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Lifelong premature ejaculation (PE) is one of the most prevalent male sexual dysfunctions. It is still not well known about the possible neural mechanisms of lifelong PE. This study tried to investigate the abnormal characteristics of brain functional networks of lifelong PE and to assess relationships of PE-related functional abnormalities with clinical symptoms. Functional magnetic resonance imaging (fMRI) data and clinical symptoms were collected from 45 lifelong PE patients and 37 healthy controls (HCs) since 2016, including disease and sexual life history, intravaginal ejaculatory latency time measured by stopwatch and other scales. The degree centrality (DC) approach were applied to distinguish altered brain functions between the two groups (p

The impact of internet use on quality of life (QoL) has become an increasing focus of academic research. This paper aims to explore the internal influencing mechanisms of internet use (i.e., leisure-oriented internet use (LIU); work-oriented internet use (WIU)) on QoL, with a focus on the multiple mediating effects of risk perception and internet addiction. We constructed a theoretical framework from a psychological perspective and tested the hypotheses using hierarchical regression analysis with a sample of 1535 participants. The results showed that: (1) LIU had a positive effect on QoL, while WIU did not have a significant impact on QoL; (2) both risk perception and internet addiction had a negative influence on QoL; (3) risk perception positively impacted internet addiction; (4) risk perception and internet addiction had multiple mediating effects on the relationship between internet use and QoL. Zhejiang Provincial Philosophy and Social Sciences Planning Project of China (20NDQN285YB), Zhejiang Provincial Natural Science Foundation of China (LQ20G020014), and the Fundamental Research Funds for the Provincial Universities of Zhejiang (GK209907299001-212).

Infectious bursal disease (IBD) is an acute and highly contagious immunosuppressive disease caused by the infectious bursal disease virus (IBDV), which seriously threatens the healthy development of the poultry industry. Since its spread to China in the early 1990s, the very virulent IBDV (vvIBDV) characterized by high lethality, has been the focus of prevention and control. However, the novel variant IBDV (nVarIBDV), which has been widely prevalent in China since 2017, has brought a new threat to the poultry industry. In this study, the prevalence of IBDV in the important poultry-raising areas of China from 2019 to 2020 was detected. Of these, 45.1% (101/224) of the samples and 61.9% (26/42) of the chicken flocks were shown to be positive for IBDV. For 50 IBDVs, the sequences of the hypervariable region of the VP2 gene in segment A and of the B-marker of the VP1 gene in segment B were analyzed. The results revealed the coexistence of a number of different IBDV genotypes, including A2dB1 (nVar, 26/50, 52.0%), A3B3 (HLJ0504-like, 15/50, 30.0%), A1B1 (classical, 1/50, 2.0%), and A8B1 (attenuated, 1/50, 2.0%). This indicated that the newly emerging nVarIBDV of A2dB1 and the persistently circulating HLJ0504-like vvIBDV of A3B3 are the two important epidemic strains. Furthermore, we established that segment reassortment has occurred among these circulating strains. This study is the first to reveal the novel epidemic characteristics of IBDV since the report of the emerging nVarIBDV of A2dB1 in China.

Infectious bursal disease virus (IBDV) is a non-enveloped, bi-segmented double-stranded RNA virus and the causative agent of a poultry immunosuppressive disease known as infectious bursal disease (IBD). The novel variant IBDV (nVarIBDV) recently posed a great threat to the development of the poultry industry. In this study, we identified a novel segment-reassortant IBDV strain, IBDV-JS19-14701 (Genotype A2dB3). Phylogenic analysis showed that Segments A and B of IBDV-JS19-14701 were derived from emerging nVarIBDV (Genotype A2dB1) and long-prevalent HLJ0504-like strains (Genotype A3B3) in China, respectively. The pathogenicity of IBDV-JS19-14701 was further evaluated via animal experiments. IBDV-JS19-14701 exhibited a similar virulence to chickens with the nVarIBDV. The identification of this reassortment event is beneficial for understanding the epidemiology of nVarIBDV and will contribute to the efficient prevention and control of IBD.

Allergic diseases have been one of the leading causes of chronic disorders in the United States. Animal studies have suggested that exposures to perchlorate, nitrate, and thiocyanate could induce allergic inflammation. However, the associations have not been examined among general populations. Here, we investigated data of 7030 participants aged ≥6 years from the National Health and Nutritional Examination Survey (NHANES) 2005-2006. Urinary levels of perchlorate, nitrate, and thiocyanate were measured by ion chromatography combined with electrospray tandem mass spectrometry. Information on allergic symptoms (hay fever, allergy, rash, sneeze, wheeze, eczema, and current asthma) was collected by questionnaire. Allergic sensitization was defined by a concentration ≥150 kU/L for total immunoglobulin E (IgE) levels. The associations were estimated using multivariate-adjusted logistic regression models. A positive association was observed for urinary nitrate and eczema (p 0.001 for the trend). Compared with quartile 1 (lowest quartile), the odds ratios of eczema with 95% confidence intervals [ORs (95% CIs)] from quartiles 2 to 4 were 1.72 (95% CI, 1.41, 2.09), 1.94 (1.53, 2.47) and 2.10 (1.49, 2.97) for urinary nitrate. In addition, urinary thiocyanate was positively related to sneeze (OR

