Resveratrol promotes apoptosis and G2/M cell cycle arrest of fibroblast-like synoviocytes in rheumatoid arthritis through regulation of autophagy and the serine-threonine kinase-p53 axis.

Introduction: Resveratrol, a polyphenol extracted from many plant species, has emerged as a promising pro-apoptotic agent in various cancer cells. However, the role of resveratrol in cell proliferation and apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis (RA-FLS) is not fully understood. The study was aimed at elucidating the role of resveratrol in cell proliferation and apoptosis of RA-FLS and the underlying molecular mechanism. Material and methods: Cultured RA-FLSs were subjected to tumour necrosis factor α (TNF-α). The cell proliferation was measured by Cell Counting Kit-8 assay. Cell apoptosis and cell cycle of RA-FLSs were determined by flow cytometry. The levels of apoptosis or autophagy or cell cycle-related protein were detected by immunoblot analysis. Results: In our study, we confirmed that resveratrol reversed TNF-α mediated cell proliferation in RA-FLS. Meanwhile, resveratrol blocked cells at the G2/M stage and reduced the ratio of S phase cells through upregulation of p53 and consequently led to apoptotic cell death. Quite interestingly, we found that resveratrol reversed TNF-α-induced autophagy. Inhibition of autophagy by resveratrol or autophagy inhibitor or Beclin-1 siRNA suppressed TNF-α mediated cell survival and promoted cell apoptosis. However, the autophagy inducer rapamycin (RAPA) reversed the effect of resveratrol on autophagy and cell proliferation. Mechanistic studies revealed that resveratrol inhibited the activation of the phosphoinositide 3-kinases/serine-threonine kinase (PI3K/AKT) pathway. Inhibition of PI3K/AKT pathway by inhibitor LY294002 or resveratrol increased the expression of p53 and decreased the expression of cycle protein (cyclin B1), which further led to block cells in the G2/M arrest. Conclusions: Our preliminary study indicated that resveratrol may suppress RA-FLS cell survival and promote apoptosis at least partly through regulation of autophagy and the AKT-p53 axis.

Esomeprazole Alleviates Cisplatin Resistance by Inhibiting the AKT/mTOR Pathway in Ovarian Cancer Cells.

Purpose: Ovarian cancer is the most lethal malignancy in gynecology. Due to limited treatment strategies and platinum resistance, newer drugs and therapeutic options are needed. Esomeprazole (ESO) has been reported to have multiple anticancer activities in preclinical and clinical research. Therefore, this study aimed to explore the anticancer effects of esomeprazole on ovarian cancer and its underlying molecular mechanisms. Methods: CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell viability and proliferation. The Transwell assay was used to evaluate cell migration and invasion capacity. Flow cytometry was used to detect cell apoptosis. Western blotting and immunofluorescence were used to detect protein expression. Results: ESO effectively inhibited the cell viability, proliferation, invasion, migration, and induced apoptosis of ovarian cancer cells in a concentration-dependent manner. Treatment with ESO decreased the expression of c-MYC, SKP2, E2F1, N-cadherin, vimentin, and matrix metalloproteinase 2 (MMP2), while it increased E-cadherin, caspase3, p53, BAX, and cleaved poly (ADP-ribose) polymerase (PARP) expression, and downregulated the PI3K/AKT/mTOR signaling pathway. Furthermore, ESO combined with cisplatin showed synergistic effects in inhibiting proliferation, invasion, and migration of cisplatin-resistant ovarian cancer cells. The mechanism may be related to the increased inhibition of c-MYC, epithelial-mesenchymal transition (EMT), and the AKT/mTOR signaling pathway and enhanced the upregulation of the pro-apoptotic protein BAX and cleaved PARP levels. Moreover, ESO combined with cisplatin synergistically upregulated the expression of the DNA damage marker γH2A.X. Conclusion: ESO exerts multiple anticancer activities and has a synergistic effect in combination with cisplatin on cisplatin-resistant ovarian cancer cells. This study provides a promising strategy to improve chemosensitivity and overcome resistance to cisplatin in ovarian cancer.

