Giant Second Harmonic Generation from Membrane Metasurfaces.

Metasurfaces have emerged as a fascinating framework for nonlinear optics, which have advantages of a compact footprint and unprecedented flexibility in manipulating light. But their nonlinear responses are generally limited by the short interaction lengths with light. Therefore, further enhancement is highly desired for building high-efficiency nonlinear devices. Here, we experimentally demonstrate a record high second harmonic generation (SHG) efficiency of 2.0 × 10-4 using lithium niobate (LN) membrane metasurfaces. Benefiting from the large refractive index contrast in the vertical direction and high fabrication quality, distinct spectral resonances and tight field confinements in the LN layer were achieved. Strong SHG peaks resulting from pump resonances of the metasurfaces were observed. Our nonlinear efficiency is more than 2 orders of magnitude larger than previously reported LN metasurfaces. The results inspire a way to improve the efficiency of nonlinear metasurfaces for ultracompact nonlinear light sources in applications of nonlinear holography, Li-Fi, beam shaping, etc.

Fixed dosing of kukoamine B in sepsis patients: Results from population pharmacokinetic modelling and simulation.

AIMS: To assess the appropriateness of the body weight or fixed dosing regimen, a population pharmacokinetic (PopPK) model of kukoamine B has been built in sepsis patients. METHODS: Plasma concentrations of kukoamine B and the covariates information were taken from 30 sepsis patients assigned into 0.06 mg/kg, 0.12 mg/kg and 0.24 mg/kg groups in a Phase IIa clinical trial. The PopPK model was built using a nonlinear mixed-effect (NLME) modelling approach. Based on the final model, PK profiles were respectively simulated 500 times applying the body weight and renal function information of 12 sepsis patients from the 0.24 mg/kg group on the body weight or the fixed dosing regimen. For each dosing regimen, PK profiles of 6000 virtual patients were obtained. Statistical analyses for Cmax and Cmin were performed. If the biases of Cmax and Cmin can all meet the criteria of ±15%, the fixed dosing regimen can substitute for the body weight dosing regimen. RESULTS: The PopPK model was successfully developed using the NLME approach. A bi-compartmental model was selected as the basic model. Renal function was identified as a statistically significant covariate of systemic clearance with the objective function value (OFV) decreasing 8.6, resulting in a 5.2% decrease in inter-individual variability (IIV) of systemic clearance. Body weight was not identified as a statistically significant covariate. Simulation results demonstrated two methods had a bias of 8.1% for Cmax , and 8.6% for Cmin . Furthermore, PK variability was lower on the fixed dosing regimen than the body weight regimen. CONCLUSIONS: Based on the simulation results, a fixed dosing regimen was recommended in the subsequent clinical trials.

[Mosaic trisomy 20: discrepancy between cyto-and molecular genetic technologies in prenatal diagnosis].

OBJECTIVE: To provide genetic counseling and prenatal diagnosis for a fetus with mosaic trisomy 20. METHODS: Chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a pregnant woman with advanced maternal age. RESULTS: The karyotype of amniotic fluid sample was 47,XN,+20, whilst the result of CMA was normal. To verify this discrepancy, CMA was performed again with the cultured amniotic fluid, which yielded a result of 47,XN,+20. FISH assay of the amniotic fluid sample was nuc ish(D20Z1)×3[11]/(D20Z1)×2[89], which indicated that about 11% of fetal cells were trisomy 20. After the fetus was born, the karyotype of peripheral blood sample was normal. CONCLUSION: The amniotic fluid sample might be mosaic trisomy 20, and a dominant growth of 47,XN,+20 cells had occurred during the culture process, resulting in alteration of amniotic fluid cell composition. Mosaic trisomy 20 indicated by FISH may be attributed to confined placental mosaicism or somatic mosaicism of trisomy 20.

UCP2 Mitigates the Loss of Human Spermatozoa Motility by Promoting mROS Elimination.

