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To study the relationship of soy foods and nuts consumption during early pregnancy with the risk of gestational diabetes mellitus (GDM).This was a prospective observational study conducted in Southwest China. Dietary information was assessed through 3-day 24-h dietary recalls at 6-14 gestational weeks. For soy foods and nuts, non-consumers were used as the reference category and the consumers were categorized into tertiles. GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24-28 gestational weeks. Log-binomial models were used to assess the effects of soy foods and nuts on GDM.Of the 1495 pregnant women, 529 were diagnosed with GDM. Median (IQRs) intakes of soy foods and nuts were 2.9 (0.0, 10.3) and 5.0 (0.0, 15.0) g/d, respectively. Our study found that, compared with the non-consumers, the highest tertile of soy foods intake was associated with a decrease in risk of GDM (RR = 0.73, 95%CI: 0.54-0.99,Consumption of soy foods and nuts are independently inversely associated with the risk of GDM during early pregnancy.

Background Genome-wide functional genetic studies of food-borne pathogens could provide a comprehensive understanding of the mechanisms underline their survival and pathogenesis in the harsh environments during food processing and infections. Traditional methods such as physical mutagenesis, chemical mutagenesis, and labeled DNA fragment insertion mutation techniques are time-consuming, labor-intensive and low precision. Although RNA-Seq and other omics methods enable high-throughput research on a genome-wide scale, the obtained results of gene transcription or expression cannot establish direct causal connection between the genetic determinants and particular functions. Scope and approach Transposon sequencing (Tn-seq) is an emerging microbial functional genomic technology based on transposon mutagenesis and high-throughput sequencing technologies, which is able to quantitatively track millions of independent mutants in a single experiment, and therefore efficiently map the “genotype-phenotype” relationship and the genetic interaction networks of a bacterium. Key findings and conclusions This article summarizes the common types and hazards of food-borne pathogens, the development of Tn-seq technology, and its applications in studying the physiology, pathogenesis, and environmental survival of food-borne pathogens.

To examine the association between fruit intake and blood glucose metabolism.Healthy singleton pregnant women with 6-14 weeks of gestation were selected in a maternal-and-child health care institution in Chengdu from February to July 2017. Dietary information was obtained by 3-day 24-hour dietary recall during each trimester, and the average daily total fruit intake per person were calculated. According to the Dietary guidelines for Chinese pregnant women(2016), insufficient rates of fruits were calculated, and the participants were divided into insufficient intake group, suitable intake group and higher intake group. Multiple linear regression was used to analyze the association between fruit intake during pregnancy and fasting blood glucose, 1-h plasma glucose and 2-h plasma glucose. Log-binomial regression model was used to analyze the association between fruit intake during pregnancy and the risk of gestational diabetes mellitus(GDM).Valid samples of 1453 cases in early pregnancy, 1049 cases in middle pregnancy were included, the age was(28.5±4.0)years old. The average fruit intake during the early and middle pregnancy(M(P25, P75)) were 279.7(180.8, 415.2) g/d and 232.0(100.0, 390.0) g/d, respectively. The insufficient rates were 18.8% and 43.2%, respectively. After adjusting for age, pre-pregnancy BMI, education level, family income, family history of diabetes, parity, physical activity, energy, vegetables, grains, red meat, and beverages, multiple linear regression result showed that compared with the insufficient fruit intake group, in the suitable fruit intake group, the fasting blood glucose level was decreased(β=-0.071, 95%CI-0.111--0.003). Results of log binomial regression analysis showed that when compared with the fruit suitable intake group during the second trimester, the insufficient intake group may increase the risk of GDM(RR=1.13, 95% CI 1.11-1.58); no association between fruit intake during the early pregnancy and blood glucose metabolism was observed.Fruit intake during pregnancy is associated with blood glucose metabolism. The appropriate amount of fruit intake may improve fasting blood glucose and insufficient intake of fruits during the second trimester may increase the risk of GDM.

Listeria monocytogenes (Lm) is a foodborne pathogen that can cause severe human illness. Standard control measures for restricting bacterial growth, such as refrigeration, are often inadequate as Lm grows well at low temperatures. To identify genes involved in growth at low temperatures, a powerful functional genomics method Tn-seq was performed in this study. This genome-wide screening comprehensively identified the known and novel genetic determinants involved in low-temperature growth. A novel gene

Background: More than one-fifth of the world’s population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. Methods: A multicenter, patient- and outcome assessor–blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. Results: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was –5.0 (95% CI, –6.5 to –3.5) mm Hg and –2.8 (95% CI, –3.7 to –1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were –10.0 (95% CI, –12.1 to –7.9) mm Hg and –3.8 (95% CI, –5.0 to –2.5) mm Hg, respectively. The effect size did not differ among cuisines ( P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, –0.1 to 0.2; P =0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups ( P =0.259), and none of the adverse events was associated with the intervention. Conclusions: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03882645.

The purpose of this study was to evaluate the association between starchy vegetable consumption and subgroup consumption in the first trimester and the risk of gestational diabetes mellitus (GDM).A prospective study (Among the 1444 participants in our study, 520 were diagnosed with GDM. The adjusted RRs (95% CIs) for GDM from the lowest to the highest quartiles of total starchy vegetable consumption were 1.00 (reference), 1.29 (1.06, 1.57), 1.13 (0.93, 1.40), and 1.26 (1.02, 1.56), respectively;A higher consumption of total starchy vegetables and potatoes in the first trimester is associated with a greater risk of GDM.

