Search

XiaoJin Sun,1,* Yang Deng,2,* PengXin Ge,3,* Qiang Peng,4 Ismatullah Soufiany,4 Lin Zhu,4 Rui Duan4 1Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu, Anhui, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 3Department of Pharmacy, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Zhu; Rui Duan, Email julinzz@163.com; duanruicpu@163.comPurpose: ACE2/Ang(1– 7)/Mas Receptor, the momentous component of the renin-angiotensin system, has been shown to be involved in Alzheimer’s disease (AD). We had previously found that enhancing brain ACE2 activity ameliorated cognitive impairment and attenuated brain neuroinflammation in SAMP8 mice, an animal model of AD. However, the exact mechanism of action of Diminazene (DIZE) has not been revealed.Methods: APP/PS1 mice were injected intraperitoneally with DIZE. Cognitive functions, neuronal and synaptic integrity, and inflammation-related markers were assessed by Morris water maze, Nissl staining, Western blotting and ELISA, respectively. Since astrocytes played a crucial role in AD-related neuroinflammation whilst miRNAs were reported to participate in modulating inflammatory responses, astrocytes of APP/PS1 mice were then isolated for high-throughput miRNAs sequencing to identify the most differentially expressed miRNA following DIZE treatment. Afterward, the downstream pathway of this miRNA in the anti-inflammatory action of DIZE was investigated using primary astrocytes.Results: The results showed that DIZE alleviated cognitive impairment and neuronal and synaptic damage in APP/PS1 mice. Simultaneously, DIZE suppressed the secretion of pro-inflammatory cytokines and the expression of NLRP3 inflammasome. Importantly, miR-224-5p was significantly up-regulated in the astrocytes of APP/PS1 mice treated by DIZE, and NLRP3 is one of the targets of miR-224-5p. Upregulation of miR-224-5p inhibited the expression of NLRP3 in Aβ 1– 42-stimulated cells, whereas miR-224-5p downregulation reversed this effect. Furthermore, the inhibition of miR-224-5p could reverse the inhibitory effect of DIZE on astrocytic NLRP3 inflammasome.Conclusion: These findings firstly suggested that DIZE could inhibit astrocyte-regulated neuroinflammation via miRNA-224-5p/NLRP3 pathway. Furthermore, our study reveals the underlying mechanism by which DIZE suppresses neuroinflammatory responses in AD mice and uncovers the potential of DIZE in AD treatment.Keywords: DIZE, miRNA-224-5p, astrocyte, NLRP3, neuroinflammation, Alzheimer’s disease

This paper develops a theoretical and empirical framework to assess the heterogeneous effects of mortgage rates on housing returns when accounting for the zero lower bound regime of the policy interest rate and state-level supply and demand conditions. Based on an interacted panel VAR estimated on a dataset comprising of all 50 U.S. states and the District of Columbia for a time period between January 1995 and December 2020, our empirical findings show that the response of housing returns to a mortgage rate shock is larger in magnitude when the federal funds rate is at its zero lower bound. Various supply and demand conditions, including housing permits, personal income, employment, and population, matter for the transmission of a mortgage rate shock to housing returns in local markets. A partial equilibrium model supports our empirical results.

This paper develops a DSGE framework featuring heterogeneous housing markets, endogenous mortgage defaults, and a banking sector. We find that the idiosyncratic mortgage risk shock plays an important role in explaining the fluctuations of house prices during the 1980s and the years leading up to the financial crisis. The same shock is also an important driving force of household loans. By placing an occasionally binding constraint on the loan-to-value ratio via a counterfactual analysis, we find that the overheating of the housing economy in the early 2000s and the subsequent crash could have been alleviated, if authorities had adopted such a macroprudential policy measure. A comparison of utility gains suggests that such a maximum loan-to-value ratio policy is preferable over an augmented Taylor rule that responds to house price growth.

