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The bulkhead additional thrust during shield tunneling, the force of friction between shield and soil, and the additional grouting pressure can cause additional stress in the surrounding soil, thereby disturbing existing buildings and structures. However, few studies focused on the disturbance situation when the shield tunneling machine approaches the receiving well. If the additional stress and deformation of the receiving well are too excessive, it could result in the collapse of the receiving well. Based on the two-stage method, this study derived the calculation formula of the additional stress and deformation of the receiving well enclosure structure caused by shield tunneling. Taking a shield machine receiving engineering as the context, this study established a numerical simulation model and compared theoretical calculation, the results of numerical simulation model and on-site monitoring data. Finally, the additional stress of the receiving well is analyzed. The research findings demonstrate that the theoretical prediction results, numerical simulation calculation results, and on-site monitoring data exhibit relatively small calculation errors, which validated the applicability of the theoretical prediction formula and numerical simulation model. As the distance between the shield machine and the receiving well decreases, the disturbance to the receiving well increases sharply. When the distance between the cutter head and the receiving well is less than three times the shield length, it is crucial to enhance the deformation monitoring of the receiving well. The primary factors affecting the additional load and deformation of the receiving well enclosure structure are the force of friction between shield and soil and the additional thrust of the cutterhead. The disturbance caused by the additional grouting pressure on the enclosure structure can be ignored.

In environmentally sensitive areas, especially the arid and semi-arid regions, the greening stability process and its influencing factors can directly affect the sustainable development of the ecological environment. In this study, multi-source remote sensing data such as land use/cover data, MODIS NDVI, and soil moisture, methods such as stability index, vegetation quantitative remote sensing, and Geodetector were employed to analyze the sustainability of the greening process in the Mu Us Sandy in 2000-2020, which were viewed from three aspects: changes in stability of land use types and function, soil moisture change and influencing factors on greening stability. The results showed that, (1) From the stability of land use types, continuous stable ecological land accounted for more than 50%, showing that decreased from northwest toward southeast. (2) From the functional stability, NDVI showed a fluctuated growth (0.035/a), with an increasing distribution pattern from northwest to southeast. Additionally, Vegetation changes were unstable and concentrated in the western part of the study area (OtogBanner and Otog Front Banner), while the eastern part was stable, in which vegetation improvement took the main position. Moreover, mobile dunes almost disappeared, and semi-fixed dunes decreased and gradually shrank to the west of the sandy area, while fixed dunes soared and were concentrated in the middle of the sandy land. (3) From the soil moisture change, soil moisture at different underground depths showed an overall increasing trend, but the deep soil moisture was higher than the shallow, and spatial distribution varied greatly. (4) From the influencing factors, natural factors significantly influence greening stability, among which precipitation had a particularly profound impact, and interactions with other natural and social factors were higher explanatory. The paper aims to explore whether the ecological environment is developing in a good and orderly direction in the Mu Us Sandy Land, and the potential factors that cause its changes, to provide a theoretical basis for scientific governance in the Mu Us Sandy Land and other arid and semi-arid areas in the future.

IntroductionThe importance of global competence has been acknowledged in medical care as well as medical education. This study aims to develop a scale assessing the global competence of medical students, determine the factor structure and internal consistency of the scale and explore the underlying factors influencing the global competence of Chinese medical students in 8-year programs.MethodsA questionnaire (Global Competence Assessment Scale for Medical Students, MS-GCAS) was developed, and a cross-sectional multicenter survey was conducted in 1062 medical students from 10 medical schools in China. Questionnaire data were analyzed using exploratory factor analysis and multiple linear regression.ResultsThe exploratory factor analysis revealed a three-factor scale. The MS-GCAS has good internal consistency (Cronbach's alpha = 0.79 to 0.87). In the multivariate regression analyses, medical education stage (pDiscussionThe MS-GCAS has the potential to serve as a tool to measure the global competence of medical students. This three-factor scale can be used by medical education researches to improve future versions. Medical schools should conduct further educational reforms to promote students' global competence.

AimsThis systematic review aimed to study the hippocampal and frontal changes of heart failure (HF) patients and HF animal models with cognitive impairment or depression.MethodsA systematic review of the literature was conducted independently by reviewers using PubMed, Web of Science, Embase, and the Cochrane Library databases.Results and conclusions30 studies were included, involving 17 pieces of clinical research on HF patients and 13 studies of HF animal models. In HF patients, the hippocampal injuries were shown in the reduction of volume, CBF, glucose metabolism, and gray matter, which were mainly observed in the right hippocampus. The frontal damages were only in reduced gray matter and have no difference between the right and left sides. The included HF animal model studies were generalized and demonstrated the changes in inflammation and apoptosis, synaptic reduction, and neurotransmitter disorders in the hippocampus and frontal lobes. The results of HF animal model studies complemented the clinical observations by providing potential mechanistic explanations of the changes in the hippocampus and frontal lobes.

ObjectivesThe objective of this research aimed to investigate the correlation involving serum albumin with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).MethodsFrom 2011 to 2020, the National Health and Nutrition Examination Survey (NHANES) surveyed 45462 participants. We used the relevant data to conduct descriptive statistics, linear regression, and Logistic regression analysis.ResultsAfter adjusting for age, sex, and race, as well as all other variables, serum albumin was significantly negatively related to DR (P0.05).ConclusionAlbumin levels in the serum have a quantitatively significant negative correlation with DR. Serum albumin levels in the blood can be used as a reference point for protracted follow-up of people with T2DM.

