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Intervertebral disc degeneration (IVDD) is a prevalent orthopedic condition with lower back pain as the predominant clinical presentation that challenges clinical treatment with few therapeutic options. Duhuo Jisheng Decoction (DHJSD) has been proven effective in the therapy of IVDD, but the precise underlying mechanisms remain not fully elucidated. The current study was designed to test our hypothesis that DHJSD may systematically correct the phenotypic disruption of the gut microbiota and changes in the serum metabolome linked to IVDD. Analysis of the active ingredients of DHJSD by ultra high performance liquid chromatography. An integrated metagenomic and metabonomic approach was used to analyze feces and blood samples from normal and IVDD rats. Compared to the control group, fiber ring pinning on the caudal 3 to caudal 5 segments of the rats caused IVDD and significantly altered the compositions of the intestinal microbiota and serum metabolites. Integrated analysis revealed commonly-altered metabolic pathways shared by both intestinal microbiota and serum metabolome of the IVDD rats. DHJSD inhibited the degenerative process and restored the compositions of the perturbed gut microbiota, particularly the relative abundance of commensal microbes of the Prevotellaceae family. DHJSD also corrected the altered metabolic pathways involved in the metabolism of glycine, serine, threonine, valine, the citric acid cycle, and biosynthesis of leucine and isoleucine. DHJSD inhibited the disc degeneration process by an integrated metagenomic and metabonomic mechanism to restore the microbiome profile and normalize the metabonomic pathways., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The digitalization of low-carbon energy technologies (LCET) provides important technical support for the transition to a greener energy system. Digitalization addresses the phenomenon of the growing application of information and communications technologies (ICT) across the economy, which is regarded as the technology convergence between ICT and other technologies. Scholars have revealed the signs that LCET and ICT are becoming increasingly interlinked, which raises the challenges for predicting and identifying the technology opportunities for innovations in the converged technology area. To address the challenges, this paper proposes a collaborative filtering approach to identify the digitalization technology opportunity of low-carbon energy technologies using patent classification and patent citation information. We applied the proposed collaborative filtering approach using a large LCET patent dataset derived from the United States Patent and Trademark Office (USPTO). The results indicate that the proposed method can effectively identify digitalization technology opportunities of LCET, and the current LCET digitalization technology opportunities identified based on this approach are mainly concentrated in the Energy storage field. The advantages of the proposed approach are that its underlying data are more readily available and its technical complexity is relatively lower, and thus, more replicable for other technology fields., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu, Cai. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Supporting cells(SCs) have been demonstrated to be a reliable source for regenerating hair cells(HCs). Previous research has reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo. However, there is limited knowledge about the impact of the material on Lgr5+ cells. In this study, Lgr5+ cells were isolated from neonatal Lgr5-EGFP-CreERT2 transgenic mice by flow cytometry and then plated on self-assembled silica beads (SB). Lgr5+ cell differentiation was observed by immunofluorescence. We found that in the direct differentiation assay, the SB group generated more hair cells than the control group(*p < 0.05). Especially in the SB group, Lgr5+ progenitors generated significantly more Myo7a+ HCs outside of the colony than in the control group(**p < 0.01). In the sphere differentiation assay, we found that the diameter of spheres in the SB group was significantly larger compared to those of the control group(**p < 0.01). However, the difference in the ratio of myo7a+ cell counts was not obvious(P>0.05). The experiment proved that the self-assembled silica beads could promote the differentiation of Lgr5+ progenitors in vitro. Our findings implicate that nanostructures of self-assembled silica beads can be used as vectors for stem cell research in the inner ear., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Alterations in the composition and abundance of the intestinal microbiota occur in non-alcoholic fatty liver disease (NAFLD). However, the results are inconsistent because of differences in the study design, subject area, and sequencing methodology. In this study, we compared the diversity and abundance of the intestinal microbiota of patients with NAFLD and healthy individuals through a systematic review and meta-analysis., Methods: Three databases (PubMed, EMBASE, and Cochrane Library) were searched from their inception to March 20, 2023. A meta-analysis was performed using Stata software to analyze variations in the richness and abundance of the intestinal microbiota in patients with NAFLD. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used for quality assessment., Results: A total of 28 articles were included. Shannon diversity was reduced in patients with NAFLD (SMD = -0.24 (95% CI -0.43-0.05, I2 = 71.7%). The relative abundance of Ruminococcus, Faecalibacterium, and Coprococcus all decreased, with total SMDs of -0.96 (95% CI -1.29 to -0.63, I2 = 4.8%), -1.13 (95% CI -2.07 to -0.19, I2 = 80.5%), and -1.66 (95% CI -3.04 to -0.28, I2 = 91.5%). Escherichia was increased in individuals with NAFLD (SMD = 1.78, 95% CI 0.12 to 3.45, I2 = 94.4%)., Conclusion: Increasing the species diversity and altering the abundance of specific gut microbiota, including Coprococcus, Faecalibacterium, Ruminococcus, and Escherichia, may be beneficial for improving NAFLD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: We aimed to describe the trends and influence factors in the prevalence, awareness, treatment, and control of hypertension among US Adults from 1999 to 2018., Methods: We utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning ten survey cycles (n = 53,496). Prevalence, awareness, treatment, and control of hypertension were calculated using survey weights. Joinpoint regression and survey-weighted generalized linear models were used to analyze trends and influence factors, respectively., Results: The estimated prevalence of hypertension increased significantly from 33.53% to 40.58% (AAPC = 0.896, P = 0.002) during 1999-2018 with dropping rate of newly diagnosed hypertension from 8.62% to 4.82% before 2014 (APC = -4.075, P = 0.001), and then rose to 7.51% in 2018 (APC = 12.302, P = 0.126). Despite modest improvements or stability in the awareness, treatment, and control since 1999, the latter two remained inadequate in 2018 at 59.52% and 51.71%. There was an uptrend in the use of angiotensin-converting enzyme inhibitors (from 24.02% to 45.71%) and angiotensin receptor blockers (from 20.22% to 38.38%), and downtrend in β-blocker (from 12.71% to 4.21%). Men were at higher risk of incidence, un-awareness, un-treatment, and un-control for hypertension. Lower income and education were associated with susceptibility to hypertension, while being married was favorable for treatment and control. Optimal health reduced the incidence of hypertension, and increased the awareness and treatment., Conclusion: Although the rate of newly diagnosed hypertension has declined slightly since 2010 in the US, the prevalence of hypertension is increasing, and treatment and control rates remain inadequate. To manage hypertension effectively, we need to focus on screening and prevention for high-risk populations, while advocating for optimal health to improve the burden of hypertension., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the growth of people's environmental awareness and the encouragement of government policies, the use of electric vehicles in logistics distribution is gradually increasing. In order to solve the dual demand of customers' simultaneous pick-up and delivery in the "last kilometer logistics", an electric vehicle routing problem with simultaneous pick-up and delivery and time window (EVRPSPDTW) is considered from the perspective of multi-objective distribution in this paper. Firstly, a decision-making model based on distribution cost and power consumption function is established. In this model, distribution cost includes transportation cost, vehicle use cost, penalty cost of not arriving on time and charging cost. Power consumption function is the energy loss caused by air resistance, tire rolling friction and transmission system. Secondly, a multi-objective genetic algorithm (NSGA-II) optimization solution with fast nondominated ranking and elite strategy is designed, and in view of the shortcomings of traditional NSGA-II, it is proposed to complete population initialization through greedy algorithm and random rules, introduce adaptive cross-mutation strategy in the chromosome crossing and mutation stage, and design three different neighborhood operators in mutation operation based on variant fitness function. Finally, the sensitivity analysis of traffic congestion coefficient further proves the effectiveness of the proposed model and the improved algorithm., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Crack is the external expression form of potential safety risks in bridge construction. Currently, automatic detection and segmentation of bridge cracks remains the top priority of civil engineers. With the development of image segmentation techniques based on convolutional neural networks, new opportunities emerge in bridge crack detection. Traditional bridge crack detection methods are vulnerable to complex background and small cracks, which is difficult to achieve effective segmentation. This study presents a bridge crack segmentation method based on a densely connected U-Net network (BC-DUnet) with a background elimination module and cross-attention mechanism. First, a dense connected feature extraction model (DCFEM) integrating the advantages of DenseNet is proposed, which can effectively enhance the main feature information of small cracks. Second, the background elimination module (BEM) is proposed, which can filter the excess information by assigning different weights to retain the main feature information of the crack. Finally, a cross-attention mechanism (CAM) is proposed to enhance the capture of long-term dependent information and further improve the pixel-level representation of the model. Finally, 98.18% of the Pixel Accuracy was obtained by comparing experiments with traditional networks such as FCN and Unet, and the IOU value was increased by 14.12% and 4.04% over FCN and Unet, respectively. In our non-traditional networks such as HU-ResNet and F U N-4s, SAM-DUnet has better and higher accuracy and generalization is not prone to overfitting. The BC-DUnet network proposed here can eliminate the influence of complex background on the segmentation accuracy of bridge cracks, improve the detection efficiency of bridge cracks, reduce the detection cost, and have practical application value., Competing Interests: The authors have declared that no competing interests exist.

