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Rationale: Hypertension is the most important risk factor for cardiovascular and cerebrovascular diseases. Getting deep insight into the pathogenesis of hypertension is necessary. Objective: To investigate the role of ANK (ankyrin) repeat domain 36 ( ANKRD36 ) in hypertension. Methods and Results: We first recruited an essential hypertension cohort and then performed genome-wide transcriptome analysis with peripheral blood mRNA. ANKRD36 was found to be significantly lower expressed in hypertension. The anchorin repeat domain mediates a variety of protein-protein interactions. The ENaC (epithelial sodium channel) genes expression was found upregulated in human umbilical vein endothelial cells with ANKRD36 knockdown by using Affymetrix expression profile chip. In human embryonic kidney epithelial cells and HEK293T (human embryonic kidney cells), ANKRD36 overexpression significantly downregulated expression of ENaC genes, and ANKRD36 knockdown upregulated their expression. The chromosome immunoprecipitation assay and yin yang 1 ( YY1 ) knockdown showed the expression of ENaC was regulated by ANKRD36 via YY1, a dual-function transcription factor ubiquitously expressed in human tissues. Immunocoprecipitation and fluorescence resonance energy transfer assay confirmed the interaction between ANKRD36 and YY1. The nucleo-cytoplasmic ratio of YY1 decreased when ANKRD36 was overexpressed and also increased when ANKRD36 was knocked down. ANK2 domain of ANKRD36 was critical to its interaction with YY1. Ankrd36 knockout mice showed higher blood pressure levels and Na + reabsorption, especially when fed with high-salt diet. Higher expression of ENaC genes was observed in renal tubular epithelial cells from the knockout mice, and Yy1 knockdown mitigated the alteration. Ankrd36 knockout mice also showed more sensitive response to ENaC inhibitor amiloride treatment. Conclusions: We identified that ANKRD36 was involved in blood pressure regulation by interacting with YY1 and then altering expression of ENaC genes. Lower expressed ANKRD36 in hypertension might be a potential therapeutic target, and the application of ENaC inhibitors on hypertension treatment might be extended when serum K + levels are closely monitored.

The objective of this study was to investigate the short- and long-term effects of different feed presentations on feed sorting and rumen pH in weaned calves. Thirty-six weaned female calves at the age of 12 wk (78 d) were raised in pairs (18 pens; n = 6/treatment) and randomly exposed to 1 of 3 feed presentation treatments: (1) concentrate ration (CON, only exposed to concentrate); (2) separate ration (CH, exposed to concentrate and hay as separate components); and (3) mixed ration (Mix, exposed to a mixed diet containing 75% concentrate and 25% hay). After 4 wk (from d 78 to 105) on different feed presentations, all weaned calves were introduced to a novel total mixed ration (TMR) for another 12 wk (from d 106 to 189). Fresh feed and orts were sampled daily before (wk 12 to 15) and after (wk 16, 17, and 28) transitioning to a TMR diet for analysis of feed sorting. Rumen fluid was sampled in wk 12, 13, 15, 16, 17, and 28 to determine rumen pH. The performance of weaned calves was affected by the different feed presentations during the pre-changing period, such that calves fed CON had a lower dry matter intake (DMI) and average daily gain than calves fed CH and Mix diets. When calves were introduced to the Mix diet, they immediately developed a higher degree of sorting behavior against the long particle fractions. Upon transition to TMR, we did not observe any differences in the performance of calves. However, the sorting behavior established in Mix calves persisted and was similar to calves previously fed the CON diet, whereas the extent of feed sorting in calves initially fed CH was less compared with that in the other 2 treatments in wk 16 and 17. Before changing the diet was transitioned to a TMR, calves fed CON had a lower rumen pH than calves fed CH and Mix. Although rumen pH in all treatments increased to the same level after the diet changed, we observed a tendency toward lower rumen pH in calves fed Mix compared with calves fed CH at wk 17, which might have resulted from the higher degree of feed sorting in these calves. However, by the end of the experiment (wk 28), feed sorting and rumen pH were similar across all treatments. These results indicated a short-term effect of previous feed presentations on subsequent feed sorting and rumen pH, but in the long term disappeared.