China has conducted surveillance for hepatitis A since 1990, and hepatitis A was highly-to-intermediately endemic in 1992 when a Chinese hepatitis A vaccine (HepA) was licensed and introduced as a family-pay vaccine. In 2008, HepA was introduced into the Expanded Program on Immunization as a free childhood vaccine.Three nationally representative surveys conducted in 1992, 2006, and 2014 assessed hepatitis B serology. The 1992 survey included hepatitis A virus (HAV) serology, and we tested sera from the 2006 and 2014 surveys for HAV antibodies. We used surveillance, seroprevalence, and vaccination status data to describe the changing epidemiology of hepatitis A in China from 1990 through 2014. Before HepA licensure, anti-HAV seroprevalence was 60% at 4 years of age, 70% at 10 years, and 90% at 59 years; incidence was 52/100,000 and peaked at 4 years. In 2006, after10 years of private sector vaccination, HepA coverage was30% among children5 years, and incidence was 5.4/100,000 with a peak at 10 years. In 2014, coverage was90% among children under 5 years; incidence was 1.9/100,000. Individuals born before the national introduction of HepA (1988-2004) had lower anti-HAV seroprevalence than earlier and later birth cohorts.The incidence of hepatitis A declined markedly following HepA introduction and improvement of sanitation and hygiene. The emerging epidemiology is consistent with disease-induced immunity having been replaced by vaccine-induced immunity, resulting in a low incidence of hepatitis A. Catch-up HepA campaigns to close the immunity gap among the 1998-2004 birth cohorts should be considered.

This paper explores the role of business cycle proxies, measured by the output gap at the global, regional, and local levels, as potential predictors of stock market volatility in the emerging BRICS nations. We observe that the emerging BRICS nations display a rather heterogeneous pattern when it comes to the relative role of idiosyncratic factors as a predictor of stock market volatility. While domestic output gap is found to capture significant predictive information for India and China particularly, the business cycles associated with emerging economies and the world in general are strongly important for the BRIC countries and weakly for South Africa, especially in the postglobal financial crisis era. The findings suggest that despite the increase in the financial integration of world capital markets, emerging economies can still bear significant exposures to idiosyncratic risk factors, an issue of high importance for the profitability of global diversification strategies.

Background Hepatitis A (HepA) vaccination and economic transitions can change the epidemiology of HepA. China’s Gross Domestic Product (GDP) per capita was known to be inversely associated with the incidence of HepA, but a deeper understanding of the epidemiology of HepA in different socio-economic regions is lacking. We compare the changing epidemiology of HepA in three socioeconomic-geographic regions of China. Methods We obtained data on all HepA cases reported through the National Notifiable Disease Reporting System and assessed trends and changes in age-specific incidence rates by age quartile and season. We categorized the country into three regions, the sequential years into five era, compared the incidence, quartile age, seasonal intensity and coverage of HepA of the three regions. Linear regression was performed to analyse trends in incidence of HepA and to analyse the association between coverage and incidence. Results The annual mean incidences of HepA in the eastern, central, and western regions decreased from 63.52/100 000, 50.57/100 000 and 46.39/100 000 in 1990–1992 to 1.18/100 000, 1.05/100 000 and 3.14/100 000 in 2012–2017, respectively. Decreases in incidence were seen in all age groups in the three regions; the incidence was highest (9.3/100 000) in the youngest age group (0–4 years) of the western region, while in the central region, the age group with the highest incidence changed from 0 to 9 years to adults ≥60 years old. In 2017, the median age of HepA cases was 43 years (Q1–Q3: 33–55), 47 years (Q1–Q3: 32–60) and 33 years (Q1–Q3: 9–52) in the eastern, central, and western provinces, respectively. Seasonal peaks became smaller or were nearly elimination nationwide, but seasonality persisted in some provinces. After the Expanded Program on Immunization (EPI) included HepA vaccine into the routine schedule in 2007, HepA coverage increased to > 80% in the three regions and was negatively association with the HepA incidence. Conclusion The incidence of HepA decreased markedly between 1990 and 2017. A socioeconomic inequity in coverage of HepA vaccine was almost eliminated after HepA vaccine was introduced into China’s EPI system, but inequity in incidence still existed in lower socio-economic developed region.

The renin-angiotensin system (RAS) is a paracrine RAS within the central nervous system (CNS) and is closely related to Alzheimer’s disease (AD). The endogenous hexapeptide angiotensin IV (Ang IV), an important component of the brain RAS, was found to rescue cognitive impairment and recover memory in previous studies. In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice. We found that the amount of AngIV in mouse tissue increased after the administration of Dihexa compared to that in the WT group. Meanwhile, Dihexa restored spatial learning and cognitive functions in the Morris water maze test. Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining. Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10. Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice. These findings highlight the brain AngIV/PI3K/AKT axis as a potential target for the treatment of AD.

