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Minimal residual disease (MRD) is an important reason for the failure of autologous hematopoietic stem cell transplantation (auto-HSCT). Reducing MRD in grafts is particularly important to improve the efficacy of auto-HSCT. Previously, we reported that ultraviolet light-emitting diode (UV LED) suppressed the expression of Bcl-2 to induce apoptosis in HL-60 cells. Leukemia can lead to severe hypoxia of the bone marrow. Therefore, this study aimed to investigate the effect of UV LED on leukemia cells under hypoxia. HL-60 cells were irradiated with a UV LED (30 J/m2) and simulated under hypoxia with cobalt chloride. We found that UV LED irradiation or CoCl2 inhibited proliferation, induced apoptosis, decreased the Bcl-2/Bax ratio, and increased the levels of caspase 3, cleaved-caspase 3, and caspase 9 in HL-60 cells. In particular, the combined application of UV and CoCl2 significantly enhanced the apoptosis of HL-60 cells. In conclusion, UV LED in hypoxia exacerbated the inhibition of proliferation and induction of apoptosis and necrosis in HL-60 cells via the regulation of caspase 3/9 and the Bcl-2/Bax ratio-dependent pathway. The application of UV LEDs in hypoxia conditions may be a promising approach to kill residual drug-resistant leukemia cells in autologous grafts.

The foundation for polarization-based terahertz applications is the acquisition of polarization information. To develop an all-electronic terahertz straightforward polarization detection system, in this paper, a terahertz polarization detector based on three antenna-coupled AlGaN/GaN high-electron-mobility transistors (HEMTs) on a single chip is designed and fabricated. The function of the direct polarization detector is proven by measuring the polarization angle of linearly polarized continuous-wave terahertz radiation at 216 GHz. The average deviation and maximum deviation of the measured polarization angle are 3.7 degrees and 10 degrees, respectively. The error comes mainly from the disturbance of the local terahertz field by the interference effect. Simulations locate the sources of interference and guide the further device design and packaging of such kind of direct polarization detectors.

Abstract Purpose Sodium-glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors are increasingly used as second-line therapies in patients with type 2 diabetes. The aim of this study was to assess the real-world effects of SGLT2 inhibitors in a multi-ethnic population in Singapore. Methods This retrospective cohort study examined patients diagnosed with and treated for diabetes from the Ministry of Health’s administrative database. Differences in outcomes between treatment groups were assessed using Poisson regression. Demographics, clinical characteristics, previous diagnoses and hospitalisations, and diabetes medication history were used for propensity score matching. Subgroup analyses by ethnicity were performed. Effect size was estimated using risk ratios (RRs) with 95% confidence intervals (CIs). Results Patients initiating SGLT2 inhibitors were more likely to achieve glycaemic control target than DPP4 inhibitor-treated patients (RR 1.09; 95% CI 1.04, 1.14). This was observed only in patients of Chinese ethnicity. A higher risk of diabetic ketoacidosis in SGLT2 inhibitor initiators was not observed. SGLT2 inhibitors were associated with reduced risk of hypoglycaemia (RR 0.69; 95% CI 0.59, 0.82) and urinary tract infection (RR 0.52; 95% CI 0.43, 0.63) but was not statistically significant for hypoglycaemia in Malay patients. Compared to DPP4 inhibitors, SGLT2 inhibitors were associated with 12% and 34% reduction in any-cause hospitalisation and all-cause mortality, respectively, potentially resulting in more than $50 million savings over 10 years. Conclusion SGLT2 inhibitors were associated with improvements in glycaemic control, reduced risk of complications, and was well tolerated. Ethnicity also plays a role and should be considered in future studies.

Icariin (ICA), extracted from Epimedium, is a flavonoid used in traditional Chinese medicine. Di(2-ethylhexyl) phthalate (DEHP) is a phthalate used in commercial products as a plasticizer that can influence the human endocrine and reproduction system. We previously found that ICA reversed DEHP-induced damage through the prevention of reactive oxygen species accumulation and promotion of testosterone secretion. Here we investigated the mechanisms of ICA in promoting testosterone secretion from murine Leydig cells. We used ICA, DEHP, the Akt agonist SC-79, the Akt inhibitor MK2206, and the Creb inhibitor KG501 to determine the effect of these treatments on the expression levels of the steroidogenic enzymes, Cyp11a1 and Hsd3b, which play critical roles in androgen production, in Leydig cells. Bioinformatic analysis was used to search for ICA-targeted proteins and their associated pathways. We found that icariin interacted with estrogen receptor on the cell membrane, leading to increased phosphorylation levels of Akt and Creb proteins and enhanced transcription of genes encoding steroidogenic enzymes and testosterone synthesis. We further investigated ICA activity in vivo using male mice pretreated with 100 mg/kg ICA and then treated with 750 mg/kg DEHP. ICA pretreatment reversed the reduced protein expression levels of Cyp11a1 and Hsd3b induced by DEHP in Leydig cells in vivo. Furthermore, while the phosphorylation levels of Akt and Creb were decreased in testes of mice exposed to DEHP alone, these effects were reversed by ICA pretreatment. These findings indicate that ICA promotes testosterone synthesis via the Esr1/Src/Akt/Creb/Sf-1 signaling pathway.