Phosphorus (P) is an essential element for crop production and a key source of nonpoint pollution in agroecosystems. In this study, we sought to analyze P levels and the factors affecting soil P availability, via P adsorption, in a typical field system that is characterized by the year-round cultivation of vegetables. A total of 190 sites were sampled from vegetable fields in Guangdong Province, South China. Within the research area, average concentrations of 124.49 mg P kg-1 and 1.55 g P kg-1 were recorded for available P (AP) and total P (TP), respectively, which are 8.53- and 1.78-fold higher, respectively, than the corresponding values recorded in 1980. The determined P adsorption maximum (Qm) averaged at 488.38 mg kg-1, which represents a reduction of 16% compared to the values obtained four decades ago. Accumulations of both TP and AP were found to be negatively correlated with the soil’s maximum adsorption buffering capacity (MBC), although no significant correlations with the soil binding energies (k) and Qm, were seen. However, soil pH was found to be significantly correlated with k and Qm. Furthermore, both free Mn oxides (Mnd) and silt concentrations in the soil were found to contribute to explaining the variations in Qm. Collectively, the findings of this study provide evidence to indicate that there has been an excessive accumulation of P in the perennial vegetable fields of Guangdong Province over the past four decades, which may have had negative effects on the P supply potential of the soil by reducing the maximum adsorption buffering capacity.

Evapotranspiration (ET) plays a crucial role in hydrological and energy cycles, as well as in the assessments of water resources and irrigation demands. On a regional scale, particularly in the agro-pastoral ecotone, clarification of the distribution of surface ET and its influencing factors is critical for the rational use of water resources, restoration of the ecological environment, and protection of ecological water sources. The SEBAL model was used to invert the regional ET based on Landsat8 images in the agro-pastoral ecotone of northwest China. The results were indirectly verified by monitoring data from meteorological stations. The correlation between ET and surface parameters was analyzed. Thus, the main factors that affect the surface ET were identified. The results show that the SEBAL model determines an accurate inversion, with a correlation coefficient of 0.81 and an average root mean square error of 0.9 mm/d, which is highly suitable for research on water resources. The correlation coefficients of normalized vegetation index, surface temperature, land surface albedo, net radiation flux with daily ET were 0.5830, 0.8425, 0.3428 and 0.9111, respectively. The normalized vegetation index and the net radiation flux positively correlated with the daily ET, while the surface temperature and land surface albedo negatively correlated with the daily ET. The correlation from strong to weak is the net radiation flux > surface temperature > normalized vegetation index > surface albedo. In terms of spatial distribution, the daily ET of water was the highest, followed by woodland, wetland, cropland, built-up land, shrub land, grassland and bare land. However, the SEBAL model overestimates the inversion of daily ET of built-up land.

Lane detection in complex road scenes is still a challenging task due to poor lighting conditions, interference of irrelevant road markings or signs, etc. To solve the problem of lane detection in the various complex road scenes, we proposed a geometric attention-aware network (GAAN) for lane detection. The proposed GAAN adopted a multi-task branch architecture, and used the attention information propagation (AIP) module to perform communication between branches, then the geometric attention-aware (GAA) module was used to complete feature fusion. In order to verify the lane detection effect of the proposed model in this paper, the experiments were conducted on the CULane dataset, TuSimple dataset, and BDD100K dataset. The experimental results show that our method performs well compared with the current excellent lane line detection networks.

[This corrects the article DOI: 10.1371/journal.pone.0214822.].

The carrying pole has existed as a load carrying tool for thousands of years and is still popular in many parts of Asia. Previous studies attempted to determine whether the elasticity of the carrying pole is energetically beneficial compared with other load carrying methods. However, conflicting results indicate that the effects of the carrying pole stiffness on the carrier are still unclear. The carrying pole exhibits more complex characteristics beyond stiffness, which invites further investigation. As the first step towards the goal, this paper explores the underlying mechanics of the carrying pole, including the structural and dynamic properties, to determine its impact on the carrier. The structure of the carrying pole is modeled and characterized by pole length, pole stiffness, and length of suspension rope. We argue that maintaining the pole's balance should be a major prerequisite during load carriage and that active feedback control from the carrier is required. Simulations reveal that the structural parameters of the pole have significant influences on the pole's balance and the interaction between the pole and the carrier. This work suggests mechanical characteristics of the carrying pole can potentially have an extensive impact on gait mechanics and energetics of the carrier.