The lobster eye telescope is promising for large-field x ray imaging in astronomy. The special structure of the lobster eye system makes the focal plane a sphere, resulting in detector defocus when the field is large. In this study, we established a model based on the principle of lobster eye imaging and simulated the imaging at different image distances. The results reveal the relationship between the defocus and position accuracy and angular resolution. To ensure the optical performance of the large field lobster eye telescope, we propose a detection system design method using multiple detectors stitched together to form a spherical-like surface and apply it to the development of the Einstein Probe/wide-field x ray telescope (EP/WXT) submodule. About 70% of the detection area is out of focus within 0.5 mm. The scanning image of the integrated WXT submodule shows good uniformity of the point spread function (PSF) for various incident angles, and the effect of defocus on imaging is acceptable.

Background Mother to child transmission of hepatitis B virus (HBV) remains the most common form of HBV infection in China. Prevention of HBV vertical transmission involves timely administration of the complete hepatitis B vaccine (HepB) series and hepatitis B immunoglobulin. Post-vaccination serological testing (PVST) is utilized to determine an infant’s outcome after HBV exposure and completion of HepB series. We aim to determine the frequency of compliance with a PVST testing cascade for HBV infected mothers and analyze factors associated with infant lost to follow up (LTFU). Methods We conducted a retrospective cohort review of previously collected data in Fujian, Jiangxi, Zhejiang and Chongqing provinces in China from 1 June 2016–31 December 2017. The study population included all HBV-exposed infants and their mothers. SAS software was used for statistical analyses. Bivariate and multivariate regression analyses (presented in odds ratio [OR] with 95% confidence intervals [CI]) were used to compare the proportional differences of factors associated with PVST not being completed. Results Among enrolled 8474 target infants, 40% of them transferred out of the study provinces without further information and 4988 were eligible for PVST. We found 20% (994) of infants were not compliant with the testing cascade: 55% of LTFU occurred because parents refused venous blood sample collection or failure of sample collection in the field, 16% transferred out after 6 months of age, and 10% of families chose to have independent, confidential PVST completed without reporting results. High PVST noncompliance rates were more likely to be from Fujian (aOR = 17.0, 95% CI: 9.7–29.9), Zhejiang (aOR = 5.7, 95% CI: 3.2–10.1) and Jiangxi (aOR = 1.9, 95% CI: 1.0–3.4), and from HBV e antigen positive mother (aOR = 1.2, 95% CI: 1.1–1.4). Conclusions This study found that the LTFU rate reached 20% in PVST program, which was a significant problem. We recommend implementing a national electronic information system for tracking HBV at risk mother-infant pairs; encourage further research in developing a less invasive means of completing PVST, and take effective measures nationally to reduce HBV stigma. Without reducing the loss to follow up rate among infants eligible for PVST, elimination of vertical HBV transmission will be impossible.

This paper examines large price run-ups with potential subsequent crashes and large price declines with potential subsequent rebounds in state-level and metropolitan-area-level housing markets in the U.S. over the past 40 years. We find that a sharper run-up in house prices predicts a higher probability of a crash, but a sharper decline does not necessarily predict a higher probability of a rebound. Changes in the effective interest rate in the local market can predict housing returns following large price run-ups, while it is harder to use the same factors to predict returns following large price declines. Such characteristics are robust to different thresholds of price movements.

The recovery of low temperature heat sources is a hot topic in the world. The ORC system can effectively use the low temperature heat source. As its main output device, the performance of the turbine is very important. The single stage transonic turbine has the characteristics of small size and large output power. In this paper, the complete design process of a transonic centrifugal turbine with R245fa in low working temperature condition is introduced. At the design conditions, the shaft power and the wheel efficiency of the centrifugal turbine can reach 1.12 MW and 83.61%, respectively. In addition, a thermodynamic ORC cycle is presented and the off-design conditions of the turbine and its influence on the system are studied in detail. The results obtained in the present work show that the single-stage transonic centrifugal turbine can be regarded as a potential choice to be applied in small scale ORC systems.