Guanidinoacetic acid (GAA) is the only precursor for the creatine synthesis of vertebrates. Creatine (Cr) and phosphocreatine (PCr) are able to provide energy for the rapid growth and development of the muscle tissue. This study evaluated the effects of dietary different levels GAA on growth performance, GAA absorption and creatine metabolism of lambs. Twenty-four 3-month-old healthy Kazakh male lambs (body weight = 27.35± 0.58 kg) were randomly divided into four groups with 6 lambs in each group. The lambs were fed with the basal diets supplemented with 0 (0 mg/kg group), 500 (500 mg/kg group), 1000 (1000 mg/kg group) and 1500 mg (1500 mg/kg group) GAA per kg diet (DM basis), respectively. The results showed that, as the GAA content of the diet increased, there was a quadratic change in DMI, with the lowest in the 500 mg/kg group and the highest in the 0 mg/kg group. The CK enzyme activity and ATP content in quadriceps muscle increased linearly with increasing levels of diary GAA in the diet. PCr levels and ADP levels in the longest dorsal muscle increased linearly with increasing levels of GAA in the diet. The relative expression of SLC6A6 and SLC6A8 mRNA in the jejunum and ileum mucosa showed a quadratic change as the dietary GAA level increased, with the lowest relative expression in both the 1500 mg/kg group. With the increase of dietary GAA level, both Cr concentration in hepatic vein plasma and the portal plasma GAA concentration shows a quadratic change, with the highest concentration in the 500 mg/kg group and the lowest concentration in the 0 mg/kg group. Therefore, dietary supplementation with 500~1000 mg/kg DM GAA is recommended for lambs., Competing Interests: The authors have declared that no competing interests exist.

Purposes: This study aimed to explore the effect of education on subjective well-being (SWB) of Chinese rural dwellers who just shook off poverty in 2019 and to investigate the mediating role of social support and moderating role of age on the association., Methods: Social support rating scale (SSRS) and General Well-Being Schedule (GWBS) were administrated among 1094 Chinese rural dwellers from Anqing, Anhui Province, China. Structural equation modeling (SEM) and multi-group SEM were performed to examine the mediating role of social support and moderating role of age in the link between education and SWB, respectively., Results: The findings indicated that social support fully mediated the relationship between education and SWB in rural residents. Age moderated the indirect relationship between education and SWB (first stage moderation model) such that the effect of education on social support would be strengthened with aging process., Conclusions: The results add to our understanding of the protective role of education in SWB among Chinese rural dwellers, and shed new light on the potential mechanisms underlying the association between education and SWB with respect to the mediating role of social support and moderating role of age., Competing Interests: The authors have declared that no competing interests exist.

Anomaly detection in network traffic is becoming a challenging task due to the complexity of large-scale networks and the proliferation of various social network applications. In the actual industrial environment, only recently obtained unlabelled data can be used as the training set. The accuracy of the abnormal ratio in the training set as prior knowledge has a great influence on the performance of the commonly used unsupervised algorithms. In this study, an anomaly detection algorithm based on X-means and iForest is proposed, named X-iForest, which clusters the standard Euclidean distance between the abnormal points and the normal cluster centre to achieve secondary filtering by using X-means. We compared X-iForest with seven mainstream unsupervised algorithms in terms of the AUC and anomaly detection rates. A large number of experiments showed that X-iForest has notable advantages over other algorithms and can be well applied to anomaly detection of large-scale network traffic data., Competing Interests: The authors have declared that no competing interests exist.

Purposes: Since a considerable number of health care workers (HCWs) were sent to Wuhan to aid COVID-19 control during the epidemic, non-frontline HCWs who stayed in local hospitals had to work overload to provide daily health care services for other health issues, which makes them more vulnerable to experience fatigue. Self-efficacy is suggested as a protective factor for fatigue. Nonetheless, less is known regarding the underlying mechanisms. This research aimed to explore the prevalence of fatigue among non-frontline HCWs during the pandemic, investigate the mediating effect of posttraumatic stress disorder (PTSD) symptoms and moderating effect of negative coping in the association between self-efficacy and fatigue., Methods: General Self-Efficacy Scale, PTSD Checklist-Civilian Version, Simplified Coping Style Questionnaire and 14-item Fatigue Scale were administrated to 527 non-frontline HCWs from Anhui Province, China. The mediating effect was examined by Mackinnon's four-step procedure, while Hayes PROCESS macro was used to test the moderated mediation model., Results: The prevalence of fatigue among non-frontline HCWs was 56.7%. The effect of self-efficacy on fatigue was partially mediated by PTSD symptoms (ab = -0.146, SE = 0.030, 95% CI = [-0.207, -0.095]). Additionally, negative coping moderated both the direct effect of self-efficacy on fatigue (β = -0.158, P<0.001) and the mediating effect of PTSD symptoms (β = 0.077, P = 0.008). When the standard score of negative coping increased to 1.49 and over, the direct association between self-efficacy and fatigue became insignificant. Likewise, the effect of self-efficacy on PTSD symptoms had no statistical significance when the standard score of negative coping was -1.40 and lower., Conclusions: More than half non-frontline HCWs suffered from fatigue during COVID-19. For those who tend to use negative coping, it might be crucial to design programs combining the enhancement of self-efficacy, preventions for PTSD symptoms and interventions for fatigue., Competing Interests: The authors have declared that no competing interests exist.

Purposes: During the outbreak of Coronavirus Disease 2019 (COVID-19) all over the world, the mental health conditions of health care workers are of great importance to ensure the efficiency of rescue operations. The current study examined the effect of social support on mental health of health care workers and its underlying mechanisms regarding the mediating role of resilience and moderating role of age during the epidemic., Methods: Social Support Rating Scale (SSRS), Connor-Davidson Resilience scale (CD-RISC) and Symptom Checklist 90 (SCL-90) were administrated among 1472 health care workers from Jiangsu Province, China during the peak period of COVID-19 outbreak. Structural equation modeling (SEM) was used to examine the mediation effect of resilience on the relation between social support and mental health, whereas moderated mediation analysis was performed by Hayes PROCESS macro., Results: The findings showed that resilience could partially mediate the effect of social support on mental health among health care workers. Age group moderated the indirect relationship between social support and mental health via resilience. Specifically, compared with younger health care workers, the association between resilience and mental health would be attenuated in the middle-aged workers., Conclusions: The results add knowledge to previous literature by uncovering the underlying mechanisms between social support and mental health. The present study has profound implications for mental health services for health care workers during the peak period of COVID-19., Competing Interests: The authors have declared that no competing interests exist.

Background: Quantifying dose-dependent ultra-early edema and ultrastructural changes in the myocyte after drug delivery is important for the development of new mixed calcium channel blockers (CCBs)., Materials and Methods: Arterial cannulation was used to measure mean arterial pressure in real time; simultaneously, magnetic resonance imaging proton density mapping was used to quantify edema 5-55 min after the delivery of L-type CCBs, T- and L-type CCBs, and solvent to a spontaneously hypertensive rat model. Transmission electron microscopy was used to show ultrastructural changes in the myocyte., Results: Analysis of variance showed significant differences among the three groups in mean arterial pressure reduction (F = 246.36, P = 5.75E-25), ultra-early level of edema (ULE) (F = 175.49, P = 5.62E-22), and dose-dependent level of edema (DLE) (F = 199.48, P = 4.28E-23). Compared with the solvent's mean arterial pressure reduction (2.65±6.56±1.64), ULE (1.16±0.09±0.02), and DLE (0.0010±0.0001±0.0000), post hoc tests showed that T- and L-type CCBs had better mean arterial pressure reduction (90.67±11.58±2.90, P = 1.06E-24 vs. 68.34±15.19±3.80, P = 1.76E-12), lower ULE (1.53±0.14±0.04, P = 4.74E-9 vs. 2.08±0.18±0.04, P = 2.68E-22), and lower DLE (0.0025±0.0004±0.0001, P = 1.14E-11 vs. 0.0047±0.0008±0.0002, P = 2.10E-11) than L- type CCBs. Transmission electron microscopy showed that T- and L-type CCBs caused fewer ultrastructural changes in the myocytes after drug delivery than L-type CCBs., Conclusion: T- and L-type CCBs produced less ultra-early and dose-dependent edema, fewer ultrastructural changes in the myocyte, and a greater antihypertensive effect. Proton density mapping combined with arterial cannulation and transmission electron microscopy allowed for quantification of ultra-early and dose-dependent edema, antihypertensive efficacy, and ultrastructural changes in the myocyte. This is important for the evaluation of induced vasodilatory edema., Competing Interests: The authors have declared that no competing interests exist.