Exploring the interrelationship among health status, CO2 emissions, and energy use in the top 20 highest emitting economies: based on the CS-DL and CS-ARDL approaches.

Carbon dioxide emissions (CO2e) which is caused by energy use contributes to the global average surface temperature increase by 1.5 °C as compared to the mid-1800s which is causing a certain change in the climate and becoming an adverse effect on health and economy. The relationship between health status, CO2e, and energy use has yet to be thoroughly investigated in the top 20 highest emitting economies. The data from 2000 to 2019 is analyzed by using advanced techniques of cross-sectional augmented distributed lag (CS-DL) and cross-sectional augmented autoregressive distributed lag (CS-ARDL) which take into consideration crucial elements of panel data, namely dynamics, heterogeneity, and cross-sectional dependence. Moreover, cross-sectional augmented error correction method (CS-ECM) and the common dynamic process of the augmented mean group (AMG) are applied for robustness checks. The empirical findings revealed that (i) CO2e weakens the health status only in the short-run, whereas health expenditure improves the health status in the both short- and long-runs, while economic growth is not contributing to the health status in the both short- and long-runs; (ii) health expenditure and economic growth only help to mitigate CO2e in the long-run, whereas energy use causes CO2e in the both short- and long-runs; (iii) energy use causes high economic growth in the both short- and long-runs, whereas CO2e aids economic growth in the short-run but is extremely damaging to economic growth in the long-run, while in the both short- and long-runs health expenditure is not aiding the economic growth. This study provides policy recommendations on improving human health by advocating massive health expenditures, CO2e easing, promoting renewable energy use or low-emission energy, and steering the economy toward green economic growth.

Coupled electrochemiluminescent and resonance energy transfer determination of microRNA-141 using functionalized Mxene composite.

The electrochemiluminescence and resonance energy transfer (ECL-RET) method was adopted to detect miRNAs, in which the two-dimensional Ti3C2 Mxenes with high surface area modified with CdS:W nanocrystals (CdS:W NCs) were used as ECL signal emitter. Mxenes with a specific surface area of 5.2755 m2/g carried more emitters and promote ECL intensity. As an energy acceptor, BiOCl nanosheets (BiOCl NSs) have a wide UV-Vis absorption peak in the range 250 nm-700 nm, including the emission band of CdS:W NCs with 520 nm emission wavelength. Hence, BiOCl NSs are covalently bound to hairpin DNA 2 by amide bond to quench the ECL signal of CdS:W NCs. In the presence of miRNA-141, the hairpin DNA 1 modified on the GCE was unfold and then paired with hairpin DNA 2 to release miRNA-141 and quench the signal of the ECL biosensor. Then, the concentration signal of miRNA-141 was amplified by catalytic hairpin assembly. The novel specific biosensor demonstrated a satisfactory linear relationship with miRNA-141 in the range 0.6 pM to 4000 pM; the detection limit was as low as 0.26 pM (3 s/m) under the potential of 0 ~ -1.3 V and showed outstanding RSD of 1.19%. The findings of the present work with high accuracy and sensitivity will be of positive significance for the clinical diagnosis of miRNA in the future work. The construction process of the biosensor and electrochemiluminescence mechanism.

Influencing Factors of International Students' Anxiety Under Online Learning During the COVID-19 Pandemic: A Cross-Sectional Study of 1,090 Chinese International Students.