This paper evaluates the impact of housing market spillovers on a small open economy, namely South Africa, using a small open economy new Keynesian dynamic stochastic general equilibrium model which explicitly incorporates a housing sector. Using quarterly data covering the period of 1971:Q1–2015:Q3, we obtain the following set of results: (a) over the business cycle, the housing preference shock and the technology shock in the consumption sector drive most of the fluctuations of real house price; (b) the spillover effects of the housing market to the boarder economy are not negligible; (c) the central bank of South Africa has actively responded to house price movements over the past 45 years; and (d) the flexible exchange rate policy has helped South Africa maintain the macroeconomic stability to a large extent.

Summary COVID-19 was declared a pandemic by WHO on March 11, 2020, the first non-influenza pandemic, affecting more than 200 countries and areas, with more than 5·9 million cases by May 31, 2020. Countries have developed strategies to deal with the COVID-19 pandemic that fit their epidemiological situations, capacities, and values. We describe China's strategies for prevention and control of COVID-19 (containment and suppression) and their application, from the perspective of the COVID-19 experience to date in China. Although China has contained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and nearly stopped indigenous transmission, a strong suppression effort must continue to prevent re-establishment of community transmission from importation-related cases. We believe that case finding and management, with identification and quarantine of close contacts, are vitally important containment measures and are essential in China's pathway forward. We describe the next steps planned in China that follow the containment effort. We believe that sharing countries' experiences will help the global community manage the COVID-19 pandemic by identifying what works in the struggle against SARS-CoV-2.

Background To analyze the epidemiological distribution of Hepatitis B virus (HBV) genotype in the mainland of China following the implementation of effective preventive measures. Methods Five hundred and seventeen HBsAg-positive subjects aged 1–29 years surveyed in the 2014 national HBV sero-survey in the mainland of China were enrolled in the study. The full-length HBV genome was obtained by PCR amplification and sequencing. The HBV genotype was determined by phylogenetic analysis. Combined with questionnaire information, HBV genotype distribution was analyzed. Results Of the 517 HBsAg-positive subjects, 369 (71.4%) were included in the analysis. HBV genotypes found were B (45.0%), C (36.6%), D (6.0%), C/D (9.8%), B/C (2.2%), and I (0.5%). Geographic differences in HBV genotype were significant for seven regions. Three serotypes were found: adw (47.2%), adr (35.5%), and ayw (17.3%). B2 (43.9%) and C2 (25.2%) were the two major subgenotypes. The predominant genotypes differed between the Han group and the other ethnic groups. No statistical differences in genotype distribution were found by gender, age group, or hepatitis B (HepB) vaccination history. Conclusion The prevalence of HBV genotype B was higher than that of genotype C with subgenotypes B2 and C2 endemic in 1–29-year-olds in the mainland of China, after HBV prevalence has reduced significantly due to the implementation of preventive measures. HepB vaccination or other factors did not interfere with HBV genotype distribution. The surveillance of HBV genotype was essential for responding to the potential changes and impact on the preventive policies in the future.

This study aimed to evaluate glycolysis inhibitor which can effectively ameliorate arthritis by inhibiting synoviocyte activation through AMPK/NF-кB pathway in AA rats. Adjuvant arthritis (AA) rats were treated with 2-deoxyglucose (2-DG), glycolysis inhibitor. HE staining and radiological Examination were used for histopathology analysis and evaluation of joint destruction. HKII expression was quantified by immunostaining. Proliferation and migration of synoviocytes were assessed by synovicyte scores of joint, CCK8 and transwell assay. Inflammatory factors and levels of AMPK, p65 and IκBα were quantified by ELISA analysis and WB. We observed that HKII expression was positively correlated with synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction, and glycolysis inhibitor reduces the joint swelling degree, alleviates bone destruction, inhibits the proliferation and migration of synoviocyte, and reduces secretory function of synoviocytes in AA rats. In addition, we investigated that glycolysis inhibitor may inhibit activation of the NF-κB signaling pathway by activating the AMPK pathway. This study suggests the involvement of energy metabolism in the pathological inflammation process in RA joints. Glycolysis inhibitors might, therefore, provide an opportunity for therapeutic intervention.