Aiming at the problem that optimization of unit energy consumption cost and bidding cannot be accurately reflected by information management system of power plant. Based on the principle of maximizing the profit of power generation enterprises, this paper studies the bidding optimization and decision-making system of power generation companies based on parallel data, and the bidding optimization and decision-making system is developed. With parallel control structure, the system can realize continuous traversal update power enterprise unit energy consumption data. Starting from the standardization and standardization of data, the mathematical model of unit quotation is established. It realizes the functions of inquiring and analyzing the energy consumption data of the generator set and scientific guidance of the generation quotation, and provides bidding management and decision-making support for the electric power production enterprises.

Metasurfaces have powerful light field manipulation capabilities and have been researched and developed extensively in various fields. With an increasing demand for diverse functionalities, terahertz (THz) metasurfaces are also expanding their domain. In particular, integrating different functionalities into a single device is a compelling domain in metasurfaces. In this work, we demonstrate a functionally decoupled THz metasurface that can incorporate any two functions into one metasurface and switch dynamically through external excitation. This proposed metasurface is formed by the combination of split-ring resonators and phase change material vanadium dioxide ( VO 2 ). It operates in the single-ring resonant mode and double-ring resonant mode with varying VO 2 in insulating and metallic states, respectively. More importantly, the phase modulation is independent in two operating modes, and both cover a 360° cross-polarized phase with efficient polarization conversion. This characteristic makes it obtain arbitrary independent phase information on the metasurface with different modes to switch dual functions dynamically. Here, we experimentally demonstrate the functions of a tunable focal length and large-angle focus deflection of a THz off-axis parabolic mirror to verify the dual-function switching characteristics of the functionally decoupled metasurface. The functionally decoupled metasurface developed in this work broadens the way for the research and application of multifunctional modulation devices in the THz band.

Background The tricho-rhino-phalangeal syndrome-1 gene (Trps1) is an atypical GATA family member. Although current studies of Trps1 mainly focus on tumors, whether Trps1 plays a role in the male reproductive system remains unknown. Objectives The purpose of this study was to elucidate the function of Trps1 in Leydig cells, indicating its regulatory mechanism on the cell cycle. Methods Gene-silencing technology, RNA-seq, RT-qPCR, and western blotting were used to evaluate the function of Trps1 in mouse primary Leydig cells and MLTC-1 cells. In addition, ChIP-basesets and ChIP-qPCR were employed to further assess the regulatory mechanism of Trps1 in MLTC-1 cells. Results Knockdown of Trps1 in Leydig cells significantly suppressed phosphorylation of Src and Akt and expression of Ccnd1, which was accompanied by impairment of cell proliferative ability. Trps1 may affect the cell cycle through the Src/Akt/Ccnd1 signaling pathway. In addition, Trps1 may bind to the promoter of Srcin1 to regulate its transcription, thus influencing Src phosphorylation levels and the proliferation of Leydig cells. Discussion and conclusion Src increases in Leydig cells during pubertal development, suggesting its functional involvement in differentiated adult Leydig cells. Inhibition of the Src/Akt pathway would reduce Ccnd1 expression. In the present study, we found that Trps1 may regulate the phosphorylation level of Src and Akt through Srcin1, targeting Ccnd1 to influence mouse Leydig cell proliferation. These findings shed light on the regulation of Trps1 on cell proliferation and differentiation of mouse Leydig cells. This article is protected by copyright. All rights reserved.

While calpains have been implicated in neurogenesis for a long time, there is still little information regarding the specific contributions of various isoforms in this process. We took advantage of the availability of mutant mice with complete deletion of calpain-1 to analyze its contribution to neurogenesis. We first used the incorporation of BrdU in newly-generated cells in the subgranular zone of the dentate gyrus to determine the role of calpain-1 deletion in neuronal proliferation. Our results showed that the lack of calpain-1 decreased the rate of cell proliferation in adult hippocampus. As previously shown, it also decreased the long-term survival of newly-generated neurons. We also used data from previously reported RNA and miRNA sequencing analyses to identify differentially expressed genes in brain of calpain-1 knock-out mice related to cell division, cell migration, cell proliferation and cell survival. A number of differentially expressed genes were identified, which could play a significant role in the changes in neurogenesis in calpain-1 knock out mice. The results provide new information regarding the role of calpain-1 in neurogenesis and have implications for better understanding the pathologies associated with calpain-1 mutations in humans.

Enterovirus A71 (EV-A71) is the major cause of severe hand-foot-and-mouth diseases (HFMD), especially encephalitis and other nervous system diseases. EV-A71 capsid protein VP1 mediates virus attachment and is the important virulence factor in the EV-A71pathogenesis. In this study, we explored the roles of VP1 in the permeability of blood–brain barrier (BBB). Sera albumin, Evans blue, and dextran leaked into brain parenchyma of the 1-week-old C57BL/6J mice intracranially injected with VP1 recombinant protein. VP1 also increased the permeability of the brain endothelial cells monolayer, an in vitro BBB model. Tight junction protein claudin-5 was reduced in the brain tissues or brain endothelial cells treated with VP1. In contrast, VP1 increased the expression of virus receptor vimentin, which could be blocked with VP1 neutralization antibody. Vimentin expression in the VP1-treated brain endothelial cells was regulated by TGF-β/Smad-3 and NF-κB signal pathways. Moreover, vimentin over-expression was accompanied with compromised BBB. From these studies, we conclude that EV-A71 virus capsid protein VP1 disrupted BBB and increased virus receptor vimentin, which both may contribute to the virus entrance into brain and EV-A71 CNS infection.