Cervical cancer is the second most deadly gynecological tumor worldwide. MicroRNAs (miRNAs) play very important roles in tumor oncogenesis and progression. The mechanism of post-transcription regulation of WTX gene is still unknown. A series of differential miRNAs were discovered by microarray analysis comparing three pairs of primary cervical cancer specimens and their relapsed tumors from three patients. Quantitative reverse transcriptase PCR (qRT-PCR), Western Blot (WB) and Immunohistochemistry (IHC) was used to detect the expression of miR-4524b-5p and WTX in cervical cell lines and tissues. The biological function of miR-4524b-5p and WTX was investigated through knockdown and overexpression with inhibitor/siRNA and mimic/plasmid in vitro and in vivo. In this study, we found that miR-4524b-5p is highly expressed in relapsed cervical cancer specimens. Combined in vitro and in vivo experiments, showed that miR-4524b-5p could regulate the migration and invasion ability of cervical cancer. Furthermore, we also found that miR-4524b-5p could regulate the migration and invasion of cervical cancer by targeting WTX and that WTX could regulate the expression of β-catenin. Taken together, our data identified a miR-4524b-5p/WTX/β-catenin regulatory axis for cervical cancer, and miR-4524b-5p may be a potential target for cervical cancer therapy.

OBJECTIVE:The relationship among blood donation, cognition in blood donation and health condition of blood donors remains unclear. Based on our hypothesis, this study aimed to explore the mediating effect of cognition in blood donation on the relationship between blood donation and blood donors' health status. METHODS:A total of 837 participants who had prior experience in donating whole blood were recruited into a cross-sectional survey. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Questionnaire on Cognition in Non-remunerated Blood Donation were used to evaluate the health status and the level of cognition in blood donation, respectively. Blood donation referred to the cumulative times of blood donation. The mediating effect of cognition in blood donation was analyzed by applying a path model. RESULTS:The results revealed that blood donation was positively related to the physical component summary (PCS) and mental component summary (MCS) of SF-36, and cognition in blood donation was shown to have a partial mediating effect on the relationship between blood donation and both PCS and MCS. The effect size of cognition in blood donation was 24.63% in PCS and 26.72% in MCS. CONCLUSIONS:Blood donation is positively correlated with SF-36 outcomes (PCS and MCS) of blood donors, and cognition in blood donation plays a partial mediating effect in the relationship between blood donation and PCS and MCS.

Technological innovation and increased affordability have contributed to the widespread adoption of genome sequencing technologies in biomedical research. In particular large cancer research consortia have embraced next generation sequencing, and have used the technology to define the somatic mutation landscape of multiple cancer types. These studies have primarily utilised the Illumina HiSeq platforms. In this study we performed whole genome sequencing of three malignant pleural mesothelioma and matched normal samples using a new platform, the BGISEQ-500, and compared the results obtained with Illumina HiSeq X Ten. Germline and somatic, single nucleotide variants and small insertions or deletions were independently identified from data aligned human genome reference. The BGISEQ-500 and HiSeq X Ten platforms showed high concordance for germline calls with genotypes from SNP arrays (>99%). The germline and somatic single nucleotide variants identified in both sequencing platforms were highly concordant (86% and 72% respectively). These results indicate the potential applicability of the BGISEQ-500 platform for the identification of somatic and germline single nucleotide variants by whole genome sequencing. The BGISEQ-500 datasets described here represent the first publicly-available cancer genome sequencing performed using this platform.

OBJECTIVE:To evaluate the comparative efficacy and safety of saxagliptin for type 2 diabetes (T2D). METHODS:A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov and two Chinese databases for randomized controlled trials (RCTs) comparing saxagliptin with placebo or active comparators was performed up to July 2017. A complementary search was done to cover literature until March 2018. For continuous data, estimates were pooled using inverse variance methodology to calculate weighted mean differences (WMDs). Dichotomous data were presented as Mantel-Haenzel risk ratios (RRs). RESULTS:Thirty-nine references of 30 RCTs involving 29,938 patients were analyzed. Compared with placebo, saxagliptin significantly reduced glycated hemoglobin (HbA1c, WMD -0.52%, 95% CI -0.60 to -0.44) and fasting plasma glucose (WMD -13.78 mg/dL, 95% CI -15.31 to -12.25), and increased the proportion of patients achieving HbA1c

The performance of the Sha-he wastewater reclamation plant was evaluated in this study. To remove residual nitrogen after Anaerobic-Anoxic-Oxic (A2O) treatment, three multistage Anoxic-Oxic (A/O) were added to investigate the nitrogen removal efficiency and its mechanism. In addition, the constituents and evolution of dissolved organic matter (DOM) during wastewater reclamation was also investigated using a method combining fluorescence spectroscopy with fluorescence regional integration (FRI). The results suggested that multistage A/O treatment can effectively improve the nitrogen removal ability under low concentrations of carbon sources. The total nitrogen (TN) exhibits significantly positive correlation with fulvic acid-like materials and humic acid-like materials. The correlation coefficient for TN and fulvic acid-like substances (R2 = 0.810, P < 0.01) removal was greater than that of humic acid-like substances (R2 = 0.636, P < 0.05). The results indicate that nitrogen removal may be achieved with the fulvic-like and humic-like substances, and the removal effects were higher by fulvic acid-like substances than humic-like substances, mostly due to that the latter were relatively more difficult to be utilized as carbon source during the nitrogen removal process. The effluent water quality of biological treatment reached the first grade A standard of "Cities sewage treatment plant pollutant discharge standard" (GB18918-2002). In addition, the effluent from the membrane bioreactor reached the "Standards of reclaimed water quality" (SL368-2006).

