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Simple Summary: Avian influenza viruses have the ability to breach species barriers and infect mammals, posing a significant threat to public health. The H7N9 subtype of avian influenza virus that emerged in China in 2013 resulted in 1568 human infections, with an alarming mortality rate of nearly 40%. While human infections caused by avian influenza viruses typically occur sporadically, the reasons behind the widespread impact of H7N9 remain unclear. During surveillance for avian influenza in live poultry markets in eastern China in 2013, we isolated two H7N9 avian influenza viruses from seemingly healthy chickens. One of these chicken-derived viruses demonstrated the ability to bind to mammalian receptors and naturally harbored the mammalian molecular marker PB2-627K. Furthermore, this virus proved to be highly pathogenic to mice. In summary, our findings suggest that the presence of a mammal-adapted H7N9 virus in poultry in 2013 could be a significant factor explaining the unusually high number of human infections during that period. Avian influenza viruses can cross species barriers and adapt to mammals. The H7N9 subtype AIV that emerged in China in 2013 caused 1568 human infections, with a mortality rate of nearly 40%. We conducted a retrospective analysis of H7N9 viruses that were isolated in live poultry markets in 2013. We found that two avian-origin H7N9 isolates, A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013, have a similar genetic background but exhibit different pathogenicity in mice. Whole-genome alignment of the two H7N9 viruses was carried out, and only six amino acid differences mapped in five genes, including the well-known virulence molecular marker PB2-E627K. Our retrospective analysis highlighted the importance of monitoring the adaptive mutations in avian influenza viruses with zoonotic potential. [ABSTRACT FROM AUTHOR]

Built environment (BE) planning and parking policy are two major strategies for restricting car use. However, researchers usually explore the independent associations of BE and parking policy with the use of the car in commuting, and most earlier studies are limited to investigating the benefits of integrating them. This study adopts a machine learning approach to explore the associations of home and workplace BE features and parking policy with the use of the car in commuting and whether the associations of BE features are moderated by parking policy. Results suggest that workplace BE features have larger collective contributions to the use of the car in commuting than home BE features. All BE features have nonlinear associations with the use of the car in commuting, and the nonlinear patterns differ across home and workplace neighborhoods. Moreover, free parking and parking convenience have significant moderating effects on the connection between BE and the use of the car in commuting. Thus, planning practitioners and policy makers should highlight the importance of coordinating BE planning and policy making to restrict the use of the car in commuting. [ABSTRACT FROM AUTHOR]

The crucial role that the built environment plays in affecting commuting behavior has been widely examined with a primary focus on the residential built environment. Moreover, the spatial heterogeneities at residential and work locations are rarely considered simultaneously in the literature. Based on data from 2012 Changchun household travel survey, we employed a hierarchical cross-classified structural equation model to explore the relationship between the residential and workplace built environment and commuting mode choice. Additionally, the spatial heterogeneities at both residential and work locations are recognized. The estimation results provide evidence on the necessity of accommodating spatial heterogeneities at both locations. Apart from the residential built environment, all built environment attributes at work locations show significant associations with commuting mode choice. These findings suggest that urban planners should pay more attention to the industrial and commercial areas where most employment opportunities concentrate because of the role that the built environment around workplaces plays. [ABSTRACT FROM AUTHOR]

With the development of information and communication technologies (ICTs), considerable attention is being paid to the relationship between ICT use and travel behavior. However, it is unclear whether the effects of ICT use on trip generation vary across travel modes. Based on the data of 1022 respondents collected by a web-based questionnaire survey in Beijing, this study used a zero-inflated Poisson model to investigate the effects of ICT use on trip generation in different travel modes, in which ICT use was measured by both the time spent online and the Internet use frequency. The results indicated that the effects of ICT use on trip generation vary across auto, transit, and active trips. Moreover, two measurements of ICT use play essential roles in influencing a trip generation. Specifically, only the frequency of ordering food online showed a positive association with the likelihood of generating any transit trips. These findings demonstrate the importance of considering the differences across travel modes when analyzing the relationship between ICT use and trip generation. [ABSTRACT FROM AUTHOR]

This study proposes a short-term traffic flow prediction approach based on multiple traffic flow basic parameters, in which the chaos theory and support vector regression are utilized. First, a high-dimensional variable space can be obtained according to the traffic flow fundamental function. Then, a maximum conditional entropy method is proposed to determine the embedding dimension. And multiple time series are reconstructed based on the phase space reconstruction theory using the time delay obtained by mutual information method and the embedding dimension captured by the maximum conditional entropy method. Finally, the reconstructed phase space is used as the input and the support vector regression optimized by the genetic algorithm is utilized to predict the traffic flow. Numerical experiments are performed and the results show that the approach proposed has strong fitting capability and better prediction accuracy. [ABSTRACT FROM AUTHOR]

Public transport services are often improved to decrease auto-related mobility. However, it remains unclear how the built environment influences auto ownership and commuting mode choice near public transit stations. Using 3318 individuals across China, this study contributes to investigating the relationship between the built environment, auto ownership and commuting mode choice simultaneously in neighborhoods near public transit stations by employing an integration of a structural equation model (SEM) and discrete choice model (DCM). The results indicate that the built environment exhibits significant impacts on auto-related mobility near public transit stations and auto ownership plays an intermediary role between the exogenous variables and commuting mode choice, thus it can moderate the influences of built environment attributes on commuting mode choice. The results suggest that increasing green coverage rates and promoting diverse land use development strategies in transit-oriented development (TOD) areas may make contributions to auto-related mobility reduction and low-carbon travel initiatives. [ABSTRACT FROM AUTHOR]

• This study longitudinally examines the built environment, commuting and life satisfaction. • The built environment and commuting have significant within-wave effects on life satisfaction. • Active commuting shows a significantly negative lagged effect on life satisfaction. • The built environment has greater effects on husbands' life satisfaction. There is considerable interest in identifying factors of life satisfaction. However, current evidence on its relationships with the built environment (BE) and commuting has been limited to cross-sectional analyses, and few studies have identified gender differences in their links. Using two-wave survey data of 1002 pairs of spouses collected in 2014 and 2016, the study investigates the longitudinal relationships between the residential BE, commuting attributes, and life satisfaction and how the relationships differ between spouses. The results of cross-lagged models suggest that the residential BE and commuting attributes have significant effects on life satisfaction within each wave. Those who commute by active modes are more likely to have lower life satisfaction in the near future. All residential BE variables show lagged effects on husbands' life satisfaction, whereas only residential density and entropy matter to wives. The findings offer implications for transport policies and BE planning. [ABSTRACT FROM AUTHOR]

Genotype S H9N2 viruses frequently donate their internal genes to facilitate the generation of novel influenza viruses, e.g., H5N6, H7N9, and H10N8, which have caused human infection. Genotype S was originated from the replacement of F/98-like M and PB2 genes of the genotype H with those from G1-like lineage. However, whether this gene substitution will influence the viral fitness of emerging influenza viruses remains unclear. We found that H5Nx and H7N9 viruses with G1-like PB2 or M gene exhibited higher virulence and replication than those with F/98-like PB2 or M in chickens. We also determined the functional significance of G1-like PB2 in conferring increased polymerase activity and improved nucleus transportation efficiency, and facilitated RNP nuclear export by G1-like M. Our results suggest that G1-like PB2 and M genes optimize viral fitness, and thus play a crucial role in the genesis of emerging influenza viruses that cause rising prevalence in chickens. • Genotype S H9N2 AIV donate their internal gene cassette to facilitate the generation of H5N6, H7N9, etc. • Genotype S H9N2 is the substitution of G1-like PB2 and M genes for the earlier F/98-like M and PB2 of genotype H. • G1-like H9N2 PB2 and M genes enhance virulence of reassortant H5Nx and H7N9 viruses in chickens. • Genotype S H9N2 internal gene cassette is superior to that of genotype H in optimizing viral fitness in chickens. [ABSTRACT FROM AUTHOR]