Objectives:Fruit intake may influence gestational diabetes mellitus (GDM) risk. However, prospective evidence remains controversial and limited. The current study aimed to investigate whether total fruit and specific fruit intake influence GDM risk.Design:A prospective cohort study was conducted. Dietary information was collected by a 3-d 24-h dietary recall. All participants underwent a standard 75-g oral glucose tolerance test at 24–28 gestational weeks. Log-binomial models were used to estimate the association between fruit intake and GDM risk, and the results are presented as relative risks (RR) and 95 % CI.Setting:Southwest China.Participants:Totally, 1453 healthy pregnant women in 2017.Results:Total fruit intake was not associated with lower GDM risk (RR of 1·03 (95 % CI 0·83, 1·27) (Ptrend = 0·789)). The RR of GDM risk was 0·73 for the highest anthocyanin-rich fruit intake quartile compared with the lowest quartile (95 % CI 0·56, 0·93; Ptrend = 0·015). A higher grape intake had a linear inverse association with GDM risk (Q4 v. Q1: RR = 0·65; 95 % CI 0·43, 0·98; Ptrend = 0·044), and after further adjustment for anthocyanin intake, the inverse association tended to be non-linear (Q4 v. Q1: RR = 0·65; 95 % CI 0·44, 0·98; Ptrend = 0·079). However, we did not find an association between glycaemic index-grouped fruit, glycaemic load-grouped fruit or other fruit subtype intake and GDM risk.Conclusions:In conclusion, specific fruit intake (particularly anthocyanin-rich fruit and grapes) but not total fruit intake was inversely associated with GDM risk.

We aimed to examine the association between low-carbohydrate diet (LCD) scores during the first trimester and gestational diabetes mellitus (GDM) risk in a Chinese population. A total of 1455 women were included in 2017. Dietary information during the first trimester was collected by 24-h dietary recalls for 3 d. The overall, animal and plant LCD scores, which indicated adherence to different low-carbohydrate dietary patterns, were calculated. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24–28 weeks gestation. Log-binomial models were used to estimate relative risks (RR) and 95 % CI. The results showed that the multivariable-adjusted RR of GDM from the lowest to the highest quartiles of the overall LCD score were 1·00 (reference), 1·15 (95 % CI 0·92, 1·42), 1·30 (95 % CI 1·06, 1·60) and 1·24 (95 % CI 1·01, 1·52) (P = 0·026 for trend). Multivariable-adjusted RR (95 % CI) of GDM from the lowest to the highest quartiles of the animal LCD score were 1·00 (reference), 1·20 (95 % CI 0·96, 1·50), 1·41 (95 % CI 1·14, 1·73) and 1·29 (95 % CI 1·04, 1·59) (P = 0·002 for trend). After additional adjustment for gestational weight gain before GDM diagnosis, the association of the overall LCD score with GDM risk was non-significant, while the association of animal LCD score with GDM risk remained significant. In conclusion, a low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of GDM in Chinese women.

Objectives Haploid germ cell-specific nuclear protein kinase (Haspin) is a serine/threonine kinase as an atypical kinase, which is structurally distinct from conventional protein kinases. Key findings Functionally, Haspin is involved in important cell cycle progression, particularly in critical mitosis regulating centromeric sister chromatid cohesion during prophase and prometaphase, and subsequently ensuring proper chromosome alignment during metaphase and the normal chromosome segregation during anaphase. However, increasing evidence has demonstrated that Haspin is significantly upregulated in a variety of cancer cells in addition to normal proliferating somatic cells. Its knockdown or small molecule inhibition could prevent cancer cell growth and induce apoptosis by disrupting the regular mitotic progression. Given the specificity of its expressed tissues or cells and the uniqueness of its current known substrate, Haspin can be a promising target against cancer. Consequently, selective synthetic and natural inhibitors of Haspin have been widely developed to determine their inhibitory power for various cancer cells in vivo and in vitro. Summary Here our perspective includes a comprehensive review of the roles and structure of Haspin, its relatively potent and selective inhibitors and Haspin’s preliminary studies in a variety of cancers.

As a commonly used traditional Chinese herbal medicine, Erodii Herba Geranii Herba (Geranium wilfordii Maxim., Geranium carolinianum L. and Erodium stephanianum Willd.), which was known as Laoguancao (Chinese:), has high medicinal value. It has been used to dispel rheumatism, dredge the meridians, activate blood circulation, remove blood stasis, clear heat and detoxify, and stop diarrhea and dysentery. It's also used to treat eczema, sores, carbuncles, boils caused by accumulation of damp toxin.This review aimed to provide a systematic and comprehensive analysis of the current research progress in terms of the botany, ethnopharmacology, phytochemistry and pharmacological activities of Erodii Herba Geranii Herba, and discuss expectations for prospective research and implementation about this herb.Information on Erodii Herba Geranii Herba was gathered via the Internet (using Google Scholar, Baidu Scholar, Pubmed, Elsevier, ACS, Medline Plus, CNKI and Web of Science) and libraries. Additionally, information was also obtained from local books and brilliant scholars in ethnopharmacology.More than isolated 240 chemical compounds were recorded, and main compositions are tannins, flavones, organic acids and volatile oil. The pharmacoactives of Erodii Herba Geranii Herba and its active constituents are diverse, including antibacterial, antiviral, antioxidant, liver and kidney protection, anti-inflammatory and analgesic, other activities. Among them, the antibacterial, antiviral, anti-inflammatory, analgesic, antidiarrheal and other pharmacological activities of it are consistent with traditional applications.All kinds of research conducted on Erodii Herba Geranii Herba, especially in field of ethnopharmacological use, phytochemicals and pharmacology have been reviewed. There are plenty of active compounds with varied effects in Erodii Herba Geranii Herba. However, some traditional applications and pharmacological activities of Erodii Herba Geranii Herba have not been scientifically evaluated or convincing due to incomplete methods and ambiguous results, as well as the lack of clinical data. In order to verify the pharmacological activity, clinical efficacy and safety of it, a systematic and comprehensive research evaluation is also required. As an important traditional Chinese medicine, Erodii Herba Geranii Herba should be further explored to promote the development of new drugs and therapeutics for various diseases. How to make better use of it should be paid more attention to.