Pleiotrophin (PTN) is a secreted cytokine that is expressed in various cancer cell lines and human tumor such as colon cancer, lung cancer, gastric cancer and melanoma. It plays significant roles in angiogenesis, metastasis, differentiation and cell growth. The expression of PTN in the adult is limited to the hippocampus in an activity-dependent manner, making it a very attractive target for cancer therapy. RNA interference (RNAi) offers great potential as a new powerful therapeutic strategy based on its highly specific and efficient silencing of a target gene. However, efficient delivery of small interfering RNA (siRNA) in vivo remains a significant hurdle for its successful therapeutic application. In this study, we first identified, on a cell-based experiment, applying a 1:1 mixture of two PTN specific siRNA engenders a higher silencing efficiency on both mRNA and protein level than using any of them discretely at the same dose. As a consequence, slower melanoma cells growth was also observed for using two specific siRNA combinatorially. To establish a robust way for siRNA delivery in vivo and further investigate how silence of PTN affects tumor growth, we tested three different methods to deliver siRNA in vivo: first non-targeted in-vivo delivery of siRNA via jetPEI; second lung targeted delivery of siRNA via microbubble coated jetPEI; third tumor cell targeted delivery of siRNA via transferrin-polyethylenimine (Tf-PEI). As a result, we found that all three in-vivo siRNAs delivery methods led to an evident inhibition of melanoma growth in non-immune deficiency C57BL/6 mice without a measureable change of ALT and AST activities. Both targeted delivery methods showed more significant curative effect than jetPEI. The lung targeted delivery by microbubble coated jetPEI revealed a comparable therapeutic effect with Tf-PEI, indicating its potential application for target delivery of siRNA in vivo.

Unbalanced dietary intake and insufficient physical activity (PA) have been recognized as risk factors for metabolic syndrome (MetS). We aimed to examine the independent and combined effects of fruit and vegetables (FV) intake and PA on MetS.A cross-sectional survey was conducted among residents of China in 2009, with fasting blood samples collected. Participants were divided into sufficient/insufficient FV intake and adequate/ inadequate PA groups according to self-reported questionnaires. MetS was defined using the NCEP-ATPIII criteria. The difference of individual MetS components was compared across different PA or FV groups. Multivariable logistic regression was used to assess association between FV/PA and the risk of MetS. A total of 7424 adults were included in the current study. MetS was prevalent in 28.7% of participants, with 24.7% and 32.9% in male and female, respectively. Compared with those with inadequate PA and insufficient FV intake, participants with the combination of adequate PA and sufficient FV intake had the lowest risk of MetS (OR = 0.69,95%CI: 0.59-0.82), following by the group with adequate PA time but insufficient FV intake (OR = 0.74, 95%CI:0.65-0.83).Findings of the current study show that the combination of sufficient FV intake and adequate PA was significantly associated with reduced MetS risk among adult residents of China.

To evaluate the clinical safety and efficacies of percutaneous vertebroplasty (PVP), percutaneous kyphoplasty (PKP), and percutaneous mesh-container-plasty (PMCP) for the treatment of vertebral compression fractures (VCFs), a retrospective study of 90 patients with VCFs who had been treated by PVP (n = 30), PKP (n = 30), and PMCP (n = 30) was conducted. The clinical efficacies of these three treatments were evaluated by comparing their PMMA cement leakages, cement patterns, height restoration percentages, wedge angles, visual analogue scales (VAS), and oswestry disability index (ODI) at the pre- and post-operative time points. 6.67%, 3.33%, and 0% of patients had PMMA leakage in PVP, PKP, and PMCP groups, respectively. Three (solid, trabecular, and mixed patterns), two (solid and mixed patterns), and one (mixed patterns) types of cement patterns were observed in PVP, PKP, and PMCP groups, respectively. PKP and PMCP treatments had better height restoration ability than PVP treatment. PVP, PKP, and PMCP treatments had significant and similar ability in pain relief and functional recovery ability for the treatment of VCFs. These results indicate minimally invasive techniques were effective methods for the treatment of VCFs. Moreover, these initial outcomes suggest PMCP treatment may be better than both PVP treatment and PKP treatment.

Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer's disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathology in the AD brain. Recently, we showed that 14-3-3ζ is bound to tau in the PHFs and when incubated in vitro with 14-3-3ζ, tau formed amorphous aggregates, single-stranded straight filaments, double stranded ribbon-like filaments and PHF-like filaments that displayed close resemblance with corresponding ultrastructures of AD brain. Surprisingly however, phosphorylated and non-phosphorylated tau aggregated in a similar manner, indicating that tau phosphorylation does not affect in vitro tau aggregation (Qureshi et al (2013) Biochemistry 52, 6445-6455). In this study, we have examined the role of tau phosphorylation in tau aggregation in cellular level. We have found that in human M17 neuroblastoma cells, tau phosphorylation by GSK3β or PKA does not cause tau aggregation, but promotes 14-3-3ζ-induced tau aggregation by destabilizing microtubules. Microtubule disrupting drugs also promoted 14-3-3ζ-induced tau aggregation without changing tau phosphorylation in M17 cell. In vitro, when incubated with 14-3-3ζ and microtubules, nonphosphorylated tau bound to microtubules and did not aggregate. Phosphorylated tau on the other hand did not bind to microtubules and aggregated. Our data indicate that microtubule-bound tau is resistant to 14-3-3ζ-induced tau aggregation and suggest that tau phosphorylation promotes tau aggregation in the brain by detaching tau from microtubules and thus making it accessible to 14-3-3ζ.

