BMI growth trajectory from birth to 5 years and its sex-specific association with prepregnant BMI and gestational weight gain.

Objective: The purpose of the study was to identify the latent body mass index (BMI) z-score trajectories of children from birth to 5 years of age and evaluate their sex-specific association with prepregnant BMI and gestational weight gain (GWG). Methods: This was a retrospective longitudinal cohort study performed in China. In total, three distinct BMI-z trajectories from birth to 5 years of age were determined for both genders using the latent class growth modeling. The logistic regression model was used to assess the associations of maternal prepregnant BMI and GWG with childhood BMI-z growth trajectories. Results: Excessive GWG increased the risks of children falling into high-BMI-z trajectory relative to adequate GWG (OR = 2.04, 95% CI: 1.29, 3.20) in boys; girls born to mothers with prepregnancy underweight had a higher risk of low-BMI-z trajectory than girls born to mothers with prepregnancy adequate weight (OR = 1.85, 95% CI: 1.22, 2.79). Conclusion: BMI-z growth trajectories of children from 0 to 5 years of age have population heterogeneity. Prepregnant BMI and GWG are associated with child BMI-z trajectories. It is necessary to monitor weight status before and during pregnancy to promote maternal and child health.

Correction: Paper-based ELISA diagnosis technology for human brucellosis based on a multiepitope fusion protein.

[This corrects the article DOI: 10.1371/journal.pntd.0009695.].

Nano-selenium Alleviates Cadmium-Induced Mouse Leydig Cell Injury, via the Inhibition of Reactive Oxygen Species and the Restoration of Autophagic Flux.

Cadmium (Cd) is a well-known environmental pollutant that can contribute to male reproductive toxicity through oxidative stress. Nano-selenium (Nano-se) is an active single body of selenium with strong antioxidant properties and low toxicity. Some studies have addressed the potential ameliorative effect of Nano-se against Cd-induced testicular toxicity; however, the underlying mechanisms remain to be investigated. This study aimed to explore the protective effect of Nano-se on Cd-induced mouse testicular TM3 cell toxicity by regulating autophagy process. We showed that cadmium exposure to TM3 cells inhibited cell viability and elevated the level of reactive oxygen species (ROS) generation. Morphology observation by transmission electron microscope and the presence of mRFP-GFP-LC3 fluorescence puncta demonstrated that cadmium increased autophagosome formation and accumulation in TM3 cells, resulting in blocking the autophagic flux of TM3 cells. Meanwhile, cadmium remarkably increased the ratio of LC3-II to LC3-I protein expression (2.07 ± 0.31) and the Beclin-1 protein expression (1.97 ± 0.40) in TM3 cells (P < 0.01). Pretreatment with Nano-se significantly reduced Cd-induced TM3 cell toxicity (P < 0.01). Furthermore, Nano-se treatment reversed Cd-induced ROS production and autophagosome accumulation, and autophagy as evidenced by the ratio of LC3-II to LC3-I and Beclin-1 expression. In addition, ROS scavenger, N-acetyl-L-cysteine (NAC) or autophagy inhibitor, 3-methyladenine (3-MA) reversed cadmium-induced ROS generation, autophagosome accumulation, and autophagy-related protein expression levels, which confirmed that cadmium induced TM3 cell injury via ROS signal pathway and blockage of autophagic flux. Collectively, our results reveal that Nano-se attenuates Cd-induced TM3 cell toxicity through the inhibition of ROS production and the amelioration of autophagy disruption.

Identification and antibiotic resistance of Cronobacter spp. isolated from dried edible mushrooms.