With rapid economic and population growth, construction land expansion in Yangtze River economic belt in China becomes substantial, carrying significant social and economic implications. This research uses Expansion Speed Index and Expansion Intensity Index to examine spatiotemporal characteristics of construction land expansion in the Yangtze River economic belt from 2000 to 2017. Based on a STIRPAT model, driving forces of construction land expansion are measured by Principal Component Analysis and Ordinary Least Square regression. The results show that: (1) there is a clear expansion pattern regarding the time sequence in provinces/cities of the Yangtze River economic belt, with rapid expansion in the initial stage, moderate expansion in the middle stage and rapid expansion in the later stage. (2) Spatial analysis demonstrates first expansion in the lower reaches in the early stage, rapid expansion of the upper reaches in the middle and later stage, and steady expansion of the middle reaches throughout the research period. (3)There are statistical significant correlations between construction land expansion and GDP, social fixed asset investments, population at the end of the year, population urbanization rate, per capita road area, and number of scientific and technological professionals as well as secondary and tertiary industry values. Of these factors, GDP, social fixed asset investments, population urbanization rate and second industry value are important common driving forces of construction land expansion in this region. The research findings have significant policy implications particularly on coordinated development of urban agglomerations and sustainable industry upgrading when construction land expansion is concerned., Competing Interests: NO authors have competing interests.

User reliability is notably crucial for personalized cloud services. In cloud computing environments, large amounts of cloud services are provided for users. With the exponential increase in number of cloud services, it is difficult for users to select the appropriate services from equivalent or similar candidate services. The quality-of-service (QoS) has become an important criterion for selection, and the users can conduct personalized selection according to the observed QoS data of other users; however, it is difficult to ensure that the users are reliable. Actually, unreliable users may provide unreliable QoS data and have negative effects on the personalized cloud service selection. Therefore, how to determine reliable QoS data for personalized cloud service selection remains a significant problem. To measure the reliability for each user, we present a cloud service selection framework based on user reputation and propose a new user reputation calculation approach, which is named MeURep and includes L1-MeURep and L2-MeURep. Experiments are conducted, and the results confirm that MeURep has higher efficiency than previously proposed approaches., Competing Interests: The authors have declared that no competing interests exist.

Previous studies have found that high social class individuals are more dishonest than low social class ones. However, the underlying mechanism of this phenomenon is still unclear. The "ignoring negative consequences" hypothesis suggests that belonging to a high social class makes individuals ignore the negative consequences of dishonesty, whereas the "self-focused" hypothesis suggests that belonging to a high social class makes individuals focus more on the self and self-interests. The present study aims to examine these two hypotheses by measuring participants' subjective social class, narcissism, fear of negative evaluation, and tendency to be dishonest. To this end, an online survey was conducted. Results provide evidence for the self-focused hypothesis by showing that subjective social class positively predicts the tendency to be dishonest, and narcissism plays a mediating role in this relationship., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The shortage of emergency drugs in China is severe. This study aimed to characterize emergency drug shortages in China and to measure their effects., Methods: An online questionnaire based on a literature review was sent to emergency department physicians in Chinese secondary and tertiary hospitals from November 2016 to February 2017. The survey asked physicians questions about their experiences with emergency drug shortages., Results: In total, 236 physicians from 29 provinces participated in the survey. According to their responses, 90.7% of the respondents experienced drug shortages during the last year. More than half of the physicians (65.7%) reported that drug shortages occurred at least once a month. Hospitals in the eastern and western regions of China had more emergency drugs in shortage than hospitals in central China, especially those with many inpatient beds (≥800). In addition, the shortage situation was more serious in secondary hospitals than in tertiary hospitals. More respondents agreed that original medicines, injections, essential medicines, medicines without alternative agents and cheap medicines were more susceptible to shortages than generics, oral medicines, nonessential medicines, medicines with alternative agents and expensive medicines, respectively. Most respondents thought that drug shortages always, often or sometimes affected patients [delayed therapy (62.6%), longer rescue and recovery times (58.9%) and higher costs (58.7%)] and physicians [inconvenience (81.0%), higher pressure (76.5%) and harm to patient-doctor relationships (72%)] and compromised hospital reputations (55.1%)., Conclusions: The shortage of emergency drugs in China is serious, especially in secondary hospitals located in eastern and western China. Emergency drug shortages have significant effects on patients and physicians., Competing Interests: The authors have declared that no competing interests exist.

Diabetic kidney disease (DKD) is characterized by progressive glomerulosclerosis (GS). ROP mice have a sclerosis-prone phenotype. However, they develop severe, rapidly progressive GS when rendered diabetic. Since GS also develops in aged C57Bl6 mice, and can be reversed using bone marrow from young mice which have lower oxidative stress and inflammation (OS/Infl), we postulated that this might also apply to DKD. Therefore, this pilot study asked whether reducing OS/Infl in young adult sclerosis-prone (ROP) diabetic mice leads to resolution of existing GS in early DKD using safe, FDA-approved drugs.After 4 weeks of stable streptozotocin-induced hyperglycemia 8-12 week-old female mice were randomized and treated for 22 weeks as follows: 1) enalapril (EN) (n = 8); 2) pyridoxamine (PYR)+EN (n = 8); 3) pentosan polysulfate (PPS)+EN (n = 7) and 4) PPS+PYR+EN (n = 7). Controls were untreated (non-DB, n = 7) and hyperglycemic (DB, n = 8) littermates. PPS+PYR+EN reduced albuminuria and reversed GS in DB. Treatment effects: 1) Anti-OS/Infl defenses: a) PPS+PYR+EN increased the levels of SIRT1, Nrf2, estrogen receptor α (ERα) and advanced glycation endproduct-receptor1 (AGER1) levels; and b) PYR+EN increased ERα and AGER1 levels. 2) Pro-OS/Infl factors: a) PPS+PYR+EN reduced sTNFR1, b) all except EN reduced MCP1, c) RAGE was reduced by all treatments. In summary, PYR+PPS+EN modulated GS in sclerosis-prone hyperglycemic mice. PYR+PPS+EN also decreased albuminuria, OS/Infl and the sclerosis-prone phenotype. Thus, reducing OS/Infl may reverse GS in early diabetes in patients, and albuminuria may allow early detection of the sclerosis-prone phenotype., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to explore the properties of the Chinese version of the Anxiety Sensitivity Index- 3 (ASI-3) in a sample of military personnel. Using non-probabilistic sampling, the Chinese version of the ASI-3 was administered to 3,077 valid participants aged 16 to 36 years old (M = 22.35, SD = 3.57) from nine military units. The Depression Anxiety Stress Scales-21 (DASS-21) and The State-Trait Anxiety Inventory (STAI) were used to assess the construct validity. A one-way analysis of variance was conducted to compare the differences in the services and positions of the participants. It was found that ①The indices of confirmatory factor analysis met the standard values, which supported the hypothesis of the three-factor model of the original ASI-3; ②ASI-3 was significantly associated with DASS-21 in positive ways, which indicated the high convergent validity; on the other hand, the correlation between ASI-3 and TAI was relatively low, which indicated there was an empirical discrimination between anxiety sensitivity and trait anxiety. ③The Cronbach's α coefficients were 0.926 for the total scale and 0.828-0.841 for the three subscales; ④At a cut-off score of 16, the sensitivity and specificity levels were 71.1% and 76.7%, respectively, where the sum of sensitivity and specificity becomes the maximum, accompanied with improvement of PPV and NPV; ⑤There were significant findings in the ASI and subscales among the five services and four positions. This study provides new evidence that the Chinese version of the Anxiety Sensitivity Index-3 has good validity and reliability and could be applied as an effective tool to assess anxiety sensitivity in military personnel. Our recommendations to researchers and practitioners are that the three factor model should be replicated across some different special forces and the items and constructs could be modified on Chinese culture., Competing Interests: The authors have declared that no competing interests exist.