The slope of the yield curve has long been found to be a useful predictor of future economic activity, but the relationship is unstable. One change we have identified in this paper is that, starting from the 1990s, movements at the long end of the yield curve have an increase in predictive power. We use a medium-scale DSGE model with a housing sector and a yield curve as a guide to find out the sources of such change. The model implies that an increase in the short-term interest rate and a decrease in the long-term interest rate have different impacts on the economy, and to use the slope as a predictor one needs to distinguish movements at the two ends of the yield curve. Based on simulated data from the model, we find that nominal wage rigidities and the capital adjustment costs are closely related to the predictive power of the yield curve. This result is further confirmed with actual data.

There is an ongoing debate in the U.S. regarding the costs and benefits associated with statewide stay-at-home orders that were enacted in response to the COVID-19 outbreak. Many opponents of such orders claim that the economic cost, in terms of higher unemployment, may in-fact outweigh the health benefits of such policies. In this paper, we use synthetic control analysis to determine the impact of stay-at-home orders on weekly new jobless claims. Our analysis reveals that while new jobless claims spike following stay-at-home orders, similar spikes, albeit of a lower magnitude, are also observed within our synthetic control. This finding suggests that other factors outside of the policy, such as the spread of the virus and a general waning of consumer confidence, contribute significantly to the observed increase in new jobless claims.

Monocarboxylate transporter 1 (MCT1) has been reported to be correlated wtih decreased survival and advanced stage of progression in a series of human tumor cells and primary cancers. Specifically, MCT1 has been documented to be involved in tumor progression, including invasion and migration. Here, we investigated the mechanism and effect of regulation of MCT1 on invasion and migration of nasopharyngeal carcinoma (NPC) cells. In the study, we firstly demonstrated that the expression of MCT1 in CNE2Z cells was obviously higher than that in HNE1 cells. Downregulation of MCT1 inhibited the invasion and migration in CNE2Z cells, upregulated the expression of E-cadherin, TIMP (tissue inhibitor of metalloproteinase)-2 and TIMP-1, and suppressed the expression of matrix metalloproteinases (MMP)-9 and MMP-2. Correspondingly, upregulation of MCT1 enhanced the invasive and migratory potential in HNE1 cells, increased the expression of MMP-9 and MMP-2, and downregulated the expression of E-cadherin, TIMP-2 and TIMP-1. The mechanistic study demonstrated that the effect of MCT1 might be correlated with PI3K/Akt signaling pathway. LY294002, a PI3K inhibitor, increased the inhibition of invasion and migration mediated by downregulation of MCT1 in CNE2Z cells. These findings collectively suggested that MCT1 might act as a new regulator to improve invasion and migration of NPC cells and be correlated with activating the PI3K/Akt pathway.

China's hepatitis B virus (HBV) prevention policy has been evaluated through nationally representative serologic surveys conducted in 1992 and 2006. We report results of a 2014 serologic survey and reanalysis of the 1992 and 2006 surveys in the context of program policy. The 2014 survey used a 2-stage sample strategy in which townships were selected from 160 longstanding, nationally representative, county-level disease surveillance points, and persons 1-29 years of age were invited to participate. The 2014 sample size was 31,713; the response rate was 83.3%. Compared with the 1992 pre-recombinant vaccine survey, HBV surface antigen prevalence declined 46% by 2006 and by 52% by 2014. Among children

This paper shows that monetary policy has uneven impacts on local housing markets, and that the magnitude of the impacts are correlated with housing supply regulations. We apply the linearized present value model, which allows the log rent–price ratio to be decomposed into the expected present values of all future real interests rates, real housing premia, and real rent growth, to the housing markets in 23 US metropolitan statistical areas. Based on the indirect inference bias-corrected VAR estimates, we find that MSAs that are more regulated have (i) a higher variance in the log rent–price ratio, (ii) a larger share of the variance explained by real interest rate, and (iii) a stronger impulse response of house price to the real interest rate shock.

Most DSGE models with a housing market do not explicitly include a rental market and assume a tight mapping between house prices and rents over the business cycle. However, rents are much smoother than house prices in the data. We match this feature of the data by adding both an owner-occupied housing market and a rental market with nominal rigidity in a standard DSGE model. The housing preference shock explains 35% of the variation in rents but does not contribute much to the dynamics of house prices. The intertemporal preference shock accounts for more than half of the variation in house prices and contributes significantly to residential investment fluctuations through the liquidity constraint. The monetary policy shock explains little of the fluctuations in the price-rent ratio. Nominal rigidity in rental contracts plays an important role in capturing the smoothness of rents and the large variation in the price-rent ratio.

