pregnancy in humans. DATA COLLECTION Two reviewers independently abstracted data and assessed study quality. MAIN RESULTS Oral fluconazole use during the first trimester of pregnancy was marginally associated with an increased risk of congenital malformations (odds ratio [OR] 1.09, 95% CI 0.99-1.2, P = 0.088; n = 6 studies), whereas in the subgroup analysis, this association existed only for high-dose users (>150 mg) (OR 1. 19, 95% CI 1.01-1.4, P = 0.039; n = 2). Exposure to fluconazole also increased the risk of heart malformations (OR 1.31, 95% CI 1.09-1.57, P = 0.003; n = 4), cardiac septal defects (OR 1.3, 95% CI 1.1-1.67, P = 0.047; n = 3), and tetralogy of Fallot (OR 3.39 95% CI 1.71-6.74, P

Peritoneal fibrosis (PF) is characterized by progressive accumulation of extracellular matrix (ECM) components in the peritoneum under high glucose conditions. Rapamycin has previously been shown to inhibit ECM accumulation of peritoneal mesothelial cells (PMCs) and prevent PF. Here we explored the undefined mechanisms by which rapamycin inhibits ECM accumulation of PMCs. We used high-glucose peritoneal dialysis solution (PDS) in a mouse peritoneal dialysis model to induce in vivo PF and in human PMCs in vitro to stimulate ECM accumulation. The mice that received chronic PDS infusions showed typical features of PF, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and higher expressions of α-smooth muscle actin and collagen I. Rapamycin significantly ameliorated these pathological changes. There was a parallel decrease in lipid accumulation in the peritoneum of rapamycin-treated mice. Rapamycin significantly inhibited high-glucose PDS-induced ECM accumulation and reduced the lipid droplet in human PMCs in the presence of PDS. The effects of rapamycin on intracellular lipid metabolism correlated with a series of steps in lipid homeostasis; namely, a decrease in low density lipoprotein receptor-mediated lipid influx, which was mediated through the downregulation of sterol regulatory element-binding protein-2 (SREBP-2) and SREBP cleavage-activating protein (SCAP), and an increase in adenosine triphosphate-binding cassette transporter A1-mediated lipid efflux, which was mediated through the upregulation of the liver X receptor α and peroxisome proliferator-activated receptor α. We conclude that rapamycin shows a clear protective effect on high-glucose PDS-induced PF by improving the disruption of intracellular lipid homeostasis.

Introduction Human papillomavirus (HPV) vaccination has been proven to effectively protect against HPV infection and infection-associated cancer. However, there are concerns about the relationship between HPV vaccination and the risk of autoimmune disorders (ADs). Therefore, we performed a systematic review and meta-analysis to comprehensively evaluate the relationship between HPV vaccination and ADs risk. Methods To identify relevant studies, we conducted a systematic search in EMBASE and PubMed databases of scientific articles published through June 2018. Fixed or random effects models were adopted to estimate overall relative risk. Results In total, 20 studies (12 cohort studies, 6 case-control studies, and 2 randomized controlled trials) involving more than 169,000 AD events were included in our meta-analysis. Our results show that HPV vaccination was not associated with an increased risk of subsequent ADs (odds ratio [OR] = 1.003, 95% confidence interval (CI): 0.95–1.06), particularly among those with a prior ADs (OR = 0.82, 95% CI: 0.7–0.96). Most of the subgroup analysis results based on the location or type of ADs were consistent with the overall results. Conclusion No evidence of an association between HPV vaccination and ADs was found. Given the low number of estimates for individual AD, additional and larger observational studies are needed to verify our findings.