In this study, we aimed to characterize the significant DNA methylation module of seasonal allergic rhinitis.Methylation profiling E-GEOD-50222 was obtained from ArrayExpress database. Differential co-methylation network (DCN) was constructed based on the methylation data. From the DCN, we characterized multiple differential modules (M-DMs). Significant module was mapped to pathways to identify significant enriched pathways.At the criteria of absolute Pearson coefficient value 0.8, the edges were chose to construct DCN. In the DCN, 16 seed genes were identified. Seed genes were used to construct M-DMs. After statistical analysis, one significant module with p 0.05 were obtained. After pathways enrichment analysis, 17 significant pathways with p 0.05 were obtained, and most of these pathways were associated with DNA replication.One multiple differential module was identified in SAR, and seventeen significant pathways mapped by the module were identified as important factors in SAR. These results may provide new insights into the molecular mechanism of DNA methylation in SAR.

Exposure to chemical contaminants is considered as one of risk factors to the current epidemic of obesity. Acrylamide (AA) is a ubiquitous chemical contaminant in environmental waste, mainstream cigarette smoke and carbohydrate-rich foods, and widely used in industrial manufacturers and cosmetics. Few studies have highlighted the association of daily exposure to AA with obesity-related outcomes. We analyzed data from 8364 participants who aged 20-85years and were recruited in National Health and Nutrition Examination Surveys (NHANES) 2003-2006. We established the model of PROC Survey Logistic regressions via using AA biomarkers in blood, hemoglobin adducts of acrylamide and glycidamide (HbAA and HbGA), as the measure of internal exposure to AA, and assessing obesity, abdominal obesity and overweight with body mass index (BMI) or waist circumference (WC). After the adjustment of sociodemographic variables, lifestyle behaviors, and health-related factors, the ratio of HbGA to HbAA (HbGA/HbAA) was significantly associated with obesity (p for trend

Background: Long-term exposure to acrylamide (AA) from diet sources may induce oxidative stress and chronic inflammation. However, the association between AA exposure and the prevalence of cardiovascular diseases (CVD) remains unclear. Objectives: We aimed to examine the association between blood exposure levels of AA biomarkers and the prevalence of main types of CVD in a general population of US adults. Methods: We analyzed the associations between AA hemoglobin biomarkers [hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA), sum of HbAA and HbGA (HbAA+HbGA), and ratio of HbGA to HbAA (HbGA:HbAA)] and self-reported diagnosis of CVD in 8290 adults (≥20 years of age) from the National Health and Nutrition Examination Survey (NHANES) 2003–2006. Multivariable logistic regression models were employed for estimating the associations in three groups classified by the combination of smoking status and serum cotinine levels. Results: In people exposed to environmental tobacco smoke (n = 4670), HbGA, HbAA+HbGA, and HbGA:HbAA were significantly and inversely associated with the prevalence of total CVD (p

Background Dexmedetomidine (DEX), a highly sensitive α2-adrenoceptor agonist that possesses anxiolytic, sedative, and analgesic effects, has been documented as a preventative and treatment for emergence agitation (EA). The therapeutic should be given as a loading dose that is infused during a 10 min period, but if a rapid bolus injection is deemed to be hemodynamically appropriate, it would be a more opportune route of administration. So we studied the efficacy of different doses of DEX as a rapid bolus for children to prevent and treat EA. Methods One hundred patients were enrolled and randomly divided into five groups: the control group (group D1), the 0.25 μg/kg DEX group (group D2), the 0.5 μg/kg DEX group (group D3), the 0.75 μg/kg DEX group (group D4), and the 1 μg/kg DEX group (group D5). Heart rate (HR), mean blood pressure (MBP) and blood oxygen saturation (SaO2) were recorded immediately before the study drug injection (baseline) and every minute for 5 min thereafter and at the time points of the skin cut and hernial sac pull. EA and pain were assessed in the post -anesthesia care unit, and any complementary medicine and adverse events were recorded too. Results The incidence of EA was significantly decreased in group D4 and group D5 compared with D1.All groups exhibited similar baseline HR and MBP. After administered, HR and MBP were significantly decreased in all DEX group compared with group D1.In groups D3, D4 and D5, the minimal HR was decreased significantly compared with the groups D1 and duration time of minimal HR significantly prolonged in group D5, but no patient needed treatment. As the dosage increased, the recovery time was significantly prolonged. There were no significant differences in occurrence time of minimal HR, the incidence of complementary medicine and adverse events among groups. Conclusion Rapid intravenous injection (IV) bolus administration of 0.75 and 1.0 μg/kg of DEX could improve the recovery profile by reducing the incidence of EA in children. Although its use resulted in a transient decreases in HR and MBP, DEX was clinically well-tolerated in children. Trial registration No. ChiCTR-IPR-17010658. Registered 17 February 2017.

