Genetic screening of common genetic deafness in 60,391 women of childbearing age and intervention of birth defects.

Introduction: At least 60% of cases of severe hearing loss result from genetic factors. In this study genetic screening was carried out for common genetic deafness in women of childbearing age to prevent deafness and birth defects via providing genetic counseling and follow-up services for high-risk families. Material and methods: In total 60,391 pre-pregnancy/early-gestation women who received treatment in second-level or above hospitals in Weihai from February 2017 to December 2019 were selected. Venous or peripheral blood was collected to make dried blood slices on filter paper to extract genomic DNA, and high-throughput sequencing was applied to detect 20 variant sites in 4 common deafness genes (GJB2, GJB3, SLC26A4 and mitochondrial 12S rRNA) in the Chinese population. The spouses of women with deafness gene variants were sequenced. Results: In total 3,761 carriers with deafness gene variants were detected in 60,391 women of childbearing age, with a carrier rate of 6.2%. Among them, 1,739 women (2.88%) only carried GJB2 pathogenic variants. The carrying rate of c.235delC in GJB2 pathogenic variants was the highest at 2.08%. 1,553 women (2.58%) only carried SLC26A4 pathogenic variants. The carrying rate of c.919-2A>G in SLC26A4 pathogenic variants was the highest at 1.63%. 300 women (0.5%) only carried GJB3 variants, and 125 women (0.2%) carried the mitochondrial drug-sensitive gene variant. Conclusions: This screening model will greatly reduce the birth rate of children with hearing disabilities and is an effective way to prevent newborn deafness. In addition, genetic screening provided the related knowledge of hereditary deafness, especially strengthening genetic counseling and the clinical decision making from the genetic screening.

Characterization and fine mapping of a maize lesion mimic mutant (Les8) with enhanced resistance to Curvularia leaf spot and southern leaf blight.

KEY MESSAGE: A novel light-dependent dominant lesion mimic mutant with enhanced multiple disease resistance was physiologically, biochemically, and genetically characterized; the causal gene was fine mapped to a 909 kb interval containing 38 genes. Identification of genes that confer multiple disease resistance (MDR) is crucial for the improvement of maize disease resistance. However, very limited genes are identified as MDR genes in maize. In this study, we characterized a dominant disease lesion mimics 8 (Les8) mutant that had chlorotic lesions on the leaves and showed enhanced resistance to both curvularia leaf spot and southern leaf blight. Major agronomic traits were not obviously altered, while decreased chlorophyll content was observed in the mutant, and the genetic effect of the Les8 mutation was stable in different genetic backgrounds. By BSR-seq analysis and map-based cloning, the LES8 gene was mapped into a 909 kb region containing 38 candidate genes on chromosome 9 wherein no lesion mimic or disease-resistance genes were previously reported. Using transcriptomics analysis, we found that genes involved in defense responses and secondary metabolite biosynthesis were enriched in the significantly up-regulated genes, while genes involved in photosynthesis and carbohydrate-related pathways were enriched in the significantly down-regulated genes in Les8. In addition, there was an overaccumulation of jasmonic acid and lignin but not salicylic acid in Les8. Taken together, this study revealed candidate genes and potential mechanism underlying Les8-conferred MDR in maize.

Discovery of novel 1,3,5-triazines as potent antibacterial agent against urinary tract infection-causing clinical isolates of Escherichia coli via inhibition of DNA Gyrase.

A novel series of 1,3,5-triazine-phenylthiazole-pyrazole derivatives were synthesized and subsequently tested for Escherichia coli DNA Gyrase inhibitory activity where they showed excellent inhibitory activity. The top-three ranked DNA gyrase inhibitor (4e, 4g and 4h) were further subjected to antibacterial and anti-biofilm activity against clinical isolates of resistant E. coli strains obtained from Urinary Tract Infection (UTI) patients (CREC81, CREC106, CREC163). Compound 4h was identified as most potent antibacterial agent in the above study. The compound 4h was further evaluated in murine model of E. coli UTI in BALB/c mice infected by transurethral injection of CREC106 strain. Results of the study suggest that compound 4h reduces bacterial load of CREC106 in the treated mice and found approximately equipotent to Novobiocin as standard.

Low serum albumin levels and high neutrophil counts are predictive of a poorer prognosis in patients with metastatic breast cancer.