The alternating direction method of multipliers (ADMM) is an efficient splitting method for solving separable optimization with linear constraints. In this paper, an inertial proximal partially symmetric ADMM is proposed for solving linearly constrained multi-block nonconvex separable optimization, which can improve the computational efficiency by considering the ideas of inertial proximal point and linearization technique. Meanwhile, the proposed method updates the Lagrange multiplier twice and considers different relaxation factors in each iteration. Under the assumption that the generated sequence is bounded and the auxiliary function satisfies the Kurdyka-Łojasiewicz property, the global convergence of the proposed method with a more relaxed parameter range is analyzed. Moreover, some numerical results on SCAD (for smoothly clipped absolute deviation), image processing and robust PCA nonconvex problems are reported to demonstrate the efficiency and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

Although detrimental effects of commuting have been widely researched, little longitudinal evidence can be found regarding whether changes in commuting time and modes cause changes in life satisfaction. This study examines the relationships of life satisfaction with commuting from a longitudinal perspective. The effects of built environment are also examined. Using longitudinal survey data from 4505 respondents in China, the findings show that the increase in commuting time associates with losses in life satisfaction. Switching from non-active modes to active modes associates with increases in life satisfaction. Nonetheless, switching from active modes to non-active modes only reduces life satisfaction for people who experienced changes in some specific built environment attributes (e.g., increasing population density). Most changes in built environment associate with life satisfaction changes. The findings suggest that policy and planning efforts to promote active commuting and reduce commuting time (e.g., providing walkable and cyclist-friendly environment and promoting job–housing balance) should continue. [ABSTRACT FROM AUTHOR]

• N-cystaminylbiguanide prevents cell death of TH-positive neurons and alleviates motor deficits. • N-cystaminylbiguanide promotes GSH synthesis by activating Gcl. • N-cystaminylbiguanide shows Anti-ROS and anti-inflammatory properties. • N-cystaminylbiguanide regulates the expression of BDNF in brain. Parkinson's disease (PD) is a common neurodegenerative disease characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN), which is highly associated with oxidative stress. Antioxidants are therefore considered as potential therapies in PD treatment. In this study, we examined the neuroprotective effect of a cysteamine-based biguanide N-cystaminylbiguanide (MC001) in the MPTP mouse model of PD. The results showed that MC001 prevented neuron cell death and alleviated motor deficits in the MPTP mouse model of PD. Both in vitro and in vivo data indicated that MC001 may exert its neuroprotective effect by alleviating ROS production, suppressing neuroinflammation, and upregulating BDNF expression. Further mechanistic studies revealed that MC001 promoted GSH synthesis by inducing the expression of Glutamate-cysteine ligase catalytic subunit (Gclc) and enhancing the activity of Glutamate-cysteine ligase (Gcl). Our results suggest that MC001 warrants further investigation as a potential candidate for the treatment of PD. [ABSTRACT FROM AUTHOR]

Accumulating evidences suggest that Tryptophan hydroxylase 2 (TPH2) gene is associated with major depressive disorder (MDD) and cognitive function. In present study, we aimed to explore the association of cognitive disturbances in patients with late-onset depression (LOD) in the Chinese Han population. One hundred and ninety unrelated LOD patients who met DSM-IV criteria for major depressive disorder were recruited for the study and 155 normal controls were recruited from local community. All subjects completed the demographic assessments. Furthermore, 97 patients and 44 controls completed a series of neuropsychological tests. Patients and normal controls were genotyped for TPH2 (rs4290270 and rs7305115) variants using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results of our analysis indicated no significant differences in the frequencies of the single alleles and genotypes of two polymorphisms in TPH2 gene between LOD patients and normal controls. Haplotype association indicated that no differences were found in the frequencies of haplotype between two groups. A significant main effect of rs4290270 genotype on Verbal Fluency Test (VFT) test performance was found ( P < 0.05). There was a significant interactive effect of rs7305115 polymorphisms and depression diagnosis on Symbol Digit Modalities Test (SDMT) ( P < 0.05). After controlling for covariates, the subjects with carriers of GG genotype in rs7305115 had more better SDMT performance compared to AG and AA carriers in LOD groups. The result suggests that there is a major effect of rs4290270 in TPH2 on cognitive function alone. Moreover, an interaction of rs7305115 polymorphisms and depression diagnosis may be associated with the cognitive function. Further studies in a large sample are needed to replicate the genetic role in the LOD patients. [ABSTRACT FROM AUTHOR]

Aims Increasing evidence suggests that the catechol- O-methyltransferase ( COMT) gene might be associated with cognition in patients with mental disorders and healthy people. The metabolic pathways of COMT and methylenetetrahydrofolate reductase ( MTHFR) are closely interconnected. In this study, we aimed to examine whether the COMT-MTHFR genotype interacted with cognitive function in late-onset depression ( LOD) patients and COMT Val/ Val homozygous individuals who also carried the MTHFR T allele and had poor neuropsychological test performance. Methods Ninety-seven unrelated LOD patients who met DSM-IV criteria for major depressive disorder were recruited for the study and 103 normal controls were recruited from the local community. All of these patients and 44 normal controls completed a series of neuropsychological tests. Patients and normal controls were genotyped for COMT (rs4680) and MTHFR (rs1801133) variants using polymerase chain reaction-restriction fragment length polymorphism. Results There were no significant differences in the frequencies of the single alleles and genotypes of two polymorphisms between LOD patients and normal controls. No main effects of COMT or MTHFR genotype on any neuropsychological test performance were observed. There was a significant interactive effect of COMT Val158 Met and MTHFR C677T polymorphisms on the Symbol Digit Modalities Test independent of diagnosis ( P < 0.05). After controlling for covariates, the subjects with COMT Met/ Met and MTHFR C/ C genotype had better Symbol Digit Modalities Test performance. Conclusions The results suggest no major effect of COMT or MTHFR on cognitive function alone. However, an interaction of COMT Val158 Met and MTHFR C677T polymorphisms may be associated with cognitive function. Further studies in a large sample are needed to replicate the genetic role in the LOD patients. [ABSTRACT FROM AUTHOR]

Abstract: Microwave-Assisted Pyrolysis (MAP) is a highly scalable process that has the potential to realize the Distributed Biomass Energy Production System (DBEPS) concept. This study was to illustrate the heating properties of MAP when applied to biomass, and to demonstrate the feasibility of manipulating the heating operation to fully utilize exothermic reactions as a means to save energy. Alternate microwave heating of corn stover revealed exothermic reactions occurring in temperature ranges of 188.4–224.0°C and 367.0–387.0°C. These exothermic reactions can potentially sustain the pyrolysis reactions in the absence of external heat sources, indicating that alternative dielectric heating is a practical energy-saving operation mode for MAP. Analysis of the liquid products obtained from different heating intervals suggests that it is possible to selectively extract the primary pyrolysis products by collecting the condensables at specific heating times. The solid chars produced during MAP have desirable microwave absorbent properties and could be recycled in the MAP process. [Copyright &y& Elsevier]