Background: Hospitals are vulnerable to fires and the evacuation process is challenging. However, face-to-face fire prevention and evacuation training may take healthcare workers' time away from patient care; therefore, effective on-line training may be warranted. We carried out and examined the effectiveness of an on-line education and training of fire prevention and evacuation training for healthcare workers in China by a randomized controlled trial using convenience sampling from five public hospitals in China., Methods: A total of 128 participants were recruited between December 2014 and March 2015. The authors built a webpage that included the informed consent statement, pre-test questionnaire, video training, and post-test questionnaire. After completing the pre-test questionnaire, participants were randomly assigned to watch the intervention video (basic response to a hospital fire) or the control video (introduction to volcanic disasters). A 45-item questionnaire on knowledge of fire prevention and evacuation was administered before and after the video watching. This questionnaire were further divided into two subscales (25-item generic knowledge of fire response and 20-item hospital-specific knowledge of fire prevention and evacuation). One point was awarded for each correct answer., Results: Half of the participants (n = 64, 50%) were randomized into the intervention group and the remaining 64 (50%) were randomized into the control group. For generic knowledge of fire prevention and evacuation, those in the intervention group improved significantly (from 16.16 to 20.44, P < 0.001) while the scores of those in the control group decreased significantly (from 15.27 to 13.70, P = 0.03). For hospital-specific knowledge of fire prevention and evacuation, those in the intervention group (from 10.75 to 11.33, P = 0.15) and the control group (from 10.38 to 10.16, P = 0.54) had insignificant change. For total score, those in the intervention group improved significantly (from 26.91 to 31.77, P < 0.001) while those in the control group decreased insignificantly (from 25.64 to 23.86, P = 0.07). After the intervention, the difference between the scores of the intervention group and the control group on all three knowledge areas of fire prevention and evacuation (generic, hospital-specific, and total) were significant (all Ps < 0.05)., Conclusions: An on-line fire training program delivered via educational video can effectively improve healthcare workers' knowledge of fire prevention and evacuation., Trial Registration: Clinicaltrials.gov NCT02438150., Competing Interests: The authors have declared that no competing interests exist.

Noise induced hearing loss (NIHL), a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA) was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09 respectively) are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53). The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers.

Objective: To analyze the clinicopathologic characteristics and prognosis of patients with squamous cell carcinoma localized to different supraglottic subregions., Methods: Clinicopathologic data were reviewed retrospectively for 111 patients with supraglottic squamous cell carcinoma who were diagnosed between January 1, 1995 and December 31, 2005 and were initially treated with surgery. DNA from human papillomavirus (HPV) 16 and (or /and) HPV 18 were detected in all the 111 supraglottic carcinoma specimens using in situ hybridization. Survival analysis was performed by Kaplan-Meier analysis, factors were compared using log-rank test, and prognostic factors were determined using Cox proportional hazards model. The relationship between subregions and clinicopathologic factors was analyzed using Chi-square tests., Results: HPV prevalence differed between patients with aryepiglottic fold carcinoma and ventricle carcinoma (P < .05). The local-regional control rates, overall survival rates or cancer specific survival rates were significantly different between different subregions. Univariate analysis indicated that pTNM classification, pN spread, and subregion were associated with prognosis (P < .05). Multivariate analysis indicated that pTNM classification and subregion were associated with supraglottic carcinoma prognosis. The survival rate was better for patients with carcinoma of the epiglottis or ventricular bands compared to those with carcinoma in the aryepiglottic fold or ventricle (P = .012)., Conclusions: Subregion may be a new prognostic factor for supraglottic squamous cell carcinoma. Different supraglottic carcinoma subregions have distinct clinical features such as HPV expression, lymph node metastasis rate, local-regional control and prognosis. Therefore, it is necessary to subdivide supraglottic squamous cell carcinomas into several subregion groups to individualize therapy.

Aim: To determine the rate of abdominal lymph node metastasis after radical surgery for esophageal cancer and define the radiotherapy target area., Methods: Of the 1593 patients who underwent R0 radical esophagectomy for thoracic esophageal squamous cell carcinoma (TE-SCC), 148 developed abdominal lymph node (LN) metastases within three years of surgery. During that time interval, patients were examined by various imaging methods (enhanced computer tomography, magnetic resonance imaging, and positron emission tomography-CT) at set time points. The emerging recurrence pattern, preferred sites for abdominal metastasis, and correlation with added clinical factors were carefully recorded, to permit for delineation of a target area for radiotherapy., Results: We found postoperative metastatic abdominal LNs in 9.3% of the patients treated for esophageal cancer. Lesions in the upper, middle, and lower esophageal segments metastasized to abdominal LNs at 2.3%, 7.8%, and 26.6% (P < 0.0001), respectively. Of all cases, 4.8% had fewer than two affected LNs, while 20.1% had more than three metastatic LNs (P< 0.0001). The metastasis rates of negative and positive celiac LNs were 4.6% and 22.7%, respectively. Abdominal LN metastasis rates for the following LNs: 16a2 and 16a1 of para-aortic, celiac artery, posterior surface of the pancreatic head and common hepatic artery were 64.9%, 41.2%, 37.8%, 32.4%, and 20.9%, respectively. The overall rate of metastasis to these groups of LNs was 91.9%., Conclusion: This study determined that stations 16a1 and 16a2 of the para-aortic, truncus coeliacus, posterior surface of the pancreatic head, and arteria hepatica communis lymph nodes were the preferred sites for abdominal LN metastasis, thus defining target areas for postoperative radiotherapy.

The modern Western diet is rich in advanced glycation end products (AGEs). We have previously shown an association between dietary AGEs and markers of inflammation and oxidative stress in a population of end stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). In the current pilot study we explored the effects of dietary AGEs on the gut bacterial microbiota composition in similar patients. AGEs play an important role in the development and progression of cardiovascular (CVD) disease. Plasma concentrations of different bacterial products have been shown to predict the risk of incident major adverse CVD events independently of traditional CVD risk factors, and experimental animal models indicates a possible role AGEs might have on the gut microbiota population. In this pilot randomized open label controlled trial, twenty PD patients habitually consuming a high AGE diet were recruited and randomized into either continuing the same diet (HAGE, n = 10) or a one-month dietary AGE restriction (LAGE, n = 10). Blood and stool samples were collected at baseline and after intervention. Variable regions V3-V4 of 16s rDNA were sequenced and taxa was identified on the phyla, genus, and species levels. Dietary AGE restriction resulted in a significant decrease in serum Nε-(carboxymethyl) lysine (CML) and methylglyoxal-derivatives (MG). At baseline, our total cohort exhibited a lower relative abundance of Bacteroides and Alistipes genus and a higher abundance of Prevotella genus when compared to the published data of healthy population. Dietary AGE restriction altered the bacterial gut microbiota with a significant reduction in Prevotella copri and Bifidobacterium animalis relative abundance and increased Alistipes indistinctus, Clostridium citroniae, Clostridium hathewayi, and Ruminococcus gauvreauii relative abundance. We show in this pilot study significant microbiota differences in peritoneal dialysis patients' population, as well as the effects of dietary AGEs on gut microbiota, which might play a role in the increased cardiovascular events in this population and warrants further studies.