Breast cancer is a severe disease with high incidence and mortality rates in menopausal women. Previous studies have shown that nutritional status and inflammation play a significant role in the development of breast cancer. However, whether serum albumin (ALB) and neutrophils (NE) accelerate the progression of this disease remains unclear. In the present study, a total of 94 cases of newly diagnosed metastatic breast cancer were assessed. For analysis, 26 risk factors including ALB and NE were assessed. Multivariate Cox proportional hazards regression analysis was then used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for continuous and categorical covariates. Compared with the control group, patients with disease progression, low levels of ALB, higher NE, counts, and higher neutrophil to lymphocyte ratio counts were associated with worse overall survival (OS). When these risk factors were fitted into a multivariate regression model, progression [P<0.001, HR=3.03 (1.62-5.66)], NE counts ≥3.370×109 [P=0.004, HR=2.15 (1.27-3.65)] and ALB levels <43.275 g/l [P=0.008, HR=0.47 (0.27-0.82)] remained statistically significant factors for a worse OS. These independently associated risk factors were used to form an OS estimation nomogram. The constructed nomogram demonstrated good accuracy in estimating risk, with a bootstrap-corrected C index of 0.686. We further collected data on 30 patients for external validation and found the nomogram had an accuracy of 83.3%. In conclusion, low serum ALB levels and increased NE counts were predictive of a poorer prognosis in patients with metastatic breast cancer. Nomograms based on the multivariate analysis showed a good predictive ability for estimating the risk of OS.

Thermodynamic and Kinetic Binding Behaviors of Human Serum Albumin to Silver Nanoparticles.

A nanoparticle, under biological milieu, is inclined to be combined with various biomolecules, particularly protein, generating an interfacial corona which provides a new biological identity. Herein, the binding interaction between silver nanoparticles (AgNPs) and human serum albumin (HSA) was studied with transmission electron microscopy (TEM), circular dichroism (CD), and multiple spectroscopic techniques. Due to the ground state complex formed mainly through hydrophobic interactions, the fluorescence titration method proved that intrinsic fluorescence for HSA was probably statically quenched by AgNPs. The complete thermodynamic parameters were derived, indicating that the interaction between HSA and AgNPs is an entropy-driven process. Additionally, synchronous fluorescence and CD spectrum results suggested the conformational variation it has upon binding to AgNPs and the α-helix content has HSA visibly decreased. The kinetic experiments proved the double hysteresis effect has in HSA's binding to the AgNPs surface. Moreover, the binding has between HSA and AgNPs follows the pseudo-second-order kinetic characteristic and fits the Freundlich model for multilayer adsorption. These results facilitate the comprehension about NPs' underlying biological effects under a physiological environment and promote the secure applications of NPs biologically and medically.

BTG2 as a tumor target for the treatment of luminal A breast cancer.

As one of the most common breast cancer subtypes, luminal A breast cancer is sensitive to endocrine-based therapy and insensitive to chemotherapy. Patients with luminal A subtype of breast cancer have a relatively good prognosis compared with that of patients with other subtypes of breast cancer. However, with the increased incidence in endocrine resistance and severe side effects, simple endocrine therapy has become unsuitable for the treatment of luminal A breast cancer. Therefore, identifying novel therapeutic targets for luminal A breast cancer may accelerate the development of an effective therapeutic strategy. The bioinformatical analysis of the current study, which included KEGG and GO analyses of the GSE20437 dataset containing 24 healthy and 18 breast cancer tissue samples, identified key target genes associated with breast cancer. Moreover, survival analysis results revealed that a low expression of BTG2 was significantly associated with the low survival rate of patients with breast cancer, indicated that B-cell translocation gene 2 (BTG2) may be a potential target in breast cancer. However, BTG2 may be cancer type-dependent, as overexpression of BTG2 has been demonstrated to suppress the proliferation of pancreatic and lung cancer cells, but promote the proliferation of bladder cancer cells. Since the association between BTG2 and luminal A-subtype breast cancer remains unclear, it is important to understand the biological function of BTG2 in luminal A breast cancer. Based on the expression levels of estrogen receptor, progesterone receptor and human epidermal growth factor receptor, MCF-7 cells were selected in the present study as a luminal A breast cancer cell type. MTT, Transwell invasion and wound healing assays revealed that overexpression of BTG2 suppressed the levels of MCF-7 cell proliferation, migration and invasion. In addition, the downregulation of BTG2 at the mRNA and protein level was also confirmed in luminal A breast tumor tissue, which was consistent with the results in vitro. These results indicated that BTG2 may act as an effective target for the treatment of luminal A breast cancer.

Long non-coding RNA small nucleolar RNA host gene 7 expression level in prostate cancer tissues predicts the prognosis of patients with prostate cancer.