Abstract: Background: The insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene has been implicated in susceptibility to major depressive disorder (MDD) and its treatment response; however, a large number of studies have reported inconsistent results. The aim of this study is to examine the role of I/D polymorphism of ACE gene in MDD risk and its treatment response by a case–control study and meta-analysis. Methods: Three hundred and sixty eight depressed patients who met DSM-IV criteria for major depressive disorder and 371 normal controls were recruited for the study. We searched Pubmed, Embase, CNKI, Wanfang, and Weipu database, covering all papers until March 31, 2011. Statistical analysis was performed using the software STATA 10.0. Results: Genotype and allele distributions of ACE I/D were not significantly different between case and control groups. No significant association with treatment response was discovered. A total of 2479 cases and 7744 controls in 15 case–control studies were included in this meta-analysis. The results indicated that the D/D homozygote carriers had an 18% increased risk of MDD, when compared with the homozygotes I/I and heterozygote I/D [odds ratio (OR)=1.18, 95% confidence interval (CI):1.04–1.33]. In the subgroup analysis, significant elevated risks were associated with D/D homozygote carriers in Caucasians (OR=1.20 and 95% CI: 1.04–1.38 for D/D vs I/D+I/I) but not in Asians. Moderate trends of an increased risk in the D allele carriers from total sample (OR, 1.15; 95% CI: 1.02–1.30) was also observed. The D/D homozygote carriers were associated with a 28% increased risk of MDD relative to the homozygotes I/I (OR 1.28; 95% CI: 1.11–1.49). In subgroup analysis, Caucasians showed significant association (OR 1.30; 95% CI: 1.09–1.56). No association was found in the Asian groups. No publication bias was observed in this meta-analysis by using the Egger method. Conclusions: The ACE I/D polymorphism is not associated with MDD and its treatment response in a Chinese case–control study. Meta-analysis evidence suggests that the I/D polymorphism of ACE gene may be a risk factor of major depressive disorder in Caucasians. [Copyright &y& Elsevier]

Abstract: Objective: Improving evidence suggest that neurotrophic growth factor systems might be involved in the pathophysiology of major depressive disorder (MDD). The glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor-β-family, which plays a role in the development and function of hippocampal cells. This study was aimed to test whether GDNF in plasma was abnormal in late-onset depression (LOD), and whether it was associated with the cognitive impairment of LOD. Methods: The plasma GDNF levels in LOD patients (n=27) before antidepressant treatment and normal control subjects (n=28) were measured with the ELISA method. All subjects were assessed by neuropsychological tests and Hamilton Depression Rating Scale (HDRS). Results: The performance of neuropsychological tests of the LOD group except TMT-B was significantly poorer than those of the control group. The plasma GDNF levels in LOD patients were significantly increased compared to control subjects (P <0.05). Furthermore, the increase of plasma GDNF level was significantly positively correlated with Digit Span Test backward score in LOD patients, and negatively associated with TMT-B performance. Conclusions: The findings suggest that LOD patients in acute phase have extensive impairments of cognitive function, and higher plasma GDNF might be involved in the pathogenesis of LOD, which may be associated with the cognitive dysfunction in LOD. [Copyright &y& Elsevier]

Abstract: Understanding the spatial distribution and apportioning the sources of water pollution are important in the study and efficient management of water resources. In this work, we considered data for 13 water quality variables collected during the year 2004 at 46 monitoring sites along the Qiantang River (China). Fuzzy comprehensive analysis categorized the data into three major pollution zones (low, moderate, and high) based on national quality standards for surface waters, China. Most sites classified as “low pollution zones” (LP) occurred in the main river channel, whereas those classified as “moderate and high pollution zones” (MP and HP, respectively) occurred in the tributaries. Factor analysis identified two potential pollution sources that explained 67% of the total variance in LP, two potential pollution sources that explained 73% of the total variance in MP, and three potential pollution sources that explained 80% of the total variance in HP. UNMIX was used to estimate contributions from identified pollution sources to each water quality variable and each monitoring site. Most water quality variables were influenced primarily by pollution due to industrial wastewater, agricultural activities and urban runoff. In LP, non-point source pollution such as agricultural runoff and urban runoff dominated; in MP and HP, mixed source pollution dominated. The pollution in the small tributaries was more serious than that in the main channel. These results provide information for developing better pollution control strategies for the Qiantang River. [Copyright &y& Elsevier]

We isolated and identified 201 Newcastle disease viruses (NDVs) from domestic ducks in a 5-year surveillance study at live bird markets in Eastern China. Seventy-three of these isolates were characterized biologically and genetically. Fusion protein (F) genes of these isolates were amplified by reverse transcription-polymerase chain reaction and sequenced. Intracerebral pathogenicity index tests in 1-day-old specific-pathogen-free chickens and the mean death time of embryonated fowl eggs in addition to the cleavage site analysis of the F-protein precursor for these viruses showed that they were all avirulent NDVs. Phylogenetic analysis based on partial sequences of the F gene showed that 30 isolates clustered into the class I clade and the other 43 isolates clustered into genotype I of class II, but diverged from the vaccine virus Queensland V4, which is extensively used in China. Most class I viruses (18/30) formed a separate branch closest to the Hong Kong live bird market strains that have been recently designated as genotype 3, while the rest (12/30) were closely related to some European viruses within genotype 2. All of the 43 class II genotype I viruses diverged from viruses originally assigned to genotype Ia and formed a separate sublineage designated as Ib with water bird isolates from the Far East, suggesting the possible transmission between the wild and domestic waterfowl. The results in the present study clearly showed that the domestic duck population carries avirulent NDVs with genetic divergence regularly and may act as one of the important reservoirs. [ABSTRACT FROM AUTHOR]

Abstract: There are few data available for the trends of antimicrobial resistance of Salmonella enterica subspecies enterica serovar Pullorum (S. Pullorum) in China and other parts of the world. Thus, the objective of this study was to evaluate the changes in antimicrobial resistance of S. Pullorum isolated from diseased chickens in China from 1962 to 2007. A total of 450 S. Pullorum isolates were tested for their susceptibility to 17 antimicrobials in a disk diffusion method. 39–95% of the isolates displayed a high level of resistance, particularly against ampicillin, carbenicillin, streptomycin, tetracycline, trimethoprim and sulfafurazole. Isolates exhibited increased resistance to carbenicillin, spectinomycin, trimethoprim, trimethoprim/sulfamethoxazole and nalidixic acid during the study period. Moreover, 56.2% of the isolates exhibited multiple drug resistance (MDR; resistance≥4 antimicrobials) and showed an increasing trend between 1970–1979 and 2000–2007. Therefore, the results suggest that certain measures, including continued surveillance of antimicrobial resistance and the rational use of antimicrobials, are necessary and important in order to control the rapid increase in antimicrobial resistance in S. Pullorum. [Copyright &y& Elsevier]

The relationships between the built environment (BE) and car dependence have been thoroughly evaluated, with a primary focus on the residential BE; however, the effects of the BE at workplaces have remained largely unexplored. Little is known about the potential nonlinear effects of the BE at both locations. Using data from a household travel survey in Changchun, China, we aimed to reveal the nonlinear effects of the residential and workplace BE on car dependence by building a gradient boosting decision trees model. The results show that the BE at both locations has strong explanatory power for car ownership and car purchasing intention. With relative contributions values of 17.90% and 18.13%, respectively, the BE at workplaces contributes less to explaining the two dependent variables than the BE at residences. All BE attributes show nonlinear effects on car ownership, and car purchasing intention and the effects differ between residential and workplace locations. • This study examines the effects of the built environment (BE) on car ownership and car purchasing intention. • The BEs at both residential and workplace locations show impacts on two dependent variables. • The relative contributions of the BE at residences are larger than the BE at workplaces. • The effects of all BE attributes at both locations are nonlinear. [ABSTRACT FROM AUTHOR]