To compare the efficacy of using covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (UCSEMSs) to treat objective jaundice caused by an unresectable malignant tumor.We performed a comprehensive electronic search from 1980 to May 2015. All randomized controlled trials comparing the use of CSEMSs and UCSEMSs to treat malignant distal biliary obstruction were included.The analysis included 1417 patients enrolled in 14 trials. We did not detect significant differences between the UCSEMS group and the CSEMS group in terms of cumulative stent patency (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.19-4.53; p = 0.93, I2 = 0%), patient survival (HR 0.77, 95% CI 0.05-10.87; p = 0.85, I2 = 0%), overall stent dysfunction (relative ratio (RR) 0.85, M-H, random, 95% CI 0.57-1.25; p = 0.83, I2 = 63%), the overall complication rate (RR 1.26, M-H, fixed, 95% CI 0.94-1.68; p = 0.12, I2 = 0%) or the change in serum bilirubin (weighted mean difference (WMD) -0.13, IV fixed, 95% CI 0.56-0.3; p = 0.55, I2 = 0%). However, we did detect a significant difference in the main causes of stent dysfunction between the two groups. In particular, the CSEMS group exhibited a lower rate of tumor ingrowth (RR 0.25, M-H, random, 95% CI 0.12-0.52; p = 0.002, I2 = 40%) but a higher rate of tumor overgrowth (RR 1.76, M-H, fixed, 95% CI 1.03-3.02; p = 0.04, I2 = 0%). Patients with CSEMSs also exhibited a higher migration rate (RR 9.33, M-H, fixed, 95% CI 2.54-34.24; p = 0.008, I2 = 0%) and a higher rate of sludge formation (RR 2.47, M-H, fixed, 95% CI 1.36-4.50; p = 0.003, I2 = 0%).Our meta-analysis indicates that there is no significant difference in primary stent patency and stent dysfunction between CSEMSs and UCSEMSs during the period from primary stent insertion to primary stent dysfunction or patient death. However, when taking further management for occluded stents into consideration, CSEMSs is a better choice for patients with malignant biliary obstruction due to their removability.

Shiraia bambusicola P. Henn. is a pathogenic fungus of bamboo, and its fruiting bodies are regarded as folk medicine. We determined and analyzed its complete mitochondrial DNA sequence (circular DNA molecule of 39,030 bp, G + C content of 25.19%). It contains the typical genes encoding proteins involved in electron transport and coupled oxidative phosphorylation (nad1-6 and nad4L, cob and cox1-3), one ATP synthase subunit (atp6), 4 hypothetical proteins, and two genes for large and small rRNAs (rnl and rns). There is a set of 32 tRNA genes comprising all 20 amino acids, and these genes are evenly distributed on the two strands. Phylogenetic analyses based on concatenated mitochondrial proteins indicated that S. bambusicola clustered with members of the order Pleosporales, which is in agreement with previous results. The gene arrangements of Dothideomycetes species contained three regions of gene orders partitioned in their mitochondrial genomes, including block 1 (nad6-atp6), block 2 (nad1-cox3) and block 3 (genes around rns). S. bambusicola displayed unique special features that differed from the other Pleosporales species, especially in the coding regions around rns (trnR-trnY). Moreover, a comparison of gene orders in mitochondrial genomes from Pezizomycotina revealed that although all encoded regions are located on the same strand in most Pezizomycotina mtDNAs, genes from Dothideomycetes species had different orientations, as well as diverse positions and colocalization of genes (such as cox3, cox1-cox2 and nad2-nad3); these distinctions were regarded as class-specific features. Interestingly, two incomplete copies of the atp6 gene were found on different strands of the mitogenomic DNA, a finding that has not been observed in the other analyzed fungal species. In our study, mitochondrial genomes from Dothideomycetes species were comprehensively analyzed for the first time, including many species that have not appeared in previous reports.

OBJECTIVES:To analyze the gender difference in life expectancy in Chinese urban people and explore the age-specific and cause-specific contributions to the changing gender differences in life expectancy. METHODS:Data of life expectancy and mortality were obtained from "Annual statistics of public health in China." The gender difference was analyzed by decomposition method, including age-specific decomposition and cause-specific decomposition. RESULTS:Women lived much longer than men in Chinese urban areas, with remarkable gains in life expectancy since 2005, respectively. The gender difference reached a peak in 2007. Mortality difference between men and women in the 60-79 age group made the largest contributions to the gender gap in life expectancy in all 6 years. Among causes of death, cancers, circulatory diseases and respiratory diseases made the largest contributions to the gender gap. 33-38% of the gender gap were caused by cancers, among which lung cancer contributed 0.6 years of the overall gap. The contribution of cancers to the gender gap reduced over time, mostly influenced by the narrowing effect of liver cancer on gender gap. Traffic accidents and suicide were the external causes influencing the gender gap, contributing 10-16% of the overall difference. CONCLUSION:Public health efforts to reduce excess mortalities for cancers, circulatory disease, respiratory diseases, and suicide among men in particular might further narrow the gender gap in life expectancy in Chinese cities.