BACKGROUND/AIMS: To demonstrate the function of uncoupling protein 2 (UCP2) in the regulation of human spermatozoa motility. METHODS: Semen samples were collected from donors with either normal spermatozoa motility (normospermia [NS]) or poor spermatozoa motility (asthenospermia [AS]). UCP2 protein in spermatozoawas quantified by Western blotting. The level of mitochondrial reactive oxygen species (mROS) was evaluated by MitoSOX Red. The activity of mitochondrial membrane potential (MMP) in spermatozoa was evaluated by a JC-1 assay and the ATP level was monitored by a luciferin-luciferase assay. RESULTS: UCP2 was expressed in both NS and AS groups, with the former exhibiting a higher level than the latter. Immunofluorescence analysis shows that UCP2 is mainly located at the mid-region of human spermatozoa. The inhibition of UCP2 by a highly selective inhibitor, Genipin, results in not only impaired spermatozoa mobility (P<.05) but also an elevated level of mROS (P<.05), suggesting that UCP2 is involved in the maintenance of the spermatozoa mobility, which probably is achieved by promoting mROS elimination. Furthermore, H2O2 treatment of spermatozoa increases the mROS level coupled with the loss of spermatozoa mobility. Unexpectedly, this treatment also has a positive impact on the expression of UCP2 within a certain range of supplemental H2O2, indicating the moderate mROS level possibly serves as a feedback signal to stimulate the expression of UCP2. Finally, the treatment of spermatozoa by an ROS scavenger, N-acetyl-l-cysteine (NAC),decreases the level of mROS and increases the curvilinear velocity (VCL) of spermatozoa, but the UCP2 level is not affected. CONCLUSION: These results suggest an UCP2-mROS-motility regulatory system exists for maintaining spermatozoa mobility in humans. In such a system, UCP2 fulfills its function by promoting mROS elimination, and slightly over-produced mROS in turn serves as a signal to stimulates the expression of UCP2. This regulatory system represents a new potential target for the discovery of novel pharmaceuticals for the treatment of patients with low spermatozoa motility.

Effects of Folpet, Captan, and Captafol on Human Aromatase in JEG-3 Cells.

BACKGROUND: Estradiol, produced by aromatase (CYP19A1), is very important for reproduction. Folpet, captan, and captafol belong to the phthalimide class of fungicides. They are used to protect the leaves of plants or fruits. They could be endocrine disruptors and may disrupt CYP19A1 activity. METHODS: In the present study, we investigated the effects of folpet, captan, and captafol on estradiol production and human CYP19A1 activity in JEG-3 cells. RESULTS: Folpet, captan, and captafol decreased estradiol production in JEG-3 cells in a concentration-dependent manner. Folpet, captan, and captafol inhibited human CYP19A1 with inhibitory concentration (IC50) values of 3.55, 10.68, and 1.14 µmol/L respectively. These chemicals competitively inhibited human CYP19A1. Molecular docking simulation analysis showed that they tended to bind to the steroid-binding pocket of the CYP19A1. However, the required concentrations may not be relevant to the negligible systemic exposures in humans to these chemicals. CONCLUSION: Folpet, captan, and captafol are potential inhibitors of human CYP19A1.

Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms.

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development.

Oxidative-stress-induced nuclear to cytoplasmic relocalization is required for Not4-dependent cyclin C destruction.

