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Abstract The genus Jeilongvirus comprises non-segmented negative-stranded RNA viruses that are classified within the Paramyxoviridae family by phylogeny. Jeilongviruses are found in various reservoirs, including rodents and bats. Rodents are typical viral reservoirs with diverse spectra and zoonotic potential. Little is currently known about jeilongviruses in rodents from central China. The study utilized high-throughput and Sanger sequencing to obtain jeilongvirus genomes, including those of two novel strains (HBJZ120/CHN/2021 (17,468 nt) and HBJZ157/CHN/2021 (19,143 nt)) and three known viruses (HBXN18/CHN/2021 (19,212 nt), HBJZ10/CHN/2021 (19,700 nt), HBJM106/CHN/2021 (18,871 nt)), which were characterized by genome structure, identity matrix, and phylogenetic analysis. Jeilongviruses were classified into three subclades based on their topology, phylogeny, and hosts. Based on the amino acid sequence identities and phylogenetic analysis of the L protein, HBJZ120/CHN/2021 and HBJZ157/CHN/2021 were found to be strains rather than novel species. Additionally, according to specific polymerase chain reaction screening, the positive percentage of Beilong virus in Hubei was 6.38%, suggesting that Beilong virus, belonging to the Jeilongvirus genus, is likely to be widespread in wild rodents. The identification of novel strains further elucidated the genomic diversity of jeilongviruses. Additionally, the prevalence of jeilongviruses in Hubei, China, was profiled, establishing a foundation for the surveillance and early warning of emerging paramyxoviruses.

Abstract Over the past decade, learning engagement has received increasing attention from researchers. As a critical factor in college students’ academic achievement, learning engagement is significant in students’ long-term future development and social creativity. Present studies show that the overall level of college students’ learning engagement is low, which is highly unfavourable to educational quality and long-term development. There is no doubt about the position of the university library in academic circles. However, the influence of the university library environment on college students’ learning engagement has not been fully explored. The data in this study came from a survey of 45 Chinese universities. This paper investigates the relationship between the university library environment, students’ interaction, and students’ learning engagement. The results showed differences in Chinese college students’ learning engagement in liberal arts and sciences majors. The learning engagement of liberal arts majors is much lower than that of science students. We found that the library environment has an important influence on college students’ learning engagement. And the library environment can affect college students’ learning engagement through the intermediary role of interactive participation among students. In addition, for liberal arts students, the direct effect of the library environment on their learning engagement is more significant. However, for science students, the influence of the library environment on their learning engagement is more strongly intermediated by the students’ interaction. Therefore, future construction and renovation of library environments should cater not only to the diverse needs of different academic disciplines, especially liberal arts students who need special attention but also guide more students to interact friendly through the spatial characteristics of the library so as to improve the overall learning engagement of college students.

Desert steppe is widely distributed in wind erosion regions, and is also an important potential dust emission source in the regions. Recognition of dust emission characteristics of desert steppe is the foundation for accurate simulation of dust emission in wind erosion regions; however, few related studies have been conducted in desert steppe areas. In this study, we selected four sites in a region of desert steppe to conducting dust emission observations, analyzing the characteristics of horizontal saltation flux and vertical dust flux, identifying the suitable models for desert steppe, and examining the relationship between saltation bombardment efficiency and wind friction speed (u*). The results revealed the following: the supply of saltation particles in most desert steppe is unlimited, the intensity of saltation is reasonably high, and the modified Owen-type model is suitable for predicting sediment transport above desert steppe. Dust emission intensity in desert steppe is lower than that in other land use types under similar wind speeds. Schemes based on saltation bombardment theory (i.e., the MB95, Shao93, and Kok12 schemes) were found suitable for predicting vertical dust flux above desert steppe, the Kok12 dust emission scheme performed slightly better than the other two schemes. Saltation bombardment is the main mechanism for dust emission when u*s exceeds a threshold u*s (u*ts), but aerodynamic entrainment also plays an important role in dust emission, especially when u*s