• This study examines the impacts of commuting behavior, haze pollution and its changes on life satisfaction. • Active commuters have higher life satisfaction while commuters using public transit have lower life satisfaction. • Long commuting time leads to losses in life satisfaction. • Haze pollution mitigates the negative impacts of public transit, but strengthens losses induced by commuting time. The effects of air pollution and commuting behavior on life satisfaction have received increasing research interests. However, the literature pays scant attention to haze pollution and its moderating effects on the relationship between commuting behavior and life satisfaction. Using two-round of cross-sectional survey data across 92 Chinese cities, this paper analyzes the impacts of haze pollution and commuting behavior on life satisfaction, and the moderating effects of haze pollution on the link between commuting behavior and life satisfaction. The findings suggest that haze pollution and its changes are important triggers of life satisfaction. Moreover, the effects of changes in haze pollution correlate with basic haze pollution levels. Active commuters report higher life satisfaction, while transit commuters report lower life satisfaction. Longer commutes cause losses in life satisfaction. Additionally, haze pollution mitigates the losses in life satisfaction for commuters using public transit, but strengthens the negative effect of commuting time. [ABSTRACT FROM AUTHOR]

One common goal of urban planning is to promote health, where the built environment (BE) is believed to play an essential role. This study provides new evidence for the links between body mass index (BMI) and the BE at different geographic scales in a unified framework. Based on a sample of 10,962 individuals across 95 cities in China, this study explores the collective effects of the BE attributes at neighborhood and city levels on BMI using a gradient boosting decision tree (GBDT) approach. Moreover, whether the relationships between the city-level BE attributes and BMI vary across social groups is revealed. The results indicate that the city-level BE attributes have larger collective effects on BMI than the neighborhood-level BE attributes. Specifically, population size is the greatest contributor to predicting BMI, with a relative importance of 13.92% among all influential factors. Moreover, it is found that the effects of city-level BE attributes vary across different social groups. These findings suggest it is of vital importance for urban planners to coordinate both neighborhood- and city-level BE planning to deter the risks of obesity, and urban planning can be more effective if it is implemented considering local socio-demographic characteristics. • This study examines the effects of neighborhood and city-level built environment on BMI. • The relative importance of each influential factor is revealed. • City-level built environment has the greatest contribution to predicting BMI. • The effects of socio-demographics are moderated by the city-level built environment. [ABSTRACT FROM AUTHOR]

• Life events and changes in the built environment (BE) show impacts on commuting mode shift. • The gender differences between the spouses' travel behavior are identified. • Most life events show significant impacts on both the spouse' travel behavior. • Changes in the BE characteristics are more influential on the wife's commuting mode shift. Considerable attention has been paid to the determinants of commuting mode shift patterns. However, the literature provides little evidence on the impacts of changes in the built environment (BE) on commuting mode shift, and few studies shed light on the gender differences in the impacts of influential factors. Based on longitudinal data from China, this study explores how life events and changes in the BE influence commuting mode shift and whether the impacts differ between household couples. The results identify significant differences in the impacts of the influential factors between household couples. Most life events show significant impacts on the spouses' commuting mode shift, whereas changes in the BE characteristics are more influential on the wife's modal shift behavior. These findings suggest that urban planners and policy makers should better understand the gender differences to develop gender-equal transportation systems when implementing urban planning and transportation strategies. [ABSTRACT FROM AUTHOR]

Much of prior research has shown a growing interest in determinants of subjective well-being (SWB). However, relatively less research has explored the causal effects of commute and built environment (BE) on SWB, and there is little knowledge regarding how these connections differ between household members. The study examines both cross-sectional and longitudinal connections between commute, BE, and SWB, as well as the variations in these connections between couples, by analyzing longitudinal survey data of dual-earner households from Chinese cities. The results indicate that the increase in commute duration results in lower SWB. Shifting to active modes is shown to increase SWB. Nonetheless, shifting in the opposite direction shows no significant effect. All BE changes are correlated with the husbands' SWB changes, whereas only changes in neighborhood categories and neighborhood density appear to matter for wives. The findings indicate that planning strategies can complement transport policies aimed at enhancing SWB. • The study examines both cross-sectional and longitudinal connections between commute, BE, and SWB. • The increase in commute duration leads to declined SWB. • Shifting to active modes is shown to increase SWB. • Husbands' SWB is more sensitive to changes in BE. • There are variations in the determinants of SWB between couples. [ABSTRACT FROM AUTHOR]

Anaplasma bovis, causative agent of bovine anaplasmosis, is usually identified by nested-PCR amplifying the rrs gene. However, it is difficult to determine the genetic relationship among different variants within A. bovis using this gene because of high conservation. In this study, two tick species, identified as Rhipicephalus microplus and Haemaphysalis longicornis based on morphological and molecular methods by analyzing COI gene, were collected from cattle, goat or sheep. Subsequently, A. bovis was initially detected by PCR amplifying the rrs gene in ticks in Shaanxi Province, China. The sequencing and Blast results showed that some false positive samples were found when only based on the amplification of partial rrs gene, presenting these sequences resembled those of other Alphaproteobacteria rather than A. bovis. Although major surface proteins genes were proposed and used successfully to identify members within Anaplasmataceae, these genes were unavailable for A. bovis. Hence, primers targeting the groEL gene were designed and a PCR assay was developed. The PCR products were sequenced and similarity and phylogenetic analysis suggested all these sequences are the groEL gene of A. bovis. In addition, phylogenetic analysis based on the groEL gene also revealed the genetic diversity of A. bovis worldwide, as well as in Shaanxi Province of China, which wasn't reflected by analyzing the rrs gene. In sum, groEL gene is important for molecular detection and phylogenetic analysis of A. bovis. • GroEL gene is useful for detection of A. bovis. • GroEL gene is valuable to the phylogenetic analysis of A. bovis. • Genetic diversity of groEL gene for A. bovis in Shaanxi. [ABSTRACT FROM AUTHOR]

The linear complementary problem (LCP) is a unified formulation for linear and quadratic programming problems. Therefore, it has many applications in practical problems like bimatrix game. We prove that it makes sense to look for sparse LCP solutions. A l 2 − l 1 regularization technique transforms the original sparse optimization problem into an unconstrained one. Thereafter, a linearized ADMM (for alternating direction method of multipliers) is designed to solve the regularization model. Then, using a penalty function approach, we propose an efficient sequential linearized ADMM to find the sparse LCP solutions. Finally, numerical experiments prove that the sparse solution of LCPs can be solved efficiently, and is competitive with other state-of-the-art algorithms. A practical application in bimatrix game is also reported. [ABSTRACT FROM AUTHOR]