To investigate the folate intake level of early pregnant women and its influencing factors in Chengdu.The healthy singleton pregnant women with 8-14 weeks of pregnancy in an obstetrical clinic of maternal-and-child health care institution in Chengdu in 2017 were selected as the object of the study. The basic information of pregnant women was collected by questionnaire survey, and the dietary intake of all kinds of food in early pregnancy was collected by 3-day 24-hour dietary recall method, and the average daily intake of folate was calculated according to China Food Composition(2018). A self-designed questionnaire was used to collect the use of folic acid supplements in pregnant women in the past one month, and the average daily intake of folic acid supplements was calculated. According to the Chinese Dietary Reference Intakes(2013), the folate intakelt;600 μg DFE/d was defined as insufficient, and folic acid supplements intake ≥1000 μg/d was defined as excessive. The influencing factors of folate intake were analyzed by binary Logistic regression model.A total of 1579 valid samples were included. The average folate intake of early pregnant women in Chengdu was 865.8(778.6, 1461.0) μg DFE/d, the average dietary folate intake was 145.4(101.9, 200.7) μg/d, and the average folic acid supplements intake was 400.0(400.0, 800.0) μg/d. The rate of insufficient intake of folate in early pregnancy was 12.1%, and the rate of excessive intake of folic acid supplements was 13.0%. Compared with the primiparous group, the risk of insufficient folate intake was higher in the multiparous group(OR=1.708, 95%CI 1.175-2.482). Compared with the low income group, risk of insufficient folate intake in the medium and high income group was lower(OR=0.660, 95%CI 0.477-0.913); taking folic acid supplements before pregnancy has a lower risk of overdose of folic acid than the non-taking group(OR=0.594, 95%CI 0.423-0.835).The phenomenon of insufficient intake of total folate and excessive intake of folic acid supplements coexists among women in early pregnancy in Chengdu, and the rational use of folic acid supplements is worthy of attention.

Wenqi Wang,* Xin Feng,* Yu Du, Cen Liu, Xinxin Pang, Kunxiu Jiang, Xirui Wang, Yonggang Liu School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonggang Liu Email liuyg0228@163.comPurpose: Pinocembrin is a dihydroflavonoid, which is widely found in several plant species. Although pinocembrin has good pharmacological activity, it has poor water solubility and low bioavailability. Therefore, we have modified the structure of pinocembrin with a combination of different amino acids to solve this problem. Moreover, the effect of the antiaging activity of them has not been explored. We aim to investigate the effect of pinocembrin and its amino acid derivatives on the aging of Caenorhabditis elegans.Methods: Pinocembrin was spliced with different amino acids in order to obtain their corresponding derivatives. The preliminary research of pinocembrin and its amino acid derivatives on antiaging effect was studied by using the C. elegans model. Among all the compounds, the one shows the best antiaging effect was then studied on antiaging mechanism. The protective effect on nematodes under emergency conditions was explained by detecting the ROS content and sod-3p::GFP fusion protein expression in nematodes; the possible anti-aging mechanism of nematodes was determined by DAF-16 nuclear localization experiment and the survival curve of transgenic nematodes model under stress conditions.Results: Pb-3 showed the best effect on increasing tolerance to thermal and oxidative stress and reduce the accumulation of lipofuscin. In the assay of C. elegans, pb-3 reduced intracellular ROS accumulation. Application of pb-3 to the transgenic mutant TJ356 induced the translocation of the transcription factor DAF-16 from the cytosol to the nucleus, and modulated the expression of SOD-3 (downstream genes of daf-16), which regulates longevity in C. elegans. Moreover, pb-3 did not prolong the lifespan of daf-16, age-1, daf-2 and hsp16.2 mutants, suggesting that these genetic pathways are involved in mediating the antiaging effects of pb-3.Conclusion: The antioxidant and antiaging properties of pb-3 may involve in the DAF-16/FOXO transcription process. Pinocembrin amino acid derivatives might be a novel agent for antiaging therapy.Keywords: pinocembrin, antiaging, oxidative stress, amino acid derivatives, Caenorhabditis elegans, DAF-16/FOXO transcription factorsCorrigendum for this paper has been published

