Publications by authors named "Aihua Wang"

220 Publications

Glyphosate exposure attenuates testosterone synthesis via NR1D1 inhibition of StAR expression in mouse Leydig cells.

Sci Total Environ 2021 Apr 25;785:147323. Epub 2021 Apr 25.

Northwest A&F University, Yangling 712100, Shaanxi, China; Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

Glyphosate is a broad-spectrum herbicide that impairs testosterone synthesis in mammals. Leydig cells (LCs), the primary producers of testosterone, demonstrate rhythmic expression of circadian clock genes both in vivo and in vitro. The nuclear receptor NR1D1 is an important clock component that constitutes the subsidiary transcriptional/translational loop in the circadian clock system. Nr1d1 deficiency resulted in diminished fertility in both male and female mice. However, whether NR1D1 is involved in the glyphosate-mediated inhibition of testosterone synthesis in LCs remains unclear. Here, the involvement of NR1D1 in glyphosate-mediated inhibition of testosterone synthesis was investigated both in vitro and in vivo. Glyphosate exposure of TM3 cells significantly increased Nr1d1 mRNA levels, but decreased Bmal1, Per2, StAR, Cyp11a1, and Cyp17a1 mRNA levels. Western blotting confirmed elevated NR1D1 and reduced StAR protein levels following glyphosate exposure. Glyphosate exposure also reduced testosterone production in TM3 cells. In primary LCs, glyphosate exposure also upregulated Nr1d1 mRNA levels and downregulated the mRNA levels of other clock genes (Bmal1 and Per2) and steroidogenic genes (StAR, Cyp17a1, Cyp11a1, and Hsd3b2), and inhibited testosterone synthesis. Moreover, glyphosate exposure significantly reduced the amplitude and shortened the period of PER2::LUCIFERASE oscillations in primary LCs isolated from mPer2 knock-in mice. Four weeks of oral glyphosate upregulated NR1D1 at both the mRNA and protein levels in mouse testes, and this was accompanied by a reduction in StAR expression. Notably, serum testosterone levels were also drastically reduced in mice treated with glyphosate. Moreover, dual-luciferase reporter and EMSA assays revealed that in TM3 cells NR1D1 inhibits the expression of StAR by binding to a canonical RORE element present within its promoter. Together, these data demonstrate that glyphosate perturbs testosterone synthesis via NR1D1 mediated inhibition of StAR expression in mouse LCs. These findings extend our understanding of how glyphosate impairs male fertility.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147323DOI Listing
April 2021

Ufmylation regulates granulosa cell apoptosis via ER stress but not oxidative stress during goat follicular atresia.

Theriogenology 2021 Apr 22;169:47-55. Epub 2021 Apr 22.

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address:

Follicular atresia is primarily caused by granulosa cell (GC) apoptosis, although the mechanisms are largely unknown. Ufmylation is a recently identified ubiquitin-like post-translational modifier that plays an important role in cell proliferation and apoptosis. The purpose of this study was to investigate the effects of Ufmylation on GC apoptosis during goat follicular atresia. Ubiquitin-fold modifier 1 (UFM1) and its target DDRGK domain containing 1 (DDRGK1) proteins were identified in granulosa cells (GCs) isolated from all stages of preantral follicles and from healthy (HF), early atretic (EF) and progressed atretic (PF) antral follicles. The expression levels were higher in GCs derived from antral atretic follicles than healthy follicles. Although the viability of GCs was not affected after overexpression of UFM1, siRNA-mediated UFM1 silencing significantly inhibited GC proliferation and induced apoptosis. Notably, components of the ufmylation pathway were significantly upregulated in GCs induced by the ER stress agent tunicamycin (Tm) and thapsigargin (Tg), but not affected by oxidative stress inducer HO. Furthermore, UFM1 silencing markedly increased the apoptosis of GCs upon Tg treatment by stimulating the ER stress-related gene expression. Our results provide evidence that UFM1 and its target DDRGK1 are expressed in the goat GCs during follicular development and atresia, and ufmylation may play an important role in the prevention of ER stress but not oxidative stress-induced GCs apoptosis.
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http://dx.doi.org/10.1016/j.theriogenology.2021.04.009DOI Listing
April 2021

Low-dose bisphenol A impairs the function of mouse decidual stromal cells by activating LUMAN-mediated unfolded protein response.

Food Chem Toxicol 2021 Apr 27;153:112242. Epub 2021 Apr 27.

College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China. Electronic address:

The nonsteroidal estrogenic compound bisphenol A (BPA) is widely present in several industrial and medical products including plastic food containers and sealants in dentistry. There are growing concerns on the toxic effects of this compounds since BPA is known to have reproductive toxicity. This study evaluated the effects of low-dose BPA exposure on decidual stromal cells (DSCs) of mice. The results showed that although 10 nM of BPA have no significant effect on the cell viability, it alters the expression of decidualization-related genes including Prl8a2, Prl3c1, Ptgs2, and Mmp2. Moreover, we found that low-dose BPA exposure induces UPR response in DSCs. However, the expression of the three major UPR receptors (Perk, Ire 1, and Xbp1) did not change significantly. Interestingly, the expression of Luman, a novel receptor of UPR, was significantly upregulated in a dose-dependent manner. Lentivirus containing shLuman sequence was used to generate stable Luman silencing DSCs. It's showed that Luman knockdown could affect the expression of decidualization-related genes in decidual cells after BPA treatment. In summary, these results suggest that Luman plays a key role in low dose BPA-induced decidual toxicity of DSCs in mouse.
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http://dx.doi.org/10.1016/j.fct.2021.112242DOI Listing
April 2021

Synergetic loss of heavy metal and phosphorus: Evidence from geochemical fraction and estuary sedimentation.

J Hazard Mater 2021 Mar 23;416:125710. Epub 2021 Mar 23.

School of Environment, State Key Laboratory of Water Environment Simulation, Beijing Normal University, Beijing 100875, China.

The synergetic loss mechanism of heavy metals (HMs) and phosphorus (P), as well as the relationships between their different geochemical fractions remain unclear. This study employs field research, source identification and sedimentary geochemistry in Yellow River basin to investigate the internal mechanisms of the different geochemical fractions, terrestrial source signatures, and synergetic loss fluxes. The average contents of As, Cd, Cr, Cu, Pb, Zn and P in the basin were 8.29 mg/kg, 0.15 mg/kg, 47.52 mg/kg, 11.78 mg/kg, 10.65 mg/kg, 46.56 mg/kg and 578.78 mg/kg, respectively. Based on Pearson's correlation and redundancy analyses, the impact factors on the transport of HMs and P, and the internal relationships between different geochemical fractions were analyzed. According to the constant rate of supply (CRS) model, the terrestrial losses of As, Cd, Cr and Cu showed significant positive relationships with the TP flux, with r value of 0.981, 0.991, 0.996 and for 0.984, respectively. It has been proven that the extensive fine particles in the Yellow River basin carry a large amount of diffuse pollutants, thus ultimately increasing the estuarine pollutant load. This research provides new insights from the level of microscopic fractions to macroscopic fluxes to investigate the impacts of anthropogenic activity on regional environmental changes.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125710DOI Listing
March 2021

Dopamine agonists for preventing ovarian hyperstimulation syndrome.