The yeast cyclin-C-Cdk8p kinase complex represses the transcription of a subset of genes involved in the stress response. To relieve this repression, cyclin C is destroyed in cells exposed to H(2)O(2) by the 26S proteasome. This report identifies Not4p as the ubiquitin ligase mediating H(2)O(2)-induced cyclin C destruction. Not4p is required for H(2)O(2)-induced cyclin C destruction in vivo and polyubiquitylates cyclin C in vitro by utilizing Lys48, a ubiquitin linkage associated with directing substrates to the 26S proteasome. Before its degradation, cyclin C, but not Cdk8p, translocates from the nucleus to the cytoplasm. This translocation requires both the cell-wall-integrity MAPK module and phospholipase C, and these signaling pathways are also required for cyclin C destruction. In addition, blocking cytoplasmic translocation slows the mRNA induction kinetics of two stress response genes repressed by cyclin C. Finally, a cyclin C derivative restricted to the cytoplasm is still subject to Not4p-dependent destruction, indicating that the degradation signal does not occur in the nucleus. These results identify a stress-induced proteolytic pathway regulating cyclin C that requires nuclear to cytoplasmic relocalization and Not4p-mediated ubiquitylation.

First-in-Human Safety, Tolerability, and Pharmacokinetics of Single-Dose Kukoamine B Mesylate in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Phase I Study.

INTRODUCTION: Kukoamine B mesylate (KB) is a mesylate chrysamine B targeting lipopolysaccharides and CpG DNA, two potential treatment targets in sepsis. METHODS: This first-in-human, randomized, double-blind, placebo-controlled, phase I study was conducted from July 2014 to May 2015 to explore the safety, tolerability, and pharmacokinetics of KB in healthy subjects. This study consisted of a pre-phase (four participants; KB at 0.005 mg/kg) and a dose escalation phase (eight participants/dose group, randomized 6:2 to KB or placebo; KB at 0.02, 0.04, 0.08, 0.12, 0.24, and 0.48 mg/kg). The primary endpoint was safety. RESULTS: Fifty-two participants were enrolled, including four in the pre-phase and 48 in the dose escalation phase. Among the 40 participants who received KB, 12 (30.0%) experienced adverse events (AEs), while two (16.7%) experienced AEs among 12 participants who received the placebo. The most common AEs in the KB group were headache (5.0%), influenza (5.0%) and positive white blood cell in urine (5.0%). After the administration of KB, the mean plasma elimination half was around 1.61-4.24 h. The relationship between the KB plasma exposure of KB and the administered dose was not linear. The percentage of cumulative urinary excretion of KB was similar among the different dose groups (21.7-35.2%) and the urinary excretion of KB decreased significantly about 8 h after administration. CONCLUSIONS: Single-dose KB demonstrated favorable safety and tolerability in healthy subjects at the dose level of 0.005-0.48 mg/kg. KB exhibited a non-linear pharmacokinetic profile with a half-life of about 1.61-4.24 h, which mainly distributed in plasma. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02219971.

Genetic analysis and prenatal diagnosis of a pedigree with developmental retardation due to paternal 8q/18q translocation.

Balanced reciprocal chromosomal translocation carriers will have greater risk to experience recurrent miscarriages, embryonic death, and infertility. We show the pedigree carrying a paternal karyotype which was reported first. This research helps to better understand the clinical manifestations and prognosis of patients with this rare chromosomal abnormality.

Exosomal miR-543 derived from umbilical cord mesenchymal stem cells ameliorates endometrial fibrosis in intrauterine adhesion via downregulating N-cadherin.

INTRODUCTION: Human umbilical cord mesenchymal stem cells (UCMSCs) play an important role in repairing the damaged endometrium of intrauterine adhesion (IUA). Meanwhile, exosomes released by UCMSCs can mediate intercellular communication by delivering miRNAs. It has been shown that miR-543 level was reduced in IUA tissues. However, the role of miR-543 in the progression of IUA remains largely unknown. Therefore, we investigated the role of UCMSCs-derived exosomal miR-543 in IUA. METHODS: In this study, human endometrial epithelial cells (hEECs) were treated with TGF-ß1 for mimicking endometrial fibrosis in vitro. In addition, the IUA-like mouse model in vivo was established by a dual damage method of curettage and LPS infection. RESULTS: The level of miR-543 was markedly reduced in hEECs exposed to TGF-ß1 and in endometrium tissues of IUA mice. Additionally, miR-543 could be transferred from UCMSCs to hEECs via exosomes. Meanwhile, exosomal miR-543-derived from UCMSCs significantly reduced the expressions of N-cadherin, α-SMA, fibronectin 1 and elevated the expression of E-cadherin in TGF-ß1-treated hEECs. Furthermore, UCMSCs-derived exosomal miR-543 attenuated IUA-induced endometrial fibrosis in vivo, as shown by the decreased N-cadherin, α-SMA and fibronectin 1 protein expressions. DISCUSSION: Collectively, UCMSCs-derived exosomal miR-543 was able to prevent endometrial fibrosis both in vitro and in vivo via downregulating N-cadherin. These results may provide an insight into the clinical treatment for IUA.