Background The potential hazards of acrylamide (AA) have been proposed due to its lifelong exposure. However, the association between AA exposure and mortality remains unclear. Objectives We evaluated the prospective association of AA hemoglobin adducts (HbAA and HbGA) with all-cause and cardiovascular disease (CVD) mortality in U.S. population from National Health and Nutrition Examination Survey (NHANES) 2003–2006. Methods We followed 5504 participants who were ≥25 years of age for an average of 6.7 years at the baseline examination with annual linkage to the NHANES statistics database. Using AA hemoglobin biomarkers [HbAA, HbGA, sum of HbAA and HbGA (HbAA + HbGA), and ratio of HbGA to HbAA (HbGA/HbAA)], we determined mortality from all-causes and CVD through Cox proportional hazard regression analysis with multivariable adjustments both in non-smoker group and smoker group. In addition, subgroup analyses and sensitivity analyses were further conducted. Results After adjusting for sociodemographic, life behavioral and cardiovascular risk factors in non-smoker group, HbAA was positively associated with all-cause mortality (p for trend = 0.0197) and non-CVD mortality (p for trend = 0.0124). HbGA and HbGA/HbAA were inversely associated with all-cause mortality (p for trend = 0.0117 and 0.0098, respectively) and CVD mortality (p for trend=0.0009 and 0.0036, respectively). The multivariable adjusted hazard ratios (HRs) [95% confidence intervals (CIs)] of the upper three quartiles were 0.472 (95% CI: 0.283–0.786), 0.517 (95% CI: 0.299–0.894) and 0.470 (95% CI: 0.288–0.766) between HbGA/HbAA and all-cause mortality comparing with the lowest quartile, respectively. No significant associations were found between HbAA + HbGA and mortality in non-smoker group, and between all AA hemoglobin biomarkers and mortality in smoker group. Conclusions Hemoglobin biomarker levels of AA were strongly associated with mortality in general U.S. non-smoker adults. These findings proposed a continuous public health concern in relation to environmental and dietary exposure to AA.

Galectins are β-galactoside binding lectins that play crucial roles in innate immunity in vertebrates and invertebrates through their conserved carbohydrate-recognition domains (CRDs). In the present study, single- and four-CRD-containing galectins were identified in oyster Crassostrea gigas (designated CgGal-2 and CgGal-3). The open reading frames (ORFs) of CgGal-2 and CgGal-3 encode polypeptides of 200 and 555 amino acids, respectively. All CRDs of CgGal-3 include two consensus motifs essential for ligand-binding, and a novel motif is present in CgGal-2. Pathogen-associated molecular pattern (PAMP) profiles were determined for recombinant rCgGal-2 and rCgGal-3, and rCgGal-2 displayed low binding affinity for PAMPs, while rCgGal-3 bound various PAMPs including glucan, lipopolysaccharide (LPS), and peptidoglycan (PGN) with relatively high affinity. Furthermore, rCgGal-2 and rCgGal-3 exhibited different microbe binding profiles; rCgGal-2 bound to Gram-negative bacteria (Escherichia coli and Vibrio vulnificus) and fungi (Saccharomyces cerevisiae and Pichia pastoris), while rCgGal-3 bound to these microbes but also to Gram-positive bacteria (Micrococcus luteus). In addition, rCgGal-3 possessed microbial agglutinating activity and coagulation activity against fungi and erythrocytes, respectively, but rCgGal-2 lacked any agglutinating activity. Carbohydrate binding specificity analysis showed that rCgGal-3 specifically bound D-galactose. Furthermore, rCgGal-2 and rCgGal-3 functioned as opsonin participating in the clearance against invaders in C. gigas. Thus, CgGal-2 with one CRD and CgGal-3 with four CRDs are new members of the galectin family involved in immune responses against bacterial infection. Differences in the organisation and amino acid sequences of CRDs may affect their specificity and affinity for nonself substances.

Acrylamide (AA), an environmental pollutant, has been linked to neurotoxicity, genotoxicity and carcinogenicity. AA is widely used to synthesize polymers for industrial applications, is widely found in Western-style carbohydrate-rich foods and cigarette smoke, and can also be detected in human umbilical cord blood and breast milk. This is the first study that demonstrated the cardiac developmental toxicity of AA in zebrafish embryos. Post-fertilization exposure to AA caused a clearly deficient cardiovascular system with a shrunken heart and abortive morphogenesis and function. Disordered expression of the cardiac genes, myl7, vmhc, myh6, bmp4, tbx2b and notch1b, as well as reduced number of myocardial cells and endocardial cells, indicated the collapsed development of ventricle and atrium and failed differentiation of atrioventricular canal (AVC). Although cell apoptosis was not affected, the capacity of cardiomyocyte proliferation was significantly reduced by AA exposure after fertilization. Further investigation showed that treatment with AA specifically reduced the expressions of nkx2.5, myl7 and vmhc in the anterior lateral plate mesoderm (ALPM) during the early cardiogenesis. In addition, AA exposure disturbed the restricted expressions of bmp4, tbx2b and notch1b during atrioventricular (AV) valve development and cardiac chambers maturation. Our results showed that AA-induced cardiotoxicity was related to decreased cardiac progenitor genes expression, reduced myocardium growth, abnormal cardiac chambers morphogenesis and disordered AVC differentiation. Our study demonstrates that AA exposure during a time point analogous to the first trimester in humans has a detrimental effect on early heart development in zebrafish. A high ingestion rate of AA-containing products may be an underlying risk factor for cardiogenesis in fetuses.