The Honghe-Hani landscape in China is a UNESCO World Natural Heritage site due to the beauty of its thousands of rice terraces, but these structures are in danger from the invasive crayfish Procambarus clarkii. Crayfish dig nest holes, which collapse terrace walls and destroy rice production. Under the current control strategy, farmers self-report crayfish and are issued pesticide, but this strategy is not expected to eradicate the crayfish nor to prevent their spread since farmers are not able to detect small numbers of crayfish. Thus, we tested whether environmental DNA (eDNA) from paddy-water samples could provide a sensitive detection method. In an aquarium experiment, Real-time Quantitative polymerase chain reaction (qPCR) successfully detected crayfish, even at a simulated density of one crayfish per average-sized paddy (with one false negative). In a field test, we tested eDNA and bottle traps against direct counts of crayfish. eDNA successfully detected crayfish in all 25 paddies where crayfish were observed and in none of the 7 paddies where crayfish were absent. Bottle-trapping was successful in only 68% of the crayfish-present paddies. eDNA concentrations also correlated positively with crayfish counts. In sum, these results suggest that single samples of eDNA are able to detect small crayfish populations, but not perfectly. Thus, we conclude that a program of repeated eDNA sampling is now feasible and likely reliable for measuring crayfish geographic range and for detecting new invasion fronts in the Honghe Hani landscape, which would inform regional control efforts and help to prevent the further spread of this invasive crayfish.

The purpose of this study is to analyze the motion status of swimmers during their gliding stage using a numerical simulation method. This simulation strategy is conducted by solving the 3D incompressible Navier-Stokes equations using the Realizable k-ε turbulence closure equations in combination with the Six Degrees of Freedom (6-DOF) method. The uneven mass distribution of a swimmer and the roughness of the surface of the body are taken into consideration. The hydrodynamic characteristics and movement characteristics of the swimmers at different launch speeds were analyzed. The calculated results suggest that an optimal instant for starting propulsive movement is when the velocity of the swimmer decreases by 1.75 m/s to 2.0 m/s from an initial horizontal velocity of 3.1 m/s to 3.5 m/s., Competing Interests: The authors have declared that no competing interests exist.

Recent studies suggested that forkhead box class O3 (FOXO3) functions as a key regulator for the insulin/insulin-like growth factor-1signaling pathway that influence aging and longevity. This study aimed to comprehensively elucidate the association of common genetic variants in FOXO3 with human longevity in a Chinese population. Eighteen single-nucleotide polymorphisms (SNPs) in FOXO3 were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. No nominally significant effects were found. However, when stratifying by gender, four SNPs (rs10499051, rs7762395, rs4946933 and rs3800230) previously reported to be associated with longevity and one novel SNP (rs4945815) showed significant association with male longevity (P-values: 0.007-0.032), but all SNPs were not associated with female longevity. Correspondingly, males carrying the G-G-T-G haplotype of rs10499051, rs7762395, rs4945815 and rs3800230 tended to have longer lifespan than those carrying the most common haplotype A-G-C-T (odds ratio = 2.36, 95% confidence interval = 1.20-4.63, P = 0.013). However, none of the associated SNPs and haplotype remained significant after Bonferroni correction. In conclusion, our findings revealed that the FOXO3 variants we tested in our population of Chinese men and women were associated with longevity in men only. None of these associations passed Bonferroni correction. Bonferroni correction is very stringent for association studies. We therefore believe the effects of these nominally significant variants on human longevity will be confirmed by future studies., Competing Interests: The authors have declared that no competing interests exist.

Objective: Drug shortages were a complex global problem. The aim of this study was to analyze, characterize, and assess the drug shortages, and identify possible solutions in Shaanxi Province, western China., Methods: A qualitative methodological approach was conducted during May-June 2015 and December 2015-January 2016. Semi-structured interviews were performed to gather information from representatives of hospital pharmacists, wholesalers, pharmaceutical producers, and local health authorities., Results: Thirty participants took part in the study. Eight traditional Chinese medicines and 87 types of biologicals and chemicals were reported to be in short supply. Most were essential medicines. Five main determinants of drug shortages were detected: too low prices, too low market demands, Good Manufacturing Practice (GMP) issues, materials issues, and approval issues for imported drugs. Five different solutions were proposed by the participants: 1) let the market decide the drug price; 2) establish an information platform; 3) establish a reserve system; 4) enhance the communication among the three parties in the supply chain; and 5) improve hospital inventory management., Conclusions: Western China was currently experiencing a serious drug shortage. Numerous reasons for the shortage were identified. Most drug shortages in China were currently because of "too low prices." To solve this problem, all of the stakeholders, especially the government, needed to participate in managing the drug shortages., Competing Interests: The authors have declared that no competing interests exist.

Background: Co-infection with hepatitis C virus (HCV) has become the most common cause of death in human immunodeficiency virus (HIV) infected patients on antiretroviral therapy. The distribution of HCV genotypes varies with geographical regions and time, and limited studies have focused on the HCV genotype in HIV/HCV co-infection., Methods: The distribution of HCV genotypes was evaluated in 414 patients with HIV/HCV co-infection in three regions (South, Central and Northwest) of China from 2008 to 2010. The NS5B region of HCV was characterized using nested reverse transcription polymerase chain reaction. Nucleotide sequences obtained were subjected to phylogenetic analysis, and genotypes were assigned using published reference genotypes., Results: Genotype 3 was the most prevalent HCV strain (36.2%), followed by genotype 6 (30.0%), genotype 1 (28.5%), genotype 2 (5.1%), and genotype 5 (0.2%). The distribution varied geographically. Genotype 6 (37.6%) was the predominant strain while genotype 1 (20.2%) was less common in the South compared to the Central and Northwest regions (all P < 0.001). The distribution also varied temporally. There was no significant difference in genotype distribution in Guangdong (a province in the South region), between patient cohorts from 2005-2008 and 2009-2010. However, outside Guangdong, genotypes 3 and 6a became significantly more prevalent (22.4% vs.42.2%, P< 0.001; 8.0% vs. 19.8%, P = 0.004), and genotype 1 less prevalent (54.4% vs.26.6%, P< 0.001) over time., Conclusion: The most dramatic shift in genotypic distribution was the movement of HCV genotypes 3 and 6a outside of Guangdong in HIV/HCV co-infected patients. This movement appeared closely associated with transmission via injected drug use., Competing Interests: The authors have declared that no competing interests exist.

Aim: The purpose of the study was the simultaneous measurement of all the different components of the AGE-RAGE axis as well as several non-invasive markers of cardiovascular disease (CVD) in a cohort of newly diagnosed diabetic patients., Materials and Methods: In 80 newly diagnosed diabetic patients we measured serum carboxymethyllysine (CML), soluble RAGE (sRAGE) and peripheral mononuclear (PMNC) RAGE and AGER1 mRNA together with ICAM-1, VCAM-1, and malondialdehyde (MDA). We also assessed cardiovascular function by measurement of flow-mediated vasodilation (FMD), intima-media thickness (IMT) and arterial stiffness. Univariant correlation analysis was used to determine correlation between the variables in the study and multiple regression analysis was used to examine the association between the AGE-RAGE axis components and FMD, IMT and arterial stiffness., Results: Serum CML correlated positively with sRAGE, PMNC RAGE, HOMA-IR, ICAM-1, VCAM-1 and MDA, but inversely with PMNC AGER1. sRAGE and RAGE was positively correlated with AGER; IMT was positively correlated with HOMA-IR, ICAM-1, VCAM-1, MDA, and sRAGE and arterial stiffness had correlation with HOMA-IR, ICAM-1, VCAM-1, MDA, CML, sRAGE, AGER1 and RAGE. In multivariate analysis we found a significant relationship between CML with PMNC RAGE, HOMA-IR; sRAGE with VCAM-1 and MDA; PMNC RAGE with PMNC AGER1and CML; PMNC AGER1 with PMNC RAGE; FMD with sRAGE, CML and HbA1c; IMT with sRAGE, and arterial stiffness with sRAGE, sCML and AGER1., Conclusions: We found significant and strong associations between the different components of the AGE-RAGE axis and also found significant association between AGE-RAGE axis markers, especially sRAGE with several noninvasive markers of cardiovascular disease risk. sRAGE, an easily measured parameter in blood, may potentially be used as a surrogate marker of AGEs-RAGE in patients with diabetes.