Cronobacter spp. is an important foodborne pathogen that can cause life-threatening diseases in infants and immunocompromised adults. The present study was carried out to understand the prevalence and characterization of Cronobacter spp. in dried edible mushrooms in Jiangsu province, China. Cronobacter isolates were identified and genotyped by multilocus sequence typing (MLST); the antimicrobial susceptibility of Cronobacter strains was determined by the disk diffusion method; the biofilm formation ability of Cronobacter spp. was assessed using the microtiter plate method. The overall prevalence of Cronobacter spp. in dried edible mushrooms was 14.8%, with the highest contamination rate of after 37.2% found in Auricularia auricular. The Cronobacter isolates were identified as C. sakazakii (n = 26), C. malonaticus (n = 2), C. dublinensis (n = 2) and C. turicensis (n = 1). The MLST scheme produced 20 sequence types (STs), two of which were newly identified. ST148 was the most prevalent ST (n = 5), followed by ST4 (n = 3), ST17 (n = 3), ST64 (n = 3), and ST540 (n = 2). One (3.2%) and 15 (48.4%) Cronobacter isolates were resistant to tetracycline and meropenem, respectively. In contrast, all of the tested isolates were susceptible to the remaining 14 antibiotics. Moreover, 20 (64.5%) Cronobacter isolates showed weak ability to produce biofilm, but no isolates showed strong or moderate biofilm-forming ability. PRACTICAL APPLICATION: Our findings revealed a high genetic diversity of Cronobacter spp. in dried edible mushrooms and provided new epidemiological evidence for the widespread existence of Cronobacter spp. in such products. The presence of Cronobacter spp. in dried edible mushrooms may pose potential risks to human health and enhancing the hygiene of such products are necessary to ensure food safety.

A Multi-Epitope Fusion Protein-Based p-ELISA Method for Diagnosing Bovine and Goat Brucellosis.

In recent years, the incidence of brucellosis has increased annually, causing tremendous economic losses to animal husbandry in a lot of countries. Therefore, developing rapid, sensitive, and specific diagnostic techniques is critical to control the spread of brucellosis. In this study, bioinformatics technology was used to predict the B cell epitopes of the main outer membrane proteins of Brucella, and the diagnostic efficacy of each epitope was verified by an indirect enzyme-linked immunosorbent assay (iELISA). Then, a fusion protein containing 22 verified epitopes was prokaryotically expressed and used as an antigen in paper-based ELISA (p-ELISA) for serodiagnosis of brucellosis. The multi-epitope-based p-ELISA was evaluated using a collection of brucellosis-positive and -negative sera collected from bovine and goat, respectively. Receiver operating characteristic (ROC) curve analysis showed that the sensitivity and specificity of detection-ELISA in diagnosing goat brucellosis were 98.85 and 98.51%. The positive and the negative predictive values were 99.29 and 98.15%, respectively. In diagnosing bovine brucellosis, the sensitivity and specificity of this method were 97.85 and 96.61%, with the positive and negative predictive values being identified as 98.28 and 97.33%, respectively. This study demonstrated that the B cell epitopes contained in major antigenic proteins of Brucella can be a very useful antigen source in developing a highly sensitive and specific method for serodiagnosis of brucellosis.

Selenite induced breast cancer MCF7 cells apoptosis through endoplasmic reticulum stress and oxidative stress pathway.

Selenium is an essential trace element for human, and has anti-tumor effects. In this study, we investigated the anti-tumor activity of sodium selenite (Na2SeO3) and explored its possible mechanisms involved in a breast cancer cell line. We found that Na2SeO3 could inhibit the cell viability of MCF7 cells, yet with minimal damage to human umbilical vein endothelial cells (HUVECs). The results of Hoechst staining and Western Blot showed that Na2SeO3 induced apoptosis of MCF7 cells. Na2SeO3 activated endoplasmic reticulum stress (ERS), as evidenced by the up-regulation of ERS-related proteins, including ATF6, p-eIF2α, ATF4, and CHOP, and the down-regulation of PERK. ATF6, p-eIF2α and apoptosis were decreased by pre-treatment with an ERS inhibitor (4-PBA). Na2SeO3 activated oxidative stress (OS) through increasing ROS generation and decreasing mitochondrial membrane potential (MMP) which induced apoptosis. Pre-treatment with an antioxidant (NAC) attenuated Na2SeO3-induced OS and cell apoptosis. Furthermore, ERS and OS had mutual effects. Pre-treatment with 4-PBA could act against the up-regulation of ROS and the down-regulation of MMP. Pre-treatment with NAC attenuated the expression of ATF6. At the same time, we found that treatment with Na2SeO3 promoted the phosphorylation of p38 and JNK, while inhibiting the phosphorylation of ERK. However, the up-regulation was inhibited after pre-treatment of NAC, and pre-treatment with 4-PBA inhibited the increase only of p38. Based on these results, our study provides a mechanistic understanding of how Na2SeO3 has antitumor effects against MCF7 cells through the OS and ERS pathway. OS and ERS interact with each other, and p38 is regulated by them.