A codelivery system that sequentially releases its contents is an effective strategy to enhance anticancer efficacy. Here, we fabricated multicomponent-based liposomes (T/CM-L) loaded with sodium tanshinone IIA sulfonate (STS) and a small-sized microemulsion of celastrol (CM), which shows synergistic anti-breast cancer activity through the initial release of STS for modulation of the tumor microenvironment, and subsequent release of CM (and its payloads) for eradication of tumor tissues. In vitro studies exhibited that T/CM-L induced massive apoptosis of MCF-7 cells, indicating a coordinated cytotoxicity against cancer cells. Once the liposomes had accumulated at the tumor site, STS was released from T/CM-L in the first place to repair abnormal vessels as well as to decrease the level of fibroblasts. Owing to the barriers of the microemulsion and the liposomes, the celastrol was then unloaded at a moderate rate to kill the tumor cells, which resulted in the shrinkage of the tumor size. Furthermore, T/CM-L displayed diminished systemic toxicity compared to celastrol used alone. Our work offers a novel strategy for combination anticancer treatment and holds promising potential not only for breast cancer treatment, but also for the treatment of other solid tumors.

Icariin has a significant anti-osteoporotic activity, but its clinical application is limited due to a poor oral bioavailability especially under pathological conditions like osteoporosis. Based on the intestinal absorption and metabolism characteristics of icariin in the osteoporosis rats, a kind of simple enteric capsules containing icariin and snailase was designed to overcome this issue in this study. Snailase was secleted as the most efficient exogenous hydrolase of icariin and the related hydrolysis reaction parameters were optimized in the artificial intestinal liquid. Moreover, the hydrolysates of icariin were proved more effective in promoting the rat calvarial osteoblast proliferation than icariin by the MTT assay. Therefore, snailase and icariin were packed into the enteric-coated capsules at an appropriate mass ratio of 1:1 to prepare the icariin loaded enteric-coated capsules (IECs), and then the in vitro release and in vivo pharmacokinetic behavior of IECs was evaluated. Icariin was almost completely hydrolyzed within 4h and approximately 89% of the total flavonoid had been released from IECs at 0.75h in the release medium, which met the requirement of the Chinese Pharmacopoeia on enteric preparations and the Weibull function model. The pharmacokinetic data showed IECs could significantly improved the integrated oral bioavailability of icariin by 50% compared to the IP (icariin without the snailase) in the ovariectomized rats, but no obvious difference was observed in the sham rats. The aforementioned results suggested that such a strategy of icariin combined with the snailase held a great potential in promoting the intestinal hydrolysis and absorption of icariin in the osteoporosis status, providing new research ideas for the active ingredients of traditional Chinese medicine with similar properties.

Background: Perchlorate, nitrate, and thiocyanate are well-known thyroid disrupters and may contribute to changes in body weight. However, the associations between environmental exposure to these chemicals and obesity-related outcomes remain unclear. Objectives: We aim to examine the urinary levels of perchlorate, nitrate, and thiocyanate and their associations with obesity and abdominal obesity in the U.S. population. Methods: Here, we investigated the data of 16,265 adults aged 20–85 years from the National Health and Nutritional Examination Survey (NHANES) in 2001–2014. Urinary levels of perchlorate, nitrate, and thiocyanate were measured by ion chromatography combined with electrospray tandem mass spectrometry. Obesity and abdominal obesity were defined by the body mass index and waist circumference, respectively. Logistic regression models were used to estimate the associations. Results: Overall, 5794 (35.6%) cases of obesity and 9090 cases (55.9%) of abdominal obesity were observed among the participants. In multivariable-adjusted logistic regression models, urinary nitrate was inversely associated with obesity (p = 0.0022 for trend), while urinary thiocyanate was positively related to obesity (p

The aim of this study is to demonstrate the enhanced therapeutic efficacy of anticancer drugs on drug-resistant breast cancer using multicomponent microemulsions (ECG-MEs) as an oral delivery system. The etoposide-loaded ECG-MEs were composed of coix seed oil and ginsenoside Rh2 (G-Rh2), both of which possess not only the synergistic antitumor effect with etoposide, but also have excipient-like properties. Orally administrated ECG-MEs were demonstrated to be able to accumulate at the tumor site following crossing the intestines as intact vehicles into the blood circulation. The spatiotemporal controlled release characteristics of ECG-MEs brought about the efficient P-gp inhibition by the initially released G-Rh2 and the increased intracellular accumulation of the sequentially released etoposide. The combination antitumor activity of etoposide, G-Rh2 and coix seed oil using ECG-MEs was verified on the xenograft drug-resistant breast tumor mouse models. In addition, the safety evaluation studies indicated that treatment with ECG-MEs did not cause any significant toxicity in vivo. These findings suggest that ECG-MEs as an oral formulation may offer a promising strategy to treat the drug-resistant breast cancer.