Short-term intermittent hypoxia (IH) is common in patients with acute respiratory disorders. Although prolonged exposure to hypoxia induces atrophy and increased fatigability of skeletal muscle, the response to short-term IH is less well known. We hypothesized that the diaphragm and limb muscles would adapt differently to short-term IH given that hypoxia stimulates ventilation and triggers a superimposed exercise stimulus in the diaphragm.We determined the structural, metabolic, and contractile properties of the mouse diaphragm after 4 days of IH (8 hours per day, 30 episodes per hour to a FiO2 nadir=6%), and compared responses in the diaphragm to a commonly studied reference limb muscle, the tibialis anterior. Outcome measures included muscle fiber size, assays of muscle proteolysis (calpain, ubiquitin-proteasome, and autophagy pathways), markers of oxidative stress and mitochondrial function, quantification of intramyocellular lipid and lipid metabolism genes, type I myosin heavy chain (MyHC) expression, and in vitro contractile properties.After 4 days of IH, the diaphragm alone demonstrated significant atrophy (30% decrease of myofiber size) together with increased LC3B-II protein (2.4-fold) and mRNA markers of the autophagy pathway (LC3B, Gabarapl1, Bnip3), whereas active calpain and E3 ubiquitin ligases (MuRF1, atrogin-1) were unaffected in both muscles. Succinate dehydrogenase activity was significantly reduced by IH in both muscles. However, only the diaphragm exhibited increased intramyocellular lipid droplets (2.5-fold) after IH, along with upregulation of genes linked to activated lipid metabolism. In addition, although the diaphragm showed evidence for acute fatigue immediately following IH, it underwent an adaptive fiber type switch toward slow type I MyHC-expressing fibers, associated with greater intrinsic endurance of the muscle during repetitive stimulation in vitro.Short-term IH induces preferential atrophy in the mouse diaphragm together with increased autophagy and a rapid compensatory metabolic adaptation associated with enhanced fatigue resistance.

The fruit of Pyrus ussuriensis is typically climacteric. During ripening, the fruits produce a large amount of ethylene, and their firmness drops rapidly. Although the molecular basis of climacteric fruit ripening has been studied in depth, some aspects remain unclear. Here, we compared the transcriptomes of pre- and post-climacteric fruits of Chinese pear (P. ussuriensis c.v. Nanguo) using RNA-seq. In total, 3,279 unigenes were differentially expressed between the pre- and post-climacteric fruits. Differentially expressed genes (DEGs) were subjected to Gene Ontology analysis, and 31 categories were significantly enriched in the groups 'biological process', 'molecular function' and 'cellular component'. The DEGs included genes related to plant hormones, such as ethylene, ABA, auxin, GA and brassinosteroid, and transcription factors, such as MADS, NAC, WRKY and HSF. Moreover, genes encoding enzymes related to DNA methylation, cytoskeletal proteins and heat shock proteins (HSPs) showed differential expression between the pre- and post-climacteric fruits. Select DEGs were subjected to further analysis using quantitative RT-PCR (qRT-PCR), and the results were consistent with those of RNA-seq. Our data suggest that in addition to ethylene, other hormones play important roles in regulating fruit ripening and may interact with ethylene signaling during this process. DNA methylation-related methyltransferase and cytoskeletal protein genes are also involved in fruit ripening. Our results provide useful information for future research on pear fruit ripening.

Coevolution is important for the maintenance of the interaction between a ligand and its receptor during evolution. The interaction between axon guidance molecule Slit and its receptor Robo is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the mechanism of coevolution between Slit and Robo remains unclear. In this study, we found that coordinated amino acid changes took place at interacting sites of Slit and Robo by comparing the amino acids at these sites among different organisms. In addition, the high level correlation between evolutionary rate of Slit and Robo was identified in vertebrates. Furthermore, the sites under positive selection of slit and robo were detected in the same lineage such as mosquito and teleost. Overall, our results provide evidence for the coevolution between Slit and Robo.

Axon guidance molecule Slit is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the function of Slit in the silkworm Bombyx mori was unknown. Here we showed that the structure of Bombyx mori Slit (BmSlit) was different from that in most other species in its C-terminal sequence. BmSlit was localized in the midline glial cell, the neuropil, the tendon cell, the muscle and the silk gland and colocalized with BmRobo1 in the neuropil, the muscle and the silk gland. Knock-down of Bmslit by RNA interference (RNAi) resulted in abnormal development of axons and muscles. Our results suggest that BmSlit has a repulsive role in axon guidance and muscle migration. Moreover, the localization of BmSlit in the silk gland argues for its important function in the development of the silk gland.