Cochrane Database Syst Rev 2021 04 14;4:CD008605. Epub 2021 Apr 14.

School of Women's and Infants' Health, The University of Western Australia, King Edward Memorial Hospital and Fertility Specialists of Western Australia, Subiaco, Perth, Australia.

Background: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment.  OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment.

Search Methods: We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature.

Selection Criteria: We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events.

Data Collection And Analysis: Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements  by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence.

Main Results: The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage  or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy  or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported.

Authors' Conclusions: Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.
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http://dx.doi.org/10.1002/14651858.CD008605.pub4DOI Listing
April 2021

Effects of the combination therapy of electric field stimulation and polyethylene glycol in the ex vivo spinal cord of female rats after compression.

J Neurosci Res 2021 Apr 12. Epub 2021 Apr 12.

Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing, China.

The application of electric field stimulation (EFS) can reduce the cation influx after spinal cord injury. However, regenerated cation influx and reestablished injury potential are observed after EFS. Polyethylene glycol (PEG) is popular as an effective cell membrane fusion agent. This study aims to determine the effects of the combination therapy of EFS and PEG in the ex vivo spinal cord after compression. The ex vivo spinal cords of female rats with compression injury were incubated in a double sucrose gap recording chamber (DSGRC) and randomly divided into the following four groups: (1) compression group: compression only, (2) EFS group: EFS for 15 min, (3) PEG group: PEG treatment for 4 min, and (4) EFS + PEG group: EFS for 15 min and PEG treatment for 4 min. The hematoxylin-eosin staining was performed to measure the necrotic area of the spinal cords. The gap potential was detected, and the area under the curve of the gap potential was calculated. The intracellular cation concentration, membrane permeability, and compound action potential were measured and quantified. Results revealed no significant difference in the necrotic areas among different groups, and the compression model of the ex vivo spinal cord in the DSGRC had high consistency and stability. The combination therapy could attenuate cation inflow, promote cell membrane restoration, and promote the functional recovery of the spinal cord conduction after compression in ex vivo spinal cords.
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http://dx.doi.org/10.1002/jnr.24839DOI Listing
April 2021

Complete nucleotide sequence of a novel partitivirus from Brassica campestris L. ssp. chinensis.

Arch Virol 2021 Mar 26. Epub 2021 Mar 26.

Wuhan Vegetable Research Institute, Wuhan Academy of Agricultural Sciences, Wuhan, Hubei, China.

In the present work, we report the discovery and complete genome sequence of a novel partitivirus identified from Brassica campestris L. ssp. chinensis, which we have named "Brassica campestris chinensis cryptic virus 1" (BCCV1). Next-generation sequencing (NGS) combined with adapter-ligation-mediated amplification allowed assembly of the full-length genome sequence of BCCV1. The genome of BCCV1 contains two dsRNA segments, dsRNA1 (1595 bp) and dsRNA2 (1591 bp), which encode a conserved RNA-dependent RNA polymerase (RdRp) and a putative capsid protein (CP), respectively. Homology searches and phylogenetic analysis of the 479-aa RdRp and 438-aa CP showed that BCCV1 is a new member of the genus Deltapartitivirus, family Partitiviridae. This is the first report of the identification of a member of the family Partitiviridae in Brassica campestris L. ssp. chinensis.
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http://dx.doi.org/10.1007/s00705-021-05041-xDOI Listing
March 2021

RNA-Seq Analysis Reveals the Role of Omp16 in -Infected RAW264.7 Cells.

Front Vet Sci 2021 4;8:646839. Epub 2021 Mar 4.

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

Brucellosis is an endemic zoonotic infectious disease in the majority of developing countries, which causes huge economic losses. As immunogenic and protective antigens at the surface of spp., outer membrane proteins (Omps) are particularly attractive for developing vaccine and could have more relevant role in host-pathogen interactions. Omp16, a homolog to peptidoglycan-associated lipoproteins (Pals), is essential for survival . At present, the functions of Omp16 have been poorly studied. Here, the gene expression profile of RAW264.7 cells infected with vaccine strain 2 ( S2) and ΔOmp16 was analyzed by RNA-seq to investigate the cellular response immediately after entry. The RNA-sequence analysis revealed that a total of 303 genes were significantly regulated by S2 24 h post-infection. Of these, 273 differentially expressed genes (DEGs) were upregulated, and 30 DEGs were downregulated. These DEGs were mainly involved in innate immune signaling pathways, including pattern recognition receptors (PRRs), proinflammatory cytokines, and chemokines by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In ΔOmp16-infected cells, the expression of 52 total cells genes was significantly upregulated and that of 9 total cells genes were downregulated compared to S2-infected RAW264.7 cells. The KEGG pathway analysis showed that several upregulated genes were proinflammatory cytokines and chemokines, such as interleukin (IL)-6, IL-11, IL-12β, C-C motif chemokine (CCL2), and CCL22. All together, we clearly demonstrate that ΔOmp16 can alter macrophage immune-related pathways to increase proinflammatory cytokines and chemokines, which provide insights into illuminating the pathogenic strategies.
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http://dx.doi.org/10.3389/fvets.2021.646839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970042PMC
March 2021

A novel negative-stranded RNA virus of the order Bunyavirales identified in Brassica campestris L. ssp. chinensis.

Arch Virol 2021 May 15;166(5):1525-1528. Epub 2021 Mar 15.

Wuhan Vegetable Research Institute, Wuhan Academy of Agricultural Sciences, Wuhan, Hubei Province, China.