Long non-coding small nucleolar RNA host gene 7 (lncRNA SNHG7) is located on chromosome 9q34.3 in length of 984 bp. SNHG7 has been found to play the role of oncogene in varieties of cancers, and its dysregulation has been found to be associated with carcinogenesis and progression. In the present study, we examined the expression of SNHG7 in prostate cancer tissues and in paired adjacent normal prostate tissues, and we further explored the clinical significance and prognostic value of SNHG7 in prostate cancer patients.A total of 127 prostate cancer tissues were collected from prostate cancer patients who underwent radical prostatectomy between April 2011 and March 2019 at the department of urology, Pudong New Area People's Hospital. Real-time quantitative polymerase chain reaction experiment was performed to detect the relative expressions of SNHG7 in the prostate cancer tissues and normal prostate tissues. The Kaplan-Meier method was used to create survival curves and the log-rank test was used to determine statistical significance. A Cox proportional hazard analysis was used to evaluate the prognostic factors in univariate and multivariate analyses.Compared with paired adjacent normal prostatic tissues, SNHG7 expression was increased in prostate cancer tissues (P < .001). Increased SNHG7 expression correlated with Gleason score (P = .021), bone metastasis (P = .013), pelvic lymph node metastasis (P = .008), and TNM stage (P = .007). Multivariate Cox regression analyses revealed increased SNHG7 expression was independently associated with a poor prognosis of prostate cancer patients (hazard ratio [HR] = 2.839, 95% confidence interval [CI] = 1.921-8.382, P = .038).This study showed that lncRNA-SNHG7 was overexpressed in prostate cancer tissues, and it might contributes to the development and progression of prostate cancer. Furthermore, the SNHG7 expression was associated with the prognosis of prostate cancer, suggesting a potential target for the treatment and prognosis of prostate cancer. Nevertheless, the underlying modulatory mechanism by which SNHG7 aggravates prostate cancer progression need to be further studied.

[Analysis of GJB2, SLC26A4, GJB3 and 12S rRNA gene mutations among patients with nonsyndromic hearing loss from eastern Shandong].

OBJECTIVE: To explore the characteristics of mutations of four common pathogenic genes (GJB2, SLC26A4, GJB3 and 12S rRNA) among patients with nonsyndromic hearing loss (NSHL) from eastern Shandong. METHODS: Peripheral blood samples of 420 NSHL patients were collected, and a hereditary-deafness-gene microarray was used to detect GJB2 c.235delC, c.299-300delAT, c.35delG and c.176del16 mutations, GJB3 c.538C>T mutation, SLC26A4 c.2168A>G and c.IVS7-2A>G mutations, and 12S rRNA c.1555A>C and c.1494C>T mutations. For patients carrying single heterozygous mutations, the coding regions of the above genes were analyzed with Sanger sequencing. RESULTS: The results of the microarray assay and Sanger sequencing showed that 84 patients (20.00%) carried GJB2 mutations, with c.235delC (16.43%) and c.299-300delAT (7.86%) being most common. Seventy-five patients (17.86%) carried SLC26A4 mutations, for which c.IVS7-2A>G accounted for 15.71%. In addition, 5.95% of patients carried 12S rRNA mutations. Only one patient was found to carried GJB3 mutation (c.538C>T). CONCLUSION: Common pathogenic mutations for NSHL in eastern Shandong included GJB2 c.235delC and SLC26A4 c.IVS7-2A>G. Of note, 5.95% of patients were due to 12S rRNA m.1555A>G mutation, which gave a frequency greater than other regions of China.

2D nanoporous Ni(OH)2 film as an electrode material for high-performance energy storage devices.

A two-dimensional (2D) nanoporous Ni(OH)2 film was successfully developed from triethanolamine (TEA) as the alkali source and soft template using a scalable hydrothermal technique. The nanostructured Ni(OH)2 film was flexible and translucent, and could be directly compressed on a current collector. Owing to the uniform well-defined morphology and stable structure, the Ni(OH)2 film binder-free electrode displayed a high specific capacity, exceptional rate capability, and admirable cycle life. The specific capacitance was 453.6 mA h g-1 (1633 F g-1) at 0.5 A g-1. The assembled Ni(OH)2//activated carbon (AC) asymmetric supercapacitor (ASC) device had an energy density of 58.7 W h kg-1 at a power density of 400 W kg-1. These prominent electrochemical properties of Ni(OH)2 were attributed to the high electrical conductivity, high surface area, and unique porous architecture. Free tailoring, binder-free, and direct pressing were the most significant achievements of the Ni(OH)2 film in the development of high-performance energy storage devices.

Solvothermal synthesis of NiWO4 nanostructure and its application as a cathode material for asymmetric supercapacitors.