Newcastle disease virus (NDV) has been extensively studied as a promising oncolytic virus for killing tumor cells in vitro and in vivo in clinical trials. However, the viral components that regulate the oncolytic activity of NDV remain incompletely understood. In this study, we systematically compared the replication ability of different NDV genotypes in various tumor cells and identified NP protein determines the oncolytic activity of NDV. On the one hand, NDV strains with phenylalanine (F) at the 450th amino acid position of the NP protein (450th-F-NP) exhibit a loss of oncolytic activity. This phenotype is predominantly associated with genotype VII NDVs. In contrast, the NP protein with a leucine amino acid at this site in other genotypes (450th-L-NP) can facilitate the loading of viral mRNA onto ribosomes more effectively than 450th-F-NP. On the other hand, the NP protein from NDV strains that exhibit strong oncogenicity interacts with eIF4A1 within its 366–489 amino acid region, leading to the inhibition of cellular mRNA translation with a complex 5' UTR structure. Our study provide mechanistic insights into how highly oncolytic NDV strains selectively promote the translation of viral mRNA and will also facilitate the screening of oncolytic strains for oncolytic therapy. Author summary: The oncolytic potential of NDV has gained significant attention in the context of clinical trials. Therefore, it is crucial to systematically compare the oncolytic activities of different NDV subtypes and understand their underlying mechanisms. Our previous investigations revealed that genotype VII NDVs, predominant during the fourth epidemic, exhibit heightened avian pathogenicity compared to other subtypes. Interestingly, in tumor cells, NDV strains of varying virulence and genotypes possess some oncolytic capacity. However, in several genotype VII strains, the NP protein fails to facilitate the efficient loading of viral mRNA onto ribosomes. This is primarily attributed to the presence of phenylalanine at the 450th amino acid position of the NP protein. Additionally, it loses its ability to inhibit the eIF4A1-relative cellular mRNA translation through interaction with eIF4A1, mainly because of differences in its non-conserved region (366-489aa) of NP protein compared to other genotypes. These significantly hinder its ability to establish effective infections in tumor cells. Our study provides valuable insights for oncolytic NDV strain screening and enhances understanding of the functional role of NP protein. [ABSTRACT FROM AUTHOR]

Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) and trigger different types of cell death, including apoptosis. Newcastle disease virus (NDV) can naturally infect most birds. Additionally, it serves as a promising oncolytic virus known for its effective infection of tumor cells and induction of intensive apoptotic responses. However, the involvement of lysosomes in NDV-induced apoptosis remains poorly understood. Here, we demonstrate that NDV infection profoundly triggers LMP, leading to the translocation of cathepsin B and D and subsequent mitochondria-dependent apoptosis in various tumor and avian cells. Notably, the released cathepsin B and D exacerbate NDV-induced LMP by inducing the generation of reactive oxygen species. Additionally, we uncover that the viral Hemagglutinin neuraminidase (HN) protein induces the deglycosylation and degradation of lysosome-associated membrane protein 1 (LAMP1) and LAMP2 dependent on its sialidase activity, which finally contributes to NDV-induced LMP and cellular apoptosis. Overall, our findings elucidate the role of LMP in NDV-induced cell apoptosis and provide novel insights into the function of HN during NDV-induced LMP, which provide innovative approaches for the development of NDV-based oncolytic agents. Author summary: Our study investigates the role of lysosomes in Newcastle disease virus (NDV)-induced cell apoptosis. We found that NDV infection leads to lysosomal membrane permeabilization (LMP) and the release of cathepsin B and D enzymes. This triggers mitochondria-dependent apoptosis in various tumor and avian cells. The released cathepsin B and D exacerbate LMP by generating reactive oxygen species. Additionally, the viral Hemagglutinin neuraminidase protein degrades lysosome-associated membrane proteins (LAMP1 and LAMP2), contributing to LMP and apoptosis. These findings provide insights into NDV-induced cell apoptosis and highlight the potential of targeting lysosomes for the development of NDV-based oncolytic therapies. [ABSTRACT FROM AUTHOR]

Short-term traffic flow forecasting is a key component of intelligent transportation system, yet difficult to be forecasted reliably, and accurately. A novel hybrid forecasting model is proposed by combining three predictors, namely, the autoregressive integrated moving average (ARIMA), back propagation neural network (BPNN) and support vector regression (SVR). First, it is assumed that all previous intervals can have influence on the predicted interval and then the entropy-based gray relation analysis method is applied to analyze the correlation and determine the length of time constrain window. Second, an improved Euclidean distance is employed to identify the similarity. Furthermore, the rank-exponent method is utilized to rank the results according to the similarity and fuse the predicted values of the predictors. Finally, a numerical experiment is implemented, which indicates that the performance of forecasting results is superior to the conventional ones. [ABSTRACT FROM AUTHOR]

Replication of Newcastle disease virus (NDV) is regulated by various host mechanisms, but the role of the extracellular signal-regulated kinase (ERK) pathway in regulating NDV replication is an open question. In this study, the relationship between the ERK pathway and NDV replication was investigated. NDV activated the ERK signaling in chicken embryo fibroblasts at the late stage of infection, correlating to expression of viral proteins. Specific blockage of the ERK pathway activation significantly decreased the transcription and translation levels of viral genes as well as virus replication and the cytopathogenic effect caused by NDV. Our results demonstrate that activation of the ERK pathway is required for NDV replication. [ABSTRACT FROM AUTHOR]

Background: Genotype S H9N2 viruses have become predominant in poultry in China since 2010. These viruses frequently donate their whole internal gene segments to other emerging influenza A subtypes such as the novel H7N9, H5N6, and H10N8 viruses. We recently reported that the PB2 and M genes of the genotype S H9N2 virus, which are derived from the G1-like virus, enhance the fitness of H5Nx and H7N9 avian influenza viruses in chickens and mice. However, whether the G1-like PB2 and M genes are preferentially incorporated into progeny virions during virus reassortment remains unclear; whether the G1-like PB2 and M genes from different subtypes are differentially incorporated into new virion progeny remains unknown. Results: We conducted a reassortment experiment with the use of a H7N9 virus as the backbone and found that G1-like M/PB2 genes were preferentially incorporated in progeny virions over F/98-like M/PB2 genes. Importantly, the preference varied among G1-like M/PB2 genes of different subtypes. When competing with F/98-like M/PB2 genes during reassortment, both the M and PB2 genes from the H7N9 virus GD15 showed an advantage, whereas only the PB2 gene from the H9N2 virus CZ73 and the M gene from the H9N2 virus AH320 displayed the advantage. Conclusion: Our findings highlight the preferential and variable advantages of H9N2-derived G1-like M and PB2 genes in incorporating them into H7N9 progeny virions over SH14-derived F/98-like M/PB2 genes. [ABSTRACT FROM AUTHOR]

Urban rail transit (URT) is often implemented in order to reduce car ownership and use. However, it is still unclear how the impacts of the built environment on car dependence differ in transit-oriented development (TOD) areas and non-TOD areas. Based on 2012 Changchun household travel survey data, this study aims to explore whether the relationships between the built environment and household vehicle kilometers traveled (VKT) vary between station and non-station areas by employing a multi-group structural equation model (SEM). The results suggest that the effects of the built environment on household VKT vary between station and non-station areas. Additionally, the results confirm the remarkable role that the built environment plays in influencing car ownership and use by revealing the direct, indiract and total effects. These findings provide a better understanding of the inherent mechanism by which URT moderates the impacts of the built environment on car ownership and use. It suggests that, for urban planners and policy makers, promoting compact land use strategies can have a positive effect on reducing car use, and URT implementation can effectively strengthen the effects. [ABSTRACT FROM AUTHOR]

