Early embryonic failure caused by a novel mutation in the TUBB8 gene:A case report

BACKGROUND This study aimed to explore the relationship between gene mutations and early embryonic development arrest and to provide more possibilities for the diagnosis and treatment of repeated implantation failure.CASE SUMMARY Here,we collected and described the clinical data of a patient with early embryonic development stagnation after repeated in vitro fertilization attempts for primary infertility at the Department Reproductive Center of Zaozhuang Maternal and Child Healthcare Hospital.We also detected the whole-exon gene of the patient's spouse and parents,and conducted bioinformatics analysis to determine the pathogenesis of the gene.CONCLUSION A novel mutant of the TUBB8 gene[c.602G>T(p.C201F)]was identified,and this mutant provided new data on the genotype-phenotype relationships of related diseases.

Discrimination of foodborne pathogenic bacteria using synchrotron FTIR microspectroscopy

Traditional Fourier transform infrared(FTIR)spectroscopy has been recognized as a valuable method to characterize and classify kinds of microorganisms.In this study,combined with multivariate statistical analysis,synchrotron radiation-based FTIR(SR-FTIR) microspectroscopy was applied to identify and discriminate ten foodborne bacterial strains.Our results show that the whole spectra(3000-900 cm^(-1)) and three subdivided spectral regions(3000-2800,1800-1500 and 1200-900 cm^(-1),representing lipids,proteins and polysaccharides,respectively) can be used to type bacteria.Either the whole spectra or the three subdivided spectra are good for discriminating the bacteria at levels of species and subspecies,but the whole spectra should be given preference at the genus level.The findings demonstrate that SR-FTIR microspectroscopy is a powerful tool to identify and classify foodborne pathogenic bacteria at the genus,species and subspecies level.

Numerical simulations on material flow behaviors in whole process of friction stir welding

A finite element model based on solid mechanics was developed with ABAQUS to study the material flow in wholeprocess of friction stir welding （FSW）, with the technique of tracer particles. Simulation results indicate that the flow pattern of thetracer particles around the pin is spiral movement. There are very different flow patterns at the upper and lower parts of the weld. Thematerial on the upper surface has the spiral downward movement that is affected by the shoulder and the lower material has the spiralupward movement that is affected by the pin. The velocity of the material flow on the periphery of the stirring pin is higher than thatat the bottom of the stirring pin. The material can be rotated with a stirring pin a few times, agreeing well with the previousexperimental observation by tungsten tracer particles.

Clonal spread of Escherichia coli O101:H9-ST10 and O101:H9-ST167 strains carrying fosA3 and blaCTX-M-14 among diarrheal calves in a Chinese farm,with Australian Chroicocephalus as the possible origin of E.coli O101:H9-ST10

During a 2018 antimicrobial resistance surveillance of Escherichia coli isolates from diarrheal calves in Xinjiang Province,China,an unexpectedly high prevalence(48.5%)of fosfomycin resistance was observed.This study aimed to reveal the determinants of fosfomycin resistance and the underlying transmission mechanism.Polymerase chain reaction(PCR)screening showed that all fosfomycin-resistant E.coli carried the fosA3 gene.Pulsed-field gel electrophoresis(PFGE)and southern blot hybridization revealed that the 16 fosA3-positive isolates belonged to four different PFGE patterns(i.e.,A,B,C,D).The fosA3 genes of 11 clonally related strains(pattern D)were located on the chromosome,while others were carried by plasmids.Whole-genome and long-read sequencing indicated that the pattern D strains were E.coli O101:H9-ST10,and the pattern C,B,and A strains were O101:H9-ST167,O8:H30-ST1431,and O101:H9 with unknown ST,respectively.Among the pattern C strains,the blaCTX-M-14 gene was co-localized with the fosA3 gene on the F18:A-:B1 plasmids.Interestingly,phylogenetic analysis based on core genome single nucleotide polymorphisms(cgSNPs)showed that the O101:H9-ST10 strains were closely related to a Australian-isolated Chroicocephalus-origin E.coli O101:H9-ST10 strain producing CTX-M-14 and FosA3,with a difference of only 11 SNPs.These results indicate possible international dissemination of the high-risk E.coli clone O101:H9-ST10 by migratory birds.