Paper-based ELISA diagnosis technology for human brucellosis based on a multiepitope fusion protein.

BACKGROUND: Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen. CONCLUSIONS: B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations.

Anthocyanin from purple sweet potato attenuates lead-induced reproductive toxicity mediated by JNK signaling pathway in male mice.

The present work aimed to explore the protective effect of APSP on Pb-induced reproductive toxicity and possible mechanism. APSP (100 mg/kg) was administered to Pb-intoxicated (0.2% lead acetate) male Kunming mice once daily by oral gavage for 6 weeks. Our results showed that APSP exerted male reproductive protection effects as showed by attenuated Pb-induced testicular injury, improved sperm count and motility, and reduced sperm abnormality rate. APSP also restored Pb-induced decrease in both enzymatic and non-enzymatic antioxidants, and GSH/GSSG ratio, but inhibited lipid peroxidation in serum and testes. Moreover, APSP downregulated Pb-induced Bax mRNA and protein expressions, suppressed activation of caspase-3, upregulated Bcl-2 protein expression, and prevented Pb-induced DNA damage. APSP treatment also interfered with Pb-induced testicular JNK signaling through inhibition of JNK mRNA expression and phosphorylation, resulting in inhibition of c-Jun expression. These effects of APSP were abolished by Pb. In conclusion, APSP represents a potential therapeutic agent for preventing Pb-caused reproductive toxicity, which is attributed to its antioxidant and anti-apoptotic properties, as well as, modulation of JNK signaling pathway.

Comparative analysis of the main outer membrane proteins of Brucella in the diagnosis of brucellosis.

Brucellosis has placed a heavy economic burden on numerous countries and has consumed considerable medical resources worldwide. To improve the specificity and sensitivity of serological methods for diagnosing brucellosis, it is important to develop new diagnostic antigens. Brucella outer membrane proteins(omps) possess good immunogenicity, but there is a scarcity of comparative studies of these proteins in the clinical diagnosis of brucellosis. In this study, six recombinant Brucella outer membrane proteins, omp10, omp16, omp19, omp25, omp31 and BP26, were expressed in prokaryotic cells and utilized as diagnostic antigens. The clinical sera of humans, bovines and goats with brucellosis were analyzed by indirect ELISA using these proteins, lipopolysaccharide(LPS) and Rose Bengale Ag, served as positive-control antigens. In diagnosing human and goat serum, BP26 exhibited the highest diagnostic accuracy of 96.45% and 95.00%, respectively, while omp31 exhibited the strongest ability to detect Brucella in bovine serum with an accuracy of 84.03%. Cross-reaction experiments also confirmed that the diagnostic specificities of omp31 and BP26 were higher than those of the LPS and Rose Bengale Ag antigens. The results of this study indicate that omp31 and BP26 are candidate antigens with high potential application value in the clinical diagnosis of brucellosis.

Lead acetate induces apoptosis in Leydig cells by activating PPARγ/caspase-3/PARP pathway.