Genotype S H9N2 avian influenza virus, which has been predominant in China since 2010, contributed its entire internal gene cassette to the genesis of novel reassortant influenza viruses, including H5Nx, H7N9 and H10N8 viruses that pose great threat to poultry and humans. A key feature of the genotype S H9N2 virus is the substitution of G1‐like M and PB2 genes for the earlier F/98‐like M and PB2 of genotype H virus. However, how this gene substitution has influenced viral adaptability of emerging influenza viruses in mammals remains unclear. We report here that reassortant H5Nx and H7N9 viruses with the genotype S internal gene cassette displayed enhanced replication and virulence over those with genotype H internal gene cassette in cell cultures as well as in the mouse models. We showed that the G1‐like PB2 gene was associated with increased polymerase activity and improved nuclear accumulation compared with the F/98‐like counterpart, while the G1‐like M gene facilitated effective translocation of RNP to cytoplasm. Our findings suggest that the genotype S H9N2 internal gene cassette, which possesses G1‐like M and PB2 genes, is superior to that of genotype H, in optimizing viral fitness, and thus have implications for assessing the potential risk of these gene introductions to generate emerging influenza viruses. [ABSTRACT FROM AUTHOR]

Polymerase acidic (PA) protein is a multifunctional regulator of influenza A virus (IAV) replication and pathogenesis. In a previous study, we reported that nucleolin (NCL) is a novel PA-interacting host protein. In this study, we further explored the role of NCL during highly pathogenic H5N1 avian influenza virus infection. We found that depletion of endogenous NCL in mammalian cells by siRNA targeting during H5N1 infection resulted in significantly increased viral polymerase activity, elevated viral mRNA, cRNA and vRNA synthesis, accelerated viral replication, and enhanced apoptosis and necrosis. Moreover, siRNA silencing of NCL significantly exacerbated the inflammatory response, resulting in increased secretion of IL-6, TNF-α, TNF-β, CCL-4, CCL-8, IFN-α, IFN-β and IFN-γ. Conversely, overexpression of NCL significantly decreased IAV replication. Collectively, these data show that NCL acts as a novel potential antiviral factor during H5N1 infection. Further studies exploring the antiviral mechanisms of NCL may accelerate the development of new anti-influenza drugs. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play multiple key regulatory roles in various biological processes. However, their function in influenza A virus (IAV) pathogenicity remains largely unexplored. Here, using next generation sequencing, we systemically compared the whole-transcriptome response of the mouse lung infected with either the highly pathogenic (A/Chicken/Jiangsu/k0402/2010, CK10) or the nonpathogenic (A/Goose/Jiangsu/k0403/2010, GS10) H5N1 virus. A total of 126 significantly differentially expressed (SDE) lncRNAs from three replicates were identified to be associated with the high virulence of CK10, whereas 94 SDE lncRNAs were related with GS10. Functional category analysis suggested that the SDE lncRNAs-coexpressed mRNAs regulated by CK10 were highly related with aberrant and uncontrolled inflammatory responses. Further canonical pathway analysis also confirmed that these targets were highly enriched for inflammatory-related pathways. Moreover, 9 lncRNAs and 17 lncRNAs-coexpressed mRNAs associated with a large number of targeted genes were successfully verified by qRT-PCR. One targeted lncRNA (NONMMUT011061) that was markedly activated and correlated with a great number of mRNAs was selected for further in-depth analysis, including predication of transcription factors, potential interacting proteins, genomic location, coding ability and construction of the secondary structure. More importantly, NONMMUT011061 was also distinctively stimulated during the highly pathogenic H5N8 virus infection in mice, suggesting a potential universal role of NONMMUT011061 in the pathogenesis of different H5 IAV. Altogether, these results provide a subset of lncRNAs that might play important roles in the pathogenesis of influenza virus and add the lncRNAs to the vast repertoire of host factors utilized by IAV for infection and persistence. [ABSTRACT FROM AUTHOR]

Nuclear factor kappa B (NF-κB) plays a crucial role in inflammation and immune responses. Our previous studies have demonstrated that the innate immune response affect H5N1 virus virulence in mice. In this study, we first showed that the PA protein of the highly pathogenic avian influenza virus strain CK10 had the strongest inhibitory effect on NF-κB activation when compared with other genes, and that it acted in a dose independent-manner. We then determined the critical amino acids of PA that contribute to this effect. Furthermore, PA also inhibited NF-κB-regulated inflammatory factors, including IL-6, IL-2, Nos-2 and TNF-α. However, the inhibitory effect on NF-κB activation mediated by PA was not associated with nuclear translocation of p65. [ABSTRACT FROM AUTHOR]

Nucleoprotein (NP) functions crucially in the replicative cycle of influenza A virus (IAV) via forming the ribonucleoprotein complex together with PB2, PB1, and PA proteins. As its high conservation, NP ranks one of the hot targets for design of universal diagnostic reagents and antiviral drugs for IAV. Here, we report an anti-NP murine monoclonal antibody (mAb) 5F10 prepared from traditional lymphocyte hybridoma technique with the immunogen of a clade 2.3.4.4 H5N1 subtype avian influenza virus. The specificity of mAb 5F10 to NP protein was confirmed by immunofluorescence assay and western blotting, and the mAb 5F10 could be used in immunoprecipitation and immunohistochemistry assays. Importantly, mAb 5F10 possessed broad-spectrum reactivity against H1~H11 subtypes of avian influenza viruses, including various HA clades of H5Nx subtype. In addition, mAb 5F10 also showed good affinity with H1N1 and H3N2 subtype influenza viruses of swine and human origin. Furthermore, the recognized antigenic epitope of mAb 5F10 was identified to consist of the conserved amino acid motif 81EHPSA85 in the second flexible loop region of NP protein through screening the phage display peptide library. Collectively, the mAb 5F10 which recognizes the novel universal NP linear B-cell epitope of IAV with diverse origins and subtypes will be a powerful tool for NP protein-based structural, functional, and mechanistic studies, as well as the development of detection methods and universal vaccines for IAV. Key points: • A broad-spectrum mAb against various subtypes and sources of IAV was developed • The mAb possessed good reactivity in IFA, western blot, IP, and IHC assays • The mAb targeted a novel conserved linear B-cell epitope involving 81EHPSA85 on NP protein [ABSTRACT FROM AUTHOR]

We previously reported a pair of H5N1 avian influenza viruses which are genetically similar but differ greatly in their virulence in mice. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly lethal to mice, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is avirulent. In this study, to investigate the host factors that account for their virulence discrepancy, we compared the pathology and host proteome of the CK10- or GS10-infected mouse lung. Moderate lung injury was observed from CK10-infected animals as early as the first day of infection, and the pathology steadily progressed at later time point. However, only mild lesions were observed in GS10-infected mouse lung at the late infection stage. Using the quantitative iTRAQ coupled LC-MS/MS method, we first found that more significantly differentially expressed (DE) proteins were stimulated by GS10 compared with CK10. However, bio-function analysis of the DE proteins suggested that CK10 induced much stronger inflammatory response-related functions than GS10. Canonical pathway analysis also demonstrated that CK10 highly activated the 'Acute Phase Response Signaling,' which results in a wide range of biological activities in response to viral infection, including many inflammatory processes. Further in-depth analysis showed that CK10 exacerbated acute lung injury-associated responses, including inflammatory response, cell death, reactive oxygen species production and complement response. In addition, some of these identified proteins that associated with the lung injury were further confirmed to be regulated in vitro. Therefore, our findings suggest that the early increased lung injury-associated host response induced by CK10 may contribute to the lung pathology and the high virulence of this virus in mice. [ABSTRACT FROM AUTHOR]