Antibody-based therapeutics provides novel and efficacious treatments for a number of diseases. Traditional experimental approaches for designing therapeutic antibodies rely on raising antibodies against a target antigen in an immunized animal or directed evolution of antibodies with low affinity for the desired antigen. However, these methods remain time consuming, cannot target a specific epitope and do not lead to broad design principles informing other studies. Computational design methods can overcome some of these limitations by using biophysics models to rationally select antibody parts that maximize affinity for a target antigen epitope. This has been addressed to some extend by OptCDR for the design of complementary determining regions. Here, we extend this earlier contribution by addressing the de novo design of a model of the entire antibody variable region against a given antigen epitope while safeguarding for immunogenicity (Optimal Method for Antibody Variable region Engineering, OptMAVEn). OptMAVEn simulates in silico the in vivo steps of antibody generation and evolution, and is capable of capturing the critical structural features responsible for affinity maturation of antibodies. In addition, a humanization procedure was developed and incorporated into OptMAVEn to minimize the potential immunogenicity of the designed antibody models. As case studies, OptMAVEn was applied to design models of neutralizing antibodies targeting influenza hemagglutinin and HIV gp120. For both HA and gp120, novel computational antibody models with numerous interactions with their target epitopes were generated. The observed rates of mutations and types of amino acid changes during in silico affinity maturation are consistent with what has been observed during in vivo affinity maturation. The results demonstrate that OptMAVEn can efficiently generate diverse computational antibody models with both optimized binding affinity to antigens and reduced immunogenicity.

Le Châtelier's principle is the cornerstone of our understanding of chemical equilibria. When a system at equilibrium undergoes a change in concentration or thermodynamic state (i.e., temperature, pressure, etc.), La Châtelier's principle states that an equilibrium shift will occur to offset the perturbation and a new equilibrium is established. We demonstrate that the effects of stabilizing mutations on the rigidity ⇔ flexibility equilibrium within the native state ensemble manifest themselves through enthalpy-entropy compensation as the protein structure adjusts to restore the global balance between the two. Specifically, we characterize the effects of mutation to single chain fragments of the anti-lymphotoxin-β receptor antibody using a computational Distance Constraint Model. Statistically significant changes in the distribution of both rigidity and flexibility within the molecular structure is typically observed, where the local perturbations often lead to distal shifts in flexibility and rigidity profiles. Nevertheless, the net gain or loss in flexibility of individual mutants can be skewed. Despite all mutants being exclusively stabilizing in this dataset, increased flexibility is slightly more common than increased rigidity. Mechanistically the redistribution of flexibility is largely controlled by changes in the H-bond network. For example, a stabilizing mutation can induce an increase in rigidity locally due to the formation of new H-bonds, and simultaneously break H-bonds elsewhere leading to increased flexibility distant from the mutation site via Le Châtelier. Increased flexibility within the VH β4/β5 loop is a noteworthy illustration of this long-range effect.

A new protocol was established for the regeneration of Solanum nigrum by frog egg-like bodies (FELBs), which are novel somatic embryogenesis (SE) structures induced from the root, stem, and leaf explants. The root, stem, and leaf explants (93.33%, 85.10%, and 100.00%, respectively) were induced to form special embryonic calli on Murashige and Skoog (MS) medium containing 1.0 mg/L 2,4-dichlorophenoxyacetic acid, under dark condition. Further, special embryonic calli from the root, stem, and leaf explants (86.97%, 83.30%, and 99.47%, respectively) were developed into FELBs. Plantlets of FELBs from the three explants were induced in vitro on MS medium supplemented with 5.0 mg/L 6-benzylaminopurine and 0.1 mg/L gibberellic acid, and 100.00% plantlet induction rates were noted. However, plantlet induction in vivo on MS medium supplemented with 20 mg/L thidiazuron showed rates of 38.63%, 15.63%, and 61.30% for the root, stem, and leaf explants, respectively, which were lower than those of the in vitro culture. Morphological and histological analyses of FELBs at different development stages revealed that they are a novel type of SE structure that developed from the mesophyll (leaf) or cortex (stem and root) cells of S. nigrum.

BACKGROUND: Many insects enter a developmental arrest (diapause) that allows them to survive harsh seasonal conditions. Despite the well-established ecological significance of diapause, the molecular basis of this crucial adaptation remains largely unresolved. Sitodiplosis mosellana (Gehin), the orange wheat blossom midge (OWBM), causes serious damage to wheat throughout the northern hemisphere, and sporadic outbreaks occur in the world. Traits related to diapause appear to be important factors contributing to their rapid spread and outbreak. To better understand the diapause mechanisms of OWBM, we sequenced the transcriptome and determined the gene expression profile of this species. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed de novo transcriptome analysis using short-read sequencing technology (Illumina) and gene expression analysis with a tag-based digital gene expression (DGE) system. The sequencing results generated 89,117 contigs, and 45,713 unigenes. These unigenes were annotated by Blastx alignment against the NCBI non-redundant (nr), Clusters of orthologous groups (COG), gene orthology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. 20,802 unigenes (45.5% of the total) matched with protein in the NCBI nr database. Two digital gene expression (DGE) libraries were constructed to determine differences in gene expression profiles during diapause and non-diapause developmental stages. Genes related to diapause were analyzed in detail and in addition, nine diapause-related genes were analyzed by real time PCR. CONCLUSIONS/SIGNIFICANCE: The OWBM transcriptome greatly improves our genetic understanding and provides a platform for functional genomics research of this species. The DGE profiling data provides comprehensive information at the transcriptional level that facilitates our understanding of the molecular mechanisms of various physiological aspects including development and diapause stages in OWBM. From this study it is evident that various genes coding metabolic enzymes are crucial for diapause and metamorphosis.

