Objective To explore the association between folic acid supplementation during periconcerptional period and congenital heart disease in newborns to provide scientific evidence for making intervening measures.Methods Using stratified random cluster sampling,a total of 30 counties were sampled from Shaanxi Province.A questionnaire survey was conducted among childbearing-aged women pregnant between January 2010 and November 2013.All of the included women had definite pregnancy outcomes and had signed the consent form.Logistic regression was performed to investigate the association between folic acid supplementation during pregnancy and congenital heart disease in newborns.Results In total,28 354 questionnaires were available for analysis.The overall prevalence of congenital heart disease among live-birth neonates in the present study was 7.3‰.The percentage of childbearing-age women who had taken folic acid supplementation during pregnancy was 64.4％,while only 17.2％ of them took folic acid according to the specification.Taking folic acid regularly during pregnancy was associated with a lower risk of congenital heart disease among the newborns (OR 0.502,95％ CI:0.279 0.902).The multiple-factor analysis results also showed that taking folic acid regularly during periconcerptional period could reduce the risk of congenital heart disease (adjusted OR=0.512,P=0.046) when we controlled the family background factors,mother factors and exposure risk factors during pregnancy.However,no association was found between irregularly taking folic acid during periconcerptional period and the risk of congenital heart disease.Conclusion Taking folic acid according to the specification during periconcerptional period (taking folic acid during 3 months before pregnancy to 3 months after pregnancy with a daily dose of 0.4mg for more than 90 days) may prevent congenital heart disease of newborns.

OBJECTIVE: To explore the genetic basis for a Chinese patient featuring cleidocranial dysplasia(CCD). METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and suspected variant was verified by Sanger sequencing. RESULTS: WES has identified a missense c.460G>T (p.Val154Phe) (GRCh37/hg19) variant of the RUNX2 gene. The variant was located in the Runt domain, a highly conserved region (PM1); it was not present in either the Genome Aggregation Database or the 1000 Genomes Project (PM2), and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3); the clinical phenotype of the patient was highly consistent with that of cleidocranial dysplasia (PP4). Furthermore, the variant was unreported in medical literature and was absent in both parents (PS2). Based on the American College of Medical Genetics and Genomics guidelines, the c.460 G>T variant of RUNX2 gene was predicted to be pathogenic (PS2+PM1+PM2+PP3+PP4). CONCLUSION The c.460G>T (p.Val154Phe) variant of the RUNX2 gene probably underlay the clinical phenotype in the patient. Above finding has enabled accurate diagnosis and expanded the spectrum of RUNX2 variants.
China ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit/genetics* ; Humans ; Mutation ; Whole Exome Sequencing

Ninety six female patients with chronic renal failure were randomly allocated into combination group (n =48) and control group (n =48).In combination group patients received both kidney transplantation and hematopoietic stem cell infusion,in control group patients underwent kidney transplantation only.The results showed that chronic rejection in the combination group was lower than that in the control group [2％(1/48)vs.17％ (8/48),P＜0.05)].The 1-,3-,5-and 10 y-survival rates of kidney in the combination group were 98％ (47/48),94％ (45/48),83％ (34/41) and 9/17,respectively,those in control group were 98％ (47/48),90％ (43/48),76％ (31/41) and 7/17,respectively.Infusion of donor hematopoietic stem cells can augment chimerism in early postoperative period and significantly reduce the rate of graft rejection,which is beneficial for the quality of life of the recipients.

OBJECTIVETo investigate the expression characteristics of human beta-defensin-2 (HBD-2) mRNA and protein in salivary gland benign and malignant tumor tissues, as well as in salivary gland inflammation.

METHODSThe expression of HBD-2 in salivary gland benign tumor, salivary gland cancer, inflammation tissues and normal salivary gland tissues were detected by polymerase chain reaction (PCR), real-time polymerase chain reaction (Real-Time PCR) and immunohistochemical. The differences expression of HBD-2 mRNA and protein were analyzed.

RESULTSRT-PCR results showed that HBD-2 mRNA expression in salivary gland benign tumors, salivary gland cancer, and inflammation tissues was 6.468-, 0.334-, and 10.563-fold higher than that in normal tissues, respectively (P < 0.05). HBD-2 was expressed in the nuclei of these organs and malignant tissues.