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown. Therefore, we further explored its possible mechanism. We subcutaneously injected 5 U hirudin into STZ-induced WT mice or Gasdermin D (Gsdmd)−/− (KO) mice daily for 12 weeks, respectively, and evaluated their kidney injury. Next, glomerular endothelial cells (GECs), renal tubular epithelial cells (RTECs), and bone-marrow-derived macrophages (BMDMs) were isolated from WT mice and treated with hirudin in the presence of high glucose/lipopolysaccharides and ATP to measure the release of interleukin-18 and interleukin-1β. Kidney injury induced by STZ injection was significantly ameliorated by hirudin through inhibiting Gsdmd-mediated pyroptosis in the mice, not Caspase 1-mediated apoptosis. Meanwhile, hirudin also suppressed pyroptosis in primary GECs, RTECs, and BMDMs in vitro. Moreover, the deletion of Gsdmd reduced pyroptosis and kidney injury both in vivo and in vitro. We also found that hirudin regulated the expression of Gsdmd by inhibiting interferon regulatory factor 2 (Irf2). Hirudin ameliorated Gsdmd-mediated pyroptosis by inhibiting irf2, leading to the improvement of kidney injury. Therefore, hirudin might serve as a potential therapeutic strategy to treat DN.

Background Peritoneal fibrosis is one of the major complications induced by peritoneal dialysis (PD). Damaged integrity and function of peritoneum caused by peritoneal fibrosis not only limits the curative efficacy of PD and but affects the prognosis of patients. However, the detailed mechanisms underlying the process remain unclear and therapeutic strategy targeting TGF‐β is deficient. Transforming growth factor‐β (TGF‐β) signaling participates in the progression of peritoneal fibrosis through enhancing mesothelial-mesenchymal transition of mesothelial cells. Methods The study aims to demonstrate the regulatory role of Sirtuin1 (SIRT1) to the TGF‐β signaling mediated peritoneal fibrosis. SIRT1−/− mice were used to establish animal model. Masson’s staining and peritoneal equilibration assay were performed to evaluate the degree of peritoneal fibrosis. QRT-PCR assays were used to estimate the RNA levels of Sirt1 and matrix genes related to peritoneal fibrosis, and their protein levels were examined by Western blot assays. Results SIRT1 significantly decreased in vivo post PD treatment. SIRT1 knockout exacerbated peritoneal fibrosis both in vivo and vitro. Overexpression of SIRT1 efficiently inhibited peritoneal fibrosis by inhibiting the peritoneal inflammation and the activation of TGF‐β signaling. Conclusion SIRT1 ameliorated peritoneal fibrosis both in vivo and in vitro through inhibiting the expression of protein matrix induced by TGF‐β signaling.

To evaluate the red meat intake of pregnant women in Chengdu area and explore the effect of red meat intake in the first and second trimesters on gestational diabetes mellitus(GDM).From February to July 2017, a prospective study was conducted among healthy singleton pregnant women within 8-14 weeks of gestation in a prenatal clinic of maternal-and-child medical institution in Chengdu City through purposive sampling. Data on maternal demographic characteristics was collected through questionnaire in early pregnancy. 3-day 24 hour dietary recall was used to collect dietary intake information in the first and second trimesters. The 75 g oral glucose tolerance test(OGTT)was conducted at 24 to 28 weeks of gestation, and GDM was diagnosed according to the Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes in China(2014). Multivariate unconditional Logistic regression model was used to explore the association between tertiles of red meat intake and the risk of GDM in the first and second trimesters.A total of 985 valid samples were followed up. The mean intake of total meat and red meat in middle pregnancy(102. 9 g/d and 74. 6 g/d) was higher than that in early pregnancy(70. 7 g/d and 52. 0 g/d). The difference was statistically significant(Plt;0. 05). Red meat accounted for 73. 6% and 72. 5% of total meat intake in early and middle pregnancy, respectively. After adjusting the confounding factors, multivariate unconditional Logistic regression analysis showed the risk of GDM was 1. 499 times(95%CI 1. 028-2. 185) in the highest red meat intake(gt;86 g/d)women compared with the lowest red meat intake(lt;44 g/d) women in the second trimester. No association was found between red meat intake in the first trimester and the occurrence of GDM(OR=1. 029, 95%CI 0. 716-1. 481).Pregnant women in Chengdu area have excessive intake of red meat in the second trimester. Higher intake of red meat in the second trimester(gt;86 g/d) may increase the risk of gestational diabetes.

To investigate the effects of Tongluo Digui decoction on renal injury and streptozotocin-induced podocyte autophagy in diabetic rats.Male Sprague-Dawley rats were randomly divided into six groups: normal, model, Tongluo Digui decoction (high, medium, and low dose) and valsartan. Streptozotocin was injected intraperitoneally to replicate the diabetic animal model. After 8 weeks, proteinuria was evaluated to establish the diabetic nephropathy model. Treatments were administered daily via the intragastric route. At 16 weeks after gavage, we determined 24 h urine protein concentration, and blood glucose, serum creatinine, and urea nitrogen concentrations. Then, rats were sacrificed, and kidneys were harvested and stained with periodic acid-Schiff to evaluate the pathological changes in glomeruli, including glomerular podocytes by transmission electron microscopy. Western blot analysis was used to determine the expression of nephrin, podocin, p62, beclin-1, LC3Ⅱ/Ⅰ, and p-mTOR/mTOR protein in kidney tissues.Compared with the model group, Tongluo Digui decoction was associated with decreases in 24 h urine protein concentration, and blood glucose, hemoglobin A1c, serum creatinine, urea nitrogen concentrations, total serum protein and albumin. Concurrently, mesangial mesenteric broadening and fusion of foot processes were reduced, the glomerular basement membrane was not significantly thickened, and the number of podocytes and the number of autophagosomes in the podocytes was increased. Further, expression of nephrin, podocin, LC3Ⅱ, and beclin-1 protein in kidney tissue was up-regulated, while expression of p62 protein was down-regulated and mTOR phosphorylation was inhibited.Tongluo Digui decoction may inhibit the progression of diabetic nephropathy by inhibiting mTOR phosphorylation, thereby increasing autophagy to protect podocytes and reducing proteinuria.