Background: China contributes to almost half of the esophageal cancer cases diagnosed globally each year. However, the prognosis information of this disease in this large population is scarce. Methods: Data on a population-based cohort consisting of residents of Shandong Province, China who were diagnosed with esophageal cancer during the period from 2005 to 2014 were analyzed. The cancer-specific survival rates were estimated using Kaplan–Meier analysis. Discrete-time multilevel mixed-effects survival models were used to investigate socioeconomic status (SES) disparities on esophageal cancer survival. Results: The unadjusted 1-, 3-, and 5-year cause-specific survival rates were 59.6% [95% confidence interval (CI), 59.2%–59.9%], 31.9% (95% CI, 31.5%–32.3%), and 23.6% (95% CI, 23.1%–24.0%), respectively. Patients of blue-collar occupations had higher risk of esophageal cancer–related death than those of white-collar occupations in the first 2 years after diagnosis. Rural patients had higher risk of death than urban patients in the first 3 years after diagnosis. The risks of esophageal cancer–related death among patients living in low/middle/high SES index counties were not different in the first 2 years after diagnosis. However, patients living in high SES index counties had better long-term survival (3–5 years postdiagnosis) than those living in middle or low SES index counties. Conclusions: Socioeconomic inequalities in esophageal cancer survival exist in this Chinese population. Higher individual- or area-level SES is associated with better short-term or long-term cancer survival. Impact: Elucidation of the relative roles of the SES factors on survival could guide interventions to reduce disparities in the prognosis of esophageal cancer.

The rectification of terahertz radiation in a periodically almost-depleted graphene structures with dual grating gate is studied. Plasmonic electron-hole ratchet based rectified current grows with decreasing the Fermi energy of charge carriers in the gated parts of graphene. It is shown that the charge carriers accumulated at boundaries of depleted parts of graphene enhance the magnitude and inhomogeneity of oscillating electric field of the plasmon, which leads to significant growth in the rectification efficiency. Interaction of plasmon modes in different gated parts of graphene can increase the rectification efficiency due to excitation of the hybrid plasmon modes.

Preimplantation embryo development is characterized by drastic nuclear reprogramming and dynamic stage-specific gene expression. Key regulators of this earliest developmental stage have not been revealed. In the present study, a “non-classical” nuclear-localization pattern of eIF1A was observed during early developmental stages of mouse preimplantation embryo before late-morula. In particular, eIF1A is most highly expressed in the nuclear of 2-cell embryo. Knockdown eIF1A by siRNA microinjection affected the development of mouse preimplantation embryo, resulted in decreased blastocyst formation rate. CDX2 protein expression level significantly down-regulated after eIF1A knockdown in morula stage. In addition, the mRNA expression level of Hsp70.1 was also decreased in 2-cell embryo. The results indicate an indispensable role of eIF1A in mouse preimplantation embryos.

Background. At present, the new crown virus is spreading around the world, causing all people in the world to wear masks to prevent the spread of the virus. Problem. People with masks have found a lot of trouble for face recognition. Finding a feasible method to recognize faces wearing masks is a problem that needs to be solved urgently. Method. This paper proposes a mask recognition algorithm based on improved YOLO-V4 neural network and the integrated SE-Net and DenseNet network and introduces deformable convolution. Conclusion. Compared with other target detection networks, the improved YOLO-V4 neural network used in this paper improves the accuracy of face recognition and detection with masks to a certain extent.

d-Psicose 3-epimerase (DPEase) can catalyze the isomerization of d-fructose to be rare sugar d-psicose, which has wide application prospects in the food and medical fields. In this study, the DPEase gene from Agrobacterium tumefaciens was constructed into plasmid pMA5, and was successfully expressed in the host Bacillus subtilis WB600 (B. subtilis). After optimization of the fermentation conditions, whole recombinant B. subtilis WB600/pMA5-At-DEPase(O) cells produced d-psicose from d-fructose with a conversion rate of 29.01 ± 0.19%, which could be used for the efficient synthesis of d-psicose. To further improve the whole recombinant B. subtilis application, B. subtilis cells were immobilized onto a gel bead biocatalyst by Ca-alginate. After optimization of the biotransformation conditions, the conversion rate of the immobilized biocatalyst reached 20.74 ± 0.39%, which was lower than the free cells. However, the results showed that the immobilized biocatalyst had higher thermal/pH stability and storability, and the gel beads could be recycled for at least six batches. The results showed that the amount of d-psicose generated reached 32.83 ± 2.56 g/L with the immobilized biocatalyst after six times biotransformation, whereas the free cells produced only approximately 10.44 ± 0.07 g/L. The results showed that immobilized recombinant B. subtilis cells are promising to use for the efficient synthesis of d-psicose.