Objective: We conducted the following cross-sectional study to comprehensively assess the anxiety among Chinese international students who studied online during the COVID-19 pandemic and its influencing factors. Methods: Questionnaires were distributed through "Sojump," and a total of 1,090 valid questionnaires were collected. The questionnaire was divided into two parts: general situation and anxiety assessment of students. The former used a self-made questionnaire, and the international general GAD-7 scale was used to measure anxiety. Chi-square test was used to analyze the differences between groups, and logistic regression analysis was performed for the factors with differences. Results: Anxiety was found in 707 (64.9%) of 1,090 international students. Chi-square test and multivariate Logistic regression analysis showed that the incidence of anxiety was higher in the group under 22 years of age than in the group over 22 years of age (68% vs. 61%, p = 0.015; OR = 1.186, 95% CI 1.045-1.347, p = 0.008); International students living in big cities had a higher incidence of anxiety than those living in rural areas (67% vs. 60%, p = 0.022; OR = 1.419, 95%CI 1.038-1.859, p = 0.011); international students who socialized 3 times or less monthly had a higher incidence of anxiety than those who socialized more than 3 times per month (68% vs. 58%, p = 0.003; OR = 1.52, 95%CI 1.160-1.992, p = 0.002); international students who expected purely online teaching had a higher incidence of anxiety than those who expected purely offline teaching or dual-track teaching (72% vs. 64%, p = 0.037; OR = 1.525, 95%CI 1.069-2.177, p = 0.02); international students with a subjective score of online learning experience of 6 or less had a higher incidence of anxiety than those with subjective scores of more than 6 (70% vs. 60%, p = 0.001, OR = 1.25, 95%CI 1.099-1.422, p = 0.001). However, gender, emotional status, BMI, major of study, vaccination status, and degree type had no significant difference in the incidence of anxiety among international students who studied online during the COVID-19 pandemic. Conclusion: During COVID-19, international students who were younger, came from big cities, had low social frequency, expected purely online teaching, and had poor experience of online classes were risk factors for anxiety during online classes.

The nonlinearity and nonlinear convergence of CO2 emissions: Evidence from top 20 highest emitting countries.

Carbon dioxide (CO2) is the most prevalent greenhouse gas that triggers climate change, which in turn leads to catastrophic effects on trade, business, human health, and other areas. Understanding the characteristics and tendency of CO2 emissions will improve policy making and mitigation strategies. Understanding the linearity or nonlinearity and convergence or divergence of CO2 emissions is essential for selecting appropriate modeling techniques and for designing reliable policies. Therefore, this paper investigates the nonlinearity and nonlinear convergence of CO2 emissions among the world's top 20 highest emitting countries, which account for 80% of the world's total emissions. To check the nonlinearity of CO2 emissions, the McLeod-Li nonlinearity test, the Terasvirta nonlinearity test, and the Brock-Dechert-Scheinkman-LeBaron nonlinearity test are employed. The convergence or divergence of CO2 emissions is checked by using the Kilic nonlinear unit root test, the Hu and Chen nonlinear unit root test, and the Park and Shintani nonlinear unit root test. The findings revealed that the CO2 emissions process in all the 20 countries is nonlinear; 17 countries exhibit convergence in CO2 emissions while the other 3 countries diverged from 1960 to 2018. Based on the results, the nonlinear nature of CO2 emissions requires special attention from scholars when selecting estimation techniques for CO2 emissions. For countries with convergence, emissions trends can be used to forecast future values of CO2 emissions. Moreover, strong policy actions are required to achieve convergence in the countries with divergence.

Developing a Health-Spatial Indicator System for a Healthy City in Small and Midsized Cities.

A recent examination of the significant role of public health has prompted calls to re-investigate how the urban environment affects public health. A vital part of the solution includes Healthy City initiatives that have been the subject of extensive policies, implications, and practices globally. However, the existing literature mainly focuses on big cities and metropolitan areas, while investigations into small and midsized cities (SMCs) are lacking, and thus reflect the underlying issues of health inequity. This study develops an indicator system for evaluating Healthy City initiatives in SMCs, linking urban design and public health, supported by the analyzed opinions from experts collected using both questionnaires and interviews. The indicator system includes six primary dimensions and 37 variables: urban form and transportation (UFT); health-friendly service (HFS); environmental quality and governance (EQG); community and facility (CF); green and open space (GOS); and ecological construction and biodiversity (ECB). A fuzzy synthetic evaluation technique was used to assess the relative importance of factors, emphasizing the importance of UFT, HFS, and EQG, with importance indexes of 0.175, 0.174, and 0.174, respectively. This indicator system is helpful for SMCs seeking to construct a Healthy City in the future, and is based on urban design and governance inputs and for enhancing the Healthy City knowledge base of cities of varied scales.