Here, we report the full-length genome sequence of a novel cogu-like virus identified in Brassica campestris L. ssp. Chinensis (B. campestris), an economically important vegetable in China. This virus, tentatively named "Brassica campestris chinensis coguvirus 1" (BCCoV1), has a bipartite genome that consists of two RNA molecules (RNA1 and RNA2). The negative-stranded (ns) RNA1 is 6757 nt in length, encoding the putative RNA-dependent RNA polymerase (RdRp), and the ambisense RNA2 is 3061 nt long, encoding the putative movement protein (MP) and nucleocapsid protein (NP). A homology search of the RdRp, MP, and NP showed that they are closely related to five other recently discovered negative-stranded RNA (nsRNA) viruses infecting plants, belonging to the new genus Coguvirus. Phylogenetic analysis of the 252-kDa RdRp confirmed the classification of this virus, showing that BCCoV1 possibly belongs to the genus Coguvirus, family Phenuiviridae, order Bunyavirales. The present study improves our understanding of the viral diversity in B. campestris and the evolution of nsRNA viruses.
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http://dx.doi.org/10.1007/s00705-021-05031-zDOI Listing
May 2021

Metabolic process and spatial partition dynamics of Atrazine in an estuary-to-bay system, Jiaozhou bay.

J Hazard Mater 2021 Feb 27;414:125530. Epub 2021 Feb 27.

The First Institute of Oceanography, Ministry of Natural Resources, 6 Xianxialing Road, Qingdao 266061, China.

The spatial distributions of atrazine and six types of metabolites in water, suspended particulate sediment (SPS), and surface sediment in an estuary-to-bay system were analyzed. The water distance of metabolites demonstrated that degradation was more active in coastal zone and the Desisopropylatrazine had the shortest half-distance of 1.6 Km from the river mouth. The dechlorination-hydroxylation metabolites were the dominant pollutants in the bay and the Didealkyl-atrazine (DDA), Deisopropylhydroxy-atrazine (DIHA), and Deethylhydroxy-atrazine (DEHA) had higher concentrations in all three mediums. The DDA had the biggest content (6.58 ng/g) in the coastal sediment. The DIHA was the only pollutant had bigger concentration during the transport, and the others continually degraded with smaller value. The spatial distributions of pollutants in sediment had different patterns in water with SPS. The water-particle phase partition coefficient (K) analysis indicated that the partition process was more active in the estuary than the bay, and the metabolites had stronger capacity than atrazine. The correlations between K with octanol-water partitioning coefficient showed their physic-chemical properties were the important factors for vertical partition between seawater with sediment. The correlations with marine environmental factors demonstrated that the metabolite type was the direct factor for the redistributions during the transport.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125530DOI Listing
February 2021

Breastfeeding competency scale (BCS); development and validation of an evaluation instrument on breastfeeding competency in third trimester pregnancy.

BMC Pregnancy Childbirth 2021 Mar 4;21(1):179. Epub 2021 Mar 4.

Department of Nursing, Shandong Provincial Qianfoshan Hospital, 16766 Jingshi Street, Jinan, 250014, Shandong province, China.

Background: Breastfeeding plays an important role in the early stages of humans and throughout the development process. Breastfeeding competency is a self-assessment of pregnant women's overall competency to breastfeeding which could predict the breastfeeding behaviours of pregnant women. However, a valid and reliable scale for assessing breastfeeding competency has not yet been developed and validated. This study was conducted to develop and validate an assessment scale designed to assess pregnant women's breastfeeding competency in the third trimester: the Breastfeeding Competency Scale (BCS).

Methods: The BCS was developed and validated over three phases between September 2018 and September 2019, and these phases included item statistical analysis, exploratory factor analysis (EFA), content validation, internal consistency assessment, split-half reliability assessment and confirmatory factor analysis (CFA).

Results: The item statistical analysis and EFA resulted in 38 items and 4 factors that explained 66.489% of the total variance. The Cronbach's α coefficients for the total scale and the 4 factors were 0.970, 0.960, 0.940, 0.822 and 0.931. The split-half reliability of the BCS was 0.894 and 0.890. CFA model showed that the 4-factor model fits the data well.

Conclusions: The BCS is a new valid and reliable instrument for assessing the breastfeeding competency of pregnant women in the third trimester.
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http://dx.doi.org/10.1186/s12884-021-03664-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934416PMC
March 2021

Circadian clock gene BMAL1 controls testosterone production by regulating steroidogenesis-related gene transcription in goat Leydig cells.

J Cell Physiol 2021 Feb 17. Epub 2021 Feb 17.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.

Testosterone is produced by Leydig cells (LCs) and undergoes diurnal changes in serum levels in rats, mice, and humans, but little is known in goats. The present study revealed that goat serum testosterone levels displayed diurnal rhythmic changes (peak time at ZT11.2). Immunohistochemical staining showed that BMAL1, a circadian clock protein, is highly expressed in goat LCs. ELISA revealed that both hCG (0-5 IU/ml) and 22R-OH-cholesterol (0-30 μM) addition stimulated testosterone synthesis in primary goat LCs in a dose-dependent manner. Treating goat LCs with hCG (5 IU/ml) significantly increased intracellular cAMP levels. Additionally, real-time quantitative polymerase chain reaction (PCR) analysis revealed that the circadian clock (BMAL1, PER1, PER2, DBP, and NR1D1) and steroidogenesis-related genes (SF1, NUR77, StAR, HSD3B2, CYP17A1, CYP11A1, and HSD17B3) showed rhythmic expression patterns in goat LCs following dexamethasone synchronization. Several Bmal1-Luc circadian oscillations were clearly observed in dexamethasone-treated goat LCs transfected with the pLV6-Bmal1-Luc plasmid. BMAL1 knockdown significantly downregulated mRNA levels of PER2, NR1D1, DBP, StAR, HSD3B2, SF1, NUR77, and GATA4, and dramatically decreased StAR and HSD3B2 protein levels and testosterone production. In contrast, BMAL1 overexpression significantly increased the mRNA and protein expression levels of StAR and HSD17B3 and enhanced testosterone production. Reporter assays revealed that goat BMAL1, or in combination with mouse CLOCK, activated goat HSD17B3 transcription in vitro. These data indicate that BMAL1 contributes to testosterone production by regulating transcription of steroidogenesis-related genes in goat LCs, providing a basis for further exploring the underlying mechanism by which the circadian clock regulates ruminant reproductive capability.
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http://dx.doi.org/10.1002/jcp.30334DOI Listing
February 2021

Identifying the competencies of China's paediatric residents: a modified Delphi method study.

BMJ Open 2021 02 17;11(2):e041741. Epub 2021 Feb 17.

School of Public Health, Capital Medical University, Beijing, China

Purpose: Standardised Training of Paediatric Resident (STPR) plays an essential role in training qualified paediatricians. Until now, China had no paediatric resident competency index system to effectively guide and evaluate the competence of paediatric residents. This study aimed to establish a competency index system for paediatric residents in China to provide a reference for improving the training system and quality of STPR.