The acidic α-amylase Gs4j-AmyA from deep-sea thermophile Geobacillus sp. is more acid-resistant than the commercial sources as it displays more than 50% of the optimum at a range of pH 4.5–7. This may allow the removal of the step of pH adjustment in starch processing and save costs. Unfortunately, this amylase is not very stable at 90–95°C. Therefore, to develop a new commercial acidic α-amylase targeted to the food industry, it is necessary to further improve the thermostability of the α-amylase Gs4j-AmyA. In this study, 11 different α-amylase mutants were obtained by site-mutagenesis. Among them, the mutant IG181–182* (IG181–182 deletion) showed significant improvement in thermostability, whose half-life at 70°C was 63.4 times longer than the wild type. Interestingly, single-site mutants C363G and N463T showed no enhancement on thermostability, while the half-lives of the combination mutants IG181–182*/C363G and IG181–182*/N463T at 70°C were further extended by 16.8 and 38.7%, respectively. Unf...

Immunoglobulin M (IgM), an important immune effector, plays a crucial role in protecting fish against various pathogens. Largemouth bass (Micropterus salmoides) is an economically important farmed fish, but the understanding of IgM characteristics and function in largemouth bass is still lacking. In the present study, the largemouth bass IgM heavy chain gene was first cloned. Sequence analysis showed that cDNA of the IgM heavy chain contains an open reading frame (ORF) of 1740 bp. The ORF of the largemouth bass IgM heavy chain encodes a polypeptide of 579 amino acids that consists of a signal peptide, a variable region (VH) and four constant regions (CH1, CH2, CH3 and CH4). Next, largemouth bass IgM was purified from serum, and polyclonal antibodies against IgM were developed using purified IgM as an antigen. Western blotting analysis showed that the polyclonal antibodies reacted with the heavy and light chains of largemouth bass IgM. Indirect immunofluorescence assay (IFA) analysis suggested that the polyclonal antibodies could also react with membrane-bound IgM (mIgM) on the surface of B cells. Flow cytometric analysis revealed that the percentages of mIgM+ B lymphocytes in the peripheral blood, spleen and head kidney were higher than those in the gill in largemouth bass. qRT-PCR analysis showed that the gene expression of the IgM heavy chain in the head kidney and spleen was significantly higher than that in the gill, intestine and skin. Moreover, indirect ELISA showed that the IgM contents in serum were higher than those in mucus and that specific serum antibody levels were significantly increased after Aeromonas hydrophila immunization. These results demonstrated that the largemouth bass IgM gene was first cloned and characterized in this study and that IgM may play a more important role in systemic immunity than in mucosal immunity.

Gastric cancer is a malignant neoplasm with a high mortality rate in the world. Nearly one million new cases occur each year. The most important measure to diagnose gastric cancer is the detection and treatment of diseases early. Gastric cancer detection is currently performed by pathologists reviewing large expanses of biological tissues, but this process is labor intensive and error-prone. In this paper, a framework for automatically detection of tumors in gastric pathology image (slide) has been proposed based on deep learning. A deep residual network with 50 layers is built by identity mapping on a dataset of pathology images. The proposed method makes the training of models easier and improves the generalization performance. Finally, the experimental results show that the F-score of our method achieves 96%. The research in auto-classification of gastric pathology images has great value for gastric cancer detection in clinical medicine.

A deep-sea thermophile, Geobacillus sp. 4j, was identified to grow on starch and produce thermostable amylase. N-terminally truncated form of Geobacillus sp. 4j α-amylase (Gs4j-amyA) was fused at its N-terminal end with the signal peptide of outer membrane protein A (OmpA) of Escherichia coli. The enzyme was over-expressed in E. coli BL21 with a maximum extracellular production of 130U/ml in shake flask. The yield of the transformant increased 22-fold as compared with that of the wild strain. The recombinant enzyme purified to apparent homogeneity by metal-affinity chromatography, exhibited a molecular mass of 62kDa. It displayed the maximal activity at 60-65°C and pH 5.5. Its half-life (t1/2) at 80°C was 4.25h with a temperature deactivation energy of 166.3kJ/mol. Compared to three commonly used commercial α-amylases, the Gs4j-amyA exhibited similar thermostable performance to BLA but better than BAA and BSA. It also showed a universally efficient raw starch hydrolysis performance superior to commercial α-amylases at an acidic pH approaching nature of starch slurry. As a new acidic-resistant thermostable α-amylase, it has the potential to bypass the industrial gelatinization step in raw starch hydrolysis.