As a multifunctional protein, the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) is involved in various biological functions. A velogenic genotype III NDV JS/7/05/Ch evolving from the mesogenic vaccine strain Mukteswar showed major amino acid (aa) mutations in the HN protein. However, the precise biological significance of the mutant HN protein remains unclear. This study sought to investigate the effects of the mutant HN protein on biological activities in vitro and in vivo. The mutant HN protein (JS/7/05/Ch-type HN) significantly enhanced the hemadsorption (HAd) and fusion promotion activities but impaired the neuraminidase (NA) activity compared with the original HN protein (Mukteswar-type HN). Notably, A494D and E495K in HN exhibited a synergistic role in regulating biological activities. Moreover, the mutant HN protein, especially A494D and E495K in HN, enhanced the F protein cleavage level, which can contribute to the activation of the F protein. In vitro infection assays further showed that NDVs bearing A494D and E495K in HN markedly impaired the cell viability. Simultaneously, A494D and E495K in HN enhanced virus replication levels at the early stage of infection but weakened later in infection, which might be associated with the attenuated NA activity and cell viability. Furthermore, the animal experiments showed that A494D and E495K in HN enhanced case fatality rates, virus shedding, virus circulation, and histopathological damages in NDV-infected chickens. Overall, these findings highlight the importance of crucial aa mutations in HN in regulating biological activities of NDV and expand the understanding of the enhanced pathogenicity of the genotype III NDV. [ABSTRACT FROM AUTHOR]

We investigated genetic and biologic characteristics of 2 Eurasian avian-like H1N1 swine influenza viruses from pigs in China that belong to the predominant G4 genotype. One swine isolate exhibited strikingly great homology to contemporaneous human Eurasian avian-like H1N1 isolates, preferential binding to the human-type receptor, and vigorous replication in mice without adaptation. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between hippocampal functional connectivity (HFC), cognitive deficits, and the influence of BDNF Val66Met polymorphism on the HFC in acute late-onset depression (LOD). Methods 26 LOD patients and 33 and normal controls (NCs) completed clinical assessments, neuropsychological testing, blood samples collecting for genotyping, and resting-state functional MRI (R-fMRI) scans. The LOD and NCs groups were further divided into four groups according to BDNF Met allele carrier or not (LOD Met−( n =8); LOD Met+( n =18); NCs Met−( n =9); NCs Met+( n =24)). Then, seed-based correlation analyses and two-way analysis of covariance (ANCOVA) were performed to explore the main effects and interactive effects of LOD and BDNF Val66Met polymorphism on the HFC. Spearman correlation was applied to examine the cognitive and emotional significance of these altered HFC networks. Results Compared with NCs, bilateral positive HFC with the right insula, left positive HFC with bilateral orbit-frontal cortex (OFC) and left precuneus, right positive HFC with right dorsolateral prefrontal cortex (dlPFC) were decreased, and bilateral negative HFC with right postcentral gyrus were reversed in LOD patients. BDNF Met allele mainly decreased bilateral positive HFC with the cerebellum. The interaction of LOD and BDNF Met allele primarily influenced the bilateral HFC with the temporal cortex and dorsal nexus. The changed HFC with the OFC, postcentral gyrus, cerebellum and temporal cortex significantly correlated to the cognitive deterioration. There was no significant association between the depressive severity and any altered HFC networks. Conclusion The cognitive deterioration in LOD patients, BDNF Met allele carriers, and LOD patients carring Met allele were associated with the changed HFC networks in the OFC/postcentral gyrus, cerebellum and temporal cortex respectively. [ABSTRACT FROM AUTHOR]

Characterizing mobility patterns between locations of people and goods is not only a long-standing research topic, but it has also critical practical applications in transportation science, spatial economics, sociology and many other fields. Despite the long history of modeling human mobility, we continue to lack a model can reflect the degree of people's perception of travel cost. Here, we present a cost opportunity model that assumes an individual choosing a destination is proportional to the number of opportunities at the destination, and inversely to the power of the number of intervening opportunities between the origin and destination. Further, we use real mobility data collected from a number of cities and countries to demonstrate the predictive ability of this simple model. The results show that the new model can reveal people's perception of travel cost and offers universal predictions for different types of mobility that are consistent with real observations, thus suggesting that the proposed model better captures the mechanism underlying human mobility. Besides, our model preserves the analytical property of being equivalent to a gravity model in the limit of a uniform population distribution. [ABSTRACT FROM AUTHOR]

Pigeon paramyxovirus type 1 (PPMV‐1) is an antigenic variant of Newcastle disease virus (NDV) which is mainly associated with infections of pigeons and has the potential to result in disease in chickens. In this study, we characterised 21 PPMV‐1 isolates from diseased pigeons in China during 2007–2019. Phylogenetic analysis revealed that all isolates belonged to genotype VI. Among them, most isolates belonged to sub‐genotype VI.2.1.1.2.2, suggesting that VI.2.1.1.2.2 has become a prevalent genotype in pigeons in China. The results showed that all PPMV‐1 isolates were mesogenic in nature according to the mean death time (MDT) and intracerebral pathogenicity index (ICPI). In vitro and in vivo studies demonstrated that two genetically closely related isolates (Pi‐11 and Pi‐10) both of which belonged to sub‐genotype VI.2.1.1.2.2 had similar replication kinetics in cells derived from pigeons, while the replication titre of Pi‐11 was significantly higher than that of Pi‐10 in cells derived from chickens. Pi‐11 and Pi‐10 could contribute to morbidity and mortality in pigeons. Remarkably, although the two viruses resulted in no apparent disease symptom in chickens, Pi‐11 could cause more severe histopathological lesions and had a stronger replication ability in chickens compared to Pi‐10. Moreover, chickens infected with Pi‐11 had higher shedding efficiency than chickens infected with Pi‐10. Additionally, several mutations within important functional regions of the fusion (F) and haemagglutinin‐neuraminidase (HN) proteins might be associated with different pathogenicity of the two viruses in chickens. Collectively, these results indicated that the Pi‐11‐like virus of pigeon origin has the potential to induce severe outbreaks in chicken flocks. These findings will help us better understand the epidemiology and evolution of PPMV‐1 in China and serve as a foundation for the further investigation of the mechanism underlying the pathogenic difference of PPMV‐1 isolates in chickens. [ABSTRACT FROM AUTHOR]

Reassortment with the H9N2 virus gave rise to the zoonotic H7N9 avian influenza virus (AIV), which caused more than five outbreak waves in humans, with high mortality. The frequent exchange of genomic segments between H7N9 and H9N2 has been well-documented. However, the reassortment patterns have not been described and are not yet fully understood. Here, we used phylogenetic analyses to investigate the patterns of intersubtype and intrasubtype/intralineage reassortment across the eight viral segments. The H7N9 virus and its progeny frequently exchanged internal genes with the H9N2 virus but rarely with the other AIV subtypes. Before beginning the intrasubtype/intralineage reassortment analyses, five Yangtze River Delta (YRD A-E) and two Pearl River Delta (PRD A-B) clusters were divided according to the HA gene phylogeny. The seven reset segment genes were also nomenclatured consistently. As revealed by the tanglegram results, high intralineage reassortment rates were determined in waves 2–3 and 5. Additionally, the clusters of PB2 c05 and M c02 were the most dominant in wave 5, which could have contributed to the onset of the largest H7N9 outbreak in 2016–2017. Meanwhile, a portion of the YRD-C cluster (HP H7N9) inherited their PB2, PA, and M segments from the co-circulating YRD-E (LP H7N9) cluster during wave 5. Untanglegram results revealed that the reassortment rate between HA and NA was lower than HA with any of the other six segments. A multidimensional scaling plot revealed a robust genetic linkage between the PB2 and PA genes, indicating that they may share a co-evolutionary history. Furthermore, we observed relatively more robust positive selection pressure on HA, NA, M2, and NS1 proteins. Our findings demonstrate that frequent reassortment, particular reassorted patterns, and adaptive mutations shaped the H7N9 viral genetic diversity and evolution. Increased surveillance is required immediately to better understand the current state of the HP H7N9 AIV. [ABSTRACT FROM AUTHOR]