Study Design And Setting: This study conducted two rounds of Delphi expert consultation survey among paediatric medical experts (n=16), followed by screening, revising and supplementing indicators using the boundary value method. Next, the analytic hierarchy process was used to determine the weight of indicators and finally establish a competency index system for paediatric residents.

Results: The results of the statistical analysis revealed a positive coefficient of 100% for both rounds of expert consultation. The expert authority coefficient values were 0.82 and 0.83, and the expert coordination coefficient test was p<0.01. After referring to experts' opinions, a competency index system for paediatric residents with 5 primary indicators, 14 secondary indicators and 73 tertiary indicators was finally formed and the weight of each indicator was calculated. The five primary indicators were professional quality (0.3187), knowledge and skills (0.2734), communication and cooperation (0.1986), lifelong learning (0.1302), and teaching ability (0.0791).

Conclusions: In this study, a competency index system for paediatric residents was constructed following the characteristics and quality requirements for paediatric residents in China and is expected to significantly improve the overall level of paediatricians' medical service quality and supply.
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http://dx.doi.org/10.1136/bmjopen-2020-041741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893650PMC
February 2021

Integrated Proteomic and Transcriptomic Analyses Reveal the Roles of Homolog of BAX Inhibitor 1 in Cell Division and Membrane Homeostasis of S2.

Front Microbiol 2021 28;12:632095. Epub 2021 Jan 28.

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

BAX inhibitor 1 (BI-1) is an evolutionarily conserved transmembrane protein first identified in a screening process for human proteins that suppress BAX-induced apoptosis in yeast cells. Eukaryotic BI-1 is a cytoprotective protein that suppresses cell death induced by multiple stimuli in eukaryotes. , the causative agent of brucellosis that threatens public health and animal husbandry, contains a conserved gene that encodes BI-1-like protein. To explore the role of the homolog of BI-1, BrBI, in S2, we constructed the deletion mutant strain and its complemented strain. deletion altered the membrane properties of S2 and decreased its resistance to acidic pH, HO, polymyxin B, and lincomycin. Additionally, deleting led to defective growth, cell division, and viability in S2. We then revealed the effect of deletion on the physiological characteristics of S2 via integrated transcriptomic and proteomic analyses. The integrated analysis showed that deletion significantly affected the expression of multiple genes at the mRNA and/or protein levels. Specifically, the affected divisome proteins, FtsB, FtsI, FtsL, and FtsQ, may be the molecular basis of the impaired cell division of the mutant strain, and the extensively affected membrane proteins and transporter-associated proteins were consistent with the phenotype of the membrane properties' alterations of the mutant strain. In conclusion, our results revealed that BrBI is a bacterial cytoprotective protein involved in membrane homeostasis, cell division, and stress resistance in S2.
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http://dx.doi.org/10.3389/fmicb.2021.632095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876416PMC
January 2021

promotes prostaglandin E synthesis by upregulating transcription in response to increasing estradiol levels in pregnant mice.

Am J Physiol Endocrinol Metab 2021 04 8;320(4):E747-E759. Epub 2021 Feb 8.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, China.

Prostaglandin G/H synthase 2 (PTGS2) is a rate-limiting enzyme in prostaglandin synthesis. The present study assessed the role of the uterine circadian clock on transcription in response to steroid hormones during early pregnancy. We demonstrated that the core clock genes (, , , and ), , and and their encoded proteins, have rhythmic expression in the mouse uterus from to () of pregnancy. Progesterone (P) treatment of cultured uterus endometrial stromal cells (UESCs) isolated from reporter gene knock-in mice on D4 induced a phase shift in oscillations. This P-induced phase shift of oscillations was significantly attenuated by the P antagonist RU486. Additionally, the amplitude of oscillations was increased by estradiol (E) treatment in the presence of P. Consistently, the mRNA levels of clock genes ( and ), , and were markedly increased by E treatment of UESCs in the presence of P. Treatment with E also promoted prostaglandin E (PGE) synthesis by UESCs. Depletion of in UESCs by small-interfering RNA (siRNA) decreased the transcript levels of clock genes ( and ), , and compared with nonsilencing siRNA treatment. knockdown also inhibited PGE synthesis. Moreover, the mRNA expression levels of clock genes ( and ), , and , and their respective proteins were significantly decreased in the uterus of mice. Thus, these data suggest that in mice promotes PGE synthesis by upregulating in response to increases in E on D4 of pregnancy. Rhythmic expression of Bmal1 and Ptgs2 was observed in the uterus isolated from of pregnant mice. E increased the expression of Bmal1 and Ptg2 in UESCs isolated from mice on D4. The expression of Ptgs2 was significantly decreased in Bmal1-siRNA treated UESCs. knockdown also inhibited PGE synthesis. Thus, these data suggest that Bmal1 in mice promotes PGE synthesis by upregulating Ptgs2 in response to increases in E on D4 of pregnancy.
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http://dx.doi.org/10.1152/ajpendo.00466.2020DOI Listing
April 2021

Clinical characteristics of patients with the de Winter electrocardiogram pattern.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2020 Dec;45(12):1431-1436

Department of Cardiology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.

Objectives: To explore the electrocardiogram manifestations and clinical characteristics of patients with the de Winter electrocardiogram pattern.

Methods: This retrospective study was performed on acute coronary syndrome (ACS), patients with culprit lesion in left anterior descending branch (LAD), who admitted to Yongchuan Hospital of Chongqing Medical University from August 2017 to October 2018. Patients were categorized into those with or without the de Winter electrocardiogram pattern. The characteristics of de Winter electrocardiogram were analyzed by the clinical data of the patients.

Results: Among 230 patients with left anterior descending branch lesion, 14 (6%) had the de Winter electrocardiogram pattern. Compared with the control group, patients with de Winter electrocardiogram pattern were younger [(53.86±10.26) years old vs (67.20± 11.60) years old <0.01], at higher LDL-C level [3.54(2.88, 4.20) mmol/L vs 2.61(2.48, 2.73) mmol/L, =0.01], in lower classification degree of cardiac function [Killip I grade 12 cases (85.71%) vs 95 cases (43.98%), =0.04], and in shorter time between onset and the first electrocardiogram [171.77(47.56, 295.97) min vs 501.92(405.12, 598.72) min, =0.01]. Coronary angiography results indicated anterior descending or diagonal branch lesions.

Conclusions: The de Winter electrocardiogram pattern syndrome in patients with acute chest pain mostly indicates that the left anterior descending or the diagonal branch is subtotal or completely occluded, which is a special ST-segment elevation myocardial infarction equivalent and should attract the clinicians' extensive attention.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2020.190276DOI Listing
December 2020

Trueperella pyogenes pyolysin inhibits lipopolysaccharide-induced inflammatory response in endometrium stromal cells via autophagy- and ATF6-dependent mechanism.