CONCLUSIONHBD-2 mRNA and protein expressions are significantly increased in salivary gland benign tumor tissues and inflammation tissues compared with those in normal salivary gland tissues, but are significantly decreased in salivary gland cancer. The protein nuclear transfer in salivary gland cancer tissues is also significantly increased.

Objective: To study the clinicopathological features, diagnostic features and differential diagnoses of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Six cases of SDSC diagnosed at Eye, Ear, Nose and Throat Hospital, Fudan University from 2016 to 2018 were retrieved; the clinical features, histomorphology, immunophenotype, radiology and outcome were analyzed with review of literature. Results: There were five men and one woman with age range of 37 years to 75 years (mean 56 years). One case was in stage T2, and 5 cases were in stage T4. Computer tomography and magnetic resonance imaging showed a mass occupying the sinonasal cavity with bone destruction in all six patients. Microscopically, the tumors had infiltrative margins. Four tumors were composed mostly of basaloid cells, which possessed high nuclear/cytoplasmic ratio,scant cytoplasm,and minimalnuclear pleomorphism; and the cells were arranged in sheets or nests in a desmoplastic stroma. Two tumors were composed of rhabdoid cells, which possessed abundant, eosinophilic cytoplasm and eccentric nuclei, often growing in a nests or sheets pattern. Immunohistochemical staining showed that 6/6 cases had complete loss of INI1, diffusely and strongly positive for CKpan, and were negative for S-100 and EBER ISH; 4/6 cases were focally positive for p63; 1/5 was focally positive for Syn and p16. The Ki-67 index was 30% to 70%. The follow-up period ranged 1-26 months, with one patient died of extensive metastases, one had local recurrence, and two had lymph node metastases; one was alive without disease, and one was lost to follow-up. Conclusions SMARCB1 (INI1)-deficient sinonasal carcinoma is mostly aggressive, with rapid progression and poor prognosis. Histomorphological spectrum predominantly consists of basaloid type and rhabdoid type. The complete loss of nuclear expression of INI1 can help to distinguish this tumor from its many mimickers.

Objective: To investigate the effect of online and offline mindfulness training on improving anxiety and depression and sleep quality of college students,and to provide a reference for mental health promotion among college students. Methods: From October 2020, a total of 1 203 university students from North China University of Technology were screened with the Self rating Anxiety Scale (SAS), Self rating Depression Scale (SDS) and Pittsburg Sleep Quality Index (PSQI) using the whole group radom cluster sampling method. Totally 103 students who met the inclusion criteria were randomly divided into 64 online and 39 offline groups. The degree of improvement in anxiety, depression and sleep quality was assessed after the intervention. Results: The SAS, SDS and PSQI scores of college students after the online and offline the mindfulness training intervention significantly decreased compared with score before the intervention( t =5.57, 5.31, 3.99; 4.88,5.02, 5.88, P <0.01). The difference in the degree of improvement in sleep quality between the two interventions, online and offline, was statistically significant ( t =-2.55， P <0.05). The less the three symptoms of anxiety, depression and sleep were combined in university students, the higher the symptom remission rate of the positive mindfulness training (25% remission rate for all three symptoms together, 40% remission rate for two symptoms together and 100% remission rate for only one symptom). Conclusion Both online and mindfulness training can be used as an effective intervention for sleep, anxiety and depression; offline mindfulness training is more effective than online in improving sleep quality in university students; mindfulness training is more effective in relieving single symptoms.

Background: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial. Objectives: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication. Methods: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway. Results: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly downregulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010. Conclusions PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.