PI3K inhibitor 3-MA promotes the antiproliferative activity of esomeprazole in gastric cancer cells by downregulating EGFR via the PI3K/FOXO3a pathway.

Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Esomeprazole (ESO) has been shown to have anticancer activity by affecting cell growth and autophagy and its mechanism in gastric cancer cells is evident. The PI3K/AKT/FOXO3a pathway is central in cancers. 3-Methyladenine (3-MA), a dual inhibitor of PI3K and autophagy, plays a synergistic role in combination with antitumor agents. In this study, we assessed the role of ESO on the PI3K/AKT/FOXO3a pathway and the beneficial effects of ESO combined with 3-MA in gastric cancer cells. Cell viability, proliferation, invasion, migration, apoptosis, autophagy, and protein expression were detected by CCK-8, EdU, Transwell, flow cytometry, immunofluorescence assay, and western blot. ESO decreased cell viability in a concentration- and time-dependent manner and increased autophagy with upregulation of LC3II and P62. Additionally, ESO inhibited the proliferation, migration, and invasion and induced the apoptosis of gastric cancer cells in a concentration-dependent manner. ESO inhibited PI3K/AKT/FOXO3a signaling and EGFR and SKP2 expression concentration-dependent. 3-MA enhanced the antiproliferative activity of ESO and synergistically inhibited PI3K/FOXO3a signaling and the expression of EGFR but not SKP2. Furthermore, pretreatment with the EGFR inhibitor AG1478 enhanced the antiproliferative activity of ESO in gastric cancer cells. In conclusion, our results suggested that the PI3K inhibitor 3-MA promotes the antiproliferative activity of ESO in gastric cancer cells by synergistically downregulating EGFR via the PI3K/FOXO3a pathway.

iTRAQ and PRM-Based Proteomic Analysis Provides New Insights into Mechanisms of Response to Triple Therapy in Patients with Rheumatoid Arthritis.

BACKGROUND: Approximately 30% of patients with rheumatoid arthritis (RA) respond poorly to combination therapy of multiple drugs. The molecular mechanisms of different responses to methotrexate + leflunomide + infliximab therapy in patients with RA were explored in this study. METHODS: Infliximab was administered to patients with RA whose disease activity score was higher than 5.1 after 1 month of combination therapy with methotrexate and leflunomide. After 14 weeks of undergoing triple therapy, patients with RA were classified as responders and non-responders. Protein profiles at baseline and 14th week were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and proteins with significant differences ≥1.2 folds change or ≤0.8 folds change were defined as differentially expressed proteins (DEPs). Overlapping DEPs between responders and non-responders were confirmed by parallel reaction monitoring (PRM). Bioinformatic analyses were performed for DEPs. RESULTS: The results revealed 5 non-responders (NRs) and 15 responders (Rs). iTRAQ analysis indicated 13 overlapping DEPs and included 6 opposite change DEPs such as testicular tissue protein Li 70, cofilin 1, fibrinogen beta chain, galectin-10, serotransferrin (TF) and albumin. The difference in serotransferrin between responders and non-responders confirmed by PRM was significant. Verification by PRM indicated that TF was elevated in the Rs group and was reduced in the NRs group. Bioinformatic analysis indicated that serotransferrin was involved in the hypoxia-inducible factor-1 pathway and ferroptosis. CONCLUSION: Serotransferrin-related molecular mechanism may be a new direction to study refractory RA.

The Value of Effective Lung Ventilation Area Ratio Based on CT Image Analysis Is a New Index to Predict the Shorter Outcome of Anti-melanoma Differentiation-Associated Protein 5 Positive Dermatomyositis Associated Interstitial Lung Disease: A Single-Center Retrospective Study.