Braz J Microbiol 2021 Jun 16;52(2):939-952. Epub 2021 Jan 16.

Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Trueperella pyogenes (T. pyogenes) is a common opportunistic pathogen of many livestock and play an important regulation role during multibacterial infection and interaction with the host by its primary virulence factor pyolysin (PLO). The purpose of this study was to investigate the regulation role of PLO which serve as a combinational pathogen with lipopolysaccharide (LPS) during endometritis. In this study, the expression of bioactive recombinant PLO (rPLO) in a prokaryotic expression system and its purification are described. Moreover, we observed that rPLO inhibited the innate immune response triggered by LPS and that methyl-β-cyclodextrin (MBCD) abrogated this inhibitory effect in goat endometrium stromal cells (gESCs). Additionally, we show from pharmacological and genetic studies that rPLO-induced autophagy represses gene expression by inhibiting NLRP3 inflammasome activation. Importantly, this study reported that ATF6 serves as a primary regulator of the cellular inflammatory reaction to rPLO. Overall, these observations suggest that T. pyogenes PLO could create an immunosuppressive environment for other pathogens invasion by regulating cellular signaling pathways.
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http://dx.doi.org/10.1007/s42770-021-00422-5DOI Listing
June 2021

A five-transgene cassette confers broad-spectrum resistance to a fungal rust pathogen in wheat.

Nat Biotechnol 2021 Jan 4. Epub 2021 Jan 4.

CSIRO Agriculture and Food, GPO Box 1700, Canberra, Australia.

Breeding wheat with durable resistance to the fungal pathogen Puccinia graminis f. sp. tritici (Pgt), a major threat to cereal production, is challenging due to the rapid evolution of pathogen virulence. Increased durability and broad-spectrum resistance can be achieved by introducing more than one resistance gene, but combining numerous unlinked genes by breeding is laborious. Here we generate polygenic Pgt resistance by introducing a transgene cassette of five resistance genes into bread wheat as a single locus and show that at least four of the five genes are functional. These wheat lines are resistant to aggressive and highly virulent Pgt isolates from around the world and show very high levels of resistance in the field. The simple monogenic inheritance of this multigene locus greatly simplifies its use in breeding. However, a new Pgt isolate with virulence to several genes at this locus suggests gene stacks will need strategic deployment to maintain their effectiveness.
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http://dx.doi.org/10.1038/s41587-020-00770-xDOI Listing
January 2021

Clinical and Imaging Prognosis in Patients with Delayed Encephalopathy after Acute Carbon Monoxide Poisoning.

Behav Neurol 2020 7;2020:1719360. Epub 2020 Dec 7.

Department of Neurology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.

Objective: To study the clinical manifestations, magnetic resonance imaging (MRI) findings, and prognosis of delayed encephalopathy after carbon monoxide poisoning (DEACMP).

Methods: The medical records of 20 patients with DEACMP were retrospectively reviewed. All the patients received hyperbaric oxygen treatment and other treatments as necessary.

Results: The patients had diverse clinical manifestations, including memory deficits, personality changes, cognitive or executive function deficits, mood disorders, Parkinsonism, dystonia or other motor impairments, and akinetic mutism. MRI revealed lesions in the bilateral cerebral white matter and/or basal ganglia. Except for the pathologically confirmed DEACMP, epileptic seizure, hemiplegia, and vegetative state, the remaining symptoms had been improved, especially the cognitive impairment, which had been decreased from 95% to 25% and psychiatric symptoms also decreased from 95% to 55% at the 6-month follow-up.

Conclusions: The prognosis of patients with DEACMP was poor, and they had a relatively severe disability. The early use of hyperbaric oxygen is of great significance to improve clinical efficacy and get a better prognosis.
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http://dx.doi.org/10.1155/2020/1719360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744233PMC
December 2020

Chromosomal abnormality: Prevalence, prenatal diagnosis and associated anomalies based on a provincial-wide birth defects monitoring system.

J Obstet Gynaecol Res 2021 Mar 28;47(3):865-872. Epub 2020 Dec 28.

NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China.

Aim: To investigate the epidemiology of chromosomal abnormalities (CA) in fetuses of all pregnancies based on a provincial-wide birth defects-monitoring system, which could provide scientific basis for making relatively policy and research.

Methods: Chromosomal abnormalities cases were collected from all hospitals in Hunan Province, China, between 2016 and 2019. The prevalence of CAs was calculated to examine associations among infant sex, maternal age and region. The rates of prenatal diagnosis and termination of pregnancy (TOP) involving CA or associated anomalies were calculated as rates or proportions.

Results: From 2016 to 2019, a total of 2 883 890 perinatal infants (28 weeks of gestation to postpartum 7 days) underwent prenatal screening and diagnostic tests, and 3181 fetuses were diagnosed as CA, with the prevalence of 11.03/10 000. The average prevalence of CAs was higher for male than female fetuses (11.33/10 000 vs 10.06/10 000) (OR = 1.13, 95% CI: 1.05-1.21), which was higher in urban areas than rural areas (23.03/10 000 vs 7.13/10 000) (OR = 3.23, 95% CI: 3.02-3.47), and the prevalence increased linearly with maternal age ( = 1821.844, P = 0.000). Among the fetuses with CAs, 3097 (97.36%) were diagnosed prenatally, and 3046 (98.35%) underwent TOP. The majority of CA were numerical abnormalities (90.18%). The main types of numerical autosomal abnormalities were trisomy 21 (6.69/10 000, 59.57%), trisomy 18 (1.13/10 000, 10.04%) and trisomy 13 (0.21/10 000, 1.88%). The main types of numerical gonosomal abnormalities were Klinefelter syndrome (0.68/10 000, 6.02%), Turner syndrome (0.49/10 000, 4.39%), Triple X syndrome (0.26/10 000, 2.29%) and 47,XYY syndrome (0.21/10 000, 1.91%). The three associated anomalies with the highest proportions were congenital heart defects (CHD) (41.06%), cleft palate or/and cleft lip (10.89%) and congenital talipes equinovarus (8.94%).

Conclusion: The prevalence of CA was lower than that reported. Chromosome detection should be further promoted including test contest and coverage, especially for urban areas, older mothers and fetuses with CHD, cleft palate or/and cleft lip or congenital talipes equinovarus.
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http://dx.doi.org/10.1111/jog.14569DOI Listing
March 2021

Efficacy and safety of yinqiao powder combined with western medicine in the treatment of pneumonia: A systematic review and meta-analysis.