Elevated levels of fructosamine are independently associated with SARS-CoV-2 reinfection:A 12-mo follow-up study

BACKGROUND The association between blood levels of fructosamine(FMN)and recurrent coronavirus disease 2019(COVID-19)is currently unclear.AIM To investigate a prospective relationship between blood levels of FMN and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)reinfection.METHODS A total of 146 Chinese hospitalized patients infected with SARS-CoV-2 were consecutively collectively recruited and followed from January 2020 to May 2021.Diagnosis of COVID-19 and SARS-CoV-2 reinfection was based on the diagnostic criteria and treatment protocol in China.The levels of FMN were determined in blood and divided into tertiles based on their distribution in the cohort of COVID-19 patients.Multivariate-adjusted hazard ratios(HRs)with 95%confidence intervals(CIs)were estimated for SARS-CoV-2 reinfection across the tertiles of FMN levels.A Cox regression model was used to generate the HR for SARS-CoV-2 reinfection in the participants in the top tertile of FMN levels compared with those at the bottom.Disease-free survival was used as the time variable,and relapse was used as the state variable,adjusted for age,gender,influencing factors such as diabetes mellitus,hypertension,and corticosteroid therapy,and clinical indexes such as acute liver failure,acute kidney failure,white blood cell(WBC)count,C-reactive protein,prognostic nutritional index(PNI),and blood lipids.Kaplan-Meier analysis with log-rank tests was used to compare the survival rate between patients with elevated FMN levels(FMN>1.93 mmol/L,the top tertile)and those with nonelevated levels.RESULTS Clinical data for the 146 patients with confirmed COVID-19[age 49(39-55)years;49%males]were analyzed.Eleven patients had SARS-CoV-2 reinfection.The SARS-CoV-2 reinfection rate in patients with elevated FMN levels was significantly higher than that in patients with nonelevated FMN(17%vs 3%;P=0.008)at the end of the 12-mo follow-up.After adjustments for gender,age,diabetes mellitus,hypertension,corticosteroid therapy,WBC count,PNI,indexes of liver and renal function,and blood lipids,patients with nonelevated FMN levels had a lower risk of SARS-CoV-2 reinfection than those with elevated FMN levels(HR=6.249,95%CI:1.377-28.351;P=0.018).Kaplan-Meier analysis showed that the cumulative survival rate of patients infected with SARSCoV-2 was higher in patients with nonelevated FMN levels than in those with elevated FMN levels(97%vs 83%;log rank P=0.002).CONCLUSION Elevated levels of FMN are independently associated with SARS-CoV-2 reinfection,which highlights that patients with elevated FMN should be cautiously monitored after hospital discharge.

Association between Genetic Variants of Transforming Growth Factor-β1 and Susceptibility of Pneumoconiosis： A Meta-analysis

Background： Transforming growth factor-beta 1 （TGF-β 1） and gene variants have been extensively studied in various human diseases. For example, TGF-β1 polymorphisms were associated with fibrosis and pneumoconiosis, but the data remained controversial. The aim of this meta-analysis was to assess the association between TGF-β1-509 C〉T [rs 1800469], ＋869 T〉C [rs 1800470], and ＋915 G〉C [rs 1800471 ] polymorphisms and pneumoconiosis, Methods： A comprehensive literature search was conducted through searching in PubMed, Embase, the Chinese Biomedical Database, and the Wei Pu （Chinese） Database by the end of April 2016. Eleven publications with 21 studies were included in this recta-analysis, covering a total of 4333 patients with pneumoconiosis and 3478 controls. Study quality was assessed, and heterogeneity and publication bias were measured. All statistical analyses were performed using STATA version 12.0 （StataCorp, College Station, TX, USA） software. Results： The data showed significant associations between TGF-β1-509 C〉T polymorphism and the risk ofpneumoconiosis development （T vs. C, odds ratio [OR] = 1.35, 95% confidence interval [CI]： 1.00-1.81, P = 0.046）; between TGF-fll ＋915 G〉C polymorphism and the pneumoconiosis risk （C vs. G, OR = 1.69, 95% CI： 1.19-2.40, P = 0.004; CG vs. GG, OR = 1.79, 95% CI： 1.23-2.60, P = 0.002; CC＋CG vs. GG, OR = 1.80, 95% CI： 1.24-2.61, P = 0.002）. In addition, the subgroup analysis of ethnicity versus pneumoconiosis types indicated a significant association of silicosis among Asian populations but not that of coal workers＇ pneumoconiosis in Caucasian populations. In contrast, no significant association was exhibited between TGF-β1 ＋869 T〉C polymorphism and risk ofpneumoconiosis. Conclusion： The polymorphisms of both TGF-β1 -509 C〉T and ＋915 G〉C are associated with increased risk of pneumoconiosis. Key words： Meta analysis; Pneumoconiosis; Polymorphism; Transforming Growth Factor-betal

Long non-coding RNA small nucleolar RNA host gene 6 aggravates pancreatic cancer through upregulation of far upstream element binding protein 1 by sponging microRNA-26a-5p