ObjectivesNation-wide hepatitis B vaccination coverage among healthcare workers (HCWs) is not well researched in China. This study aims to investigate the self-reported hepatitis B vaccination status among HCWs in China.MethodsWe conducted a cross-sectional survey of health_care workers' vaccination statuses in 120 hospitals in China by collecting demographic and vaccination data. Univariate and multivariate logistic regression analysis were used to assess factors associated with hepatitis B vaccination coverage.ResultsEighty-six percent (2,666/3,104) of respondents reported having received at least one dose of the hepatitis B vaccination and 60% (1,853/3,104) reported having completed ≥3 doses of the hepatitis B vaccination. Factors associated with completing ≥3 doses of the hepatitis B vaccination included workplaces offering free hepatitis B vaccination with vaccination management, age, medical occupation, hospital level, acceptable hepatitis B knowledge and having received training on hepatitis B. HCWs in workplaces offering a free hepatitis B vaccine with vaccination management were 1.4 times more likely (OR = 1.4, 95% CI: 1.1-1.8) to complete their hepatitis B vaccination compared to HCWs in workplaces that did not offer a free hepatitis B vaccine. Either the possession of acceptable hepatitis B knowledge or an age of 30-39 years increased the odds of complete hepatitis B vaccination by 1.3-fold (95% CIs: 1.1-1.5 and 1.1-1.7, respectively) over their referent category. The receipt of training on hepatitis B was also associated with a higher percentage of completing the hepatitis B vaccination (OR = 1.5, 95% CI: 1.2-1.8). The main self-reported reason for incomplete hepatitis B vaccination was "forgot to complete follow-up doses" among 43% (234/547) of respondents. Among those who never received any hepatitis B vaccination, only 30% (131/438) intended to be vaccinated. Obtaining immunity from work (40%) and hospitals that did not provide hepatitis B vaccination activities (40%) were the top reasons mentioned for refusing hepatitis B vaccination.ConclusionsThe complete hepatitis B vaccination rate among HCWs in China is low, and the desire of HCWs for vaccination is indifferent; therefore, education campaigns are needed. In addition, a free national hepatitis B vaccination policy for HCWs that includes vaccination management should be prioritized to improve hepatitis B coverage among HCWs who are at-risk for HBV infection.

OBJECTIVE: To observe the effects of 2-deoxyglucose inhibiting synovial pannus of adjuvant arthritis rats and to explore its potential mechanism of inhibiting angiogenesis by investigating proliferation, migration and matrigel tube formation assay in vitro. METHODS: The effect of 2-DG on synovial pannus was evaluated by histopathology of HE staining; HUVEC proliferation was determined by CCK-8 method; migration of FLS were determined by transwell; In vitro matrigel tube formation assay was made for assessing tube number of HUVEC; p-AMPK and Bcl-2 were detected by Western blot assay; AMPK signaling pathway in HUVEC was inhibited by compound C, which is an inhibitor of AMPK activation. RESULTS: 2-DG (200 mg/kg) obviously decreased appearance of synovial pannus (P < 0.01); in vitro, 2-DG (0.5 mmol/L and/or 5 mmol/L) obviously inhibited proliferation, migration and tube number of HUVEC (P < 0.01 or P < 0.001), and its effects on HUVEC were reversed by using AMPK antagonist (Compound C); Western blot showed that 2-DG (5 mmol/L) increased expression of p-AMPK and decreased expression of Bcl-2 (P < 0.05). CONCLUSION: Activating AMPK pathway and decreasing expression of Bcl-2 may the potential mechanism by which 2-DG contributes to anti-angiogenesis and effects of inhibiting proliferation, migration and tube number of HUVEC.

This paper first proposes a new vernier permanent-magnet (VPM) machine which employs two sets of permanent magnet (PM) both in the stator and the rotor. Halbach arrays are used in the stator in order to solve the problem of the flux leakage. The design process for the proposed machine is given by mutual modulation of the PMs in the stator and the rotor, and the proposed machine offers high torque capability compared with the existing machines with only PMs in the stator or in the rotor. Moreover, a flux barrier is adopted to reduce the number of PMs and minimize the torque ripple. The time-stepping finite-element method is adopted to evaluate the proposed machine, which verifies the theoretical analysis.