Background: Anti-melanoma differentiation-associated protein 5 (MDA5) positive dermatomyositis (MDA5+DM) patients have poor outcomes due to rapidly progressive interstitial lung disease (ILD). The accurate assessment of lung involvement is an urgent focus of research. Methods: A computer-aided lung interstitial image analysis technology has been developed, and a quantitative indicator named effective lung ventilation area ratio (ELVAR) that calculates the proportion of the area outside the lung interstitium in lung tissue has been established. 55 newly diagnosed MDA5+DM patients and 46 healthy individuals, matched for age and gender, were enrolled in this study. MDA5+DM patients were classified into early death group or early survival group according to their survival state within 3 months after diagnosis. Clinical characteristics, laboratory and immunological test results, lung involvement (including ELVAR value) and treatment were compared between early death group and early survival group to determine an index that can predict prognoses of patients with MDA5+DM. Results: There were significant differences between early death MDA5+DM patients and early survival MDA5+DM patients about 12 indices including age of onset, CRP, ferritin, albumin, and pulmonary involvement including severity of type I respiratory failure at diagnosis, P/F ratio, oxygen supplementation, values of ELVAR, FVC, and DLCO. The results of ROC analysis and correlation analysis showed the value of ELVAR had good diagnostic value and widely correlation with many clinical characteristics. Univariate analysis and Multivariate analysis showed four factors including age of onset, ferritin, value of ELVAR, and oxygen supplementation >4 L/min significantly value for poor prognosis in MDA5+DM patients. A cutoff value of 0.835 about ELVAR had good predictive power for mortality within 3 months in 54.2% of MDA5+DM patients. Conclusion: The value of ELVAR derived from computed tomography image analysis is a new index that can predict poor outcomes in MDA5+DM patients with rapidly progressive interstitial lung disease.

Photonic generation of quadruple bandwidth dual-band dual-chirp microwave waveforms with immunity to power fading.

A photonic method to generate and transmit quadruple bandwidth dual-band dual-chirp microwave waveforms with immunity to fiber chromatic dispersion induced power fading is proposed and experimentally demonstrated, which is suitable for Doppler blind-speed elimination, small target detection, and multiband detection in multiband radar systems. A dual-polarization dual-parallel Mach-Zehnder modulator is utilized to realize carrier-suppressed harmonic single-sideband modulation of a radio frequency carrier and carrier-suppressed DSB modulation of a baseband single-chirped waveform at two orthogonal polarization states. After photoelectronic conversion, dual-band bandwidth-quadrupling dual-chirp waveforms are generated. Moreover, different from traditional DSB-based dual-chirp signal generation, the generated dual-chirp microwave waveforms can be transmitted over fiber without power fading, which is significant in dual-band radars for one to multiple base station transmissions.

Proteomic analysis of biomarkers predicting the response to triple therapy in patients with rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) usually receive triple therapy with methotrexate (MTX), leflunomide (LEF) and infliximab (IFX), but nearly one-third of them do not respond to triple therapy. This study aimed to identify biomarkers for predicting the efficacy of triple therapy to optimize personalized treatment of RA. METHODS: All 20 enrolled patients met 2010 ACR/EULAR criteria for RA and were classified into good, moderate and non-responders (GR, MR, NR) for triple therapy. The Responders (R) were defined as the sum of GR and MR. Protein profiles of 4 responders and 4 non-responders were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and differentially expressed proteins (DEPs) with high-confidence peptides were validated in 15 responders and 5 non-responders by parallel response monitoring (PRM). RESULTS: iTRAQ identified 51 DEPs between responders and non-responders (p < 0.05, fold change >±1.2). The top five up-regulated DEPs were B7Z7M2, A0A087WZR4, Q53FL1, P08254 and G3V2V8, while the top five down-regulated proteins were Q6MZX9, B3KP77, P0DJI9, P0DJI8 and P02787. Targeted mass spectrometry by PRM identified 10 candidate biomarkers, and 3 DEPs including fibrinogen beta chain, epididymal secretory protein Li 282 and testicular tissue protein Li 70 were confirmed as predictive biomarkers. CONCLUSION: This study demonstrated the feasibility of exploring biomarkers by applying iTRAQ and PRM mass spectrometry techniques, and a panel of biomarkers were identified to predict clinical response of IFX + MTX + LEF treatment in active RA patients.