The ubiquitin ligase, Ube3a, plays important roles in brain development and functions, since its deficiency results in Angelman Syndrome (AS) while its over-expression increases the risk for autism. We previously showed that the lack of Ube3a-mediated ubiquitination of the Ca2+-activated small conductance potassium channel, SK2, contributes to impairment of synaptic plasticity and learning in AS mice. Synaptic SK2 levels are also regulated by protein kinase A (PKA), which phosphorylates SK2 in its C-terminal domain, facilitating its endocytosis. Here, we report that PKA activation restores theta burst stimulation (TBS)-induced long-term potentiation (LTP) in hippocampal slices from AS mice by enhancing SK2 internalization. While TBS-induced SK2 endocytosis is facilitated by PKA activation, SK2 recycling to synaptic membranes after TBS is inhibited by Ube3a. Molecular and cellular studies confirmed that phosphorylation of SK2 in the C-terminal domain increases its ubiquitination and endocytosis. Finally, PKA activation increases SK2 phosphorylation and ubiquitination in Ube3a-overexpressing mice. Our results indicate that, although both Ube3a-mediated ubiquitination and PKA-induced phosphorylation reduce synaptic SK2 levels, phosphorylation is mainly involved in TBS-induced endocytosis, while ubiquitination predominantly inhibits SK2 recycling. Understanding the complex interactions between PKA and Ube3a in the regulation of SK2 synaptic levels might provide new platforms for developing treatments for AS and various forms of autism.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. INNO-406 is a novel tyrosine kinase inhibitor (TKI) that possess specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. The present study aimed to confirm the anti-tumor effect of INNO-406 on CML cells, and elucidate the underlying molecular mechanism. CML cells were treated by INNO-406 at the concentration of 5, 25, 50, 100 μM at the indicated time. Cell proliferation was measured by MTT. Cell apoptosis were detected by Western blot and flow cytometry, respectively. As suggested by the findings, INNO-406 significantly inhibited the proliferation and induced apoptosis of CML cells. In addition, INNO-406 promoted the expression level of PTEN. Rescue experiment revealed that PTEN knockdown reversed the effect of INNO-406 which indicated the correlation between INNO-406 and PTEN. Further study determined that PTEN inhibited the phosphorylation of AKT and 4EBP1 and subsequently altered the expression of apoptotic proteins including bax, cytoplasmic cytochrome c (cyto-c), cleaved caspase3 and bcl-2. In vivo study further confirmed that INNO-406 inhibited the growth of CML cells by targeting PTEN. Based on the above findings, this work extended our understanding of INNO-406 in the therapy of CML and its molecular mechanism.

Background Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. INNO-406 is a novel tyrosine kinase inhibitor (TKI) that possess specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. The present study aimed to confirm the anti-tumor effect of INNO-406 on CML cells, and elucidate the molecular mechanism underlying its effect. Methods The cell proliferation and apoptosis were detected by MTT, western blot and flow cytometry respectively. Results As suggested by the findings, INNO-406 significantly inhibited the proliferation and induced apoptosis of CML cells. In addition, INNO-406 promoted the expression level of PETN. Rescue experiment revealed that PTEN knockdown reversed the effect of INNO-406 which indicated the correlation between INNO-406 and PTEN. Further study determined that PTEN inhibited the phosphorylation of AKT and 4EBP1 and subsequently altered the expression of apoptotic protein expressions including bax, cytochrome c (cyto-c), cleaved caspase3 and bcl-2. In vivo study further confirmed that INNO-406 inhibited the growth of CML cells in vivo by targeting PTEN. Conclusion Based on the above findings, this work extended our understanding of INNO-406 in the chemotherapy of CML and its molecular mechanism.

Improving employee well-being is not only a social responsibility that an enterprise should assume, but also an important means to improve its own competitiveness. Based on the theory of social information processing, this paper takes 256 employees in Jiangsu, Zhejiang, and Shanghai as samples, and finds that high-performance work systems have a significant positive impact on employees 'psychological well-being, and have a significant negative impact on employees' physical well-being To influence. In addition, the paper finds that union practice can significantly enhance the positive impact of high-performance work systems on employee psychological well-being. This provides new guidance for improving employee happiness through sound management practices.

This article reports the study design, methodological issues and early results of a pilot study testing methods for collecting nutrition, physical activity, and ultraviolet (UV) radiation exposure data in a groundbreaking study in China. Epidemiological studies suggest that exposures across the entire life course, including in utero, early childhood, and adolescence, may be important in the etiology of adult cancers and other chronic diseases. The Chinese Children and Families Cohort Study intends to follow-up subjects from the 1993 to 1995 Community Intervention Program of folic acid supplementation for the prevention of neural tube defects. This cohort is unique in that only folic acid exposure during pregnancy varies between groups as other supplements were not available, and there were nutrient deficiencies in the populations. Prior to launching a large-scale follow-up effort, a pilot study was conducted to assess the feasibility of recontacting original study participants to collect extensive diet, physical activity, and UV radiation exposure data in this population. The pilot study included 92 mothers and 184 adolescent children aged 14 to 17 years from 1 urban and 1 rural Community Intervention Program site. Subjects completed a Food Frequency Questionnaire, a 3-day food record, a physical activity questionnaire, a 3-day sun exposure diary together with 3 days of personal UV dosimetry, and 7 days of pedometry measurements and provided blood, saliva, and toenail samples. Grip strength and body composition measurements were taken, and ambient solar UV radiation was monitored in both study sites. While most of the assessments were successful, future studies would likely require different dietary intake instruments. The purpose of this report is to describe the study design and methodological issues emerging from this pilot work relevant for the follow-up of this large birth cohort.