Commercial inactivated vaccines against H9N2 avian influenza (AI) have been developed in China since 1990s and show excellent immunogenicity with strong HI antibodies. However, currently approved vaccines cannot meet the clinical demand for a live-vectored vaccine. Newcastle disease virus (NDV) vectored vaccines have shown effective protection in chickens against H9N2 virus. However, preexisting NDV antibodies may affect protective efficacy of the vaccine in the field. Here, we explored avian paramyxovirus serotype 2 (APMV-2) as a vector for developing an H9N2 vaccine via intranasal delivery. APMV-2 belongs to the same genus as NDV, distantly related to NDV in the phylogenetic tree, based on the sequences of Fusion (F) and hemagglutinin-neuraminidase (HN) gene, and has low cross-reactivity with anti-NDV antisera. We incorporated hemagglutinin (HA) of H9N2 into the junction of P and M gene in the APMV-2 genome by being flanked with the gene start, gene end, and UTR of each gene of APMV-2-T4 to generate seven recombinant APMV-2 viruses rAPMV-2/HAs, rAPMV-2-NPUTR-HA, rAPMV-2-PUTR-HA, rAPMV-2-FUTR-HA, rAPMV-2-HNUTR-HA, rAPMV-2-LUTR-HA, and rAPMV-2-MUTR-HA, expressing HA. The rAPMV-2/HAs displayed similar pathogenicity compared with the parental APMV-2-T4 virus and expressed HA protein in infected CEF cells. The NP-UTR facilitated the expression and secretion of HA protein in cells infected with rAPMV-2-NPUTR-HA. Animal studies demonstrated that immunization with rAPMV-2-NPUTR-HA elicited effective H9N2-specific antibody (6.14 ± 1.2 log2) responses and conferred complete immune protection to prevent viral shedding in the oropharyngeal and cloacal swabs from chickens challenged with H9N2 virus. This study suggests that our recombinant APMV-2 virus is safe and immunogenic and can be a useful tool in the combat of H9N2 outbreaks in chicken. [ABSTRACT FROM AUTHOR]

The objective of the study is to investigate the relationship between altered resting-state cortico-cerebellar functional connectivity (FC) and depression as well as cognitive impairment in late-onset depression (LOD). A total of 32 LOD and 39 well-matched normal controls (NCs) were recruited and underwent resting-state functional MRI (R-fMRI) scans. Seed-based correlation analysis was performed to explore the cortico-cerebellar FC. Hamilton Depression Rating Scale (HAMD) and mini-mental state examination (MMSE) were used to evaluate the depressive severity and cognitive impairment, respectively. A set of neuropsychological measurements was also applied to evaluate the detailed cognitions. Spearman correlations were applied to examine the depressive and cognitive association of these altered cortico-cerebellar networks. Compared with the NCs, LOD patients showed increased FC between the cerebellum and the right ventromedial frontal cortex (vmPFC), supplementary motor area (SMA), middle temporal gyrus (MTG), bilateral supramarginal gyrus (SMG), and anterior cingulated cortex (ACC). However, reduced cerebellar FC was observed in bilateral cerebellum, posterior cingulated cortex (PCC) and left dorsolateral prefrontal cortex (dlPFC). Moreover, the cerebellar FC with the vmPFC and ACC was positively correlated with HAMD score, whereas the cerebellar FC with the dlPFC and PCC was positively correlated with MMSE score in LOD patients. The cortico-cerebellar disconnections might underlie the pathogenesis of LOD. While depression mainly relates to the excessive cerebellar FC with the vmPFC and ACC, cognitive decline is primarily associated with the uncoupling of the cerebellar FC with the dlPFC and PCC. [ABSTRACT FROM AUTHOR]

To improve the computational efficiency, based on the generalized alternating direction method of multipliers (GADMM), we consider a class of accelerated method for solving multi-block nonconvex and nonsmooth optimization problems. First, we linearize the smooth part of the objective function and add proximal terms in subproblems, resulting in the proximal linearized GADMM. Then, we introduce an inertial technique and give the inertial proximal linearized GADMM. The convergence of the regularized augmented Lagrangian function sequence is proved under some appropriate assumptions. When some component functions of the objective function are convex, we use the error bound condition and obtain that the sequences generated by the algorithms locally converge to the critical point in a R-linear rate. Moreover, we apply the proposed algorithms to SCAD and robust PCA problems to verify the efficiency of the algorithms. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests the pivotal role of long non-coding RNA (lncRNA) in influenza virus infection. Based on next-generation sequencing, we previously demonstrated that Lnc45 was distinctively stimulated by H5N1 influenza virus in mice. In this study, we systematically investigated the specific role of Lnc45 during influenza A virus (IAV) infection. Through qRT-PCR, we first demonstrated that Lnc45 is highly up-regulated by different subtypes of IAV strains, including H5N1, H7N9, and H1N1 viruses. Using RNA-FISH and qRT-PCR, we then found that Lnc45 can translocate from nuclear to cytoplasm during H5N1 virus infection. In addition, forced Lnc45 expression dramatically impeded viral replication of H1N1, H5N1, and H7N9 virus, while abolish of Lnc45 expression by RNA interference favored replication of these viruses, highlighting the potential broad antiviral activity of Lnc45 to IAV. Correspondingly, overexpression of Lnc45 inhibited viral polymerase activity and suppressed IAV-induced cell apoptosis. Moreover, Lnc45 significantly restrained nuclear aggregation of viral NP and PA proteins during H5N1 virus infection. Further functional study revealed that the stem ring arms of Lnc45 mainly mediated the antiviral effect. Therefore, we here demonstrated that Lnc45 functions as a broad-spectrum antiviral factor to inhibit influenza virus replication probably through inhibiting polymerase activity and NP and PA nuclear accumulation via its stem ring arms. Our study not only advances our understanding of the complexity of the IAV pathogenesis but also lays the foundation for developing novel anti-IAV therapeutics targeting the host lncRNA. [ABSTRACT FROM AUTHOR]

As the causative agent of Newcastle disease (ND), Newcastle disease virus (NDV) has seriously restricted the development of the poultry industry. Previous research has shown that miRNAs, members of the small noncoding RNA family, are implicated in the regulation NDV replication through extensive interactions with host mRNAs, but whether miRNAs affect NDV replication by directly binding to the NDV antigenome remains unclear. In this study, potential Gallus gallus miRNAs targeting the antigenome of NDV were bioinformatically predicted using the online software RegRNA 2.0, and gga-miR-1603 and gga-miR-1794 were identified as targeting the viral L gene directly through dual-luciferase reporter assays. Sequence alignment analysis demonstrated that multiple genotypes of NDVs harbored highly conserved binding sites for gga-miR-1603 and gga-miR-1794 in the viral antigenome located at 8611–8634 nt and 14,490–14,514 nt, respectively. Meanwhile, we found that gga-miR-1603 and gga-miR-1794 negatively regulated the expression of viral L gene at both the RNA and protein levels, as well as viral replication in vitro. Furthermore, NDV infection had no effect on endogenous gga-miR-1603 and gga-miR-1794 expression in various avian cell lines. Overall, our present study demonstrated that gga-miR-1603 and gga-miR-1794 directly bind to the viral L gene to facilitate ts degradation and inhibit the replication of multiple genotypes of NDVs in vitro. These findings will provide us with important clues for antiviral therapy against NDV infection. [ABSTRACT FROM AUTHOR]