The study is aimed at investigating the effects of Ginkgo biloba extract EGB761 on renal tubular damage and endoplasmic reticulum stress (ERS) in diabetic kidney disease (DKD). A total of 50 C57BL/6 N mice were randomly divided into the normal group, DKD group, DKD+EGB761 group (36 mg/kg), and DKD+4-phenylbutyrate (4-PBA) group (1 g/kg). The DKD model was replicated by high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). Renal tubular epithelial cells (HK-2) were divided into the control group, high-glucose group (30 mmol/L), EGB761 group (40 mg/L, 20 mg/L, 10 mg/L), TM group, and TM+4-PBA group. After 8 weeks of administration, expressions of serum creatinine (Scr), blood urea nitrogen (BUN), 24 h urinary protein (24 h Pro), fasting blood glucose (FBG), β2-microglobulin (β2-MG), and retinol binding protein 4 (RBP4) of mice were tested. The pathological changes of renal tissue were observed. The expressions of extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) markers α-smooth muscle actin (α-SMA), E-cadherin, fibronectin, and collagen IV, as well as the ERS markers GRP78 and ATF6, were tested by Western blot, qPCR, immunohistochemistry, or immunofluorescence. EGB761 could decrease the Scr, BUN, 24 h Pro, and FBG levels in the DKD group, alleviate renal pathological injury, decrease urine β2-MG, RBP4 levels, and decrease the expression of α-SMA, collagen IV, fibronectin, and GRP78, as well as ATF6, while increase the expression of E-cadherin. These findings demonstrate that EGB761 can improve renal function, reduce tubular injury, and ameliorate ECM accumulation and EMT in DKD kidney tubules, and the mechanism may be related to the inhibition of ERS.

Ethnopharmacological relevance HuoXue JieDu Formula (HXJDF) originates from classical formulas and was formed based on clinical experience. It is composed of Euonymus alatus (Thunb.) Siebold, Panax notoginseng (Burkill) F.H. Chen, the roots of Anguina kirilowii (Maxim.) Kuntze, and Coptis omeiensis (C. Chen) C.Y.Cheng. HXJDF prevents the deterioration of diabetic retinopathy. Aim of the study To evaluate the effects of HXJDF on diabetic retinopathy in rats and investigate the roles of miRNAs in the effects of HXJDF. Materials and methods A single intraperitoneal injection of streptozotocin (STZ) (65 mg/kg) was used to induce diabetes in rats. Rats were divided into three groups: normal, diabetic, and diabetic + HXJDF. Rats were treated with HXJDF (15.4 g/kg) or water by oral gavage for twelve weeks. At the end of the treatment, rats were anaesthetized, and retinal haemodynamic changes were measured. Then, the retinas were removed and examined by haematoxylin and eosin (HE) staining and TUNEL assays. In addition, miRNA expression profiling was performed using miRNA microarrays and further validated by quantitative real-time PCR (qRT-PCR). Results Diabetes reduced peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV) and central retinal vein velocity (CRV) but increased the resistance index (RI) and pulsatility index (PI). In addition, in the diabetic group, retinal cell arrangement was disordered and loosely arranged, the retinal thickness and retinal ganglion cell (RGC) number decreased, and retinal cell apoptosis increased. In addition, 11 miRNAs were upregulated and 4 miRNAs were downregulated. After treatment, HXJDF improved retinal haemodynamics and morphologic changes, restored retinal thickness and RGC number and decreased retinal cell apoptosis. Furthermore, the changes in miRNA expression were significantly abolished by HXJDF. Conclusion HXJDF may prevent DR by regulating the expression of miRNAs.

BACKGROUND This study aimed to investigate the effects of hirudin on the production of extracellular matrix (ECM) factors by renal tubular epithelial cells in a rat model of diabetic kidney disease (DKD) and HK-2 human renal tubule epithelial cells. MATERIAL AND METHODS Sprague-Dawley rats were divided into the normal control group (n=10), the normal control+hirudin group (n=10), the DKD model group (n=12) and the DKD+hirudin group (n=12). At the end of the study, renal histopathology was undertaken, and the expression of type IV collagen, fibronectin, hypoxia-inducible factor-1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) were evaluated using immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). HK-2 cells were cultured in glucose and treated with hirudin. Protein and mRNA expression of fibronectin, type IV collagen, HIF-1alpha, and VEGF were evaluated following knockdown or overexpression of HIF-1alpha. RESULTS Hirudin significantly improved renal function in the rat model of DKD (P