Wind barriers with different parameters will change the aerodynamic force of the car on the bridge as well as the stability of the vehicle–bridge system, affecting the vehicle’s safety and comfort. A numerical simulation test was conducted on the bridge-deck with three different air permeability wind barriers under three distinct vehicles of varying sizes and wind directions, with a large-span road–rail asymmetric cable-stayed bridge serving as the engineering foundation. The results show that the roll force of the bridge is proportional to the width of the body and inversely related to the height of the train. The roll force of a vehicle is inversely proportional to its height and width. The type of vehicle and the properties of the bridge deck exert minimal influence on the stability of the bridge when a single vehicle is positioned upstream. When a single vehicle is situated downstream, the tri-component force coefficient of the bridge undergoes significant changes, and the vehicle’s impact on the bridge’s stability becomes more pronounced. When the bridge deck’s ventilation rate is at 50%, the drag coefficient of the bridge deck doubles compared to that of a bare bridge deck, and the wind pressure coefficient of the vehicle surface on the bridge approaches zero. In scenarios involving two vehicles, the shielding effect caused by the vehicles positioned upstream and downstream results in a substantial shift in the aerodynamic forces acting on the two vehicles. This increases the wake width of the bridge and generates a visible vortex in the wake.

Abstract Background The optimal treatment for multiple brain metastases has been recently controversially discussed.This study was aimed to explore the feasibility of Hippocampus-Avoidance Whole-Brain Radiotherapy plus a simultaneous integrated boost (HA-WBRT + SIB) in patients with multiple brain metastases and assess tumor control in comparison with Hippocampus-Avoidance Whole-Brain Radiotherapy (HA-WBRT) alone for brain metastases. Methods In this study, 63 patients with multiple brain metastases (≥ 4 metastases) had undergone HA-WBRT + SIB between January 2016 and December 2020 in the observation group:HA-WBRT (30 Gy in 12 fractions, the maximum dose of the hippocampus ≤ 14 Gy) plus a simultaneous integrated boost (48 Gy in 12 fractions) for brain metastases.Overall Survival (OS), Median survival,intracranial control (IC = control within the entire brain), intracranial progression-free survival (iPFS) and adverse events were compared with the control group (a HA-WBRT retrospective cohort) by propensity score matching analysis. Results After 1:1 propensity score matching,there were 56 patients in each group (the observation group, the control group). OS, median survival and iPFS were significantly longer in the observation group (18.4 vs. 10.9 months, P0.05). Conclusions HA-WBRT + SIB resulted in better OS,median survival, IC, iPFS, an acceptable risk of radiation response, and a potential way of declining neurocognitive adverse events, which may be a better treatment for patients with multiple brain metastases.

Abstract The well-being of older adults is significantly influenced by their adult children, especially in countries with less developed welfare systems. We aim to examine the relationship between children’s intergenerational support, children’s socioeconomic status and the well-being of older adults, as well as compare the differences among various elderly groups. The data in our research are from the 2014 China Longitudinal Aging Social Survey. The survey covered 29 provinces, autonomous regions and municipalities in China with 9146 valid samples. We adopted descriptive statistical analysis and structural equation modeling to analyze the data, and the bootstrap method to test the mediating effects. Our results indicate that the children’s education level and intergenerational support do not significantly affect the well-being of all groups of older adults in China. However, the financial conditions of adult children have a significant and direct impact on the well-being of all groups of older adults. From one child to multiple children, the impact of children’s financial condition on the well-being of older adults is 0.360, 0.452, 0.412 in three urban groups and 0.496, 0.468, 0.443 in three rural groups, specifically. The influence of adult children’s financial conditions on the well-being of all groups of older adults in China is significant, surpassing that of children’s education level and intergenerational support. Moreover, the impact of children’s socioeconomic status on the well-being of older adults is primarily through direct effects, with minimal intervention from intergenerational support. For older adults in China, "whether my children are living well" is more important than "what they could give me".

ABSTRACTPrevious studies generally used land use and travel flow to investigate the efficiency of the railway system in Transit-Oriented Development (TOD) cities. Furthermore, to study the association of land use and jobs–housing distribution of commuters, we can find out the potential development of rail commuting. In this research, four railway lines in Wuhan, China, were selected to explore the land use in promoting practical commuting population according to the smart-card data obtained. For land use issues, except the road density and building density, a Normalized Location-Weighted Landscape Index (NLWLI) based on the source – sink theory in landscape ecology was established to assess the jobs–housing land use around rail transit stations. Meanwhile, employment and housing details of commuters around rail transit stations were identified using smart-card data. We found that the generation of commuting flow was affected by building density and the land use of employment in the immediate vicinity of rail transit stations. The distribution of building density and commuters in a mature rail line was roughly a normal distribution. However, due to the inconsistency of land use and jobs – housing distribution around stations, the requirement of the balance of land use and jobs – housing distribution should be reduced at the scale of rail stations in the TOD planning systems. This study is the application of massive smart-card data in the field of urban research. It identifies land use issues that affect rail transit commuting flow, and can help urban planners improve the efficiency of rail transit through planning and design.