The unemployment rate is one of the most important economic indices. This article extends the work of Feng and Hu (2013) and examines the effects of potential misclassifications in labor force statuses on the different Bureau of Labor Statistics (BLS) unemployment measures. Compared to the official US unemployment rate U-3, the broader measure U-6 is more robust to such classification errors in the survey data that are used to calculate unemployment rates. If one prefers the definitions of U-3, then we offer an approach to use reported unemployment measures to proxy for the unobserved true U-3.

© 2017 The Authors Objective: To examine if geographic variations in the participation rates in the National Bowel Cancer Screening Program (NBCSP) are related to population-level socio-demographic characteristics. Methods: Data reflecting participation in the NBCSP for 504 Local Government Areas (LGAs) between July 2011 and June 2013 were extracted from the Social Health Atlas of Australia. Logistic regression models were used to examine independent associations (odds ratios [ORs]) between participation, Remoteness Area (RA) and selected socio-demographic variables. Results: Compared to the participation rate for major cities (33.4%), participation was significantly higher in inner regional areas (36.5%, OR=1.15), but was much lower in remote (27.9%, OR=0.77) or very remote areas (25.0%, OR=0.65). When controlling for study period, gender, proportion of persons aged 65 years and older, Indigenous status, cultural background and socioeconomic status, significantly higher rates were observed in all non-metropolitan areas than in major cities. Indigenous status was strongly related to the poorer participation in remote areas. Conclusions: Socio-demographic characteristics, particularly Indigenous status, cultural background and population ageing, seem to be more important drivers of regional disparities in NBCSP participation than geographic remoteness. Implications for public health: This study provides important evidence to understand the regional disparities in participating in the national screening program.

Purpose: Almost half of the global esophageal cancer (EC) deaths occurred in China. This study aims to examine the geographic spread of EC mortality in two periods in a large Chinese population. Methods: Age-standardized mortality rates (ASMRs) for 140 county-level units in Shandong Province during the periods 1970-74 and 2011-13 were derived using data from the First National Cause-of-Death Survey and the Shandong Death Registration System, respectively. ASMRs were smoothed using Area-to-Area Poisson kriging technique. Spatial scan statistics were used to detect spatial clusters with higher EC mortality and clusters with greater temporal changes in EC mortality. Results: The provincial average ASMR decreased from 13.0 per 100,000 in 1970-74 to 5.8 in 2010-13. Almost all counties or districts have experienced a decrease in EC mortality, while the reduction was particularly pronounced in the mid-west region. This study has identified a geographical cluster with much higher EC mortality rates and the clustering pattern has largely unchanged over the past 40 years. Residents living in the cluster during 1970-74 were 2.7 (95% CI: 2.2-3.4) times more likely to die from EC than the rest of the province. The corresponding risk ratio for the 2011-13 cluster was 3.7 (95% CI: 2.8-5.0). Conclusions: This study detected a geographically defined subpopulation in Shandong, China with much higher risk of dying from EC. This spatial pattern has been consistent over the past few decades. The results suggest the key drives for geographic variations in esophageal cancer may not have changed.

The rectification of terahertz radiation due to plasmonic nonlinearities in a periodic graphene structure with a dual-grating gate and an asymmetric unit cell is considered. The influence of unit-cell asymmetry on the plasmonic rectification of the terahertz radiation near higher plasmonic resonances is considered for the cases of electron and hole conduction in parts of the graphene unit cell. The current responsivity of the rectification of terahertz radiation due to the plasmonic effects of differential charge-carrier drag and electron–hole ratchet is calculated.

Accurate identification of economic recessions in a timely fashion is a major macroeconomic challenge. The so-called Sahm recession indicator ( Sahm, 2019 ), one of the most reliable early detectors of the U.S. recessions, relies on changes in unemployment rates, and is thus subject to misclassification errors in labor force statuses based on survey data. We propose a novel misclassification-errors correction to improve the predictive timeliness and provide a proper threshold value. Using historical data, we show that the adjusted unemployment-based recession indicator offers earlier identification of economic recessions.