To investigate the effects of anxiety and depression on gestational diabetes mellitus(GDM) in early pregnancy.A prospective study was conducted in 2017 to select 1426 single-child healthy pregnant women of 8-14 weeks from the Sichuan Provincial Hospital for Women and Children through a deliberate sampling method. The age was(28. 6±4. 0) years old. Basic information such as age, pre-pregnancy weight, parity, and gravidity of pregnant women was collected through questionnaire survey. The anxiety self-rating scale(SAS) and depression self-rating scale(SDS) were used to collect information of anxiety and depression in pregnant women, and their anxiety and depressive symptoms were evaluated according to the result of Chinese norm. At 24 to 28 weeks of gestation, the oral glucose tolerance test(OGTT) was conducted. GDM was diagnosed according to the Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes in China(2014). Multivariate unconditional Logistic regression was adopted to analyze the effects of anxiety and depression on GDM in pregnant women.The incidence of GDM in early pregnancy anxiety group and depression group was 41. 8% and 33. 6%, respectively. The incidence of anxiety, depression, and anxiety combined with depression were 7. 7%, 10. 5% and 4. 8%, respectively. The incidence of anxiety and depression in the group of pregnant women younger than 30 years old(9. 0% and 11. 7%) was higher than that in the group of pregnant women older than 30 years old(5. 3% and 8. 1%). The prevalence of anxiety and depression in the group of nulliparous women(8. 8% and 11. 9%) was higher than that in the group of multiparous women(5. 4% and 6. 4%). The difference was statistically significant(Plt;0. 05). After adjusting the confounding factors such as age, pre-pregnancy body mass index, family history of diabetes, gravidity, parity, energy intake, conception, education, occupation, smoking and drinking, the result showed that the risk of GDM in anxious pregnant women was increased, compared with that in non-anxious pregnant women in early pregnancy(OR=1. 556, 95% CI 1. 014-2. 387). However, the association between early pregnancy depression and the occurrence of GDM was not found(Pgt;0. 05). Compared with the non-anxiety group in the early pregnancy, the risk of GDM in the anxiety group was increased both in pregnant women under 30 years old(OR=1. 654, 95% CI 1. 004-2. 726) and nulliparous women(OR=1. 633, 95% CI 1. 013-2. 634). No correlation between anxiety and risk of GDM was observed in pregnant women over 30 years old and multiparous women(Pgt;0. 05).Anxiety in early pregnancy increases the risk of GDM. Pregnant women under 30 years old and and nulliparous women are at high risk of anxiety.

Background Inflammation-induced podocyte apoptosis plays an important role in kidney injury during diabetic nephropathy (DN). Hirudin (HIR), a natural compound extracted from leeches, can inhibit inflammation. However, whether HIR can protect the kidneys against inflammation during DN is unknown. In the present study, we aimed to study the effects of HIR on kidney damage in a DN rat model and explore its anti-inflammatory properties. Methods A streptozotocin-induced DN rat model was generated, and HIR was administered subcutaneously. Immortal podocytes and primary peritoneal macrophages were used for vitro studies. Hematoxylin and eosin staining was used to evaluate renal pathological changes; quantitative polymerase chain reaction and immunoblotting were used to detect gene expression; and TUNEL staining was used to detect apoptotic cells. Results Our results showed that HIR protected against renal injury, as indicated by kidney weight/body weight, serum creatinine, renal pathological changes, blood urea nitrogen, and detection of urine proteins. Notably, HIR treatment reduced macrophage infiltration, pro-inflammatory cytokine expression, and podocyte apoptosis in the kidney tissues of DN rats. In vitro, high glucose (HG) induced the activation of M1 macrophages, which was accompanied by increased podocyte apoptosis. HIR could decrease HG-induced podocyte apoptosis and suppress pro-inflammatory cytokine expression in podocytes in vitro. This was achieved via inhibition of p38 MAPK/NF-κB activation in renal tissues and podocytes. Conclusion HIR could inhibit inflammation via the p38 MAPK/NF-κB pathway, prevent podocyte apoptosis, and protect against kidney damage in a DN rat model.

Objective To investigate whether plasma lipid profiles are independently associated with pregnancy complications including gestational diabetes mellitus (GDM), hypertensive disorder complicating pregnancy (HDCP), and intrahepatic cholestasis of pregnancy (ICP). Study Design A prospective study was conducted among 1,704 pregnant women at three medical institutions in Chengdu, China. The concentrations of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured at gestational weeks 12 ± 1, 24 ± 1, and 34 ± 1. Logistic regression models were used to estimate the association between lipid profiles and pregnancy complications. Receiver operating characteristic analysis was performed to determine the value of lipid profiles to predict GDM and HDCP. Results After adjusting for potential confounders, TG, TC, and LDL-C in the first trimester were independently associated with GDM (TG: odds ratio [OR] =2.00, 95% confidence interval [CI]: 1.57–2.56; TC: OR = 1.38, 95% CI: 1.16–1.64; LDL-C: OR = 1.43, 95% CI: 1.14–1.79) and HDCP (TG: OR = 2.42, 95% CI: 1.56–3.78, TC: OR = 1.64, 95% CI: 1.04–2.57; LDL-C: OR = 1.87, 95% CI: 1.07–3.25). The TC concentration during the whole pregnancy (first trimester: OR = 1.53, 95% CI: 1.13–2.08; second trimester: OR = 1.31, 95% CI: 1.06–1.61; third trimester: OR = 1.39, 95% CI: 1.17–2.04) and LDL-C in the last two trimesters (second trimester: OR = 1.62, 95% CI: 1.30–2.04; third trimester: OR = 1.56, 95% CI: 1.29–1.88) were positively associated with ICP. HDL-C in the third trimester was negatively associated with the risk of ICP (OR = 0.46, 95% CI: 0.22–0.98). Combining lipid profiles in the first trimester with the other common predictors to predict GDM or HDCP owned stronger predictive power with the largest area under the curve (GDM: 0.643 [95% CI: 0.613–0.673], HDCP: 0.707 [95% CI: 0.610–0.804]) than either indicator alone. Conclusion Maternal lipid profiles during the whole pregnancy are significantly associated with GDM, HDCP, and ICP. Combining lipid profiles in the first trimester with the other common predictors could effectively improve the power of predicting GDM and HDCP.