Age-related increases in oxidant stress (OS) play a role in regulation of estrogen receptor (ER) expression in the kidneys. In this study, we establish that in vivo 17β-estradiol (E2) replacement can no longer upregulate glomerular ER expression by 21 months of age in female mice (anestrous). We hypothesized that advanced glycation end product (AGE) accumulation, an important source of oxidant stress, contributes to these glomerular ER expression alterations. We treated 19-month old ovariectomized female mice with pyridoxamine (Pyr), a potent AGE inhibitor, in the presence or absence of E2 replacement. Glomerular ERα mRNA expression was upregulated in mice treated with both Pyr and E2 replacement and TGFβ mRNA expression decreased compared to controls. Histological sections of kidneys demonstrated decreased type IV collagen deposition in mice receiving Pyr and E2 compared to placebo control mice. In addition, anti-AGE defenses Sirtuin1 (SIRT1) and advanced glycation receptor 1 (AGER1) were also upregulated in glomeruli following treatment with Pyr and E2. Mesangial cells isolated from all groups of mice demonstrated similar ERα, SIRT1, and AGER1 expression changes to those of whole glomeruli. To demonstrate that AGE accumulation contributes to the observed age-related changes in the glomeruli of aged female mice, we treated mesangial cells from young female mice with AGE-BSA and found similar downregulation of ERα, SIRT1, and AGER1 expression. These results suggest that inhibition of intracellular AGE accumulation with pyridoxamine may protect glomeruli against age-related oxidant stress by preventing an increase of TGFβ production and by regulation of the estrogen receptor.

Background: The advent of direct-acting agents (DAAs) has improved treatment of HCV in HIV co-infection, but may be limited by primary drug resistance. This study reports the prevalence of natural polymorphisms conferring resistance to NS3/4A protease inhibitors and NS5B polymerase inhibitors in treatment-naïve HIV/HCV co-infected individuals in China., Methods: Population based NS3/4A sequencing was completed for 778 treatment-naïve HIV/HCV co-infected patients from twelve provinces. NS3 sequences were amplified by nested PCR using in-house primers for genotypes 1-6. NS5B sequencing was completed for genotyping in 350 sequences. Resistance-associated variants (RAVs) were identified in positions associated with HCV resistance., Results: Overall, 72.8% (566/778) of all HCV sequences had at least one RAV associated with HCV NS3/4A protease inhibitor resistance. Variants were found in 3.6% (7/193) of genotype 1, 100% (23/23) of genotype 2, 100% (237/237) of genotype 3 and 92% (299/325) of genotype 6 sequences. The Q80K variant was present in 98.4% of genotype 6a sequences. High-level RAVs were rare, occurring in only 0.8% of patients. 93% (64/69) patients with genotype 1b also carried the C316N variant associated with NS5B low-level resistance., Conclusions: The low frequency of high-level RAVs associated with primary HCV DAA resistance among all genotypes in HIV/HCV co-infected patients is encouraging. Further phenotypic studies and clinical research are needed.

The availability of mitochondrial genome data for Aphididae, one of the economically important insect pest families, in public databases is limited. The advent of next generation sequencing technology provides the potential to generate mitochondrial genome data for many species timely and cost-effectively. In this report, we used transcriptome sequencing technology to determine all the 37 mitochondrial genes of the cowpea aphid, Aphis craccivora. This method avoids the necessity of finding suitable primers for long PCRs or primer-walking amplicons, and is proved to be effective in obtaining the whole set of mitochondrial gene data for insects with difficulty in sequencing mitochondrial genome by PCR-based strategies. Phylogenetic analyses of aphid mitochondrial genome data show clustering based on tribe level, and strongly support the monophyly of the family Aphididae. Within the monophyletic Aphidini, three samples from Aphis grouped together. In another major clade of Aphididae, Pterocomma pilosum was recovered as a potential sister-group of Cavariella salicicola, as part of Macrosiphini.

The evolutionarily conserved small G-protein Ran plays important role in nuclear translocation of proteins, cell cycle regulation, and nuclear envelope maintenance in mammalian cells and yeast. Arabidopsis Ran proteins are encoded by a family of four genes and are highly conserved at the protein level. However, their biological functions are poorly understood. We report here that AtRAN1 plays an important role in vegetative growth and the molecular improvement of stress tolerance in Arabidopsis. AtRAN1 overexpression promoted vegetative growth and enhanced abiotic tolerance, while the atran1 atran3 double mutant showed higher freezing sensitivity than WT. The AtRAN1 gene is ubiquitously expressed in plants, and the expression levels are higher in the buds, flowers and siliques. Subcellular localization results showed that AtRAN1 is mainly localized in the nucleus, with some present in the cytoplasm. AtRAN1 could maintain cell division and cell cycle progression and promote the formation of an intact nuclear envelope, especially under freezing conditions.

Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD) activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx) mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C)- and C3H fava beans-treated (C3H-FB) mice, and G6PDx-control (G6PDx-C)- and G6PDx fava beans-treated (G6PDx-FB) mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

Purpose: To investigate image quality and radiation dose of CT coronary angiography (CTCA) scanned using automatic tube current modulation (ATCM) and reconstructed by strong adaptive iterative dose reduction three-dimensional (AIDR3D)., Methods: Eighty-four consecutive CTCA patients were collected for the study. All patients were scanned using ATCM and reconstructed with strong AIDR3D, standard AIDR3D and filtered back-projection (FBP) respectively. Two radiologists who were blinded to the patients' clinical data and reconstruction methods evaluated image quality. Quantitative image quality evaluation included image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). To evaluate image quality qualitatively, coronary artery is classified into 15 segments based on the modified guidelines of the American Heart Association. Qualitative image quality was evaluated using a 4-point scale. Radiation dose was calculated based on dose-length product., Results: Compared with standard AIDR3D, strong AIDR3D had lower image noise, higher SNR and CNR, their differences were all statistically significant (P<0.05); compared with FBP, strong AIDR3D decreased image noise by 46.1%, increased SNR by 84.7%, and improved CNR by 82.2%, their differences were all statistically significant (P<0.05 or 0.001). Segments with diagnostic image quality for strong AIDR3D were 336 (100.0%), 486 (96.4%), and 394 (93.8%) in proximal, middle, and distal part respectively; whereas those for standard AIDR3D were 332 (98.8%), 472 (93.7%), 378 (90.0%), respectively; those for FBP were 217 (64.6%), 173 (34.3%), 114 (27.1%), respectively; total segments with diagnostic image quality in strong AIDR3D (1216, 96.5%) were higher than those of standard AIDR3D (1182, 93.8%) and FBP (504, 40.0%); the differences between strong AIDR3D and standard AIDR3D, strong AIDR3D and FBP were all statistically significant (P<0.05 or 0.001). The mean effective radiation dose was (2.55±1.21) mSv., Conclusion: Compared with standard AIDR3D and FBP, CTCA with ATCM and strong AIDR3D could significantly improve both quantitative and qualitative image quality.

Foodborne outbreaks caused by a mixed infection of Vibrio parahaemolyticus and norovirus have rarely been described. We reported a mixed outbreak of Vibrio parahaemolyticus and norovirus causing acute gastroenteritis in 99 staff members of a company in Guangdong, China, in May 2013, following consumption of roasted duck, an uncommon non-seafood vehicle for such mixed infection, in one meal served in the company's catering service. Epidemiological and laboratory findings indicated that a single asymptomatic food handler was the source of both pathogens, and the high rate of infection of both pathogens was exacerbated by the setting's suboptimal food hygiene practice.

Purpose: To evaluate the diagnostic value of multidetector CT (MDCT) and its multiplanar reformation (MPR), volume rendering (VR) and virtual bronchoscopy (VB) postprocessing techniques for primary trachea and main bronchus tumors., Methods: Detection results of 31 primary trachea and main bronchus tumors with MDCT and its MPR, VR and VB postprocessing techniques, were analyzed retrospectively with regard to tumor locations, tumor morphologies, extramural invasions of tumors, longitudinal involvements of tumors, morphologies and extents of luminal stenoses, distances between main bronchus tumors and trachea carinae, and internal features of tumors. The detection results were compared with that of surgery and pathology., Results: Detection results with MDCT and its MPR, VR and VB were consistent with that of surgery and pathology, included tumor locations (tracheae, n = 19; right main bronchi, n = 6; left main bronchi, n = 6), tumor morphologies (endoluminal nodes with narrow bases, n = 2; endoluminal nodes with wide bases, n = 13; both intraluminal and extraluminal masses, n = 16), extramural invasions of tumors (brokethrough only serous membrane, n = 1; 4.0 mm-56.0 mm, n = 14; no clear border with right atelectasis, n = 1), longitudinal involvements of tumors (3.0 mm, n = 1; 5.0 mm-68.0 mm, n = 29; whole right main bronchus wall and trachea carina, n = 1), morphologies of luminal stenoses (irregular, n = 26; circular, n = 3; eccentric, n = 1; conical, n = 1) and extents (mild, n = 5; moderate, n = 7; severe, n = 19), distances between main bronchus tumors and trachea carinae (16.0 mm, n = 1; invaded trachea carina, n = 1; >20.0 mm, n = 10), and internal features of tumors (fairly homogeneous densities with rather obvious enhancements, n = 26; homogeneous density with obvious enhancement, n = 1; homogeneous density without obvious enhancement, n = 1; not enough homogeneous density with obvious enhancement, n = 1; punctate calcification with obvious enhancement, n = 1; low density without obvious enhancement, n = 1)., Conclusion: MDCT and its MPR, VR and VB images have respective advantages and disadvantages. Their combination could complement to each other to accurately detect locations, natures (benignancy, malignancy or low malignancy), and quantities (extramural invasions, longitudinal involvements, extents of luminal stenoses, distances between main bronchus tumors and trachea carinae) of primary trachea and main bronchus tumors with crucial information for surgical treatment, are highly useful diagnostic methods for primary trachea and main bronchus tumors.