ABSTRACTZika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain–Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profiles of ZIKV-infected human brain microvascular endothelial cells (HBMECs) were used in this study to identify genes essential for viral replication. These genes were then used to identify novel anti-ZIKV agents and validated in publicly available data and functional wet-lab experiments. Here, we found that ZIKV effectively evaded activation of immune response-related genes and completely reprogrammed cellular transcriptional architectures. Knockdown of genes, which gradually upregulated during viral infection but showed distinct expression patterns between ZIKV- and mock infection, discovered novel proviral and antiviral factors. One-third of the 74 drugs found through signature-based drug repositioning and cross-reference with the Drug Gene Interaction Database (DGIdb) were known anti-ZIKV agents. In cellular assays, two promising antiviral candidates (Luminespib/NVP-AUY922, L-161982) were found to reduce viral replication without causing cell toxicity. Overall, our time-series transcriptome-based methods offer a novel and feasible strategy for antiviral drug discovery. Our strategies, which combine conventional and data-driven analysis, can be extended for other pathogens causing pandemics in the future.

Soil erosion is the leading cause of global environmental degradation that accelerates soil degradation through climate and land use/land cover changes. The eastern sandy region of China is located at vast arid and semi-arid desert areas, and is characterized by arid climate, extreme rainfall events, vegetation degradation and poor farming practices, with serious land desertification, sandstorm disaster and soil erosion. Soil protection is the primary way to suppress soil erosion, including windbreak and sand fixation (WSF) and soil conservation (SC) service. The spatio-temporal patterns, spatial relationships and driving factors of soil protection services (WSF and SC) in eastern sandy region of China were investigated using National Wind Erosion Survey Model of China (NWESMC) and Revised Universal Soil Loss Equation (RUSLE). The results indicated that: (1) In eastern sandy region, the total soil erosion was 17.31 × 107 t from 2000 to 2020, of which wind and water erosion was 15.8 × 107 t and 1.51 × 107 t, respectively. (2) The total amount of soil protection was 45.5 × 107 t, with WSF and SC showing opposite spatio-temporal pattern. (3) Climate factors played dominant role for the change of soil protection service, with wind speed weakening being the main reason for the weakening of WSF service, the increase of precipitation enhancing SC service. Human activities (such as ecological engineering) may play a significant part in the future. The study has implications for soil protection in arid and semiarid regions worldwide, and can offer scientific recommendations for land management and soil remediation in sandy areas of China.

LGP2 is a RIG-I-like receptor (RLR) known to bind and recognize the intermediate double-stranded RNA (dsRNA) during virus infection and to induce type-I interferon (IFN)-related antiviral innate immune responses. Here, we find that LGP2 inhibits Zika virus (ZIKV) and tick-borne encephalitis virus (TBEV) replication independent of IFN induction. Co-immunoprecipitation (Co-IP) and confocal immunofluorescence data suggest that LGP2 likely colocalizes with the replication complex (RC) of ZIKV by interacting with viral RNA-dependent RNA polymerase (RdRP) NS5. We further verify that the regulatory domain (RD) of LGP2 directly interacts with RdRP of NS5 by biolayer interferometry assay. Data from in vitro RdRP assays indicate that LGP2 may inhibit polymerase activities of NS5 at pre-elongation but not elongation stages, while an RNA-binding-defective LGP2 mutant can still inhibit RdRP activities and virus replication. Taken together, our work suggests that LGP2 can inhibit flavivirus replication through direct interaction with NS5 protein and downregulates its polymerase pre-elongation activities, demonstrating a distinct role of LGP2 beyond its function in innate immune responses.