Complement Ther Clin Pract 2021 Feb 16;42:101297. Epub 2020 Dec 16.

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.

Objective: This review aimed at systematically evaluating the efficacy and safety of Yinqiao powder combined with western medicine in the treatment of pneumonia.

Methods: A systematic search for randomized controlled trials (RCTs) focusing on pneumonia treatment using a combination of Yinqiao powder and western medicine was performed in PubMed, the Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang, Weipu (VIP) and CBM. The retrieval time limit was from the establishment of the database to June 2020. Two researchers independently screened the literature, extracted the data and evaluated the bias risk of the included studies. A meta-analysis was performed using RevMan5.3 software. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Result: Fifteen RCTs involving 1705 patients were included in the analysis. The meta-analysis results revealed the total effective rate of the treatment group [RR = 1.21, 95% CI (1.15, 1.27), P < 0.00001], bacterial clearance rate [RR = 1.13, 95% CI (1.05, 1.22), P = 0.001], adverse reactions [RR = 0.54, 95% CI (0.38, 0.76), P = 0.0005]. There were statistically significant differences in the cooling time, T cell number, procalcitonin (PCT) and C-reactive protein (CRP) value decline rate (P < 0.05). There was no statistically significant difference in the decline rate of neutrophils and leukocytes (P > 0.05).

Conclusion: The current evidence indicated that the Yinqiao powder combined with western medicine can improve total efficiency in the treatment of pneumonia patients. The combination therapy performed better when compared to western medicine alone in the cooling time, bacterial clearance rate, T cell count, decline rates of CRP and PCT as well as in the incidences of adverse reactions. However, there was no significant difference in the decline rates of neutrophils and leucocytes between the two groups. The funnel plot, Egger's test and Begg's test indicated publication bias, which may be associated with unpublished negative study results. Due to the limitation of the quality and quantity of the included studies, more high-quality studies should be performed to verify our conclusions.
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http://dx.doi.org/10.1016/j.ctcp.2020.101297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834461PMC
February 2021

Luman/CREB3 knock-down inhibit hCG induced MLTC-1 apoptosis.

Theriogenology 2021 Feb 3;161:140-150. Epub 2020 Dec 3.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, 12100, China. Electronic address:

Luman has been reported to be involved in the formation of COP II-mediated transport vesicles that affect protein transportation and secretion. Western blotting, immunohistochemistry, immunofluorescence, and RT-qPCR indicated that Luman is widely expressed in the male mouse reproductive system. In sperm, Luman was mainly located in the sperm tail, and the expression level increased with sperm maturity. In the testis, Luman was located in Leydig cells. In MLTC-1, a high-concentration hCG treatment significantly increased GRP78, ATF6, p-IRE1, and p-EIF2S1 expression but had no effect on Luman expression. To investigate the role of Luman in hCG-induced ER stress (ERS), experiments were conducted to examine the consequences of short hairpin RNA (shRNA)-mediated Luman knockdown in MLTC-1 cells. Luman knockdown decreased the percentage of S phase cells and up-regulated Cyclin A1, Cyclin B1, and Cyclin D2 expression. ELISA and WB results showed that with Luman knockdown, Cyp11a1, p-IRE1, and p-EIF2S1 expression and testosterone secretion were significantly increased, while GRP78 and CHOP expression were decreased. Flow cytometry results showed that Luman knockdown reduced MLTC-1 cell apoptosis. RT-qPCR and WB results showed that Luman knockdown significantly up-regulated BCL-2 expression and decreased Caspase-3 and BAX expression. These data suggest that Luman is widely expressed in the male mouse reproductive system. In MLTC-1 cells, Luman knockdown up-regulated p-IRE1, p-EIF2S1, and BCL-2 expression and decreased GRP78, CHOP, BAX, and Caspase-3 expression. We propose that Luman knockdown reduces cell apoptosis through the ERS pathway, thereby promoting cell survival and testosterone secretion. These findings provide new insights into the role of Luman in hCG-induced ERS.
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http://dx.doi.org/10.1016/j.theriogenology.2020.11.010DOI Listing
February 2021

Bisphenol A attenuates testosterone production in Leydig cells via the inhibition of NR1D1 signaling.

Chemosphere 2021 Jan 23;263:128020. Epub 2020 Aug 23.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, 712100, Shaanxi, China. Electronic address:

Bisphenol A (BPA) is an endocrine-disrupting compound that impairs testosterone synthesis in male mammals. A circadian clock gene deficiency leads to diminished fertility and even infertility in male mice. However, whether circadian clock signaling pathways mediate the suppressive effect of BPA on testosterone synthesis in Leydig cells (LCs) remains unknown. The present study aims to detect the effect of BPA on cellular circadian clock and testosterone synthesis in mouse LCs, and examine the mechanisms underlying NR1D1 signaling. BPA treatment significantly attenuated the transcription levels of Nr1d1 and steroidogenic genes (Hsd3b2 and Hsd17b3) in TM3 cells, but increased other circadian clock gene levels (Per2 and Dbp). BPA treatment also significantly downregulated NR1D1 and StAR protein expression, but upregulated BMAL1 protein expression in TM3 cells. Furthermore, there was a marked decline in testosterone production in BPA-treated TM3 cells. Intraperitoneal injection of BPA profoundly reduced NR1D1 and StAR protein levels and steroidogenic gene transcription levels (Cyp11a1, Hsd3b2, and Hsd17b3), while enhancing BMAL1 protein and other circadian clock gene (Per2 and Dbp) levels in mouse testes. Notably, serum testosterone levels were also drastically reduced in BPA-treated mice. Moreover, SR9009, an NR1D1 agonist, augmented testosterone production in TM3 cells via elevated expression of steroidogenic genes (StAR, Cyp11a1 and Hsd17b3). Conversely, Nr1d1 knockdown inhibited testosterone accumulation and attenuated steroidogenic gene expression. Moreover, treatment with SR9009 partially reversed the BPA effect on the circadian clock and testosterone production. Taken together, our study demonstrates that BPA perturbs testosterone production, at least partially, via inhibiting NR1D1 signaling in LCs.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128020DOI Listing
January 2021

Trend of unintentional suffocation death for infants under 1 year of age from 2009 to 2018 in Hunan, China: a cross-sectional study.

BMJ Open 2020 12 7;10(12):e038666. Epub 2020 Dec 7.

Information Management Section, Hunan Province, Changsha, Hunan, China

Objective: Few studies have addressed the unintentional suffocation of infants in China. This study is to assess the mortality rate of unintentional suffocation among infants and the differences across age groups, gender, rural versus urban locations and related healthcare services.