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This research was conducted to determine the effects of natural capsaicin extract (NCE) as an alternative to the antibiotic (chlortetracycline, CTC) on growth performance, antioxidant capacity, immune function, and meat quality of broiler chickens. A total of 168 one-day-old Arbor Acre male broiler chickens with an average weight of 46.4 ± 0.6 g were randomly allotted to 3 dietary treatments, with 7 replicates per treatment and 8 broilers per pen. These 3 dietary treatments included a corn-soybean meal basal diet (CON), a basal diet + 75 mg/kg CTC (CTC), and a basal diet + 80 mg/kg NCE (NCE). Broilers from the NCE group showed higher average daily gain compared to broilers from the CON group at all stages (P < 0.05). On d 42, NCE supplementation improved dietary nitrogen-corrected apparent metabolizable energy compared to nonsupplemented or CTC-supplemented diets (P < 0.05). The digestibility of organic matter and crude protein were higher in the NCE diet than in the CON or CTC diets (P < 0.05). Higher relative weight of bursa of Fabricius was observed in broilers fed NCE diets compared with CON (P < 0.05). Pancreatic trypsin and lipase activities were significantly increased in the NCE group compared with those in the CON group (P < 0.05). The value of lightness (L*) of breast muscles from broilers fed NCE diets was significantly lower compared to those fed CON diets (P < 0.05). Broilers fed NCE diets also had higher levels of serum total antioxidant capacity, glutathione peroxidase, superoxide dismutase, and lower levels of interleukin-1β, and tumor necrosis factor-α compared with broilers fed CON diets (P < 0.05). The liver catalase activity of broilers was also significantly increased in the NCE group than the CON group (P < 0.05). In addition, broilers from NCE group had lower concentrations of serum urea-N, low-density lipoprotein cholesterol, and total cholesterol, and higher concentration of growth hormone compared with those from the CON group (P < 0.05). Therefore, we concluded that supplementation of 80 mg/kg of NCE in diets could improve growth performance, nutrient digestibility, antioxidant status, immune function, and meat quality in broilers.

Hantavirus, a rodent-borne zoonotic pathogen, has a global distribution with 200,000 human infections diagnosed annually. In recent decades, repeated outbreaks of hantavirus infections have been reported in Eurasia and America. These outbreaks have led to public concern and an interest in understanding the underlying biological mechanisms. Here, we propose a climate-animal-Hantaan virus (HTNV) infection model to address this issue, using a unique dataset spanning a 54-y period (1960-2013). This dataset comes from Central China, a focal point for natural HTNV infection, and includes both field surveillance and an epidemiological record. We reveal that the 8-y cycle of HTNV outbreaks is driven by the confluence of the cyclic dynamics of striped field mouse (Apodemus agrarius) populations and climate variability, at both seasonal and interannual cycles. Two climatic variables play key roles in the ecology of the HTNV system: temperature and rainfall. These variables account for the dynamics in the host reservoir system and markedly affect both the rate of transmission and the potential risk of outbreaks. Our results suggest that outbreaks of HTNV infection occur only when climatic conditions are favorable for both rodent population growth and virus transmission. These findings improve our understanding of how climate drives the periodic reemergence of zoonotic disease outbreaks over long timescales.

Goose is an economically important herbivore waterfowl supplying nutritious meat and eggs, high-quality liver fat, and feathers. However, biogeograhpy of the gut microbiome of goose remains limited. The aim of this study was to investigate the microbiota inhabiting 7 different gastrointestinal locations (proventriculus, gizzard, duodenum, jejunum, ileum, cecum, and rectum) of 180-day-old geese and the short-chain fatty acids (SCFA) of their metabolites based on 16S rRNA gene sequences and gas chromatography, respectively. Consequently, 3,886,340 sequences were identified into 29 phyla and 359 genera. Proteobacteria, Firmicutes, Bacteroidetes, Cyanobacteria, and Actinobacteria were the major phyla, in which Bacteroidetes (28%) and Fusobacteria (0.8%) in the cecum were significantly higher than those in other sections (∼4.4 and 0.1%, respectively). In addition, Cyanobacteria in the gizzard (4.9%) was significantly higher than those in other gut sections except the proventriculus (2.4%). At the genus level, Bacteroides was the most dominant group in the cecum at 23.7%, which was much more than those in the 6 other sections (less than 4.6%). Moreover, Faecalibacterium and Butyricicoccus were significantly high in the cecum (P < 0.05). Results of SCFA showed that acetic and butyric acids in the cecum were significantly higher than those in the 6 other sections (P < 0.05); this result was consistent with the high abundance of Bacteroides, Faecalibacterium, Prevotella, and Butyricicoccus in the cecum. Additionally, isobutyric, isovaleric, and valeric acids were found only in the cecum. The different microbial compositions among the 7 gastrointestinal locations might be a cause and consequence of gut functional differences. All these results could offer some information for future study of the relationship between gastrointestinal microbiota and the ability of fiber utilization and adaptability.