[Association of short-term efficacy for infliximab in rheumatoid arthritis with plasma concentration and anti-drug antibody].

OBJECTIVE: To investigate the correlation between peripheral concentration of infliximab (IFX) or anti-IFX antibody titers and short-term therapeutic effect of IFX in patients with active rheumatoid arthritis (RA).
 Methods: Twenty patients with active RA were treated with combination of methotrexate (MTX), leflunomide (LEF) with IFX, and the clinical and laboratory index and the side effects were recorded before and after IFX treatment. Twenty healthy subjects were chosen as a control group.
 Results: After 14-week treatment, patients were categorized into good, moderate or no responders according to EULAR remission criteria. There were no significant differences in peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels among the 3 groups, and there were no significant correlations among ΔDAS28-CRP, peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels.
 Conclusion: Peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels can not be used as reliable predictive index for short-term effect of IFX in active RA.

Associations between the SLC22A12 gene and gout susceptibility: a meta-analysis.

OBJECTIVES: The aim of this study is to explore whether the polymorphisms of rs475688 and rs3825016 in the solute carrier family 22 member 12 (SLC22A12) gene are associated with the susceptibility to gout or hyperuricaemia. METHODS: Relevant studies were enrolled by searching databases systematically. The pooled odds ratios (ORs) with 95% confidence interval (CI) were used to evaluate the associations. Q-test and I2 statistics were used to evaluate the heterogeneity. Publication bias was evaluated using Begg's funnel plots and Egger regression test. RESULTS: A total of 7 articles involving 1216 patients and 1844 healthy controls were included in this meta-analysis. Significant association was detected between rs475688 polymorphism and gout susceptibility in three genetic models (C vs. T: OR=1.464, 95% CI 1.078-1.989, p=0.015; CC+CT vs. TT: OR=2.028, 95% CI 1.488-2.763, p=0.000; CC vs. CT+TT: OR=2.226, 95% CI 1.746-2.838, p=0.000). Significant association was observed between rs3825016 polymorphism and hyperuricaemia susceptibility only in allelic comparison (C vs. T: OR=1.274, 95% CI 1.101-1.474, p=0.001). CONCLUSIONS: The rs475688 polymorphism is associated with gout susceptibility. The correlation between rs3825016 polymorphism of SLC22A12 and hyperuricaemia susceptibility is possible.

Application of omics in predicting anti-TNF efficacy in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by progressive joint erosion. Tumor necrosis factor (TNF) antagonists are the most widely used biological disease-modifying anti-rheumatic drug in RA. However, there continue to be one third of RA patients who have poor or no response to TNF antagonists. Following consideration of the uncertainty of therapeutic effects and the high price of TNF antagonists, it is worthy to predict the treatment responses before anti-TNF therapy. According to the comparisons between the responders and non-responders to TNF antagonists by omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, rheumatologists are eager to find significant biomarkers to predict the effect of TNF antagonists in order to optimize the personalized treatment in RA.

PAX3 Promotes Cell Migration and CXCR4 Gene Expression in Neural Crest Cells.

Neural crest (NC) cells are a multipotent cell population with powerful migration ability during development. C-X-C chemokine receptor type 4 (CXCR4) is a chemokine receptor implicated to mediate NC migration in various species, whereas the underlying mechanism is not well documented yet. PAX3 is a critical transcription factor for the formation of neural crest and the migration and differentiation of NCs. In this study, we retrieved a potential PAX3 binding element in the promoter of the CXCR4 gene, and we further found that PAX3 could promote the expression of CXCR4 and facilitate the migration of NCs. We finally demonstrated that PAX3 could bind the promoter region of CXCR4 and increase CXCR4 transcription by luciferase assay and electrophoretic mobility shift assay (EMSA). These findings suggested that PAX3 is a pivotal modulator of NC migration via regulating CXCR4 expression.

[Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis].

OBJECTIVE: To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).
 Methods: Twelve patients with severe refractory RA were treated with tocilizumab. The clinical and laboratory indices and the side effects were recorded after treatment.
 Results: The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients, which were significantly improved after TCZ therapy (P<0.05), and no obvious adverse reactions were found.
 Conclusion: Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.

Development of high sensitivity 4H-SiC detectors for fission neutron pulse shape measurements.

4H-silicon carbide (4H-SiC) detectors are well suited for measurements of fission neutron pulse shape for their compact size, excellent radiation resistance, and hydrogen free composition. The aim of this study is to improve the 4H-SiC detector's sensitivity to fission neutron pulses. 4H-SiC detectors with varied epilayer thicknesses are fabricated and then tested in the pulsed neutron field of the Chinese Fast Burst Reactor II (CFBR II). The sensitivity of the 4H-SiC detector to the CFBR II neutron pulse is increased by 139.8%, with the enlargement of epilayer thickness from 20 µm to 120 µm. By employing the proton-recoil method, the sensitivity of the 4H-SiC detector to the CFBR II neutron pulse is further increased by 11.6%. With enhanced sensitivity to fission neutron pulses, 4H-SiC detectors are promising devices for high intensity neutron pulse measurements.

PAX3 inhibits ß-Tubulin-III expression and neuronal differentiation of neural stem cell.

PAX3 functions at the nodal point in neural stem cell maintenance and differentiation. Using bioinformatics methods, we identified PAX3 as a potential regulator of ß-Tubulin-III (TUBB3) gene transcription, and the results indicated that PAX3 might be involved in neural stem cell (NSC) differentiation by orchestrating the expression of cytoskeletal proteins. In the present study, we reported that PAX3 could inhibit the differentiation of NSCs and the expression of TUBB3. Further, using luciferase and electrophoretic mobility shift assays, we demonstrated that PAX3 could bind to the promoter region of TUBB3 and inhibit TUBB3 transcription. Finally, we confirmed that PAX3 could bind to the promoter region of endogenous TUBB3 in the native chromatin of NSCs. These findings indicated that PAX3 is a pivotal factor targeting various molecules during differentiation of NSCs in vitro.

[Risk factors for patent ductus arteriosus in early preterm infants: a case-control study].

OBJECTIVE: To investigate the risk factors for the occurrence of patent ductus arteriosus (PDA) and to provide a clinical basis for reducing the occurrence of PDA in early preterm infants. METHODS: A total of 136 early preterm infants (gestational age≤32 weeks) who were hospitalized between January 2013 and December 2014 and diagnosed with hemodynamicalhy significant PDA (hs-PDA) were enrolled as the case group. Based on the matched case-control principle, 136 early preterm infants without hs-PDA were selected among those who were hospitalized within the same period at a ratio of 1:1 and enrolled as the control group. The two groups were matched for sex and gestational age. The basic information of neonates and maternal conditions during the pregnancy and perinatal periods were collected. Logistic regression analysis was performed to identify the risk factors for the development of PDA. RESULTS: Univariate analysis showed that neonatal infectious diseases, neonatal respiratory distress syndrome, decreased platelet count within 24 hours after birth, and low birth weight were associated with the development of hs-PDA (P<0.05). Multivariate conditional logistic regression analysis revealed that neonatal infectious diseases (OR=2.368) and decreased platelet count within 24 hours after birth (OR=0.996) were independent risk factors for hs-PDA. CONCLUSIONS: Neonatal infectious diseases and decreased platelet count within 24 hours after birth increase the risk of hs-PDA in early preterm infants.