Background Perfluoroalkyl chemicals (PFCs) as possible cardiovascular disrupters are universally detected in humans. However, evidence from epidemiological studies appears insufficient and ambiguous. Objectives We aim to examine the serum PFCs levels and their associations with the prevalence of cardiovascular diseases (CVD) and related outcomes in general US population. Methods We investigated the serum levels of 12 major PFCs, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), 2-( N -ethyl-perfluorooctane sulfonamido) acetate (EPAH), 2-( N -methyl-perfluorooctane sulfonamido) acetate (MPAH), perfluorodecanoic acid (PFDE), perfluorobutane sulfonate (PFBS), perfluoroheptanoic acid (PFHP), perfluorononanoic acid (PFNA), perfluorooctane sulfonamide (PFSA), perfluoroundecanoic acid (PFUA), and perfluorododecanoic acid (PFDO), in 10,859 participants from the National Health and Nutritional Examination Survey (NHANES) 1999–2014. Logistic regression models were used to estimate the associations between serum PFCs and 5 self-reported CVD outcomes, including congestive heart failure, coronary heart disease, angina pectoris, heart attack, and stroke. Linear regression analyses were used to estimate the PFCs and their associations with 8 traditional CVD risk factors like serum triglyceride and total cholesterol. Results In multivariable-adjusted models, total PFCs were positively associated with total CVD ( p for trend = 0.0166), independent of traditional CVD risk factors, such as smoking status, diabetes, hypertension and serum cholesterol level. Compared with reference quartile of total PFCs levels, the multivariable adjusted odds ratios in increasing quartiles were 1.23 [95% confidence interval (CI): 0.91–1.66], 1.47 (95% CI: 1.14–1.89) and 1.45 (95% CI: 1.06–1.98) for total CVD. Similar positive associations were found if considering individual PFCs including PFOS, PFUA, MPAH, EPAH, PFDO, PFSA and PFBS. In addition, serum levels of MPAH and PFDO were positively associated with congestive heart failure; PFNA, PFDE, and PFUA were positively associated with coronary heart disease; PFUA and PFDO were positively associated with angina pectoris; and PFNA was positively associated with heart attack. Conclusions Our findings suggested that exposure to PFCs was positively associated with risk of CVD. Further longitudinal studies are needed to increase our understanding about the role of PFCs exposure in the prevalence of CVD.

Solamargine, an active ingredient of Solanum nigrum, has been previously revealed to inhibit the proliferation of cancer cells. However, the effect of solamargine on human cholangiocarcinoma cells and the underlying molecular mechanism remain unknown. In the present study, the molecular mechanism underlying the anti-cancer effect of solamargine was assessed in human cholangiocarcinoma QBC939 cells. The results of the present study revealed that solamargine inhibited the viability of QBC939 cells in a dose-dependent manner. Furthermore, solamargine significantly induced the apoptosis of QBC939 cells and altered the mitochondrial membrane potential of cells. Quantitative polymerase chain reaction analysis revealed that solamargine decreased the mRNA level of B-cell lymphoma-2 (Bcl-2), Bcl-extra-large and X-linked inhibitor of apoptosis protein but increased the mRNA level of Bcl-2-associated X protein (Bax). In addition, western blot analysis demonstrated that solamargine inhibited the protein expression of Bcl-2 and poly ADP ribose polymerase (PARP), and promoted the protein expression of Bax, cleaved PARP, caspase 3, cleaved caspase 3 and caspase 7. Therefore, the results of the present study revealed that solamargine may induce apoptosis via the mitochondrial pathway and alter the level of apoptosis-associated proteins in human cholangiocarcinoma QBC939 cells. This in vitro study demonstrated that solamargine may be an effective chemotherapeutic agent against cholangiocarcinoma in clinical practice.

Government has popularized potatoes as the staple food in China. Potatoes as a potassium-rich food show high glycemic responses after consumption. Whether potato consumption is prospectively linked with the risk of hypertension remains unclear in oriental populations. In this study, we aimed to investigate the association of potato consumption with the risk of hypertension among Chinese people.A total of 11,763 adults (≥20 years old) who were free of hypertension at baseline were enrolled from China Health and Nutrition Survey (CHNS) Cohort study in 1989-2011. Participants were excluded if they were20 years old, identified to be pregnant, and previously diagnosed with hypertension, cancers, infarction, apoplexy and diabetes at baseline. Cox proportional hazards regression models were used to estimate the associations after adjusting for potential confounders.During average 11.3 years of follow-up, 4033 incident cases of hypertension were ascertained. People who consumed more amounts of total potatoes, stir-fried potatoes, and non stir-fried potatoes had higher risk of hypertension (P for trend = 0.1225, 0.2168 and 0.0456, respectively). Multivariable hazard ratios (HRs) for increased consumption of total potatoes were 1.402 (95% confidence interval [CI], 1.270-1.548), 1.198 (95% CI, 1.014-1.415), and 1.120 (95% CI, 0.929-1.349) compared with non-consumers. However, the participants with higher intake of potato consumption were inclined to have lower risk of hypertension when excluding the non-consumers of total potatoes or stir-fried potatoes (P for trend = 0.0271 and 0.0001). In addition, a positive association of sweet potatoes intake with hypertension risk was only found in urban residents (P for trend = 0.0239).Our results showed that potato consumption was prospectively associated with hypertension in Chinese population. As the urbanization process continues along with the transition to Western-style diets, more consideration should be taken before the formulation of potato popularization is promoted in China.

The aim of this study is to explore the influence of Ganoderma lucidum-derived polysaccharides (GLP) to coix oil-based microemulsion on pharmaceutical performance and anti-lung cancer treatment. GLP-integrated coix oil-based microemulsion (MEs(PS-GLP)) exhibited a clear spherical shape, small particle size, and good hydrodynamics similar to the coix oil-based microemulsion, but showed a lower zeta potential and a better stability. Fluorescence resonance energy transfer analysis presented that GLP was integrated with microemulsion as a single system. Notably, the average molecular distance between polysaccharide and microemulsion was approximately 1.7 nm. The half-maximal inhibitory concentration of MEs(PS-GLP) against A549 cells was about 119 μg/mL. In vivo imaging studies showed that introduction of GLP promoted the tumor-specific accumulation of microemulsion in comparison with controls. In vivo, antitumor results showed that MEs(PS-GLP) markedly inhibited the tumor growth of A549-bearing xenograft nude mice and obviously improve the serum immune index. Collectively, this study demonstrates the potential mechanism of spatial relation between polysaccharides and microemulsion and validates the significances of GLP on tumoral accumulation and antitumor efficacy.