Abstract Background With the rapid development of population ageing, the international community has been paying more attention to the health problems of older adults and the age-friendly community. But there has not been enough discussion about the internal mechanism of the community-built environment that influences the health of older adults. The aim of our study was to explore the complex relationships among community-built environment, social participation, outdoor exercise, and health of older adults, as well as the differences among older adults in different income groups, particular attention was paid to the situation of low-income group. Methods This study used descriptive statistical analysis and structural equation Modeling (SEM) to make a group comparison among older adults in different income groups. The data of this study came from a sample survey in Shanghai, China. Results The study found that health difference exists among older adults in China: the lower the income, the worse the community-built environment, the worse the health. The community-built environment had an important impact on the health of older adults, especially the low-income older adults. And the community-built environment influenced the health of older adults through the intermediary role of outdoor exercise and social participation. Furthermore, the lower the income level of older adults, the stronger the direct effect of the community-built environment on their health; the higher the income level of older adults, the stronger the mediating effect of outdoor exercise and social participation on the impact of the community-built environment on their health. Conclusion Governments should pay more attention to the health and living conditions of low-income older adults and take proactive steps to help them. Community design and construction should pay more attention to the demands of low-income older adult groups, which will help to improve the health inequality of older adults, consequently enhancing older adults’ overall health.

Among enteroviruses, echovirus can cause severe illnesses in neonates or infants, with high morbidity and mortality. Autophagy, a central component of host defense mechanisms, can function against diverse infections. In the present study, we investigated the interplay between echovirus and autophagy. We demonstrated that echovirus infection increases LC3-II expression dose-dependently, accompanied by an increased intracellular LC3 puncta level. In addition, echovirus infection induces the formation of autophagosome. These results suggest that echovirus infection induces autophagy machinery. Furthermore, phosphorylated mTOR and ULK1 were both decreased upon echovirus infection. In contrast, both levels of the vacuolar protein sorting 34 (VPS34) and Beclin-1, the downstream molecules which play essential roles in promoting the formation of autophagic vesicles, increased upon virus infection. These results imply that the signaling pathways involved in autophagosome formation were activated by echovirus infection. Moreover, induction of autophagy promotes echovirus replication and viral protein VP1 expression, while inhibition of autophagy impairs VP1 expression. Our findings suggest that autophagy can be induced by echovirus infection via regulating mTOR/ULK1 signaling pathway and exhibits a proviral function, revealing the potential role of autophagy in echovirus infection.

IntroductionDuring COVID-19, the mental health of Chinese university students has been a pressing concern. But the internal mechanism of perceived campus outdoor environment and learning engagement affecting college students’ mental health during the COVID-19 pandemic has not been fully discussed.MethodsThe current study used cross-sectional data from 45 Chinese universities to explore the relationship among perceptions of campus outdoor environments, learning engagement, and college student mental health, and focused on differences among college students in different grades.ResultsOur study revealed the mental health problems of Chinese college students during the COVID-19 pandemic were more severe. The mental health of postgraduates was generally poor, and their risk of depression was higher than that of undergraduates. More importantly, for postgraduates, the direct impact of the perceived campus outdoor environment on their mental health was stronger. For undergraduates, the indirect impact of learning engagement on the effect of the perceived campus outdoor environment on their mental health was stronger.ConclusionThe results of the study have implications for campus planners, landscape architects, and university planners to pay particular attention to the needs of postgraduates for campus outdoor environments, which is of great significance to improve the overall mental health of students during the COVID-19 pandemic.

BackgroundA multitude of literature has shown that during the 2019 COVID-19 outbreak, people's reliance on social media has been closely related with serious psychological problems. The “information epidemic” has sparked each country's attention. These countries including China have tried to find the solution and taken a series of measures. In January 2021, the COVID-19 broke out again in Shijiazhuang, China. Has the impact of social media on mental health changed?MethodsOur data are based on an online survey of Chinese in January 2021, with 904 valid samples from 18 different provinces in China. We applied the methods of structural equation model analysis and the tendency value matching to conduct systematic analysis.ResultsOur research found that 38.9% of the population suffered from depression and 12.61% of the population suffered from anxiety. Chinese urban residents are more dependent on social media, with up to 80.1% of participants using social media frequently. Our research found that the relationship between social media use and residents' mental health has dramatically changed. More use of social media has been significantly associated with less depression and anxiety, especially among young people and women. Our findings are the first to reveal the relation's change between social media and mental health.ConclusionsThese findings implied that changes in the social media environment probably lead to changes in relationship between social media use and mental health since the outbreak began in 2019. Truthful and comprehensive social media information and a healthy positive social media environment can contribute to residents' mental health improvement and the fight against “information epidemic.”