This study was designed to investigate the cytotoxicity of lead acetate (Pb(AC)2, a representative air pollutant) by focusing on PPARγ/caspase-3/PARP apoptotic signaling pathway and to explore the inhibitory effect of PPARγ antagonist on apoptosis of TM3 Leydig cells. MTT assay was utilized to examine cell viability. Cell apoptosis was analyzed using a flow cytometry by staining with Annexin V-PE/7AAD staining and a fluorescence microscope by staining with Hoechst 33,258. The levels of apoptosis-related proteins were examined using western blot. From the results, Pb reduced significantly TM3 cell proliferation in concentration- and time-dependent manner. It increased significantly apoptosis; increased the PPARγ, Bax, procaspase-3, cleaved caspase-3, proPARP, cleaved PARP levels; and decreased Bcl-2 level in Pb-treated TM3 cells as compared to control cells. Furthermore, pretreatment with PPARγ antagonist significantly attenuated the apoptosis and cleavage of caspase-3 and PARP induced by Pb. Our results suggested that Pb induced cytotoxicity on TM3 Leydig cells, at least in part, by increasing PPARγ expression, stimulating cleavage of caspase-3 and PARP, and then induced cell apoptosis.

Dietary effects on breast cancer molecular subtypes, a 1:2 paired case-control study.

To explore the associations between dietary factors and breast cancer (BC) molecular subtypes. The retrospective cases were confirmed by pathological diagnosis with breast cancer were gathered in two major hospitals in Xuzhou city, China, from 2015 to 2016. These cases were classified by the meeting standard of 13th St Gallen: luminal A, luminal B, Her-2 overexpression, and triple-negative breast cancer (TNBC) subtypes. A 1:2 paired retrospective case-control study with 210 cases and 420 controls was conducted to evaluate individual dietary intake, by food frequency questionnaire (FFQ) and estimate odds ratios (ORs), by the Cox regression model. For overall breast cancer patients, the more frequency of red meat (OR = 1.002, 95% CI = 1.001-1.004) and salted food (OR = 1.003, 95% CI = 1.001-1.005) were statistically significantly associated with a greater risk of breast cancer. Beans (OR = 0.997, 95% CI = 0.995-0.999), white meat (OR = 0.993, 95% CI = 0.989-0.997), aquatic products (OR = 0.990, 95% CI = 0.984-0.996), vegetables (OR = 0.999, 95% CI = 0.999-0.999), fruit (OR = 0.998, 95% CI = 0.997-0.999), and green tea (OR = 0.997, 95% CI = 0.994-0.999) were significantly associated with a lower risk of breast cancer. For luminal breast cancer patients, beans (OR = 0.997, 95% CI = 0.994-0.999), white meat (OR = 0.992, 95% CI = 0.987-0.997), green tea (OR = 0.995, 95% CI = 0.991-0.999), and milk (OR = 0.998, 95% CI = 0.996-0.999) were protective factors. While for nonluminal breast cancer, red meat was not included in the equation, and beans (OR = 0.989, 95% CI = 0.981-0.997), white meat (OR = 0.989, 95% CI = 0.981-0.998), vegetables (OR = 0.998, 95% CI = 0.997-0.999), and milk (OR = 0.994, 95% CI = 0.989-0.999) still showed a significantly reduced risk of nonluminal breast cancer. Different dietary factors revealed different effects on the etiology of breast cancer. Red meat may be a specific risk factor for luminal-type breast cancer.

Vegetable-Fruit-Soybean Dietary Pattern and Breast Cancer: A Meta-Analysis of Observational Studies.

Breast cancer is one of the most common cancers among women worldwide, and several studies have investigated the association of dietary patterns and breast cancer. However, findings of studies are inconclusive. Therefore, we aimed to conduct a meta-analysis to summarize the available data regarding the association of vegetable-fruit-soybean dietary pattern and breast cancer. A systematic literature search was conducted via PubMed, Web of Science and EMBASE to identify eligible cohort studies before February 2019. A total of 12 cohort studies were included in the meta-analysis. The summary relative risks (RR) with 95% CI were calculated with a fixed-effects model. The overall RR of breast cancer for the highest versus lowest intake of vegetable-fruit-soybean dietary pattern was 0.87 (95% CI, 0.82-0.91), with little heterogeneity (p=0.73, I2=0%). There was no obvious publication bias according to funnel plot and Begg's and Egger's test. In summary, the evidence from this meta-analysis indicates that vegetable-fruit-soybean dietary pattern was inversely associated with breast cancer. However, well-designed randomized controlled trials are needed to elicit the clear effect of vegetable-fruit-soybean dietary pattern and breast cancer. Women can reduce the risks of breast cancer by eating more fruits and vegetables and soybeans, which is a constructive suggestion.