Acrylamide (AA) is a high production volume chemical in industrial applications and widely found in baked or fried carbohydrate-rich foods. In this study, we unravelled that AA induced developmental toxicity associated with oxidative stress status and disordered lipid distribution in heart region of developing zebrafish. Treatment with AA caused a deficient cardiovascular system with significant heart malformation and dysfunction. We also found that AA could reduce the number of cardiomyocytes through the reduced capacity of cardiomyocyte proliferation rather than cell apoptosis. The cardiac looping and ballooning appeared abnormal though cardiac chamber-specific identity in the differentiated myocardium was maintained well after AA treatment through MF20/S46 immunofluorescence assay. Furthermore, treatment with AA disturbed the differentiation of atrioventricular canal, which was demonstrated by the disordered expressions of the atrioventricular boundary markers bmp4, tbx2b and notch1b and further confirmed by the ectopic expressions of the cardiac valve precursor markers has2, klf2a and nfatc1 through whole-mount in situ hybridization. Thus, our studies provide the evidence of cardiac developmental toxicity of AA in the cardiovascular system, and also raised health concern about the harm of trans-placental exposure to high level of AA for foetuses and the risk of high exposure to AA for the pregnant women.

Skin toxicities induced by epidermal growth factor receptor inhibitors such as Erlotinib plagues clinical challenges. Chinese formulas have a unique advantage in reducing side effects. Here, we aim to investigate the skin protecting function of XiaoZhenFang (XZF), a clinical adjuvant prescription made up of Lonicerae Japonicae Flos, Lithospermum Erythrorhizon, Smilacis Glabrae Rhizoma, Forsythiae Fructus, Spirodelae Herba, Cortex Moutan and Prunellae Spica. Our data showed that XZF aqueous extract effectively reduced skin toxicities induced by Erlotinib in vivo using established mice model. Next, we used a systems pharmacology approach to investigate the pharmacological mechanism of XZF with the goal of understanding its effects at the system, organ, and molecular levels. 44 candidate compounds and 103 potential targets were identified by network pharmacology. Inflammation, cell stress and the EGFR-related signal pathways, which may participate in the skin protection afforded by XZF, were analyzed by gene enrichment. Importantly, our in vivo experimental results largely validated XZF’s mechanism of action, as predicted by the system pharmacology analysis. Our study uncovered the effect and mechanism of XZF in attenuating skin toxicities induced by EGFRI, providing a basis for the development of in-hospital preparations and new drugs for the prevention of skin toxicities.

A C-type lectin of multiple CRDs (CfLec-4) from Chlamys farreri was selected to investigate the sequence variation and functional differentiation of its CRDs. Its four CRDs with EPD/LSD, EPN/FAD, EPN/LND and EPN/YND key motifs were recombined separately. The recombinant proteins of CRD1 and CRD2 (designated as rCRD1 and rCRD2) could bind LPS and mannan, while the recombinant proteins of CRD3 and CRD4 (designated as rCRD3 and rCRD4) could bind LPS, PGN, mannan and glucan. Moreover, rCRD3 displayed broad microbe binding spectrum towards Gram-positive bacteria Staphylococcus aureus and Micrococcus luteus, Gram-negative bacteria Escherichia coli and Vibrio anguillarum, as well as fungi Pichia pastoris and Yarrowia lipolytica. These results indicated CRD3 contributed more to CfLec-4's nonself-recognition ability. Furthermore, CRD1, CRD3 and CRD4 functioned as opsonin participating in the clearance against invaders in scallops. The sequence variation in Ca2+ binding site 2 among CRDs was suspected to be associated with such functional differentiation.

A C-type lectin (CfLec-3) from Chlamys farreri with three carbohydrate-recognition domains (CRDs) was selected to dissect the possible mechanisms of PAMP binding and functional differentiation of invertebrate lectins. CfLec-3 distributed broadly and its mRNA expression in hemocytes increased significantly after stimulations with LPS, PGN or β-glucan, but not poly(I:C). The recombinant CfLec-3 (rCfLec-3) could bind PAMPs and several microbes. rCfLec-3 mediated hemocytes phagocytosis against Escherichia coli and encapsulation towards agarose beads. Obvious functional differentiation occurred among the three CRDs, as CRD1 exhibited higher activity to bind PAMPs, while CRD2/3 were expert in promoting hemocyte mediated opsonisation. The tertiary structural differences were suspected to be associated with such functional differentiation. PAMP binding abilities of CfLec-3 were determined by Ca2+-binding site 2 motif. When Pro in this motif of each CRD was mutated into Ser, their PAMP binding abilities were deprived absolutely. rCRD2 acquired mannan binding capability when its EPD was replaced by EPN, but lost when EPN in rCRD3 was changed into EPD. The Pro in Ca2+-binding site 2 was indispensable for PAMPs binding, while Asn was determinant for specific binding to mannan. It shed new insight into PAMPs binding mechanism of invertebrate C-type lectins and their functional differentiation.