The aim of this paper was to explore the effects and possible mechanisms in vitro of tea polyphenols (TP) delaying human glomerular mesangial cells (HGMCs) senescence induced by high glucose (HG). HGMCs were cultured in vitro and divided into the normal group (N, 5.5 mmol·L⁻¹ glucose), the mannitol group(MNT, 5.5 mmol·L⁻¹ glucose plus 24.5 mmol·L⁻¹ mannitol), the high dose of D-glucose group (HG, 30 mmol·L⁻¹ glucose), the low dose of TP group (L-TP, 30 mmol·L⁻¹ glucose plus 5 mg·L⁻¹ TP) and the high dose of TP group (H-TP, 30 mmol·L⁻¹ glucose plus 20 mg·L⁻¹ TP), which were cultured in 5% CO₂ at 37 °C, respectively. Firstly, the effects of TP on the cell morphology of HGMCs were observed after 72 h-intervention. Secondly, the cell cycle, the positive rate of senescence-associated-β-galactosidase (SA-β-gal) staining and the telomere length were detected, respectively. Finally, the protein expressions of p53, p21 and Rb in the p53-p21-Rb signaling pathway were investigated, respectively. And the expressions of p-STAT3 and miR-126 were examined severally. The results indicated that HG not only arrested the cell cycle in G₁ phase but also increased the positive rate of SA-β-gal staining, and shortened the telomere length. HG led to the protein over-expressions of p53, p21 and Rb and HGMCs senescence by activating the p53-p21-Rb signaling pathway. In addition, L-TP delayed HGMCs senescence by improving the cell cycle G₁ arrest, reducing SA-β-gal staining positive rate and lengthening the telomere length. L-TP reduced the protein over-expressions of p53, P21 and Rb induced by HG and inhibited the telomere-p53-p21-Rb signaling pathway. Moreover, the expression of p-STAT3 was increased and the expression of miR-126 was decreased in HGMCs induced by HG. L-TP reduced the expression of p-STAT3 and increased the expression of miR-126 in HGMCs. In conclusion, HG could induce HGMCs senescence by activating the telomere-p53-p21-Rb signaling pathway in vitro. L-TP could delay HGMCs senescence through regulating STAT3/miR-126 expressions and inhibiting the telomere-p53-p21-Rb signaling pathway activation. These findings could provide the effective interventions in clinic for preventing and treating renal cell senescence in diabetic kidney disease.

The purpose of present research was to investigate how different fertilization regimes altered soil organic nitrogen fractions and their inter-annual dynamics based on a series of long-term experiment (initiated at 1990), including: CK (non-fertilization); M (recycled pig manure); NPK (chemical fertilizer NPK); NPK + M (recycled pig manure with chemical fertilizer NPK). The results showed that soil organic nitrogen components under the different fertilization treatments presented contrastive patterns from the establishment the experiments to 2015. Generally, acid hydrolysable organic nitrogen content increased year by year. The amino acid nitrogen content under CK and NPK treatments consistently declined, although amino acid nitrogen for M and NPK+M treatments showed a increasing trend. These phenomena were probably ascribed to the utilization of soil amino acids by microbes. From 1990 to 2015, NPK treatment substantially elevated the content of acid-released ammonium nitrogen by 31.1% compared with CK (mean value across the experiment), and for the treatments using organic manure (M and NPK+M), the contents of all fractions of soil organic nitrogen increased. Notably, the increase magnitudes for NPK+M were more dramatic than those of M. These results demonstrated that combined use of organic and inorganic fertilizers could more effectively elevate soil organic nitrogen, subsequently helping to improve the capacity of soil nitrogen supply and enhance the soil fertility.依托长期定位试验(从1990年开始)的4个施肥处理(CK,不施肥;M,循环猪圈肥;NPK,单施化肥;NPK+M,化肥配施循环猪圈肥),探讨了长期施肥对潮棕壤有机氮各组分的影响并揭示了其年际变化特征.结果表明: 从试验开始至2015年,不同施肥模式下各有机氮组分呈现不同的变化趋势,其中酸解有机氮基本上表现为逐年增加的趋势;M和NPK+M处理氨基酸态氮也逐年上升,而CK和NPK处理氨基酸态氮持续下降,这可能与微生物对土壤中氨基酸的利用有关.在整个试验过程中(1990—2015年的平均值),NPK处理酸解铵态氮大幅度增加,比CK增加31.1%;在施加有机肥的2个处理中(M和NPK+M)有机氮各组分均有所提高.与M相比,NPK+M处理各有机氮组分增加的幅度更加明显,这表明有机无机肥配施能有效增加土壤有机氮,进而增强土壤供氮能力,提高土壤肥力水平.