Safety, Tolerability, and Pharmacokinetics of Kukoamine B in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Phase I Study.

INTRODUCTION: Kukoamine B (KB) is a novel sepsis therapeutic drug targeting lipopolysaccharide and CpG DNA. This study aims to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of multiple doses of KB in healthy volunteers. METHODS: Healthy volunteers were randomized at a 1:1:1:1 ratio to receive multiple intravenous infusion doses of KB 0.06 mg/kg, 0.12 mg/kg, 0.24 mg/kg or placebo (administered every 8 h per day) for 7 days and subsequently followed up for another 7 days at Peking Union Medical College Hospital. Primary endpoints were adverse events (AEs), and the secondary endpoints were PK parameters of the first administration and the last administration. RESULTS: Data of the 18 health volunteers in KB groups and 6 in the placebo group were pooled and analyzed. AEs occurred in 12 (66.67%) volunteers in the KB groups and 4 (66.67%) volunteers in the placebo group. Treatment-related adverse events (TRAEs) occurred in 8 (44.44%) volunteers in the KB groups and 2 (33.33%) volunteers in the placebo group. Hypertriglyceridemia (4 [22.22%] vs. 2 [33.33%]) and sinus bradycardia (3 [16.67%] vs. 0) were the most common AEs. The mean elimination half-life, clearance, and distribution volume of KB were 3.40-4.88 h, 9.35-13.49 L/h, and 45.74-101.90 L, respectively. The average accumulation ratios of area under the plasma concentration-time curve and maximum plasma concentration were 1.06 and 1.02, respectively. CONCLUSION: Single and multiple intravenous infusions of KB at a dose range of 0.06-0.24 mg/kg are safe and tolerable in healthy volunteers. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02690961.

Safety, tolerability, pharmacokinetics, and efficacy of kukoamine B in patients with sepsis: A randomized phase IIa trial.

PURPOSE: To evaluate the safety, tolerability, pharmacokinetics, and efficacy of kukoamine B (KB), an alkaloid compound with high affinity for both lipopolysaccharide (LPS) and oligodeoxynucle-otides containing CpG motifs (CpG DNA), in patients with sepsis-induced organ failure. MATERIALS AND METHODS: This was a multicenter, randomized, double-blind, placebo-controlled phase IIa trial. Patients with sepsis-induced organ failure were randomized to receive either KB (0.06, 0.12, or 0.24 mg/kg) or placebo, every 8 h for 7 days. Primary endpoint was safety, and secondary endpoints included pharmacokinetic (PK) parameters, changes in inflammatory mediators' level, and prognostic parameters. RESULTS: Of 44 patients enrolled, adverse events occurred in 28 patients [n = 20, 66.7% (KB pooled); n = 8, 57.1% (placebo)], while treatment emergent adverse events were reported in 14 patients [n = 10, 33.3% (KB pooled); n = 4, 28.6% (placebo)]. Seven patients died at 28-day follow-up [n = 4, 13.3% (KB pooled); n = 3, 21.4% (placebo)], none was related to study drug. PK parameters suggested dose-dependent drug exposure and no drug accumulation. KB did not affect clinical outcomes such as ΔSOFA score, vasopressor-free days or ventilator-free days. CONCLUSIONS: In patients with sepsis-induced organ failure, KB was safe and well tolerated. Further investigation is warranted. TRIAL REGISTRATION: http://ClinicalTrials.gov, NCT03237728.