Aim: To identify the prevalence and predictors of abnormal renal function among HIV-positive Chinese patients prior to antiretroviral therapy (ART) initiation and to evaluate subsequent changes in renal function after ART exposure., Methods: We conducted a nationwide cohort study of subjects who enrolled in the national Chinese ART program from January 1, 2012 to December 31, 2012. We estimated the glomerular filtration rate (eGFR) of subjects prior to and after initiating ART. Risk factors for abnormal renal function, as defined by eGFR <60 ml/min/1.73m2, at baseline and follow-up were assessed by logistic regression and Cox proportional hazards regression models, respectively., Results: Among 41,862 subjects, at ART baseline, 3.3% had a baseline eGFR <60 ml/min/1.73m2 and 24.2% had eGFR = 60-90 ml/min/1.73m2. Adjusted baseline risk factors for baseline eGFR <60 ml/min/1.73m2 were older age (Adjusted odds ratio [AOR] = 5.19, 95% confidence interval [CI]: 4.52-5.67), female (AOR = 1.68, 95% CI: 1.47-1.93), hemoglobin <120g/L (AOR = 1.68, 95% CI: 1.47-1.93), blood glucose >6.1 mmol/L (AOR = 1.46, 95% CI: 1.25-1.72), and hepatitis C co-infection (AOR = 1.36, 95% CI: 1.06-1.73). Among subjects with baseline eGFR >90 ml/min/1.73m2, the incidence of the eGFR falling to <60 ml/min/1.73m2 was 0.92/100 person-years after a median of 15.0 months of ART. Being on a tenofovir with lopinavir/ritonavir regimen (Adjusted hazard ratio [AHR] = 3.02, 95% CI: 1.96-4.66) and having an unsuppressed viral load (AHR = 2.70, 95% CI: 1.80-4.03) were independent predictors for eGFR <60 ml/min/1.73m2 after ART initiation as well as older age, female, and hemoglobin <120 g/L., Conclusion: A high proportion of HIV-positive subjects in China presented with abnormal renal function prior to ART initiation. But the incidence of the eGFR decrease after ART was low. Patient renal function should be regularly monitored by eGFR before initiating and during ART.

Background: Atrial fibrillation (AF) is the most common arrhythmias among old people. It causes serious long-term health problems affecting the quality of life. It has been suggested that the autonomic nervous system is involved in the onset and maintenance of AF in human. However, investigation of its pathogenesis and potential treatment has been hampered by the lack of suitable AF models in experimental animals., Objectives: Our aim was to establish a long-lasting AF model in mice. We also investigated the role of adrenergic receptor (AR) subtypes, which may be involved in the onset and duration of AF., Methods and Results: Trans-esophageal atrial burst pacing in mice could induce AF, as previously shown, but with only a short duration (29.0 ± 8.1 sec). We found that adrenergic activation by intraperitoneal norepinephrine (NE) injection strikingly increased the AF duration. It increased the duration to more than 10 minutes, i.e., by more than 20-fold (656.2 ± 104.8 sec; P<0.001). In this model, a prior injection of a specific β1-AR blocker metoprolol and an α1-AR blocker prazosin both significantly attenuated NE-induced elongation of AF. To further explore the mechanisms underlying these receptors' effects on AF, we assessed the SR Ca(2+) leak, a major trigger of AF, and consequent spontaneous SR Ca(2+) release (SCR) in atrial myocytes. Consistent with the results of our in-vivo experiments, both metoprolol and prazosin significantly inhibited the NE-induced SR Ca(2+) leak and SCR. These findings suggest that both β1-AR and α1-AR may play important roles in the development of AF., Conclusions: We have established a long-lasting AF model in mice induced by adrenergic activation, which will be valuable in future AF study using experimental animals, such as transgenic mice. We also revealed the important role of β1- and α1-AR-mediated signaling in the development of AF through in-vivo and in-vitro experiments.

Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis.

Nitric oxide (NO) has been shown to play an important role in the plant response to biotic and abiotic stresses in Arabidopsis mutants with lower or higher levels of endogenous NO. The exogenous application of NO donors or scavengers has also suggested an important role for NO in plant defense against environmental stress. In this study, rice plants under drought and high salinity conditions showed increased nitric oxide synthase (NOS) activity and NO levels. Overexpression of rat neuronal NO synthase (nNOS) in rice increased both NOS activity and NO accumulation, resulting in improved tolerance of the transgenic plants to both drought and salt stresses. nNOS-overexpressing plants exhibited stronger water-holding capability, higher proline accumulation, less lipid peroxidation and reduced electrolyte leakage under drought and salt conditions than wild rice. Moreover, nNOS-overexpressing plants accumulated less H2O2, due to the observed up-regulation of OsCATA, OsCATB and OsPOX1. In agreement, the activities of CAT and POX were higher in transgenic rice than wild type. Additionally, the expression of six tested stress-responsive genes including OsDREB2A, OsDREB2B, OsSNAC1, OsSNAC2, OsLEA3 and OsRD29A, in nNOS-overexpressing plants was higher than that in the wild type under drought and high salinity conditions. Taken together, our results suggest that nNOS overexpression suppresses the stress-enhanced electrolyte leakage, lipid peroxidation and H2O2 accumulation, and promotes proline accumulation and the expression of stress-responsive genes under stress conditions, thereby promoting increased tolerance to drought and salt stresses.

Objectives: The main aim of this study was to investigate the effect of CYP2B6 gene polymorphisms on efavirenz (EFV) plasma concentrations in Han Chinese patients with human immunodeficiency virus (HIV) infection., Methods: In total, 322 patients were recruited for study. EFV plasma concentrations at steady-state were determined using high-performance liquid chromatography. Genotyping for seven single nucleotide polymorphisms (SNPs), including 171+967C>A, 171+3212C>T, 171+4335T>C, 516G>T, 785A>G, 1295-913G>A, and *1355A>G of CYP2B6, was performed using ligase detection reaction (LDR). SPSS 18.0 and Haploview 4.2 were applied for statistical analyses., Results: The average EFV concentration of patients was 2.35±2.09 μg/mL. Overall, 22% patients displayed EFV concentrations out of the therapeutic range of 1-4 μg/mL (13.1% < 1 μg/mL, 9.3% > 4 μg/mL). We observed significant association of 171+967C>A, 171+4335T>C, 516G>T, 785A>G and *1355A>G with high plasma EFV levels (p<.01). The predictive accuracy values of 171+4335CC, 516TT and 785GG for EFV concentrations > 4 μg/mL were 56.7%, 56.7% and 60%, respectively. We observed strong linkage disequilibrium for 171+967C>A, 171+4335T>C, 516G>T and 785A>G, resulting in five haplotypes. The frequencies of the five haplotypes (high to low) were as follows: CCTG (0.328), ACTG (0.280), ACCT (0.189), ATTG (0.186) and ACCG (0.017). The frequency of CCTG (0.524) in patients with EFV plasma concentrations < 1 μg/mL was significantly higher than that in other patient groups, while that of ACCT (0.733) was significantly higher in patients with EFV concentrations > 4 μg/mL, relative to other patient groups. Average EFV concentrations of patients carrying ACTG (1.78 μg/mL), ACCT (7.50 μg/mL), and ATTG (1.92 μg/mL) haplotypes were markedly higher than those of patients carrying the CCTG haplotype. The predictive accuracy of ACCT for EFV > 4 μg/mL was 81%., Conclusions: Chinese patients administered standard doses of EFV require therapeutic drug monitoring or personalized medication management. Based on the current findings, we propose that 171+4335T>C, 516G>T, 785A>G and haplotype ACCT may be effectively used as genomic markers for EFV, which should aid in improving the efficacy of EFV-containing treatments and reduce the incidence of adverse reactions.