The wheat midge, Sitodiplosis mosellana, is an important pest in Northern China. We tested the hypothesis that the population structure of this species arises during a range expansion over the past 30 years. This study used microsatellite and mitochondrial loci to conduct population genetic analysis of S. mosellana across its distribution range in China. We found strong genetic structure among the 16 studied populations, including two genetically distinct groups (the eastern and western groups), broadly consistent with the geography and habitat fragmentation. These results underline the importance of natural barriers in impeding dispersal and gene flow of S. mosellana populations. Low to moderate genetic diversity among the populations and moderate genetic differentiation (F ST = 0.117) between the two groups were also found. The populations in the western group had lower genetic diversity, higher genetic differentiation and lower gene flow (F ST = 0.116, Nm = 1.89) than those in the eastern group (F ST = 0.049, Nm = 4.91). Genetic distance between populations was positively and significantly correlated with geographic distance (r = 0.56, P

Microsatellite instability (MSI) has been found in a range of human tumors, and little is known of the links between MSI and herpesvirus. In order to investigate the relationship between MSI and Gallid herpesvirus 2 (GaHV-2)-induced lymphoma, fifteen Marek's disease (MD) lymphomas were analyzed through using 46 microsatellite markers, which were amplified by PCR from DNA specimens of lymphoma and normal muscular tissues from the same chicken. PCR products were evaluated by denaturing polyacrylamide gel electrophoresis for MSI analysis. MSI was proved in all lymphomas, at least in one locus. Thirty of the 46 microsatellite markers had microsatellite alterations. These results suggested that GaHV-2-induced lymphoma in chickens is related to MSI, and this is the first report to demonstrate that MSI is associated with the GaHV-2 induced lymphoma in chicken.

Authentic induced pluripotent stem cells (iPSCs), capable of giving rise to all cell types of an adult animal, are currently only available in mouse. Here, we report the first generation of bovine iPSC-like cells following transfection with a novel virus-free poly-promoter vector. This vector contains the bovine cDNAs for OCT4, SOX2, KLF4 and c-MYC, each controlled by its own independent promoter. Bovine fibroblasts were cultured without feeders in a chemically defined medium containing leukaemia inhibitory factor (LIF) and inhibitors of MEK1/2 and glycogen synthase kinase-3 signaling ('2i'). Non-invasive real-time kinetic profiling revealed a different response of bovine vs human and mouse cells to culture in 2i/LIF. In bovine, 2i was necessary and sufficient to induce the appearance of tightly packed alkaline phosphatase-positive iPSC-like colonies. These colonies formed in the absence of DNA synthesis and did not expand after passaging. Following transfection, non-proliferative primary colonies expressed discriminatory markers of pluripotency, including endogenous iPSC factors, CDH1, DPPA3, NANOG, SOCS3, ZFP42, telomerase activity, Tra-1-60/81 and SSEA-3/4, but not SSEA-1. This indicates that they had initiated a self-sustaining pluripotency programme. Bovine iPSC-like cells maintained a normal karyotype and differentiated into derivatives of all three germ layers in vitro and in teratomas. Our study demonstrates that conversion into induced pluripotency can occur in quiescent cells, following a previously undescribed route of direct cell reprogramming. This identifies a major species-specific barrier for generating iPSCs and provides a chemically defined screening platform for factors that induce proliferation and maintain pluripotency of embryo-derived pluripotent stem cells in livestock.

SMLS (Sitobion miscanthi L type symbiont) is a newly reported aphid secondary symbiont. Phylogenetic evidence from molecular markers indicates that SMLS belongs to the Rickettsiaceae and has a sibling relationship with Orientia tsutsugamushi. A comparative analysis of coxA nucleotide sequences further supports recognition of SMLS as a new genus in the Rickettsiaceae. In situ hybridization reveals that SMLS is housed in both sheath cells and secondary bacteriocytes and it is also detected in aphid hemolymph. The population dynamics of SMLS differ from those of Buchnera aphidicola and titer levels of SMLS increase in older aphids. A survey of 13 other aphids reveals that SMLS only occurs in wheat-associated species.

Increase in the generation and deposition of amyloid-β (Aβ) plays a central role in the development of Alzheimer's Disease (AD). Elevation of the activity of γ-secretase, a key enzyme required for the generation for Aβ, can thus be a potential risk factor in AD. However, it is not known whether γ-secretase can be upregulated in vivo. While in vitro studies showed that expression of all four components of γ-secretase (Nicastrin, Presenilin, Pen-2 and Aph-1) are required for upregulation of γ-secretase, it remains to be established as to whether this is true in vivo. To investigate whether overexpressing a single component of the γ-secretase complex is sufficient to elevate its level and activity in the brain, we analyzed transgenic mice expressing either wild type or familial AD (fAD) associated mutant PS1. In contrast to cell culture studies, overexpression of either wild type or mutant PS1 is sufficient to increase levels of Nicastrin and Pen-2, and elevate the level of active γ-secretase complex, enzymatic activity of γ-secretase and the deposition of Aβ in brains of mice. Importantly, γ-secretase comprised of mutant PS1 is less active than that of wild type PS1-containing γ-secretase; however, γ-secretase comprised of mutant PS1 cleaves at the Aβ42 site of APP-CTFs more efficiently than at the Aβ40 site, resulting in greater accumulation of Aβ deposits in the brain. Our data suggest that whereas fAD-linked PS1 mutants cause early onset disease, upregulation of PS1/γ-secretase activity may be a risk factor for late onset sporadic AD.