Study on the Clinical Value of Noninvasive Prenatal Testing in Screening the Chromosomal Abnormalities of the Fetus in the Elderly Pregnant Women.

Introduction: To explore the clinical value of noninvasive prenatal testing (NIPT) in screening the chromosomal abnormalities of the fetus in the elderly pregnant women. Materials and Methods: Between January 2020 and December 2021, 1949 elderly pregnant women underwent NIPT in our hospital. At the same time, 236 elderly pregnant women received invasive prenatal diagnosis, and the pregnancy outcomes were followed-up. Results: When NIPT was used for prenatal screening of fetal chromosomal aneuploidy, its diagnostic coincidence rate for trisomy 21 was the highest, with a coincidence rate of 90.00%, and the diagnostic coincidence rate for other chromosomal abnormalities was the lowest, only 22.22%. The sensitivity, specificity, positive predictive rate, and negative predictive rate for T21 by NIPT were 100%, 99.97%, 94.28%, and 100%; for T18 were 100%, 99.92%, 72.22%, and 100%, respectively; and for T13 were 100%, 99.95%, 50%, and 100%, respectively. Patients with high risks according to NIPT results further received invasive prenatal diagnosis, and 18 cases were excluded from the follow-up. For the remaining 1933 cases in the NIPT group, there was an incidence of 2.28% of adverse pregnancy outcomes. For the remaining 234 cases in the Amniocentesis group, there was an incidence of 1.28% of adverse pregnancy outcomes. There was no significant difference between the two groups (P > 0.05). The diagnostic rate of fetal chromosomal abnormalities in pregnant women under 40 years old was about 0.39-0.79%; however, the risk for people over 40 is relatively high at 1.32-4.44%. Conclusion: The noninvasive prenatal screening of fetal DNA in the second trimester of pregnancy for elderly pregnant women has high application value in the prediction of pregnancy outcome. The high risk of pregnancy can be determined by detecting trisomy 21, 18, and 13 syndromes, and the probability of adverse pregnancy outcome increases.

A prenatal diagnosis case of partial duplication 21q21.1-q21.2 with normal phenotype maternally inherited.

BACKGROUND: Down syndrome is characterized by trisomy 21 or partial duplication of chromosome 21. Extensive studies have focused on the identification of the Down Syndrome Critical Region (DSCR). We aim to provide evidence that duplication of 21q21.1-q21.2 should not be included in the DSCR and it has no clinical consequences on the phenotype. CASE PRESENTATION: Because serological screening was not performed at the appropriate gestational age, noninvasive prenatal testing (NIPT) analysis was performed for a pregnant woman with normal prenatal examinations at 22 weeks of gestation. The NIPT results revealed a 5.8 Mb maternally inherited duplication of 21q21.1-q21.2. To assess whether the fetus also carried this duplication, ultrasound-guided amniocentesis was conducted, and the result of chromosomal microarray analysis (CMA) with amniotic fluid showed a 6.7 Mb duplication of 21q21.1-q21.2 (ranging from position 18,981,715 to 25,707,009). This partial duplication of 21q21.1-q21.2 in the fetus was maternally inherited. After genetic counseling, the pregnant woman and her family decided to continue the pregnancy. CONCLUSION: Our case clearly indicates that 21q21.1-q21.2 duplication is not included in the DSCR and most likely has no clinical consequences on phenotype.

Prenatal diagnosis by whole exome sequencing in a family with a novel TBR1 mutation causing intellectual disability.