Objective: Advances made in the past ten years highlight the notion that peroxisome proliferator-activated receptors gamma (PPARγ) has protective properties in the pathophysiology of osteoarthritis (OA). The aim of this study was to define the roles of PPARγ in AGEs-induced inflammatory response in human chondrocytes., Methods: Primary human chondrocytes were stimulated with AGEs in the presence or absence of neutralizing antibody against RAGE (anti-RAGE), MAPK specific inhibitors and PPARγ agonist pioglitazone. The expression of IL-1, MMP-13, TNF-α, PPARγ, nuclear NF-κB p65 and cytosol IκBα was determined by western blotting and real-time PCR., Results: AGEs could enhance the expression of IL-1, TNF-α, and MMP-13, but the level of PPARγ was decreased in a time- and dose-dependent manner, which was inhibited by anti-RAGE, SB203580 (P38 MAPK specific inhibitor) and SP600125 (a selective inhibitor of JNK). PPARγ agonist pioglitazone could inhibit the effects of AGEs-induced inflammatory response and PPARγ down-regulation. In human chondrocytes, AGEs could induce cytosol IκBα degradation and increase the level of nuclear NF-κB p65, which was inhibited by PPARγ agonist pioglitazone., Conclusions: In primary human chondrocytes, AGEs could down-regulate PPARγ expression and increase the inflammatory mediators, which could be reversed by PPARγ agonist pioglitazone. Activation of RAGE by AGEs triggers a cascade of downstream signaling, including MAPK JNK/ p38, PPARγ and NF-κB. Taken together, PPARγ could be a potential target for pharmacologic intervention in the treatment of OA.

Background: POTEE (POTE ankyrin domain family, member E) is a newly identified cancer-testis antigen that has been found to be expressed in a wide variety of human cancers including cancers of the colon, prostate, lung, breast, ovary, and pancreas., Aim: To measure the serum levels of POTEE in patients with non-small-cell lung cancer (NSCLC) and to explore the clinical significance of POTEE in NSCLC., Patients and Methods: 104 NSCLC patients, 66 benign lung disease patients and 80 healthy volunteers were enrolled in this study from May 2013 to February 2014. Serum POTEE levels were measured using enzyme-linked immunosorbent assay (ELISA). Numerical variables were recorded as means ± standard deviation (SD) and analyzed by independent t tests. Categorical variables were calculated as rates and were analyzed using a χ2 test or Fisher's exact test. Survival curves were estimated and compared using the Kaplan-Meier method and log-rank tests., Results: Serum POTEE levels were significantly higher in NSCLC patients than in benign lung disease patients and healthy controls (mean ± SD [pg/ml], 324.38± 13.84 vs. 156.93 ± 17.38 and 139.09 ± 15.80, P<0.001) and were significantly correlated with TNM stage. Survival analysis revealed that patients with low serum POTEE had longer progression-free survival (PFS) than those with high serum POTEE (P=0.021). Cox multivariate analysis indicated that POTEE was an independent prognostic factor of progression-free survival (P =0.009, hazard ratio, 2.440)., Conclusions: Serum POTEE level in NSCLC patients is associated with TNM stage and is a potential prognostic factor.

Sepsis is defined as a systemic inflammatory response syndrome that disorders the functions of host immune system, including the imbalance between pro- and anti-inflammatory responses mediated by immune macrophages. Sepsis could also induce acute hyperglycemia. Studies have shown that the silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+-dependent deacetylase, mediates NF-κb deacetylation and inhibits its function. Therefore, SIRT1 is likely to play an important role in high glucose-mediated inflammatory signalings. Here we demonstrate that high glucose significantly downregulates both the mRNA and protein levels of SIRT1 and upregulates the mRNA level and the release of two pro-inflammatory cytokines, IL-1β and TNF-α, in RAW264.7 macrophages. Interestingly, the reduced level of SIRT1 by high glucose is remarkably upregulated by SIRT1 activator SRT1720, while the level and the release of IL-1β and TNF-α significantly decrease with the use of SRT1720. However, when the function of SIRT1 is inhibited by EX527 or its expression is suppressed by RNAi, the upregulated level and release of IL-1β and TNF-α by high glucose are further increased. Taken together, these findings collectively suggest that SIRT1 is an important regulator in many high glucose-related inflammatory diseases such as sepsis.

In this study, we sequenced four new mitochondrial genomes and presented comparative mitogenomic analyses of five species in the genus Peirates (Hemiptera: Reduviidae). Mitochondrial genomes of these five assassin bugs had a typical set of 37 genes and retained the ancestral gene arrangement of insects. The A+T content, AT- and GC-skews were similar to the common base composition biases of insect mtDNA. Genomic size ranges from 15,702 bp to 16,314 bp and most of the size variation was due to length and copy number of the repeat unit in the putative control region. All of the control region sequences included large tandem repeats present in two or more copies. Our result revealed similarity in mitochondrial genomes of P. atromaculatus, P. fulvescens and P. turpis, as well as the highly conserved genomic-level characteristics of these three species, e.g., the same start and stop codons of protein-coding genes, conserved secondary structure of tRNAs, identical location and length of non-coding and overlapping regions, and conservation of structural elements and tandem repeat unit in control region. Phylogenetic analyses also supported a close relationship between P. atromaculatus, P. fulvescens and P. turpis, which might be recently diverged species. The present study indicates that mitochondrial genome has important implications on phylogenetics, population genetics and speciation in the genus Peirates.

Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions.

Objective: To investigate image quality and radiation dose of CT colonography (CTC) with adaptive iterative dose reduction three-dimensional (AIDR3D)., Methods: Ten segments of porcine colon phantom were collected, and 30 pedunculate polyps with diameters ranging from 1 to 15 mm were simulated on each segment. Image data were acquired with tube voltage of 120 kVp, and current doses of 10 mAs, 20 mAs, 30 mAs, 40 mAs, 50 mAs, respectively. CTC images were reconstructed using filtered back projection (FBP) and AIDR3D. Two radiologists blindly evaluated image quality. Quantitative evaluation of image quality included image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Qualitative image quality was evaluated with a five-score scale. Radiation dose was calculated based on dose-length product. Ten volunteers were examined supine 50 mAs with FBP and prone 20 mAs with AIDR3D, and image qualities were assessed. Paired t test was performed for statistical analysis., Results: For 20 mAs with AIDR3D and 50 mAs with FBP, image noise, SNRs and CNRs were (16.4 ± 1.6) HU vs. (16.8 ± 2.6) HU, 1.9 ± 0.2 vs. 1.9 ± 0.4, and 62.3 ± 6.8 vs. 62.0 ± 6.2, respectively; qualitative image quality scores were 4.1 and 4.3, respectively; their differences were all not statistically significant. Compared with 50 mAs with FBP, radiation dose (1.62 mSv) of 20 mAs with AIDR3D was decreased by 60.0%. There was no statistically significant difference in image noise, SNRs, CNRs and qualitative image quality scores between prone 20 mAs with AIDR3D and supine 50 mAs with FBP in 10 volunteers, the former reduced radiation dose by 61.1%., Conclusion: Image quality of CTC using 20 mAs with AIDR3D could be comparable to standard 50 mAs with FBP, radiation dose of the former reduced by about 60.0% and was only 1.62 mSv.

Rit, a member of the Ras family of GTPases, has been shown to promote cell survival in response to oxidative stress, in part by directing an evolutionarily conserved p38 MAPK-Akt survival cascade. Aberrant Rit signaling has recently been implicated as a driver mutation in human cancer, adding importance to the characterization of critical Rit effector pathways. However, the mechanism by which Rit-p38 signaling regulated Akt activity was unknown. Here, we identify mTORC2 as a critical downstream mediator of Rit-dependent survival signaling in response to reactive oxygen species (ROS) stress. Rit interacts with Sin1 (MAPKAP1), and Rit loss compromises ROS-dependent mTORC2 complex activation, blunting mTORC2-mediated phosphorylation of Akt kinase. Taken together, our findings demonstrate that the p38/mTORC2/Akt signaling cascade mediates Rit-dependent oxidative stress survival. Inhibition of this previously unrecognized cascade should be explored as a potential therapy of Rit-dependent malignancies.