Summary: Identification of host factors facilitating pathogen entry is critical for preventing infectious diseases. Here, we report a tagging system consisting of a viral receptor-binding protein (RBP) linked to BioID2, which is expressed on the cell surface via a GPI anchor. Using VSV or Zika virus (ZIKV) RBP, the system (BioID2- RBP(V)-GPI; BioID2-RBP(Z)-GPI) faithfully identifies LDLR and AXL, the receptors of VSV and ZIKV, respectively. Being GPI-anchored is essential for the probe to function properly. Furthermore, BioID2-RBP(Z)-GPI expressed in human neuronal progenitor cells identifies galectin-1 on cell surface pivotal for ZIKV entry. This conclusion is further supported by antibody blocking and galectin-1 silencing in A549 and mouse neural cells. Importantly, Lgals1−/− mice are significantly more resistant to ZIKV infection than Lgals1+/+ littermates are, having significantly lower virus titers and fewer pathologies in various organs. This tagging system may have broad applications for identifying protein-protein interactions on the cell surface.

Abstract Fluorescent labeling and dynamic tracking is a powerful tool for exploring virus infection mechanisms. However, for small-sized viruses, virus tracking studies are usually hindered by a lack of appropriate labeling methods that do not dampen virus yield or infectivity. Here, we report a universal strategy for labeling viruses with chemical dyes and Quantum dots (QDs). Enterovirus 71 (EV71) was produced in a cell line that stably expresses a mutant methionyl-tRNA synthetase (MetRS), which can charge azidonorleucine (ANL) to the methionine sites of viral proteins during translation. Then, the ANL-containing virus was easily labeled with DBCO-AF647 and DBCO-QDs. The labeled virus shows sufficient yield and no obvious decrease in infectivity and can be used for imaging the virus entry process. Using the labeled EV71, different functions of scavenger receptor class B, member 2 (SCARB2), and heparan sulfate (HS) in EV71 infection were comparatively studied. The cell entry process of a strong HS-binding EV71 strain was investigated by real-time dynamic visualization of EV71-QDs in living cells. Taken together, our study described a universal biocompatible virus labeling method, visualized the dynamic viral entry process, and reported details of the receptor usage of EV71. Graphic Abstract

Zika virus (ZIKV) infection in the human central nervous system (CNS) causes Guillain–Barre syndrome, cerebellum deformity, and other diseases. Astrocytes are immune response cells in the CNS and an important component of the blood–brain barrier. Consequently, any damage to astrocytes facilitates the spread of ZIKV in the CNS. Connective tissue growth factor/Nephroblastoma overexpressed gene family 1 (CCN1), an important inflammatory factor secreted by astrocytes, is reported to regulate innate immunity and viral infection. However, the mechanism by which astrocyte viral infection affects CCN1 expression remains undefined. In this study, we demonstrate that ZIKV infection up-regulates CCN1 expression in astrocytes, thus promoting intracellular viral replication. Other studies revealed that the cAMP response element (CRE) in the CCN1 promoter is activated by the ZIKV NS3 protein. The cAMP-responsive element-binding protein (CREB), a transacting factor of the CRE, is also activated by NS3 or ZIKV. Furthermore,a specific inhibitor of CREB, i.e. SGC-CBP30, reduced ZIKV-induced CCN1 up-regulation and ZIKV replication. Moreover, co-immunoprecipitation, overexpression, and knockdown studies confirmed that the interaction between NS3 and the regulatory domain of CaMKIIα could activate the CREB pathway, thus resulting in the up-regulation of CCN1 expression and enhancement of virus replication. In conclusion, the findings of our investigations on the NS3-CaMKIIα-CREB-CCN1 pathway provide a foundation for understanding the infection mechanism of ZIKV in the CNS.

Abstract Background Although social network is a known determinant of the elderly’s well-being, it is not clear, in urban-rural and age-comparison, what its structural characteristics are and how it works for well-being. The research aims to discuss the features of the elderly’s social network and the social network efficacies on the well-being of older adults in China’s urban and rural areas as well as revealing the urban-rural disparities among the elderly of different age groups. Methods In this study, descriptive statistical analysis and structural equation Modeling (SEM) were used to make a group comparison between the urban and rural elderly of different age groups. All data are quoted from 2014 China Longitudinal Aging Social Survey (CLASS). The survey adopted the multi-stage probability sampling method, targeting Chinese senior citizens aged 60 and above, the ultimate samples totaled 11,511. Results The social network of the elderly in China feature a “reverse structure” in age sequences: with ageing, family network of the elderly expand while their friend network shrink; also, the expansion scale of the rural elderly’s family network is significantly larger than that of the city’s while the shrinkage scale of their friend network is smaller compared with its urban counterpart. The effect of family network on the rural elderly’s well-being shows a remarkable increase with age. However, there is no noticeable change in urban elderly groups of different ages. Conclusion The social network characteristics of the Chinese elderly are different between different age stages. Namely, the family network and the friend network have the “reverse structure “ in age sequences. Meanwhile, the family network and the friend network have different efficacies on the well-being of the elderly in China, and the differences between urban and rural areas are even more obvious. For rural elderly, family network has very important effects on their well-being. Moreover, With the increase of age, family network’s efficacies increase gradually. For urban elderly, comparatively, family network is just as important as friend network.