The first human infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Shaanxi Province, China, in 2013, although the virus had been reported in 13 other provinces of China since 2010. We collected and analyzed a total of 4,011 samples, including 936 human serum samples, 155 animal serum samples, 895 ticks, 1,950 mosquitoes, 30 midges, and 20 sandflies. SFTSV antibodies were found in 44 human samples (4.7%) with no significant differences between males and females or across counties. The incidence rate of severe fever with thrombocytopenia syndrome was significantly higher among individuals 20-60 years of age. Moreover, SFTSV-specific antibodies were detected in goats (66.7%), cattle (13.2%), and dogs (15.0%), but not in pigs (0%). We detected the virus in Haemaphysalis concinna ticks with a prevalence rate of 21.3% (17/80 pools). All mosquito, midge, and sandfly samples were negative for SFTSV. These results support wide circulation of the virus in western China. Haemaphysalis concinna ticks may serve as a novel SFTSV vector, and the role of these ticks requires further investigation.

Objectives To explore the epidemiological, phylogeographic and migration characteristics of human rabies in Shaanxi Province, China from 2009 to 2015. Methods The collected data were described and the sequenced glycoprotein (G) and nucleoprotein (N) genes were implemented to estimate the evolutionary rates and phylogeographic patterns using BEAST v.1.8.2. Results 269 rabies cases were reported and 70.26% of the cases were male and 61.71% were between the ages of 19 to 59. The majority of the cases were farmers (83.27%). The estimated evolutionary rate of the N genes was 2.4 × 10−4substitutions/site/year and the G genes was 3.4 × 10−4. The time of the most recent common ancestor(TMRCA) was estimated around 1990. We detected viral migration paths from Sichuan, Guizhou and Hunan to Hanzhong prefecture of Shaanxi and then spreaded to Xi'an and other prefectures. Conclusions The main population affected by rabies virus was male adult farmers. The evolution rate of rabies viruses in Shaanxi was similar with the prior results reported by others and the ancestor virus should be circulating in neighboring province Sichuan around 1990 and then transmitted to Shaanxi. Promptly standard wound treatment and timely post-exposure prophylaxis should be compulsory for the dog-bitten victims. This article is protected by copyright. All rights reserved

Background Increased risks for hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus have been observed since 2005, in Xi’an, China. Despite increased vigilance and preparedness, HFRS outbreaks in 2010, 2011, and 2012 were larger than ever, with a total of 3,938 confirmed HFRS cases and 88 deaths in 2010 and 2011. Methods and Findings Data on HFRS cases and weather were collected monthly from 2005 to 2012, along with active rodent monitoring. Wavelet analyses were performed to assess the temporal relationship between HFRS incidence, rodent density and climatic factors over the study period. Results showed that HFRS cases correlated to rodent density, rainfall, and temperature with 2, 3 and 4-month lags, respectively. Using a Bayesian time-series Poisson adjusted model, we fitted the HFRS outbreaks among humans for risk assessment in Xi’an. The best models included seasonality, autocorrelation, rodent density 2 months previously, and rainfall 2 to 3 months previously. Our models well reflected the epidemic characteristics by one step ahead prediction, out-of-sample. Conclusions In addition to a strong seasonal pattern, HFRS incidence was correlated with rodent density and rainfall, indicating that they potentially drive the HFRS outbreaks. Future work should aim to determine the mechanism underlying the seasonal pattern and autocorrelation. However, this model can be useful in risk management to provide early warning of potential outbreaks of this disease., Author Summary Hemorrhagic fever with renal syndrome (HFRS, caused by hantavirus) is a zoonotic infectious disease reservoired in rodent populations worldwide, but with 90% of the total cases occurring in China. Xi’an is one of the most endemic areas in China, with a total of 7,748 confirmed HFRS cases from 2005 to 2012. HFRS came to the attention of the public when two larger outbreaks occurred in Xi’an in 2010 and 2011, with 1,366 and 1,067 cases being reported, respectively. By using 8 years of surveillance data (2005–2012) on HFRS dynamics, including data on the main rodent host reservoir, human cases, and weather conditions, we show how the epidemic dynamics of HFRS were associated with seasonality, rodent abundance, rainfall, and temperature. We find that the two larger HFRS outbreaks coincided with the abrupt increase of rodent abundance and/or rainfall. We present a statistical model revealing strong effects of seasonality and autocorrelation and additional effects of rodent density and rainfall on HFRS incidence that gives robust prediction; this approach could be a very practical tool in Xi’an.