Background:Pancreatic cancer(PC)is a highly deadly malignancy with few effective therapies.We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6(SNHG6)plays in PC cells by targeting far upstream element binding protein 1(FUBP1)via microRNA-26a-5p(miR-26a-5p).Methods::SNHG6 expression was predicted by bioinformatics,followed by verification via reverse transcription quantitative polymerase chain reaction.Then,the interactions among SNHG6,miR-26a-5p,and FUBP1 were detected through online software analysis,dual luciferase reporter assay and RNA pull-down.After that,cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6,miR-26a-5p,and FUBP1 and their roles in PC cells.Finally,the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice.A t-test,one-way and two-way analysis of variance were used for data analysis.Results::Compared with that in normal tissues,SNHG6 was highly expressed in PC tissues(1.00±0.05 vs.1.56±0.06,t=16.03,P<0.001).Compared with that in human pancreatic duct epithelial cells(HPDE6-C7),SNHG6 showed the highest expression in PANC-1 cells(1.00±0.06 vs.3.87±0.13,t=34.72,P<0.001)and the lowest expression in human pancreatic cancer cells(MIAPaCa-2)(1.00±0.06 vs.1.41±0.07,t=7.70,P=0.0015).Compared with the levels in the si-negative control group,SNHG6(0.97±0.05 vs.0.21±0.06,t=16.85,P<0.001),N-cadherin(0.74±0.05 vs.0.41±0.04,t=8.93,P<0.001),Vimentin(0.55±0.04 vs.0.25±0.03,t=10.39,P<0.001),andβ-catenin(0.62±0.05 vs.0.32±0.03,t=8.91,P<0.001)were decreased,while E-cadherin(0.65±0.06 vs.1.36±0.07,t=13.34,P<0.001)was increased after SNHG6 knockdown or miR-26a-5p overexpression,accompanied by inhibited cell proliferation,migration,and invasion.SNHG6 overexpression exerted the opposite effects.SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p.Silencing SNHG6 blocked the growth of PC in vivo.Conclusion::Silencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p,thus providing further supporting evidence for its use in PC treatment.

Apoptosis of Lewis Lung Carcinoma Cells Induced by Microwave via p53 and Proapoptotic Proteins In vivo

Background： Microwave therapy is a minimal invasive procedure and has been employed in clinical practice for the treatment of various types of cancers. However, its therapeutic application in non-small-cell lung cancer and the underlying mechanism remains to be investigated. This study aimed to investigate its effect on Lewis lung carcinoma （LLC） tumor in vivo. Methods： Fifty LLC tumor-bearing C57BL/6 mice were adopted to assess the effect of microwave radiation on the growth and apoptosis of LLC tumor in vivo. These mice were randomly assigned to 10 groups with 5 mice in each group. Five groups were treated by single pulse microwave at different doses for different time, and the other five groups were radiated by multiple-pulse treatment of a single dose. Apoptosis of cancer cells was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Western blotting was applied to detect the expression of proteins. Results： Single pulse of microwave radiation for 5 min had little effect on the mice. Only 15-min microwave radiation at 30 mW/cm2 significantly increased the mice body temperature （2.20 ± 0.82）℃ as compared with the other groups （0.78 ± 0.29 ℃, 1.24 ± 0.52 ℃, 0.78 ± 0.42 ℃, respectively）, but it did not affect the apoptosis of LLC tumor cells significantly. Continous microwave radiation exposure, single dose microwave radiation once per day for up to seven days, inhibited cell division and induced apoptosis of LLC tumor cells in a dose- and duration-dependent manner. It upregulated the protein levels of p53, Caspase 3, Bax and downregulated Bcl-2 protein. Conclusions： Multiple exposures of LLC-bearing mice to microwave radiation effectively induced tumor cell apoptosis at least partly by upregulating proapoptotic proteins and downregulating antiapoptotic proteins. Continuous radiation at low microwave intensity Ibr a short time per day is promising in treating non-small-cell lung cancer.

A novel SPINT2 missense mutation causes syndromic congenital sodium diarrhea

Congenital sodium diarrhea(CSD)is a monogenic disordercausedby specific geneticdefects that increase sodium content in the stool,resulting in intractable diarrhea.The disease was first reported by Holmberg in 1985[1].Fewerthan50cases havebeen reportedworldwide todate,mainly in Europe(Germany and Sweden)and Oceania(Australia),while no cases have been reported in China.Therearetwocategories of CSDdependingonwhetherit involves other congenital malformations:non-syndromic congenital sodium diarrhea(non-sCSD)and syndromic congenital sodium diarrhea(sCSD).Fornon-sCSD,the identified causative genes include SLC9A3 and GUCY2C,whereas sCSD is primarily caused bySPINT2mutations[2].