Sulforaphane inhibits gastric cancer stem cells via suppressing sonic hedgehog pathway.

Sulforaphane (SFN) is the major component extracted from broccoli/broccoli sprouts. It has been shown to possess anti-cancer activity. Gastric cancer is common cancer worldwide. The objective of this work was to evaluate the inhibitory effect of SFN on gastric cancer by Sonic hedgehog (Hh) Pathway. The results found that tumorsphere formation and the expression levels of gastric cancer stem cells (CSCs) markers were significantly decreased after SFN treatment. SFN also exerted inhibitory effects by suppressing proliferation and inducing apoptosis in gastric CSCs. Intriguingly, SFN inhibited the activation of Sonic Hh, a key pathway in maintaining the stemness of gastric CSCs. Upregulation of Sonic Hh pathway diminished the inhibitory effects of SFN on gastric CSCs. Collectively, these data revealed that SFN could be a potent natural compound targeting gastric CSCs via suppression of Sonic Hh pathway, which might be an promising agent for gastric cancer intervention.

Genetic Diversity, Antimicrobial Susceptibility, and Biofilm Formation of Cronobacter spp. Recovered from Spices and Cereals.

Cronobacter species are important food-borne opportunistic pathogens which have been implicated in the cause of necrotizing enterocolitis, sepsis, and meningitis in neonates and infants. However, these bacteria are routinely found in foodstuffs, clinical specimens, and environmental samples. This study investigated the genetic diversity, antimicrobial susceptibility, and biofilm formation of Cronobacter isolates (n = 40) recovered from spices and cereals in China during 2014-2015. Based on the fusA sequencing analysis, we found that the majority (23/40, 57.5%) of Cronobacter isolates in spices and cereals were C. sakazakii, while the remaining strains were C. dublinensis (6/40, 15.0%), C. malonaticus (5/40, 12.5%), C. turicensis (4/40, 10.0%), and C. universalis (2/40, 5.0%). Multilocus sequence typing (MLST) analysis produced 30 sequence types (STs) among the 40 Cronobacter isolates, with 5 STs (ST4, ST13, ST50, ST129, and ST158) related to neonatal meningitis. The pattern of the overall ST distribution was diverse; in particular, it was revealed that ST148 was the predominant ST, presenting 12.5% within the whole population. MLST assigned 12 isolates to 7 different clonal complexes (CCs), 4, 13, 16, 17, 72, 129, and 143, respectively. The results of O-antigen serotyping indicated that C. sakazakii serotype O1 and O2 were the most two prevalent serotypes. The antimicrobial susceptibility testing showed that the 40 Cronobacter isolates were susceptible to most of the antibiotics tested except for ceftriaxone, meropenem, and aztreona. Of the 40 Cronobacter strains tested, 13 (32.5%) were assessed as weak bioflim producers, one (2.5%) was a moderate biofilm producer, one (2.5%) was strong biofilm producer, and the others (62.5%) were non-biofilm producers. MLST and O-antigen serotyping have indicated that Cronobacter strains recovered from spices and cereals were genetically diverse. Isolates of clinical origin, particularly the C. sakazakii ST4 neonatal meningitic pathovar, have been identified from spices and cereals. Moreover, antimicrobial resistance of Cronobacter strains was observed, which may imply a potential public health risk. Therefore, the surveillance of Cronobacter spp. in spices and cereals should be strengthened to improve epidemiological understandings of Cronobacter infections.

Evaluation of androgen receptor transcriptional activities of some pesticides in vitro.