// Zhentao Fu 1, * , Yingmei Li 2, * , Zilong Lu 1, * , Jie Chu 1 , Jiandong Sun 3 , Jiyu Zhang 1 , Gaohui Zhang 1 , Fuzhong Xue 4 , Xiaolei Guo 1, ** and Aiqiang Xu 1, ** 1 Department for Chronic and Non-Communicable Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China 2 The Second People's Hospital of Jinan, Jinan, China 3 School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia 4 School of Public Health, Shandong University, Jinan, China * The first three authors contributed equally to this work ** The last two authors contributed equally to this work Correspondence to: Xiaolei Guo, email: guoxiaolei@126.com Aiqiang Xu, email: aqxuepi@163.com Keywords: lung cancer, spatial scan statistics, mortality, epidemiology Received: March 27, 2017 Accepted: August 06, 2017 Published: September 21, 2017 ABSTRACT Lung cancer has long been a major health problem in China. This study aimed to examine the temporal trend and spatial pattern of lung cancer mortality in Shandong Province from 1970 to 2013. Lung cancer mortality data were obtained from Shandong Death Registration System and three nationwide retrospective cause-of-death surveys. A Purely Spatial Scan Statistics method with Discrete Poisson models was used to detect possible high-risk spatial clusters. The results show that lung cancer mortality rate in Shandong Province increased markedly from 1970-1974 (7.22 per 100,000 person-years) to 2011-2013 (56.37/100, 000). This increase was associated with both demographic and non-demographic factors. Several significant spatial clusters with high lung cancer mortality were identified. The most likely cluster was located in the northern region of Shandong Province during both 1970-1974 and 2011-2013. It appears the spatial pattern remained largely consistent over the last 40 years despite the absolute increase in the mortality rates. These findings will help develop intervention strategies to reduce lung cancer mortality in this large Chinese population.

Graphene field-effect transistors (G-FETs) are being developed with ever increasing sensitivity as terahertz direct detectors at room temperature. The noise-equivalent power is being reduced towards the order of 1pW/Hz with frequency about 650 GHz. G-FET-based frequency multipliers and subharmonic mixers are becoming new active components for both millimeter and terahertz wave technologies. We report a 650-GHz G-FET coupled with terahertz antennas and a quasi-optical silicon lens for heterodyne/subharmonic detection. Heterodyne detection at 216 and 648 GHz, second-subharmonic detection at 432 GHz, and third-subharmonic detection at 648 GHz were demonstrated and characterized. Self-mixing/homodyne detection was used as a calibration tool for the power levels of the local pump source and the source to be detected. The conversion losses of heterodyne mixing at 216 GHz (off-resonant) and 648 GHz (resonant) were 38.4 dB and 57.9 dB with 12.8 dBm and −14 dBm of local pump power, respectively. The conversion loss of the second-harmonic mixing at 432 GHz is about 8 dB higher than that of the heterodyne mixing at 216 GHz. Calculations based on our quasi-static mixing model agree well with the measured conversion losses. To improve the conversion loss, more details on the G-FET noise, the optimal pump power, and the antenna should be examined.

We report a room-temperature, low-impedance and high-sensitivity terahertz direct detector based on bilayer graphene field-effect transistor (GFET). Epitaxially grown on silicon carbide, the bilayer graphene had an as-grown carrier mobility of 3000 cm 2 /Vs. The source/drain contacts were formed on the freshly cleaned graphene sheet to minimize the contact resistance and served also as terahertz antennas. The gate and the dielectric layer underneath with a length of 145 nm and a gap of 203 nm to the source/drain antennas were formed in a self-alignment process. Although the carrier mobility in the GFET was reduced to about 405 cm 2 /Vs, the high-quality ohmic contacts and the short graphene channel delivered an overall source-drain resistance less than 203 Ω. A voltage responsivity of 30 V/W and a noise-equivalent power of 51 pW/Hz 1/2 were estimated in direct detection at 0.33 THz. By using the GFET detector as a two-terminal detector, i.e., with the gate floating, a transmission-type terahertz imaging was demonstrated. Such a low-impedance GFET detector is ready to be matched to a commercial 50-Ω low-noise radio/microwave frequency amplifier allowing for high-speed homodyne detection and heterodyne detection in a quasi-optical configuration.

Pulmonary edema is a fatal complication of EV71-associated hand, foot, and mouth disease (HFMD). The pathogenesis of EV71-induced pulmonary edema remains largely unclear. In this study, we aimed to explore the roles of the capsid protein VP1 in the occurrence of EV71-induced pulmonary edema. The intranasal inoculation of recombinant VP1 protein caused lung inflammation with an elevation of inflammatory cytokines and neutrophils infiltration. Moreover, neutrophil extracellular traps (NETs) were observed in the lung parenchyma of the mice treated with VP1. VP1 directly induced the formation of NETs, which depended on PAD4. VP1 also damaged the lung barrier via the reduction of the tight junction protein occludin. Moreover, the EV71 attachment receptor vimentin was increased upon VP1 administration. In contrast, NETs decreased vimentin levels, suggesting a novel role for NETs in viral immune defense. These results evidenced a direct role of VP1 in EV71-induced pulmonary edema and demonstrated that NETs may be both harmful and beneficial in EV71 infection.

Esophageal cancer (EC) is a leading cause of cancer death in China. Within Shandong Province, a geographic cluster with high EC mortality has been identified, however little is known about how area-level socioeconomic status (SES) is associated with EC mortality in this province. Multilevel models were applied to EC mortality data in 2011–13 among Shandong residents aged 40+ years. Area-level SES factors consisted of residential type (urban/rural) of the sub-county-level units (n = 262) and SES index (range: 0–10) of the county-level units (n = 142). After adjustment for age and sex, residents living in rural areas had a 22% (95% CI: 13–32%) higher risk of dying from EC than those in urban areas. With each unit increase in the SES index, the average risk of dying from EC reduced by 10% (95% CI: 3–18%). The adjustment of area-level SES variables had little impact on the risk ratio of EC mortality between the high-mortality cluster and the rest of Shandong. In conclusion, rural residence and lower SES index are strongly associated with elevated risks of EC death. However, these factors are independent of the high mortality in the cluster area of Shandong. The underlying causes for this geographic disparity need to be further investigated.