Design: A cross-sectional study on unintentional suffocation death of infants under 1 year of age in Hunan Province from 2009 to 2018.

Setting: Hunan Province, with a population of 74 million, has an area of 210 000 square kilometres and 123 counties/districts.

Participants: The total data of 4109 unintentional suffocation deaths of infants in Hunan Province from 2009 to 2018 was collected, including 2331 boys, 1766 girls, 12 infants of unknown gender, 2906 rural children and 1203 urban children.

Main Outcome Measure: The unintentional suffocation mortality rate of infants is defined as the number of unintentional suffocation deaths of children under 1 year of age per 100 000 live births in the same year.

Results: The infant mortality rate showed a downward trend from 2009 to 2018. Infant unintentional suffocation death decreased first and then fluctuated. The proportion of unintentional suffocation death to infant death showed an upward trend in fluctuation. Boys and rural children had higher mortality rates than those of girls and urban children. A total of 43.5% of the deaths occurred in winter. Forty-eight per cent of the unintentional suffocations were infants between 1 and 4 months of age. A total of 46.4% of the deaths occurred at home, and 71.6% were not treated; approximately 81.8% of the untreated cases were mainly due to a lack of time to get to the hospital. A total of 65.2% of the deaths were diagnosed postmortem.

Conclusion: The mortality rate of unintentional suffocation among infants in Hunan Province should attract the attention of the population, and measures should be taken according to epidemiological investigations.
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http://dx.doi.org/10.1136/bmjopen-2020-038666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722815PMC
December 2020

The risk factors of adverse pregnancy outcome for pre-pregnancy couples in Hunan, China: A cross-sectional study based on population.

Medicine (Baltimore) 2020 Nov;99(45):e23094

NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital), 58 Xiangchun Road, Changsha, Hunan, China.

To identify the prevalence of chronic disease and behavior risk factors of adverse pregnancy outcome for pre-pregnancy couples in Hunan province, China.A retrospective study including cross-sectional datas from the Free Pre-pregnancy Health Check (FPHC) surveillance system of Hunan, China in 2019 was conducted. Microsoft Excel 2010 was used for preliminary data analysis. The fowllowing descriptive analysis, t-tests, and Chi-Squared tests were carried out using SPSS 25.0.Among 419,971 couples, 182,450 (21.72%) individuals were older than 35 years, 257,471(69.48%) couples planned to have a second or additional child and 114,892 (27.36%) individuals had a history of adverse pregnancy outcomes. The mean number of risk factors of adverse pregnancy outcome was higher in males than that in females (2.17 per male vs 1.92 per female). The prevalence/proportions of hypertension, increased psychological pressure, high alanine transaminase or creatinine, smoking, passive smoke exposure, alcohol use, and exposure to environmental risk factors were higher in males than that in females (2.43% vs 1.35%, 0.68% vs 0.54%, 12.80% vs 5.93%, 2.52% vs 1.47%, 27.70% vs 0.24%, 10.94% vs 3.58%, 15.62% vs 1.07%, and 1.46% vs 1.15%, respectively). The proportion of females with an abnormal cervix was 3.35%, and the proportion of males with abnormal wrapping was 1.90%. The prevalence/proportions of anemia and work-related pressure or social tensions were higher in females than that in males (5.53% vs 0.51%, 15.39% vs 13.61%, and 8.22% vs 7.88%, respectively).History of adverse pregnancy outcomes and age olderthan 35 years were important risk factors for pre-pregnancy couples in Hunan province. The mean number of risk factors was higher in males than that in females. Hypertension, increased psychological pressure, high alanine transaminase and creatinine levels, smoking, passive smoke exposure, alcohol use, and exposure to dangerous environmental factors were the major risk factors for males. Anemia, work-related pressure and social tensions were the major risk factors for females.
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http://dx.doi.org/10.1097/MD.0000000000023094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647632PMC
November 2020

Zearalenone perturbs the circadian clock and inhibits testosterone synthesis in mouse Leydig cells.

J Toxicol Environ Health A 2021 Feb 4;84(3):112-124. Epub 2020 Nov 4.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University , Yangling, China.

Zearalenone (ZEA), a mycotoxin, is known to impair reproductive capability by disrupting the synthesis and secretion of testosterone by Leydig cells (LCs), although the mechanism is unknown. Robust rhythmicity of circadian clock and steroidogenic genes were identified in LCs. The aim of this study was to examine whether ZEA significantly attenuated the transcription of core clock genes (, and ) as well as steroidogenic genes (, and ) in mouse testis Leydig cell line (TM3). Western blotting confirmed declines in BMAL1, NR1D1, and StAR protein levels. ZEA also suppressed secreted testosterone levels. In primary LCs, isolated from PER2::LUCIFERASE reporter gene knock in mice, ZEA diminished the amplitude of expression, and induced a phase shift and period extension. In primary LCs, ZEA also suppressed the expression levels of core clock and steroidogenic genes, reduced protein levels of BMAL1, and decreased testosterone secretion. expression of core clock and steroidogenic genes were reduced in testes of mice exposed to ZEA for 1 week leading to decreased serum testosterone levels. In summary, data suggest that ZEA may impair testosterone synthesis through attenuation of the circadian clock in LCs culminating in reproductive dysfunction in male mammals .
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http://dx.doi.org/10.1080/15287394.2020.1841699DOI Listing
February 2021

Relationship of miRNA-146a to systemic lupus erythematosus: A PRISMA-compliant meta-analysis.

Medicine (Baltimore) 2020 Oct;99(40):e22444

Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine.

Background And Objective: miRNA-146a is a microRNA that plays an important role in systemic lupus erythematosus (SLE). Several studies have examined the role of miRNA-146a in SLE, but have demonstrated equivocal or even contradictory conclusions. Therefore, this meta-analysis aimed to assess the role of miRNA-146a in SLE by examining data from previous studies.

Methods: A meta-analysis of relevant papers published before August 31, 2019, in the WanFang, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), PubMed, EMBASE, and Web of Science databases was performed to verify the relationship of miRNA-146a expression level to SLE. Two investigators independently extracted the data and conducted a quality assessment of the studies. All statistical analyses were performed using Stata 14.0. Trial sequence analysis (TSA) was conducted to assess the quality and strength of the studies using the TSA software.