Objective: Calcium-sensing receptors (CaSRs) regulate systemic calcium homeostasis. Intracellular calcium concentration changes are initiating factors of endoplasmic reticulum stress and cell autophagy. Recent research has revealed that CaSRs play an important role in myocardial ischemia/reperfusion injury and other cardiovascular diseases. However, it remains unclear whether CaSRs are involved in lipopolysaccharide (LPS)-induced cardiomyocyte injury. Methods: Cultured neonatal rat cardiomyocytes were treated with LPS, with or without pretreatment by a CaSR specific agonist SC-211006 or CaSR specific antagonist SC-207394. The ultrastructure of cardiomyocytes was observed using a transmission electron microscope, and the expression of CaSR, GRP78, LC3B, CytC and Bcl-2 proteins were detected by western blot. Results: Compared with the control group, LPS increased cardiomyocyte injury and the expression of CaSR, GRP78, LC3B and CytC proteins, but decreased the expression of Bcl-2. Compared with the LPS group, pretreatment with SC-211006 further enhanced cardiomyocyte damage and the expression of CaSR, GRP78, LC3B and CytC, but reduced the expression of Bcl-2. Conversely, pretreatment with SC-207394 decreased cardiomyocyte injury and the protein expression of CaSR, GRP78, LC3B and CytC, but increased the expression of Bcl-2. Conclusion: Our results suggest that CaSRs are involved in LPS-induced rat cardiomyocyte injury via the activation of endoplasmic reticulum stress and autophagy.

Based on an 11-year fertilizer field trial (located at the lower liaohe river plain), the effects of different organic manure application rates on the accumulations of heavy metals (Cu, Zn, Cd and Cr) in surface soil (0-20 cm), and the leaching characteristic and vertical migration pattern of heavy metal have been investigated in this rainfed agro-ecosystem using undisturbed soil columns. The result showed that the content of heavy metal in surface soil was elevated with the increase of manure application. The increasing magnitude was in the order of CdCuZnCr. According to the Chinese soil quality standard (GB15618-1995), the application of manure (not exceeding 50 t · ha⁻¹) did not result in serious heavy metal pollution in the surface soil. Chromium met the Grade I , and Cu and Zn met the Grade II; whereas, Cd was almost exceeded the threshold of Grade III. The potential risk of Cd in soil should be paid more attentions in future research. According to the National water quality standard (GB/T14848-93), the Cu and Cd concentrations in leachate samples were up to the Grade II except only a few samples that fell in Grade III. Furthermore, Cr in the leachate all matched Grade I water quality standard. These results indicated long-term application of manure (not exceeding 50 t · ha⁻¹) in our site had not induced contaminant risks of heavy metals in underground water. In addition, the Cu, Zn and Cd (except Cr) in leachate all declined with the increase of soil depth, indicating the low capacity of vertical migration of heavy metal. Among the four heavy metals, Zn and Cr tended to be leached into deep soil, whereas Cu and Cd were more prone to be accumulated in surface soil.