In Gram-negative bacteria, lipopolysaccharide transport (Lpt) protein LptA and LptC form a complex to transport LPS from the inner membrane (IM) to the outer membrane (OM). Blocking the interaction between LptA and LptC will lead to the defect of OM and cell death. Therefore, Lpt protein interaction could be used as a target to screen new drugs for killing Gram-negative bacteria. Here we used biolayer interferometry (BLI) assay to detect the interaction between LptA and LptC, with the aim to develop a method for screening the LptA/LptC interaction blockers in vitro. Firstly, LptC and LptA with or without signal peptide (LptAfull or LptAno signal) were expressed in E. coli BL21(DE3). The purified proteins were then labeled with biotin and the super streptavidin (SSA) biosensor was blocked with diluent. The biotin labeled protein sample was mixed with the sensor, and then the binding of the protein with a series of diluted non biotinylated protein was detected. At the same time, non-biotinylated protein was used as a control. The binding of biotinylated protein to a small molecule IMB-881 and the blocking of interaction were also detected by the same method. In the blank control, the biosensor without biotinylated protein was used to detect the serially diluted samples. The signal response constant was calculated by using steady analysis. The results showed that biotinylated LptC had a good binding activity with LptAfull and LptAno signal with KD value 2.9e⁻⁷±7.9e⁻⁸ and 6.0e⁻⁷±2.8e⁻⁸, respectively; biotinylated LptAno signal had a good binding activity with LptC, with a KD value of 9.6e⁻⁷±7.2e⁻⁸. All binding curves showed obvious fast binding and fast dissociation morphology. The small molecule compound IMB-881 can bind to LptA to block the interaction between LptA and LptC, but has no binding activity with LptC. In summary, we developed a method for detecting the LptA/LptC interaction based on the BLI technology, and confirmed that this method can be used to evaluate the blocking activity of small molecule blockers, providing a new approach for the screening of LptA/LptC interaction blockers.
Carrier Proteins ; Escherichia coli/metabolism* ; Escherichia coli Proteins/metabolism* ; Interferometry ; Membrane Proteins/metabolism*

Acetic acid is a common inhibitor present in lignocellulosic hydrolysate. Development of acetic acid tolerant strains may improve the production of biofuels and bio-based chemicals using lignocellulosic biomass as raw materials. Current studies on stress tolerance of yeast Saccharomyces cerevisiae have mainly focused on transcription control, but the role of transfer RNA (tRNA) was rarely investigated. We found that some tRNA genes showed elevated transcription levels in a stress tolerant yeast strain. In this study, we further investigated the effects of overexpressing an arginine transfer RNA gene tR(ACG)D and a leucine transfer RNA gene tL(CAA)K on cell growth and ethanol production of S. cerevisiae BY4741 under acetic acid stress. The tL(CAA)K overexpression strain showed a better growth and a 29.41% higher ethanol productivity than that of the control strain. However, overexpression of tR(ACG)D showed negative influence on cell growth and ethanol production. Further studies revealed that the transcriptional levels of HAA1, MSN2, and MSN4, which encode transcription regulators related to stress tolerance, were up-regulated in tL(CAA)K overexpressed strain. This study provides an alternative strategy to develop robust yeast strains for cellulosic biorefinery, and also provides a basis for investigating how yeast stress tolerance is regulated by tRNA genes.
Acetic Acid ; DNA-Binding Proteins/metabolism* ; Fermentation ; Leucine ; RNA, Transfer/genetics* ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism* ; Transcription Factors

Gram-negative bacteria have become the main pathogens and cause serious clinical problems with increased morbidity and mortality. However, the slow discovery of new antimicrobial agents is unable to meet the need for the treatment of bacterial infections caused by drug-resistant strains. The interaction of L12 and L10 is essential for ribosomal function and protein synthesis. In this study, a yeast two-hybrid system was established to successfully detect the interaction between L12 and L10 proteins from gram-negative bacteria , which allows us to screen compounds that specifically disrupt this interaction. With this system, we identified two compounds IMB-84 and IMB-87 that block L12-L10 interaction and show bactericidal activity against . We used glutathione--transferase (GST) pull-down and surface plasmon resonance (SPR) assays to demonstrate that these compounds disrupt L12-L10 interaction and the target of compounds was further confirmed by the overexpression of target proteins. Moreover, protein synthesis and elongation factor G-dependent GTPase activities are inhibited by two compounds. Therefore, we have identified two antibacterial agents that disrupt L12-L10 interaction by using yeast two-hybrid system.