OBJECTIVE: To provide prenatal diagnosis for a pregnant woman with genetic history of intellectual disability. CASE REPORT: A Chinese pedigree with intellectual disability was collected in this study. Cytogenetic analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) followed by Sanger validation were conducted to identify the genetic pathogenesis. A novel heterozygous deletion c.370_374delTTCCC in TBR1 gene was identified, leading to a frameshift mutation starting at Phe124 followed by a premature stop codon at position 141 (p.Phe124Valfs∗18). Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. Prenatal diagnosis indicated the absence of this mutation, and the family decided to continue the pregnancy after genetic counseling. CONCLUSION: Our findings demonstrated the significance of genetic testing in the diagnosis of intellectual disability. This work also confirmed the effectiveness of WES in prenatal diagnosis.

Exposure-Response Modeling to Support Dosing Selection for Phase IIb Development of Kukoamine B in Sepsis Patients.

Aim: Kukoamine B, a small molecule compound, is being developed for the treatment of sepsis in a Phase II clinical trial. The objective of this study was to optimize dosing selection for a Phase IIb clinical trial using an exposure-response model. Methods: Data of 34 sepsis patients from a Phase IIa clinical trial were used in the model: 10 sepsis patients from the placebo group and a total of 24 sepsis patients from the 0.06 mg/kg, 0.12 mg/kg, and 0.24 mg/kg drug groups. Exposure-response relationship was constructed to model the impact of the standard care therapy and area under curve (AUC) of kukoamine B to the disease biomarker (SOFA score). The model was evaluated by goodness of fit and visual predictive check. The simulation was performed 1,000 times based on the built model. Results: The data of the placebo and the drug groups were pooled and modeled by a nonlinear mixed-effect modeling approach in sepsis. A latent-variable approach in conjunction with an inhibitory indirect response model was used to link the standard care therapy effect and drug exposure to SOFA score. The maximum fraction of the standard care therapy was estimated to 0.792. The eliminate rate constant of the SOFA score was 0.263/day for the standard care therapy. The production rate of SOFA score (Kin) was estimated at 0.0569/day and the AUC at half the maximal drug effect (EAUC50) was estimated at 1,320 h*ng/mL. Model evaluation showed that the built model could well describe the observed SOFA score. Model-based simulations showed that the SOFA score on day 7 decreased to a plateau when AUC increased to 1,500 h*ng/mL. Conclusion: We built an exposure-response model characterizing the pharmacological effect of kukoamine B from the standard care therapy in sepsis patients. A dose regimen of 0.24 mg/kg was finally recommended for the Phase IIb clinical trial of kukoamine B based on modeling and simulation results.

Identification of a novel TP63 mutation causing nonsyndromic cleft lip with or without cleft palate.

BACKGROUND: Cleft lip with or without cleft palate (CL/P) is the most common craniofacial anomaly with a high incidence of live births. The specific pathogenesis of CL/P is still unclear, although plenty of studies have been conducted. Variations of tumor protein 63 (TP63) was reported to be related to the phenotype of CL/P. The case discussed in this report involves a pedigree with mutation at TP63 gene, and the variation was not reported before. CASE PRESENTATION: A Chinese pedigree with CL/P was collected in this study. The proband is a 3-year-old boy with the phenotype of CL/P, while his global development and intelligence are normal. After two CL/P repair operations, he looks almost normal. The proband's uncle and grandmother both have the phenotype of CL/P. Cytogenetic analysis and chromosomal microarray analysis (CMA) were performed, followed by whole exome sequencing (WES) and sanger validation. Analysis of WES revealed a variant of C>T at nucleotide position 1324 (1324C>T) of TP63 gene, possibly producing a truncated protein with a premature stop codon at amino acid position 442 (p.Q442*). This mutation was localized at the oligomerization domain (OD) of TP63 and might impair the capacity of p63 oligomerization. CONCLUSION: The mutation in TP63 was recognized to be the possible cause of the phenotype of CL/P in this pedigree. This report provides some evidence for the clinical diagnosis of CL/P. And our study also provides clinical evidence for the molecular mechanism of TP63 gene causing nonsyndromic cleft lip with or without cleft palate (NSCL/P).