Enterovirus 71 (EV71) is one of the most important etiological agents for hand–foot–mouth disease. Compared with coxsackievirus A16 infection, EV71 infection is often associated with severe central nervous system complications, such as encephalitis, encephalomyelitis, and acute flaccid paralysis in infants and young children. In this study, we constructed a recombinant baculovirus with T7 ribonucleic acid polymerase under the control of a cytomegalovirus promoter and simultaneously engineered the T7 promoter upstream of a full-length EV71 complementary deoxyribonucleic acid. After transduction into mammalian cells, typical cytopathic effects (CPEs) and VP1 signals were detected in cells transfected with recombinant baculovirus. Additionally, viral particles located in the cytoplasm of human rhabdomyosarcoma cells (Rd) and Vero cells were observed by electron microscope, indicating that EV71 was recovered using a Bac-to-Bac expression system in vitro. After four passages, the rescued virus had a growth curve and plaque morphology similar to those of the parental virus. Furthermore, the Vp1 gene and the protein from the mouse brain were detected by reverse transcription polymerase chain reaction and immunohistochemistry after intracerebral injection of purified recombinant baculovirus. Typical CPEs were observed after inoculation of the supernatant from mouse brain to Rd cells, revealing a reconstruction of EV71 in vivo. Thus, we established a new approach to rescue EV71 based on a baculovirus expression system in vitro and in vivo, which may provide a safe and convenient platform for fundamental research and a strategy to rescue viruses that currently lack suitable cell culture and animal models.

BackgroundThis study aimed to assess the clinical utility of the advanced lung cancer inflammation index (ALI) as a prognostic indicator for patients with cholangiocarcinoma (CCA) and construct a prognostic nomogram based on ALI.MethodsA total of 97 CCA patients who received radical resection were included. The optimal cut-off point for ALI was identified by X-tile analysis. COX regression analysis were used to identify risk factors of overall survival (OS) and disease-free survival (DFS). A predictive nomogram for DFS was constructed.ResultsThe optimal cut-off value for preoperative ALI was 31.8. 35 (36.1%) patients were categorized into the low-ALI group and 62 (63.9%) patients into the high-ALI group. Low ALI was independently associated with hypoproteinemia and lower body mass index (BMI) (all P < 0.05). COX regression analysis revealed that preoperative ALI level (HR = 0.974, P = 0.037) and pathological TNM stage (HR = 7.331, P < 0.001) were independently correlated with OS for patients with CCA, and preoperative ALI level (HR = 0.978, P = 0.042) and pathological T stage (HR = 1.473, P = 0.035) remained to be independent prognostic factors for DFS in CCA patients. Using time-dependent ROC analysis, we found that ALI was better at predicting prognosis than other parameters, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI) in terms of OS and DFS. A nomogram predicting DFS was built (C-index: 0.73 95%CI: 0.67–0.79).ConclusionsALI may be useful for prognosis assessment for patients with CCA.