Ding Qu,1 Yihua Ma,1 Wenjie Sun,1,2 Yan Chen,1 Jing Zhou,1 Congyan Liu,1 Mengmeng Huang1 1Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 2Department ofPharmaceutics, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China Abstract: A microemulsion-based synergistic dual-drug codelivery system was developed for enhanced cell apoptosis by transporting coix seed oil and etoposide into A549 (human lung carcinoma) cells simultaneously. Results obtained by dynamic light scattering showed that an etoposide (VP16)-loaded coix seed oil microemulsion (EC-ME) delivery system had a small size around 35 nm, a narrow polydispersity index, and a slightly negative surface charge. The encapsulating efficiency and total drug loading rate were 97.01% and 45.48%, respectively, by high-performance liquid chromatography. The release profiles at various pH values showed an obvious pH-responsive difference, with the accumulated amount of VP16 released at pH 4.5 (and pH 5.5) being 2.7-fold higher relative to that at pH 7.4. Morphologic alteration (particle swelling) associated with a mildly acidic pH environment was found on transmission electron microscopy. In the cell study, the EC-ME system showed a significantly greater antiproliferative effect toward A549 cells in comparison with free VP16 and the mixture of VP16 and coix seed oil. The half-maximal inhibitory concentration of the EC-ME system was 3.9-fold and 10.4-fold lower relative to that of free VP16 and a mixture of VP16 and coix seed oil, respectively. Moreover, fluorescein isothiocyanate and VP16 (the green fluorescent probe and entrapped drug, respectively) were efficiently internalized into the cells by means of coix seed oil microemulsion through intuitive observation and quantitative measurement. Importantly, an EC-ME system containing 20 µg/mL of VP16 showed a 3.3-fold and 3.5-fold improvement in induction of cell apoptosis compared with the VP-16-loaded microemulsion and free VP16, respectively. The EC-ME combination strategy holds promise as an efficient drug delivery system for induction of apoptosis and treatment of lung cancer. Keywords: microemulsion, synergistic effect, dual-drug codelivery, coix seed oil, apoptosis induction

C-type lectins are a superfamily of Ca(2+)-dependent carbohydrate-recognition proteins consisting of at least one carbohydrate-recognition domain (CRD), which play significant roles in nonself-recognition and clearance of invaders. The immune function of a C-type lectin (AiCTL-7) with EPD/WSD motifs from Argopectens irradians was investigated in the present study. The recombinant protein of AiCTL-7 (rAiCTL-7) could bind LPS, PGN, mannan, yeast glucan and poly I:C in vitro, and displayed a broader microbes binding spectrum towards Gram-positive bacteria Staphylococcus aureus, Gram-negative bacteria Escherichia coli, Vibrio anguillarum, as well as fungi Pichia pastoris and Yarrowia lipolytica. Moreover, it could also inhibit the growth of E. coli and significantly (P < 0.01) mediate the cell-cell adhesion in vitro. The results clearly suggested that EPD/WSD motifs containing lectin AiCTL-7 could serve as PRR with wider recognition spectrum, and function both as collectin and selectin participating in the immunity against invaders in scallops. It could be inferred that the diversity and complexity of motifs in Ca(2+) binding site 2 in CRDs endowed C-type lectins with comprehensive recognition spectrum and multiple immune functions against complex living environment.

Iodothyronine deiodinase is responsible for the deiodination of thyroxine T4 to T3, and involved in the complex neuroendocrine-immune regulatory network to optimize the immune response in vertebrate. In this study, the full-length cDNA of an iodothyronine deiodinase (designated as CfDx) was cloned from scallop Chlamys farreri. The complete cDNA sequence of CfDx was of 1404 bp and contained an open reading frame of 900 bp encoding a polypeptide of 299 amino acids. The deduced amino acid sequence of CfDx contained an in-frame TGA stop codon probably encoding an essential selenocysteine (SeC), and there was a conserved region of about 15 amino acids surrounding the SeC residue. The CfDx mRNA transcripts were detected in all the tested tissues, including haemocytes, hepatopancreas, kidney, adductor muscle, gonad, gill and mantle, with the higher expression level in hepatopancreas and kidney. After LPS stimulation, the CfDx mRNA expression level in haemocytes increased significantly at 12 h (25.35-fold, P < 0.05) and 24 h (7.62-fold, P < 0.05), and the concentration of T3 in haemolymph increased significantly at 12 h (3.62 ng dL(-1), P < 0.05) even the concentration of T4 did not change significantly. After scallop received an injection of 50 mu g CfDx dsRNA, the expression level of CfDx mRNA in haemocytes began to decrease significantly at 36 h and maintained the relative low level (about 0.3-fold of the PBS control group) from 36 to 72 h, but the ratio of T4/T3 in haemolymph began to increase at 36 h (2.31-fold, P < 0.05) and kept increasing from 36 to 72 h comparing with that in the PBS control group. These results indicated that CfDx was a homologue of iodothyronine deiodinase in scallop C. Jarred, and it might be involved in the immunomodulation via regulating the concentration of thyroid hormones T3 and T4 in the haemolymph of scallop. (C) 2012 Elsevier Ltd. All rights reserved.