Zoonoses are increasingly recognized as an important burden on global public health in the 21st century. High-resolution, long-term field studies are critical for assessing both the baseline and future risk scenarios in a world of rapid changes. We have used a three-decade-long field study on hantavirus, a rodent-borne zoonotic pathogen distributed worldwide, coupled with epidemiological data from an endemic area of China, and show that the shift in the ecological dynamics of Hantaan virus was closely linked to environmental fluctuations at the human-wildlife interface. We reveal that environmental forcing, especially rainfall and resource availability, exert important cascading effects on intra-annual variability in the wildlife reservoir dynamics, leading to epidemics that shift between stable and chaotic regimes. Our models demonstrate that bimodal seasonal epidemics result from a powerful seasonality in transmission, generated from interlocking cycles of agricultural phenology and rodent behavior driven by the rainy seasons., Author Summary Pathogens shared with wildlife cause more than 60% of human infectious diseases. However, there is a scarcity of comprehensive modeling of zoonotic disease dynamics at the wildlife-human interface. Here, we use 30 years of monthly rodent-hantavirus monitoring to show that the complex seasonality in human spillover results from the interplay between an ecological cascade that shapes reservoir infection dynamics and seasonal agricultural cycles that in turn determine human-wildlife contact patterns.

SUMMARYThe transmission of haemorrhagic fever with renal syndrome (HFRS) is deeply influenced by the reservoir and hantavirus prevalence rate. In this study, a surveillance on human HFRS cases, relative rodent abundance, and hantavirus infection prevalence was conducted in Shaanxi province, China, during 1984–2012. A generalized linear model with Poisson-distributed residuals and a log link was used to quantify the relationship between reservoir, virus and HFRS cases. The result indicated that there was a significant association of HFRS incidence with relative rodent density and the prevalence rate. This research provides evidence that the changes of infection prevalence in the reservoir could lead directly to the emergence of a new epidemic. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.

The aim of the present study was to analyze an outbreak of hemorrhagic fever with renal syndrome (HFRS), caused by a Hantavirus, in college students in the northern urban area of Xi’an in 2012. The outbreak affected six students and included two deaths. The epidemiological survey revealed that both of the deceased cases were misdiagnosed initially, and treatment was delayed. Furthermore, a higher rodent population density and lower HFRS vaccine coverage were observed in the affected area, which indicates a possible role in the outbreak. Rattus norvegicus (Rn) and Mus musculus (Mm) were the predominant host populations in the area. Genotyping revealed that all HVs from patients and rodents were Hantaan virus (HTNV). Sequence analysis of the S segments revealed that the HTNVs reported in this study had high similarity with strains reported in 2011 and 1985, but these viruses diverged from a strain isolated in 1984 and the HTNV prototype strain 76-118. Detection of anti-HV IgG and amplification of the S segment of HTNV from a non-natural HTNV reservoir indicates that further investigations by increased rodent trapping are necessary.

To study the proliferation and location of Hantaan virus (HV) in gamasid mites and chigger mites and the significance of gamasid mites and chigger mites as vectors of transmission of hemorrhagic fever with renal syndrome (HFRS).Gamasid mites collected from the nests of wild rodents and chigger mites collected from the bodies of wild rodents and thick growth of grass in the field were raised. Two oligonucleotide primers were developed based on the gene fragments of cDNA of HV 76 - 118 strain to be used in RT-PCR. RNA was extracted from the suspension of the gamasid mites from the nests where rodents no HV had been found in whose lungs lived and from the unfed larvae of chigger mites, being formed groups of 5, 10, 30, or 50 individuals. RT-PCR was conducted to detect the HV-RNA in such suspension. The larvae, nymphs, and imagines of both kinds of mites were ground to make suspension at an interval of 20 days. Vero-E(6) cells were inoculated to measure the titer of 50% tissue culture infective dose (TCID(50))/ml of HV. Frozen sections of larvae, nymphs, and imagines of both kinds of mites were made. RT-PCR and in situ hybridization were conducted to detect the distribution of HV-positive particles. Monoclonal antigen technique was used to compare the antigenicity of the HV-RNA from the rodents, mites, and patients from the same epidemic areas.HV-RNA was detected in gamasid mites and chigger mites. Except in the larvae of chigger mites 60 days after collection, titers of HV were detected and increased gradually in mites at different stages of life cycle. HV-RNA positive particles were detected in the epithelial cells of midgut and ovary, with the signal denser and more numerous in nymphs than in larvae. The genotypes of HV from rodents, mites and patients in the same endemic areas were identical: HTN type virus.HV can be transmitted transstadially and proliferated in mites, gamasid mites and chigger mites play the role of vectors of transmission for HFRS.