As an important part of global semi-arid grassland, adequately understanding the spatio-temporal variability of evapotranspiration (ET) and water balance (WB, defined as precipitation-ET) over the temperate semi-arid grassland of China (TSGC) could advance our understanding of climate, hydrological and ecological processes over global semi-arid areas. Based on the largest number of in-situ ET measurements (13 flux towers) within the TSGC, we applied the support vector regression (SVR) method to develop a high-quality ET dataset for the TSGC from 1982 to 2015. The model performed well in validation against flux tower‐measured data and comparison with water-balance derived ET. The annual ET ranged from 226 to 294 mm yr-1 with an average of 250 mm yr-1 and an insignificant trend during 1982-2015. Nevertheless, ET increased significantly during 1982-1998, and turn to decrease during 1999-2011. Regional WB, which approximately represents water availability, fluctuated without a significant trend for entire period. But the annual mean WB at 1999-2011 decreased by 26.1% compared with that before 1998. On average, ET was dominated by climatic factors, especially precipitation, rather than human activities. The reversal of ET trend after 1998 was predominantly explained by the slow increase of precipitation, the stalled increase of temperature, and the significantly decreasing radiation. The revegetation programs exacerbated the evaporative water consumption significantly in some areas after 1998, such as Yellow River Basin. The variation of WB was mainly driven by precipitation, whether in time or space. In addition, the spatio-temporal difference between our SVR ET dataset with four widely used global ET datasets (i.e., GLEAM, FLUXCOM, MODIS, and BESS) suggested that none of these four products can capture both the magnitude and variability of ET well in the TSGC, and local observations are of great importance.

Background/Aims: Urotensin II (UII) and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN). The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress) and Epithelial-mesenchymal transition (EMT) in DN in vivo and in vitro. Methods: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. Results: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1), fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. Conclusions: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN.

Tritium analysis in water is an important part of environmental radiation monitoring. At present, tritium in water is generally measured by liquid scintillation counting (LSC). To optimize the pretreatment process and improve the efficiency of tritium analysis via LSC, a pretreatment device for tritium analysis in water based on a reverse osmosis (RO) film was developed. This paper introduces the system composition and carries out the following experimental studies: First, the comprehensive performance of the device was studied by performing repeated analyses, and the pretreatment time can be reduced by approximately 77% compared with that of the traditional method; then, the device was used to process tritium samples with different concentrations to verify the negligible impact of any tritium residue in the RO film; finally, the reliability of the results is verified by comparing with the traditional atmospheric distillation pretreatment method under the same measurement conditions. The results showed the developed method has the advantages of a simple operation and a high degree of automation, which effectively improves the efficiency of tritium analysis in water.

Objective Kidney is the most common location of microangiopathy in diabetic patients, and we designed this study to investigate the effects of hirudin on renal microangiopathy in STZ-induced diabetes rats and in vitro. Methods We established a diabetes model by intraperitoneal injection of STZ and administered hirudin daily by subcutaneous injection. HE staining was used to assess kidney pathological changes. Western blot and immunochemistry was used to detect the protein expression. Glomerular endothelial cells (GEC) in normal rats were assessed by cell scratch test for migration ability and tubule formation experiment for angiogenesis ability. Results Compared with DN rats without any treatment, the serum creatinine, serum Cys C, 24-hour urine protein of DN rats with hirudin treatment were significantly decrease, the kidney/body weight and glomerular area of DN rats with hirudin treatment were all significantly decrease, and also significant improvement in renal pathology revealed by HE staining in DN rats after treating with hirudin. Moreover, we also found that hirudin coun not only significantly increase the prothrombin time and aivated partial thromboplastin time in DN rats, but also significantly decrease the expression of VEGF and TM-1 protein in kidney tissues of DN rats. In vitro, we found that high glucose could promote the migration and angiogensis of GEC, and significantly increased the expression of VEGF and Ang protein, but significantly decreased the expression of THBS1 and Arg1 protein. More importantly was that hirudin could inhibit the migration and angiogensis of GEC, and reversed HG-induced the expression of VEGF, Ang, THBS1 and Arg1 protein in GEC. In addition, we also found that hirudin could not only decrease HG-enhanced the activity of RhoA in GEC, but also decrease HG-enhanced the expression of p-MYPT1/MYPT1, p-p38/p38 protein in GEC. Conclusion Hirudin reduces nephropathy microangiopathy in STZ-induced diabetes, and might be related to hirudin inhibiting glomerular endothelial cell migration and angiogenesis through Rho-kinase and subsequent p38MAPK/NF-kB signaling pathway.