Organophosphates and pyrethroids are among the most common pesticides currently in use worldwide. Several pesticides have been reported to possess hormonal activities, and thus are classified as endocrine disruptors. The present study was planned to evaluate potential androgenic and antiandrogenic activities of the pesticides. The selected chemicals are three organophosphate pesticides including dichlorvos, parathion and trichlorphon, and two pyrethroid pesticides including permethrin and cypermethrin. We evaluated the pesticides for androgen receptor (AR)-mediated mechanisms using a human AR reporter gene assay in African monkey kidney cell line CV-1 transiently transfected with the constructed reporter gene plasmid pMMTV-CAT and the hAR expression plasmid AR/pcDNA3.1. We demonstrated that parathion showed significant inhibitory effects on the transcriptional activity induced by 1 nM of DHT with IC(50) value of (2.01+/-0.42) x 10(-7) M, though trichlorphon and dichlorvos lacked this activity. The two pyrethroid pesticides permethrin and cypermethrin exhibited lower activity than parathion with IC(50) value of (5.68+/-2.20) x 10(-5) and (6.80+/-2.30) x 10(-5) M, respectively. On the other hand, we failed to find AR-mediated androgenic activities of the tested chemicals. It is suggested that parathion possesses the highest activity, and permethrin and cypermethrin acted as poor antiandrogens. The present study provides insight into the mechanism of the pesticides.

[Study on the relationship between compositions of hyperuricemia and metabolic syndrome].

OBJECTIVE: To study the relationship between compositions of hyperuricemia and metabolic syndrome among residents aged > or =20 years. METHODS: A stratified cluster sampling was conducted with 7887 dwellers recruited and examinaed. Blood samples were then collected for serum detection. Available data was analyzed using SPSS 13.0. RESULTS: The incidence rates of obesity, hypertension and hyperglycemia for hyperuricemia were 53.4% with OR = 2.568 (95% CI: 2.103-3.137), 38.8% with OR= 2.157 (95% CI: 1.856-2.508) and 21.9% with OR = 1.850 (95% CI: 1.552-2.205) respectively. Along with the increase of uric acid, body mass index changed the most followed by triglyceridemia. The change of hyperglycemia for men and cholesterol for women were not prominent. Conclusion The relationship between compositions of hyperuricemia and metabolic syndrome was close, suggesting that hyperuricemia might serve as one of the compositions of metabolic syndrome and could contribute to the prevention and control of cardiovascular and cerebrovascular diseases.

[A community-based case-control study on risk factors of hyperuricemia among residents in the community].

OBJECTIVE: To investigate the risk factors of hyperuricemia among residents aged >/= 20 years. METHODS: A community based case-control study was conducted in 286 patients with 858 controls without hyperuricemia. Available data were analyzed by mono-factorial and multi-factorial logistic regression methods using SPSS 10.0 software. RESULTS: 17 factors related to exposure were identified for hyperuricemia the mono-factorial analysis when; five factors were selected through multiple factoral logistic regression model at P = 0.05 level. The risk factors on hyperuricemia were: hypertriglyceridemia (OR = 3.069), alcohol consumption (OR = 2.032), obesity (OR = 1.802), taste of spicy food (OR = 1.877) and hyperglycemia (OR = 1.622). CONCLUSION: Hyperuricemia is a disease associated with environment and style-life. Changing lifestyle, such as decreasing alcohol consumption and adopting proper structure of diet may prevent or decrease the chance of getting hyperuricemia and gout.

[Principle of "multiple ecological niche of one-species (variety)" and its application in high yield cotton cultivation].

The multiple ecological niche of one-species (variety) (MENOS) population is formed by one species (variety), but the ecological units have different temporal, spatial, nutritional, temperature, or water ecological niche. The formation of MENOS population is characterized by its specific object, one species (variety), multiple layer canopy, human being's active adjustment, specific niche breadth, and overlap and separation of ecological units. This paper analyzed the characteristics of the super high yield cotton population with dual ecological niche of one-species (variety) (DENOS). As for the yield components, MENOS has the characteristics of high yield canopy and different yield plants.