Background and objective With the universal infant hepatitis B vaccination (HepB) program, China has made remarkable achievements to prevent and control hepatitis B. In order to further reduce hepatitis B virus (HBV) infection, the Chinese government is considering implementing a widespread adult HBV vaccination campaign. We performed an economic analysis of two different adult HepB vaccination strategies for 21–59-years-olds: vaccination without screening and screening-based vaccination. Methods Cost-benefit analyses were conducted. All 21–59-year-olds were divided into two groups: young adults (ages 21–39) and middle-aged adults (ages 40–59). Costs and benefits were estimated using the direct cost and societal (direct and indirect costs) perspectives. All costs and benefits were adjusted to 2014 US dollars, where future values were discounted at a 3% annual rate. We calculated benefit-cost ratios (BCRs) of the two vaccination strategies for the two different age groups. Sensitivity analyses varied key parameters within plausible ranges. Results Among young adults, the direct and societal BCRs for a vaccination campaign with no screening would be 1.06 and 1.42; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 1.19 and 1.73. Among middle-aged adults, the direct and societal BCRs for a vaccination campaign without screening would be 0.59 and 0.59; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 0.68 and 0.73. Conclusion The results of our study support a HepB vaccination campaign for young adults. Additionally, a vaccination campaign with screening appeared to provide greater value than a vaccination without screening.

This study bridges strategic management and supply chain management domains by examining how firms’ structural characteristics in supply networks influence competitive dynamics. We theorize causal ...

This paper utilizes the recently developed methods of compressing the parameters and the data for a high-dimensional vector autoregression (VAR) to forecast economic policy uncertainty (EPU) of Brazil, China, India and Russia (BRIC) based on EPUs of additional 18 developed and developing countries. In line with the recent literature on spillover of EPUs across countries, we show that incorporating information of EPUs of other countries does indeed produce gains in forecasting the EPU of the BRIC bloc, irrespective of whether we compress the parameters or the data.

Introduction Since 2008, two types of hepatitis A (HepA) vaccines were integrated into the expanded program on immunization (EPI) in China. Children were given either one dose of live attenuated HepA (L-HepA) or two doses of inactivated HepA (I-HepA), depending on geographic regions. We sought to evaluate the impact of the EPI on HepA incidence in China. Methods We reviewed the epidemiology of HepA during 2004–2016 from National Notifiable Disease Reporting System (NNDRS). We collected data of L-HepA and I-HepA coverage from Children Immunization Information Management System (CIIMS). Based on the regions where two types of HepA vaccines were used, the coverage and incidence of HepA were compared over time. Results In 2008–2016, the HepA vaccine coverage was 98.8% among target children, with 99.6% in I-HepA region and 98.7% in L-HepA region. HepA incidence declined by 78.0% and 82.3% in L-HepA region and I-HepA region, respectively, without significant difference. Dramatic decline were seen in all age groups of both regions. Conclusion The study suggests that the EPI, with high coverage for both I-HepA and L-HepA, had positive impact on HepA incidence in China.

Vaccination in prevention mother-to-child transmission (PMTCT) of hepatitis B has been recommended since plasma-derived hepatitis B vaccines became available in China in 1986; however, less study evaluated practice effectiveness of PMTCT systematically. We conducted a prospective survey to evaluate the effectiveness of PMTCT practices in 3 provinces of southern China. We selected prefectures with low timely birth dose coverage in Yunnan, Guangxi, and Hunan provinces. Infants born to HBsAg positive mothers were evaluated at 7–12 months of age. We tested hepatitis B virus (HBV) surface antigen (HBsAg) and HBV e antigen (HBeAg) of mothers and tested HBsAg of infants born to HBsAg positive mothers using Enzyme-linked Immunosorbent Assay (ELISA) at provincial CDC laboratories. We used logistic regression analysis to analyze the risk factors for HBV infection. Among 3,094 infants born to HBsAg positive mothers, 172 were positive for HBsAg (5.6%). HBeAg status of pregnant women, timely birth dose (TBD) of hepatitis B vaccine were major predictors for HBV infection of infants. PMTCT practices greatly reduced the prevalence of HBsAg among infants born to HBsAg positive mothers China. However, the effectiveness of strategies used in PMTCT varied. HBsAg screening for pregnant women, monitoring of infants born to HBsAg positive mother should be enhanced to evaluate the effectiveness of program.