The first cell lineage differentiation occurs during the development of mouse 8-cell embryo to blastocyst. Akt is a potent kinase whose role during blastocyst formation has not been elucidated. In the present study, immunofluorescence results showed that the Akt protein was specifically localized to the outer cells of the morula. Akt-specific inhibitor MK2206 significantly inhibited mouse blastocyst formation and resulted in decreased expression of the trophectoderm marker Cdx2 and led to granular distribution of ERα in the cytoplasm. Furthermore, knockdown of ERα by siRNA microinjection can also lead to a decrease in the development rate of mouse blastocysts, accompanied by a decrease in the expression level of Yap protein. We conclude that Akt may be indispensable for the first cell lineage differentiation of mouse.

This study aimed to explore the geographic distribution and risk clusters of pancreatic cancer mortality from 2011 to 2013 in Shandong, China, and to detect the differences between urban and rural areas. Our data were obtained from the Shandong Death Registration System (SDRS) and were adjusted according to the underreporting level. The distribution of mortality was displayed with GIS-based maps at the county level. The results showed an increasing trend in pancreatic cancer mortality from the western region to the eastern region of Shandong. Additionally, four significant risk clusters were detected, and the most likely cluster was focused in the northeastern and northern regions. Urban-rural differences in the mortality distribution and risk clusters were also detected. In conclusion, our study identified pancreatic cancer mortality clusters in Shandong in urban and rural areas; these results can contribute to the development of effective and targeted strategies to control pancreatic cancer in different areas.

Background Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. Methods In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. Results The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). Conclusions Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.

Infertility caused by environmental pollution is becoming a global problem, but an effective prevention or treatment is lacking. Icariin (ICA) is a flavonoid used in traditional Chinese medicine. The present study investigated the possible roles of ICA in preventing testicular dysfunction caused by di(2-ethylhexyl) phthalate (DEHP), one of the most studied environmental endocrine disruptors. Cultured mouse Leydig cells were pretreated with ICA and exposed to DEHP to determine ICA effects upon cell proliferation, reactive oxygen species (ROS) levels, mitochondrial membrane potential (Δψm), testosterone levels and the expression of transcription factor SF-1 and steroidogenic enzymes (CYP11, 3β-HSD and 17β-HSD), which play critical roles in androgen production. Our results showed that ICA reversed the adverse effect of DEHP on Leydig cell proliferation, and decreased ROS levels and elevated Δψm levels. Also, ICA promoted testosterone production and up-regulated the expression of SF-1 and steroidogenic enzymes. We investigated ICA actions in vivo, using male mice administrated DEHP followed by ICA. Exposure to DEHP decreased epididymal sperm counts and disrupted seminiferous tubules, and both of these effects were reversed by ICA treatment. These results showed that the mechanisms of ICA in protecting mouse testes against DEHP-induced damage involves the prevention of ROS accumulation and promotion of testosterone secretion.

Plasmon in two-dimensional electron gas (2DEG) has long been considered as a promising active medium for terahertz emitters and detectors. However, the efficiency of terahertz plasmonic devices is severely limited by the high damping rate of plasma wave in solid state. In addition to the enhancement of plasmon lifetime by using 2DEGs with higher carrier mobility, engineering on the boundary condition and electromagnetic environment of plasmon cavity helps to preserve the plasmon states. Here we report on terahertz reflection spectroscopy of plasmon states in a grating-coupled AlGaN/GaN-2DEG plasmonic device at 7 K in equilibrium with ambient blackbody irradiation. Localized plasmon states and plasmon-polariton states were observed when the core plasmonic device is integrated with a silicon lens and when it is embedded in a terahertz Fabry-Perot cavity, respectively. Simulation results including the reflection spectra and total reflection power agree well with the measured results. The Rabi splitting is found to be inversely proportional to the resonance frequency, and follows a linear relation with the square root of the sheet electron density. A normalized coupling ratio, ΩRω0≈0.13, is achieved between the Rabi splitting ΩR and the resonance frequency ω0. The coupling ratio could be further increased to allow for ultrastrong coupling between terahertz photons and plasmons.

International patterns suggest germ cell testicular cancer (GCTC) incidence may be lower in lower latitudes. To investigate this possibility, we examined GCTC incidence by latitude (population centroid in 2000) for men ≥15 years within two reasonably homogeneous countries, the United States and Australia. In the United States, we examined age-adjusted incidence/latitude trends using data from states (2001-2010) and local-area registries (1980-2011). In Australia, we evaluated incidence/latitude trends in 61 Statistical Divisions (2000-2009). In U.S. White men (68 566 cases), state incidences increased by latitude, rising 5.74% (4.45-7.05%) per 5°North latitude increment. Similar trends were found for seminoma and nonseminoma subtypes (P < 0.001). In U.S. Black men (2256 cases), the association was also seen (4.9%; 0.2-9.7%). In local U.S. data, similar increases in incidence with latitude were present in each of the last three decades. In Australia (6042 cases), the incidence increased by 4.43% (95% CI: 1.54-7.39%) per 5°South, and trends for subtypes were similar. Thus, we found that incidence of GCTC in both White and Black men increased significantly with distance from the equator, approximately 1% per degree within the range of latitudes studied.