Results: Six publications, involving 151 SEL patients and 132 healthy individuals as controls were included in this meta-analysis. The results showed that the expression of miRNA-146a was associated with SLE risk [standard mean difference (SMD) = -1.21, 95% confidence interval (95% CI) (-2.18, -0.23), P = .015]. The stratified analysis revealed that the expression of miRNA-146a was highly related to higher SLE risk among Asian (SMD = -1.30, 95% CI (-2.52, -0.07), P = .038) and Caucasian (SMD = -0.72, 95% CI (-1.20, -0.24), P = .003) populations. Besides, the serum levels of miRNA146a were significantly different (SMD = -1.73, 95% CI (-3.11, -0.36), P = .014). The TSA revealed that the cumulative Z-curve crossed the typical boundary value, and reached the TSA monitoring boundary, but did not reach the required information size. This indicates that even if the cumulative sample size did not meet required information size, no more trials were needed and a reliable conclusion was reached in advance. Sensitivity analyses indicated the instability of the meta-analysis.

Conclusions: Overall, the expression of miRNA-146a is associated with SLE risk. Therefore, miRNA-146a is a promising candidate for the effective diagnosis of SLE. But, due to the limitations of this study, it is necessary to cautiously explain the results of this study.

Systematic Review Registration: PROSPERO CRD42019151381.
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http://dx.doi.org/10.1097/MD.0000000000022444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535641PMC
October 2020

Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy.

Front Physiol 2020 11;11:868. Epub 2020 Sep 11.

Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, China.

Corpus luteum (CL) is a transient endocrine tissue that produces progesterone for maintaining pregnancy in mammals. In addition, the regression of CL is necessary for the initiation of the estrous cycle. Extensive research has shown that the prostaglandin F2α (PGF2α) induces the regression of CL in ruminants. However, the mechanisms of endoplasmic reticulum (ER) stress and autophagy in the regression of goat CL induced by PGF2α are still unclear. In this study, ovaries of dioestrus goats and goats that were 3 months pregnant were collected to detect the location of the ER stress-related protein GRP78. The relationship between the different stages of the luteal phase of goat CL during the estrous cycle and changes in the expression of ER stress-related proteins and autophagy-related proteins was confirmed by western blot analysis. The results showed that both ER stress and autophagy were activated in the late luteal phase of the goat CL. To reveal the function of ER stress and autophagy in the CL regression process induced by PGF2α, we used 4-phenyl butyric acid (4-PBA) and chloroquine (CQ) for inhibiting ER stress and autophagy, respectively. Through the apoptotic rate detected by the flow cytometry and the expression of ER stress- and autophagy-related proteins detected by western blotting, we demonstrated that ER stress promoted goat luteal cell apoptosis and autophagy, and that apoptosis can be enhanced by the inhibition of autophagy. In addition, knockdown of EIF2S1, which blocked the PERK pathway activation, promoted apoptosis by reducing autophagy in goat luteal cells treated with PGF2α. In conclusion, our study indicates that ER stress promotes goat luteal cell apoptosis to regulate the regression of CL and activates autophagy to inhibit the goat luteal cell apoptosis via PERK signaling pathway.
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http://dx.doi.org/10.3389/fphys.2020.00868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516216PMC
September 2020

UFMylation is associated with LPS-induced inflammatory response in goat endometrial epithelial cells.

Reprod Domest Anim 2020 Dec 27;55(12):1725-1734. Epub 2020 Oct 27.

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

The endometrium plays an important role in the defence against invading pathogens, although the mechanisms are not clear. UFMylation is a recently discovered novel ubiquitination-like modification system that plays a pivotal role in inflammation and the immune response. The purpose of this study was to investigate the effects of UFMylation on lipopolysaccharide (LPS)-induced inflammatory responses in immortalized goat endometrial epithelial cells (gEECs). Ubiquitin-fold modifier conjugating enzyme 1 (UFM1) and DDRGK domain containing 1 (DDRGK1) were mainly localized in the luminal epithelium and glandular epithelium of mouse and goat endometrial tissues. The expression levels of UFM1, ubiquitin-like modifier activating enzyme 5 (UBA5), UFM1 specific ligase 1 (UFL1) and DDRGK1, as key components of the UFMylation system, were significantly activated by 5 μg/mL LPS-induced inflammatory response in gEECs for 6 hr. Meanwhile, the expression levels of interleukin-6 (IL-6) were significantly upregulated, and tumour necrosis factor-α (TNF-α) was significantly down-regulated after overexpression of UFM1 in gEECs. Additionally, we observed UFM1 and DDRGK1 were markedly increased on LPS-stimulated mouse endometritis in vivo. In conclusion, the current study demonstrated that UFMylation was significantly activated by LPS and might be involved in regulating inflammatory response in gEECs.
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http://dx.doi.org/10.1111/rda.13832DOI Listing
December 2020

Bta-miR-34b inhibits proliferation and promotes apoptosis via the MEK/ERK pathway by targeting MAP2K1 in bovine primary Sertoli cells.

J Anim Sci 2020 Oct;98(10)

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.

Immature Sertoli cell (SC) proliferation determines the final number of mature SCs and further regulates spermatogenesis. Accumulating evidence demonstrated that microRNAs (miRNAs) play an important role in SC proliferation, differentiation, and apoptosis. However, the effect and molecular mechanism of miRNA on bovine immature SC remain to be poorly understood. In this study, miRNA sequencing of testes collected in mature (24-mo old) and immature (neonatal) bulls was conducted to determine the miRNA expression profiles. MicroRNA-34b was one of the differentially expressed miRNAs and was selected for in-depth functional studies pertaining to SC growth. The results showed that miR-34b mimic transfection in primary Sertoli cells (PSC) inhibited cell proliferation and induced cell cycle arrested at G2 phase and decreased the expression of cell cycle-related genes such as CCNB1, CDK1, CDC25C, and C-MYC. MicroRNA-34b overexpression also leads to increased cell apoptosis, with proapoptotic genes P53 and BAX upregulated, while antiapoptotic gene BCL2 decreased. However, miR-34b knockdown had the opposite effects. Through a combination of transcriptome sequencing, bioinformatics analysis, dual-luciferase reporter assay, and Western blotting, mitogen-activated protein kinase kinase1 (MAP2K1), also known as MEK1, was identified as a target of miR-34b. In addition, PSC proliferation inhibition was mediated by cell cycle arrest and apoptosis with MAP2K1 interference. Overexpression of MAP2K1 effectively reversed the miR-34b-repressed PSC cell growth. Moreover, both miR-34b overexpression and MAP2K1 knockdown decreased the protein levels of P-ERK1/2, while MAP2K1 overexpression showed opposite effects. In summary, data suggest that miR-34b regulates PSC proliferation and apoptosis through the MEK/ERK signaling pathway. These data provide a theoretical and experimental framework for further clarifying the regulation of cell growth in PSC of bovine.
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http://dx.doi.org/10.1093/jas/skaa313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598574PMC
October 2020