Based on a long-term experiment in Shenyang Experimental Station, the effect of manure application on the contents and budgets of Cu, Zn and Cd in the arable soil was studied. The experiment included four treatments: no mature addition (CK), mature addition 10 t · ha⁻¹ year⁻¹(M1), 25 t · ha⁻¹ year⁻¹ (M2), and 50 t · ha⁻¹ year⁻¹(M3). The result showed that Cu, Zn and Cd in soil were accumulated with manure application and prolongation of experiment, and the accumulative magnitude increased with increasing of manure application. The average annual growth rates of the heavy metals in the four treatments (CK, M1, M2, M3) were 2.83%, 6.56%, 7.54%, 8.96%; 0.03%, 3.44%, 4.53%, 6.64% and 1.51%, 8.01%, 10. 27%, 16. 08% for Cu, Zn and Cd, respectively. After six years of the experiment, the content of Cd in the M3 treatment was quite close to the threshold of Chinese Soil Quality Standard Grade III (1 mg · kg⁻¹, GB15618-1995). After 12 years of the experiment, the contents of Cu in the mature-amended treatments fell in the Chinese Soil Quality Standard Grade III, which should be paid more attention. Although the heavy metals in soil were gradually accumulated, the Cu, Zn and Cd levels in crop grain were still below the National Food Contamination Standards (GB2762-2005; GB13106-91; GB15199-94), indicating the contents of heavy metals in crop produced from contaminated soil might not exceed the corresponding standards. The contents of Cu, Zn and Cd in the straw were much greater than those in the grain. The removal of heavy metal by crop was in the order of M3M2M1CK. The average amounts of Cu, Zn and Cd annually removed from the soil in the four treatments (CK, M1, M2 and M3) were 35.68, 47.80, 63.65, 69.64; 249.14, 375.22, 375.16, 444.44, and 0.83, 1.39, 1.64, 1.66 g · ha⁻¹, respectively. The contents of heavy metals in organic manure varied in different years: the contents of Cu and Zn increased year by year, while Cd presented a decreasing trend. The average amounts of Cu, Zn and Cd annually remained in the soil in the treatments M1, M2 and M3 were 2 283.0, 5 763.7, 11585.4; 2 483.3, 6 771.4, 13 849.2 and 4.8, 13.9, 29.5 g · ha⁻¹, respectively. Since the heavy metals in organic manure markedly fluctuated in different years, the average residuals can only reflect the changing trend. Therefore, the residuals of heavy metals in the soil could be accurately predicted only according to status of manure in a given year.

The transcription factor, interferon regulatory factor 5 (IRF5), is important in the induction of type I interferon, proinflammatory cytokines and chemokines, and is involved in autoimmune diseases and tumourigenesis. However, the mechanisms underlying the transcriptional regulation of wild‑type IRF5 remain to be fully elucidated. The present study was primarily designed to clarify whether specificity protein 1 (Sp1) was involved in the regulation of IRF5. Initially, the IRF5 promoter region was cloned and its promoter activity was examined using Hela and HEK 293 cells. Deletion analyses revealed that the region spanning ‑179 to +62 was the minimal promoter of IRF5. Bioinformatics analyses showed that this region contained three putative Sp1 binding sites, and mutational analyses revealed that all the Sp1 sites contributed to transcriptional activity. Secondly, the overexpression of Sp1 was found to increase the activity of the IRF5 promoter and the mRNA level of IRF5, determined using reporter gene assays and polymerase chain reaction analysis, respectively. By contrast, treatment with mithramycin and Sp1 small interfering RNA significantly reduced the activity of the IRF5 promoter and the mRNA level of IRF5. Finally, the results of an electrophoretic mobility shift assay and a chromatin immunoprecipitation assay demonstrated that Sp1 bound to the promoter region of IRF5 in vitro and in vivo. These results suggested that the Sp1 transcription factor is the primary determinant for activating the basal transcription of the IRF5.

Glioma represents one of the main causes of cancer-related death worldwide. Unfortunately, its exact molecular mechanisms remain poorly understood, which limits the prognosis and therapy. This study aimed to identify the critical genes, transcription factors and the possible biochemical pathways that may affect glioma progression at transcription level. After downloading micro-array data from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between glioma and normal samples were screened. We predicted novel glioma-related genes and carried on online software DAVID to conduct GO enrichment and transcription factor analysis of these selected genes. String software was applied to construct a PPI protein interaction network, as well as to find the key genes and transcription factors in the regulation of glioma. A total of 97 DEGs were identified associated with cancer, the GO enrichment analysis indicated these DEGs were mainly relevant to immune responses as well as regulation of cell growth. In addition, the transcription factor analysis showed these DEGs were regulated by the binding sites of transcription factors GLI2, SP1, SMAD7, SMAD3, RELA, STAT5B, CTNNB1, STAT5A, TFAP2A and SP3. PPI protein interaction network analysis demonstrated the hub nodes in the interaction network were EGFR, TGFB1, FN1 and MYC. The hub DEGs may be the most critical in glioma and could be considered as drug targets for glioma therapy after further exploration. Besides, with the identification of regulating transcription factors, the pathogenesis of glioma at transcription level might be brought to light.