LncRNA-ATB Promotes the Tumorigenesis of Ovarian Cancer via Targeting miR-204-3p.

BACKGROUND: Ovarian cancer ranks fifth among the most prevalent cancer type in females all over the world. It is the second most frequent malignant tumor which accounts for 3% of cancer in females. Therefore, to explore the mechanism of carcinogenesis in ovarian cancer is important to develop new treatment methods. It has been previously found that lncRNA-ATB could promote the tumorigenesis of malignant tumors. However, the role of lncRNA-ATB during the progression of ovarian cancer remains unclear. METHODS: Gene expressions in tissues or cells were detected by using qRT-PCR. Western blot was performed to investigate the protein expressions in ovarian cancer cells. Cell apoptosis was tested by flow cytometry. Moreover, the correction between lncRNA-ATB and miR-204-3p was examined by Dual-luciferase reporter assay and RNA pulldown. Cell proliferation and invasion were detected by CCK-8, Ki-67 staining and transwell assay, respectively. Finally, xenograft mice model was established to confirm the result of in vitro experiments. RESULTS: LncRNA-ATB silencing significantly inhibited the proliferation and induced apoptosis of ovarian cancer cells. In addition, luciferase activity suggested that lncRNA-ATB negatively regulated miR-204-3p in ovarian cancer. Besides, Nidogen 1 (NID1) was the direct target of miR-204-3p. Overexpression of NID1 could notably reverse the inhibitory effect of lncRNA-ATB knockdown on the progression of ovarian cancer. Finally, lncRNA-ATB silencing notably attenuated the severity of ovarian cancer in vivo. CONCLUSION: Downregulation of lncRNA-ATB significantly inhibited the tumorigenesis of ovarian cancer in vitro and in vivo, which may serve as a potential novel target for the treatment of ovarian cancer.

EspR promotes mycobacteria survival in macrophages by inhibiting MyD88 mediated inflammation and apoptosis.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), leading to about a million deaths each year. EspR is a DNA binding protein of Mtb which regulates expression of multiple genes and the activity of ESX-1 secretion system of the bacteria, with itself being secreted out as a substrate of ESX-1. We explored the function of secreted EspR in host cells by overexpressing the protein in murine macrophage cell line RAW264.7, infecting the cells with BCG which does not secrete EspR, and evaluating the antimicrobial responses of the cells. We found that EspR resulted in an increased intracellular bacteria load in macrophages. This is due to its inhibition on BCG induced expression of inflammatory cytokines and inducible nitric oxide synthase (iNOS), as well as host cell apoptosis. Mechanism study showed that EspR directly interacted with adaptor protein myeloid differentiation factor 88 (MyD88), suppressed MyD88 dependent Toll-like receptor (TLR) and IL-1R signal activation, thus reduced inflammatory responses and apoptosis in macrophages and promoted mycobacteria survival.

[C1772T polymorphism of hypoxia-inducible factor-1 alpha gene in Han ethnic population from Northern China].

OBJECTIVE: To analyze the distribution of single nucleotide polymorphism C1772T (SNP/C1772T) in hypoxia-inducible factor -1 alpha (HIF-1 alpha) gene in Han ethnic population from Northern China. METHODS: Allele frequencies in a sample of 206 healthy Chinese Hans were determined by polymerase chain reaction followed by restriction fragment length polymorphism. RESULT: The genotype frequencies of C1772T observed in Chinese Hans were 93 % and 7% for CC and CT respectively; and allele frequencies were 96% and 4 %for C and T respectively. There was significant difference in distribution of allele frequencies between Chinese Hans and Caucasian. CONCLUSION: The single nucleotide polymorphism of C1772T in HIF-1 alpha gene has difference in different ethnic population.