Assessing the response of soil heterotrophic and autotrophic respiration to climate change is critical for forecasting terrestrial carbon cycle behavior in the future. In the present study, we conducted a drought experiment in Vitexnegundo var. heterophylla shrub ecosystem of the Middle Taihang Mountain. Three precipitation manipulation treatments (natural conditions/ambient precipitation (CK), reduced precipitation by 30% (PE30), and reduced precipitation by 60% (PE60)) were used to study the impact of different levels of precipitation exclusion on total soil respiration (Rs) and its heterotrophic (Rh) and autotrophic (Ra) components. Our results showed that the rates of Rs and its components were significantly decreased under the precipitation exclusion treatments. The proportion of Rh in Rs reduced from 72.6% for CK to 71.9% under PE60. The annual cumulative C fluxes of Rs decreased by 47.8 g C m−2 in PE30 and 106.0 g C m−2 in PE60, respectively. An exponential relationship was observed between the rate of each soil respiration component and soil temperature in all treatments ( p < 0.01). Moreover, each soil respiration component rate was better represented by a quadratic model which included soil moisture ( p < 0.01). However, including both of soil temperature and soil moisture did not explain more variation in soil respiration components compared than the regression model with soil moisture only. In addition, excluding precipitation increased the temperature sensitivity (Q10 values) of Rs and its Ra and Rh components compared to the control. Collectively, our findings suggest that increased drought will inhibit the release of carbon from the soil to the atmosphere, and will likely decrease the contribution of Rh to Rs in this semiarid shrubland ecosystem.

PurposeTo identify immune-related co-expressed genes that promote CD8+ T cell infiltration in bladder cancer, and to explore the interactions among relevant genes in the tumor microenvironment.MethodWe obtained bladder cancer gene matrix and clinical information data from TCGA, GSE32894 and GSE48075. The “estimate” package was used to calculate tumor purity and immune score. The CIBERSORT algorithm was used to assess CD8+ T cell proportions. Weighted gene co-expression network analysis was used to identify the co-expression modules with CD8+ T cell proportions and bladder tumor purity. Subsequently, we performed correlation analysis among angiogenesis factors, angiogenesis inhibitors, immune inflammatory responses, and CD8+ T cell related genes in tumor microenvironment.ResultsA CD8+ T cell related co-expression network was identified. Eight co-expressed genes (PSMB8, PSMB9, PSMB10, PSME2, TAP1, IRF1, FBOX6, ETV7) were identified as CD8+ T cell-related genes that promoted infiltration of CD8+ T cells, and were enriched in the MHC class I tumor antigen presentation process. The proteins level encoded by these genes (PSMB10, PSMB9, PSMB8, TAP1, IRF1, and FBXO6) were lower in the high clinical grade patients, which suggested the clinical phenotype correlation both in mRNA and protein levels. These factors negatively correlated with angiogenesis factors and positively correlated with angiogenesis inhibitors. PD-1 and PD-L1 positively correlated with these genes which suggested PD-1 expression level positively correlated with the biological process composed by these co-expression genes. In the high expression group of these genes, inflammation and immune response were more intense, and the tumor purity was lower, suggesting that these genes were immune protective factors that improved the prognosis in patients with bladder cancer.ConclusionThese co-expressed genes promote high levels of infiltration of CD8+ T cells in an immunoproteasome process involved in MHC class I molecules. The mechanism might provide new pathways for treatment of patients who are insensitive to PD-1 immunotherapy due to low degrees of CD8+ T cell infiltration.

Abstract The morbidity and mortality of prostate carcinoma has increased in recent years and has become the second most common ale malignant carcinoma worldwide. The interaction mechanisms between different genes and signaling pathways, however, are still unclear. Methods Variation analysis of GSE38241, GSE69223, GSE46602 and GSE104749 were realized by GEO2R in Gene Expression Omnibus database. Function enrichment was analyzed by DAVID.6.8. Furthermore, the PPI network and the significant module were analyzed by Cytoscape, STRING and MCODE.GO. Pathway analysis showed that the 20 candidate genes were closely related to mitosis, cell division, cell cycle phases and the p53 signaling pathway. A total of six independent prognostic factors were identified in GSE21032 and TCGA PRAD. Oncomine database and The Human Protein Atlas were applied to explicit that six core genes were over expression in prostate cancer compared to normal prostate tissue in the process of transcriptional and translational. Finally, gene set enrichment were performed to identified the related pathway of core genes involved in prostate cancer. Result Hierarchical clustering analysis revealed that these 20 core genes were mostly related to carcinogenesis and development. CKS2, TK1, MKI67, TOP2A, CCNB1 and RRM2 directly related to the recurrence and prognosis of prostate cancer. This result was verified by TCGA database and GSE21032. Conclusion These core genes play a crucial role in tumor carcinogenesis, development, recurrence, metastasis and progression. Identifying these genes could help us to understand the molecular mechanisms and provide potential biomarkers for the diagnosis and treatment of prostate cancer.