While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation.

SummaryA CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO) mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

The present study aimed to understand spirituality and its relationships with socioeconomic status (SES), religious background, social support, and mental health among Indian university students. It was hypothesized that (1) female university students will be more spiritual than male university students, (2) four domains of spirituality will differ significantly across socioeconomic and religious background of the university students in addition to social support, and (3) there will be a positive relationship between spirituality and mental health of university students, irrespective of gender. A group of 475 postgraduate students aged 20-27 years, 241 males and 234 females, from various disciplines of Pondicherry University, India, participated in the study. Students' background was collected using a structured questionnaire. Overall spirituality and its four dimensions were measured using the Spirituality Attitude Inventory, while mental health status was estimated based on scores of the psychological subscale of the WHO Quality of Life Questionnaire. Female students were significantly more spiritual than male students, particularly in spiritual practice and sense of purpose/connection. Hindu religion and lower family income were associated with lower spirituality. Higher spirituality was associated with congenial family environment and more support from teachers and classmates. There was a strong association between overall spirituality and two spirituality domains (spiritual belief and sense of purpose/connection) with better mental health. Findings suggest an opportunity for open dialogue on spirituality for university students as part of their mental health and support services that fosters a positive mind set and enhancement of resilience.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by deficiency of maternally inherited UBE3A, an ubiquitin E3 ligase. Despite recent progress in understanding the mechanism underlying UBE3A imprinting, there is no effective treatment. Further investigation of the roles played by UBE3A in the central nervous system (CNS) is needed for developing effective therapies.This review covers the literature related to genetic classifications of AS, recent discoveries regarding the regulation of UBE3A imprinting, alterations in cell signaling in various brain regions and potential therapeutic approaches. Since a large proportion of AS patients exhibit comorbid autism spectrum disorder (ASD), potential common molecular bases are discussed.Advances in understanding UBE3A imprinting provide a unique opportunity to induce paternal UBE3A expression, thus targeting the syndrome at its 'root.' However, such efforts have yielded less-than-expected rescue effects in AS mouse models, raising the concern that activation of paternal UBE3A after a critical period cannot correct all the CNS defects that developed in a UBE3A-deficient environment. On the other hand, targeting abnormal downstream cell signaling pathways has provided promising rescue effects in preclinical research. Thus, combined reinstatement of paternal UBE3A expression with targeting abnormal signaling pathways should provide better therapeutic effects.

Epidemiological studies suggest an association between pesticides and the incidence of Parkinson’s disease (PD). Individuals are likely to be exposed to numerous natural or synthetic environmental agents by ingestion, inhalation, or skin contact. Here, we describe a novel environment-contact administration of rotenone model, in which male C57BL/6 mice (15 per group per time-point) were placed in one bedding-free, rotenone-applied cage for 2 h every day over a period of 2–6 weeks, mimicking the common ways a person may be exposed to pesticides. Our results showed that rotenone exposure had no detrimental effect on body weights of mice during 6 weeks, nor did it cause systemic toxicity (HPLC analysis of rotenone in blood and brain, as well as complex I activity measurements in brain and muscle), but it caused significant impairments in motor function (open field test, pole test, and rotarod test) from 4 weeks that were responsive to apomorphine. Accordingly, rotenone caused significant dopamine depletion from the striatum (HPLC analysis), nigrostriatal degeneration (quantitative tyrosine hydroxylase immunohistochemistry and western blot), and accumulation of α-synuclein in the substantia nigra and striatum (α-synuclein immunohistochemistry) in a time-dependent manner. In addition, rotenone-exposed mice also developed deficits in gastrointestinal and olfactory function (fecal pellet output and buried food pellet test) prior to the motor dysfunction. Furthermore, we observed that α-synuclein accumulated in the anterior olfactory nucleus and the enteric nervous system at 2 weeks. In summary, this novel rotenone model was able to reproduce many key aspects of PD progression. Therefore, it provides new insight into how environmental factors could trigger PD and provides a useful tool for studying PD pathogenesis and testing neuroprotective strategies.

We report an attempt to improve the sensitivity of terahertz detection based on self-mixing in antenna-coupled field-effect transistors by enhancing the field-effect factor and the antenna factor with a reduced gate length and a reduced antenna-gate gap, respectively. An optical noise equivalent power (NEP) of 3.7 pW/Hz at 0.65 THz was achieved in a GaN/AlGaN high-electron-mobility transistor (HEMT) with a gate length of 300 nm and an antenna-gate gap of 200 nm at room temperature. It was found that the antenna factor was inversely proportional to the antenna-gate gap, and the responses upon coherent/incoherent terahertz irradiation were well described by the self-mixing model. To fill the NEP gap of 0.1−1 pW/Hz between room-temperature and cryogenic detectors by HEMT-based detectors at room temperature, impedance match needs to be carefully considered.