Red radishes were dried using air-impingement jet drying (AIJD) at different temperatures of 50 °C, 60 °C, and 70 °C. The color displayed a significant change, while the total anthocyanin content (TAC), and DPPH· and ABTS·+ scavenging activities were dramatically decreased in AIJD-dried red radishes compared to fresh red radishes. Using UHPLC-QqQ-MS/MS analysis, eight pelargonidin glucosides and two cyanidin glucosides were identified in red radishes. The pelargonidin-3-(p-coumaroyl)diglucoside-5-(malonyl)glucoside (P3PD) and pelargonidin-3-(feruloyl)diglucoside-5-(malonyl)glucoside (P3FD) signified the two primary anthocyanins in red radishes. AIJD caused the degradation of P3PD and P3FD while following the second-order kinetic equation. The degradation rate and half-life (t1/2) of the P3PD degradation increased with the elevation of the AIJD temperature, while that of P3FD decreased. The enthalpy of activation presented values between 2.87 kJ/mol and 3.04 kJ/mol for P3FD, and between 37.07 kJ/mol and 37.23 kJ/mol for P3PD. The positive ΔG suggested that the degradation of P3PD and P3FD was a non-spontaneous reaction. The transition state displayed lower structural freedom than the P3PD and P3FD, as evidenced by the negative ΔS. These results could contribute to inhibiting the degradation of anthocyanins in red radishes during processing.

Diabetic nephropathy (DN) is a major complication of diabetes, and the dysfunction of endoplasmic reticulum (ER) plays an important role in its pathogenesis. ERp44, an ER resident chaperone protein, has been implicated in the modulation of ER stress, however, its role and mechanism in DN are not determined. Here, we show that ERp44 expression is upregulated in the glomeruli of db/db mice, a rodent model of type 2 diabetes. When ERp44 is depleted by in vivo shRNA-mediated knockdown, the features associated with DN including albuminuria level and glomerular basement membrane (GBM) thickness are aggravated, therefore suggesting a detrimental role of ERp44 depletion in DN progression. We further show that ERp44 depletion exacerbates ER stress in DN in db/db mice, and that attenuating ER stress with the chemical chaperone TUDCA remarkably diminishes the aggravated DN features caused by ERp44 depletion. These results suggest that the exacerbated ER stress is a critical factor for the detrimental effect of ERp44 depletion on DN progression in db/db mice. Thus, our study links the role of ERp44 in DN with ER stress regulation and may offer a potential therapeutic strategy to interfere DN progression.

Aims/Introduction: Irisin is a newly identified myokine which can promote energy expenditure. Urotensin II (UII) is identified as the most potent mammalian vasoconstrictor to date. Previous studies showed that UII can aggravate insulin resistance while irisin alleviate insulin resistance. Through this study, it is our aim to elucidate if UII can induce insulin resistance and also have an association with the irisin level in hemodialysis (HD) patients. Materials and Methods: One hundred and twenty-eight patients on maintenance hemodialysis treatment and forty healthy subjects were enrolled in this study. Blood irisin concentrations and UII concentrations were measured by ELISA and RIA respectively. The body composition was analyzed by bioelectrical impedance. Results: The serum irisin levels and UII levels were both significantly lower in HD patients in comparison to that of the healthy subjects. The serum irisin levels were lower in HD patients with protein energy wasting than those of the patients without protein energy wasting. The independent determinants of circulating Ln (irisin) (the natural logarithm of irisin) were UII lean body mass and patients with protein energy wasting. Conclusions: Our results are the first to provide the clinical evidence of the association among irisin, UII, and protein energy wasting. Our results hint that UII and protein energy wasting might inhibit the release or synthesis of irisin from skeletal muscles in HD patients.

Aim/Introduction Urotensin II (UII) and autophagy have been considered as important components in the pathogenesis of diabetic nephropathy. The present study explores whether UII can regulate autophagy in kidney and its effect in diabetes. Materials and Methods Immunohistochemistry and western blot were conducted on the kidney tissues of diabetic UII receptor (UT) gene knock-out mice, wild type diabetic mice, and normal control mice. For in vitro experiment, HK-2 cells were treated with UII (10-7 mol/L) in the presence or absence of UT antagonist, SB-657510, (10-6 mol/L) or autophagy inducer Rapamycin (10-3 mol/L) for 12 h. Markers for autophagy (LC3-II, p62/SQSTM1) and extracellular matrix (fibronectin, collagen IV) were analyzed. Results In diabetic UT knock-out mice, expression of LC3-II is increased and p62 is reduced in comparison to that of the normal diabetic mice. Fibronectin and collagen IV are down-regulated in diabetic UT knock-out mice when compared to that of the normal diabetic mice. For in vitro cell experiment, UII is shown to inhibit expression LC3-II and increase expression of p62 in comparison to that of the normal control. Treatment with SB-657510 can block UII-induced down-regulation of LC3-II and upregulation of p62 while inhibiting UII-induced upregulation of fibronectin and collagen IV. Adding autophagy inducer Rapamycin also inhibited UII-induced upregulation of fibronectin and collagen IV. Conclusion Our study is the first to show that UII can down-regulate autophagy in kidney while accompanying the increased production of ECM in early diabetes. Our in vitro study also demonstrates that upregulation of autophagy can decrease UII-induced production of ECM in HK-2 cell. This article is protected by copyright. All rights reserved.