3-Bromopyruvate (3BP) is an energy-depleting drug that inhibits Hexokinase II activity by alkylation during glycolysis, thereby suppressing the production of ATP and inducing cell death. As such, 3BP can potentially serve as an anti-tumorigenic agent. Our previous research showed that 3BP can induce apoptosis via AKT /protein Kinase B signaling in breast cancer cells. Here we found that 3BP can also induce colon cancer cell death by necroptosis and apoptosis at the same time and concentration in the SW480 and HT29 cell lines; in the latter, autophagy was also found to be a mechanism of cell death. In HT29 cells, combined treatment with 3BP and the autophagy inhibitor 3-methyladenine (3-MA) exacerbated cell death, while viability in 3BP-treated cells was enhanced by concomitant treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk) and the necroptosis inhibitor necrostatin (Nec)-1. Moreover, 3BP inhibited tumor growth in a SW480 xenograft mouse model. These results indicate that 3BP can suppress tumor growth and induce cell death by multiple mechanisms at the same time and concentration in different types of colon cancer cell by depleting cellular energy stores.

Background Since March 2014, the Ebola Virus Disease (EVD) outbreak in West Africa disrupted health care systems - especially in Guinea, Liberia and Sierra Leone – with a consequential stress on the area’s routine immunization programs. To address perceived decreased vaccination coverage, Sierra Leone conducted a catch-up vaccination campaign during 24–27 April 2015. We conducted a vaccination coverage survey and report coverage estimates surrounding the time of the EVD outbreak and the catch-up campaign. Methods We selected 3 villages from each of 3 communities and obtained dates of birth and dates of vaccination with measles vaccine (MV) and the 3rd dose of Pentavalent vaccine (Pentavalent3) of all children under 4 years of age in the 9 selected villages. Vaccination data were obtained from parent-held health cards. We calculated the children’s MV and Pentavalent3 coverage rates at 3 time points, 1 August 2014, 1 April 2015, and 1 May 2015, representing coverage rates before the EVD outbreak, during the EVD outbreak, and after the Maternal and Child Health Week (MCHW) catch-up campaign. Results The final sample size was 168 children. MV coverage among age-eligible children was 71.3% (95% confidence interval [CI]: 62.1% - 80.4%) and 45.7% (95% CI: 29.2% - 62.2%) before and during the outbreak of EVD, respectively, and was 56.8% (95% CI: 40.8% - 72.7%) after the campaign. Pentavalent3 coverage among age-eligible children was 79.8% (95% CI: 72.6% - 87.0%) and 40.0% (95% CI: 22.5% - 57.5%) before and during the outbreak of EVD, and was 56.4% (95% CI: 39.1% - 73.4%) after the campaign. Conclusions Coverage levels of MV and Pentavalent3 were low before the EVD outbreak and decreased further during the outbreak. Although the MCHW catch-up campaign increased coverage levels, coverage remained below pre-outbreak levels. High-quality supplementary immunization activities should be conducted and routine immunization should be strengthened to address gaps in immunity among children in this EVD-affected area.

Shikonin, a natural small agent, has shown inhibitory effect in many kinds of cells, which increases intracellular reactive oxygen species (ROS) level and causes mitochondrial injury. In this study, shikonin showed good inhibitory effect on nasopharyngeal carcinoma CNE-2Z cells in vivo and vitro. The results presented here revealed that ROS levels increased markly after shikonin treated. The electron microscopy displays the change in ultrastructure of CNE-2Z cells after treatment for shikonin, which indicated that shikonin induced necroptosis. Shikonin-induced cell death was inhibited by a necroptosis inhibitor, necrostatin-1 (Nec-1), while the activity was unaffected by the caspase inhibitor z-VAD-fmk. Furthermore, we have demonstrated that the activation of receptor-interacting kinase (RIP) led to necroptosis. Meanwhile, shikonin also significantly inhibited tumor growth in a CNE-2Z xenograft mouse model. Taken together, shikonin induced CNE-2Z cells death by producing ROS as a necroptosis inducer. It could serve as a new therapeutic agent for treating CNE-2Z cells.