This study proposes a facile solvothermal synthesis of nickel tungstate (NiWO4) nanowires for application as a novel cathode material for supercapacitors. The structure, morphology, surface area and pore distribution were characterized and their capacitive performances were investigated. The results showed that the NiWO4 nanowires synthesized in ethylene glycol solvent could offer a high specific capacitance of 1190 F g-1 at a current density of 0.5 A g-1 and a capacitance retaining ratio of 61.5% within 0.5-10 A g-1. When used as a cathodic electrode of an asymmetric supercapacitor (ASC), the NiWO4 nanowire based device can be cycled reversibly in a high-voltage region of 0-1.7 V with a high specific capacitance of 160 F g-1 at 0.5 A g-1, which therefore contributed to an energy density of 64.2 W h kg-1 at a power density of 425 W kg-1. Moreover, 92.8% of its initial specific capacitance can be maintained after 5000 consecutive cycles (5 A g-1). These excellent capacitive properties make NiWO4 a credible electrode material for high-performance supercapacitors.

Interference of Notch 2 inhibits the progression of gliomas and induces cell apoptosis by induction of the cell cycle at the G0/G1 phase.

Glioblastoma is the most common type of malignant brain tumor with a poor prognosis. The Notch signaling pathway is often aberrantly activated in glioma cells. In order to determine the expression of Notch 2 and to evaluate its possible prognostic value in malignant glioblastoma, specimens from 32 patients and 20 controls were analyzed using immunohistochemical staining and reverse transcription quantitative polymerase chain reaction. The expression of Notch 2 in the glioma tissues was significantly higher compared with that in the normal brain tissues (P<0.01). Subsequently, endogenous Notch 2 interference was effectively performed by specific small hairpin (sh)RNA in the glioma cancer cell line U251. The results from an MTT assay and from Annexin V-fluorescein isothiocyanate/propidium iodide staining indicated that interference of Notch 2 significantly inhibited the proliferation and induced the apoptosis of U251 cells. In addition, the cell cycle was analyzed using flow cytometry and the results revealed that Notch 2 shRNA induced cell cycle arrest at the G0/G1 phase in U251 cells. Additionally, proteins associated with the cell cycle and cell proliferation were detected using western blot analysis. The data demonstrated that the expression of P21, cyclin D and phosphorylated retinoblastoma was significantly inhibited in the Notch 2 shRNA-transfected U251 cells. The results of the present study provide further insights into the effects of Notch 2 and a molecular reference for brain tumor therapy.

[Combined surgical and endovascular treatments of complex cerebral arteriovenous malformation in hybrid operating room].

OBJECTIVE: To summarize the clinical experiences of microsurgical and endovascular treatments of complicated arteriovenous malformation (AVM) in the conditions of hybrid operating room. METHODS: The clinical data were collected and analyzed for 8 patients of complex AVM between June 2012 to June 2013. There were Spetzler grade III (n = 2) and grade IV (n = 6). And the lesions were complicated with intracranial aneurysms (n = 3) and located in motor area (n = 2) and basal ganglia (n = 2). Five cases of AVM with cerebral hemorrhage underwent emergency surgery, including digital subtraction angiography (DSA) plus intraoperative embolization plus surgical resection of AVM plus intraoperative DSA (iDSA). Two cases underwent embolization plus aneurysm surgery while another had AVM embolization plus AVM resection and γ knife treatment. RESULTS: All surgical procedures, including iDSA, were completed in the same hybrid operating room. There was no change of surgical position or intraoperative mortality. Five patients of AVM hemorrhage undergoing emergency hematoma evacuation had no residue of AVM on iDSA. Their postoperative consciousness improved without neurological dysfunction. Two patients of limb paralysis recovered to paresis at 3 months postoperation. One case with blurry vision improved somewhat. Two cases undergoing elective surgery had a complete resection of AVM after embolization. CONCLUSION: Surgery plus endovascular treatment in hybrid operating room is efficacious for complex cerebral AVM. It avoids multiple surgeries and inspections. And any lesion residue may be assessed immediately with postoperative DSA.

Chemiluminescence detection of permanganate index (CODMn) by a luminol-KMnO4 based reaction.

A novel chemiluminescence (CL) system for determination of permanganate index (CODMn) combined with flow injection analysis has been proposed in this study. On the basis of the chemiluminescent reaction of luminol-KMnO4 system, light emission caused by luminol-KMnO4 system was detected by the photomultiplier tube, and its intensity caused by the appearance of KMnO4 after sample digestion was inversely proportional to CODMn. Effects for CODMn determining such as pH, concentrations and interference were investigated in detail. A detection limit of 0.3 mg/L CODMn with a linear range of 0.3--200 mg/L for its theoretical CODMn was obtained under the optimized experimental conditions. The relative standard deviation was 4.3% for 5.0 mg/L CODMn (n = 11). This CL flow system for determining CODMn was simple, rapid, and suitable for automatic analysis. The data obtained by the present method were fairly in good agreement with those obtained by the standard titrimetric method. It has been applied to determine real samples with satisfactory results.