Abstract Background Many viruses depend on the extensive membranous network of the endoplasmic reticulum (ER) for their translation, replication, and packaging. Certain membrane modifications of the ER can be a trigger for ER stress, as well as the accumulation of viral protein in the ER by viral infection. Then, unfolded protein response (UPR) is activated to alleviate the stress. Zika virus (ZIKV) is a mosquito-borne flavivirus and its infection causes microcephaly in newborns and serious neurological complications in adults. Here, we investigated ER stress and the regulating model of UPR in ZIKV-infected neural cells in vitro and in vivo. Methods Mice deficient in type I and II IFN receptors were infected with ZIKV via intraperitoneal injection and the nervous tissues of the mice were assayed at 5 days post-infection. The expression of phospho-IRE1, XBP1, and ATF6 which were the key markers of ER stress were analyzed by immunohistochemistry assay in vivo. Additionally, the nuclear localization of XBP1s and ATF6n were analyzed by immunohistofluorescence. Furthermore, two representative neural cells, neuroblastoma cell line (SK-N-SH) and astrocytoma cell line (CCF-STTG1), were selected to verify the ER stress in vitro. The expression of BIP, phospho-elF2α, phospho-IRE1, and ATF6 were analyzed through western blot and the nuclear localization of XBP1s was performed by confocal immunofluorescence microscopy. RT-qPCR was also used to quantify the mRNA level of the UPR downstream genes in vitro and in vivo. Results ZIKV infection significantly upregulated the expression of ER stress markers in vitro and in vivo. Phospho-IRE1 and XBP1 expression significantly increased in the cerebellum and mesocephalon, while ATF6 expression significantly increased in the mesocephalon. ATF6n and XBP1s were translocated into the cell nucleus. The levels of BIP, ATF6, phospho-elf2α, and spliced xbp1 also significantly increased in vitro. Furthermore, the downstream genes of UPR were detected to investigate the regulating model of the UPR during ZIKV infection in vitro and in vivo. The transcriptional levels of atf4, gadd34, chop, and edem-1 in vivo and that of gadd34 and chop in vitro significantly increased. Conclusion Findings in this study demonstrated that ZIKV infection activates ER stress in neural cells. The results offer clues to further study the mechanism of neuropathogenesis caused by ZIKV infection.

Enterovirus 71 (EV71) is the major causative pathogen of human hand, foot, and mouth disease (hHFMD) and has evolved to use various cellular receptors for infection. However, the relationship between receptor preference and EV71 virulence has not been fully revealed. By using reverse genetics, we identified that a single E98K mutation in VP1 is responsible for rapid viral replication in vitro. The E98K mutation enhanced binding of EV71-GZCII to cells in a heparan sulfate (HS)-dependent manner, and it attenuated the virulence of EV71-GZCII in BALB/c mice, indicating that the HS-binding property is negatively associated with viral virulence. HS is widely expressed in vascular endothelial cells in different mouse tissues, and weak colocalization of HS with scavenger receptor B2 (SCARB2) was detected. The cGZCII-98K virus bound more efficiently to mouse tissue homogenates, and the cGZCII-98K virus titers in mouse tissues and blood were much lower than the cGZCII virus titers. Together, these findings suggest that the enhanced adsorption of the cGZCII-98K virus, which likely occurs through HS, is unable to support the efficient replication of EV71 in vivo. Our study confirmed the role of HS-binding sites in EV71 infection and highlighted the importance of the HS receptor in EV71 pathogenesis.

21-4N is a typical heat resistant steel used as the material of exhaust valves. The application of cross wedge rolling to manufacture preform for valves has the advantages of higher efficiency and better quality. In this study, cross wedge rolling of 21-4N with an area reduction ratio of 65% was experimentally studied. Twelve groups of different tool parameters of cross wedge rolling tests were carried out. It is found that a larger stretching angle or a smaller forming angle is better for surface quality. When the stretching angle is 7° and the forming angle is less than 25°, a smooth surface can be obtained. Furthermore, the influence of stretching angle on central quality is not obvious, but a greater forming angle is prone to get a better central quality. When the forming angle is larger than 30°, no central damage was found in the workpieces. Considering the balance of surface quality and central quality, a stretching angle of 7° and a forming angle of 30° is a suitable combination for cross wedge rolling of 21-4N with an area reduction ratio of 65%.

Enterovirus A71 (EVA71) is a human enterovirus belonging to the Picornaviridae family and mostly causes hand-foot-and-mouth disease in infants. Viperin is an important interferon-stimulated gene with a broad antiviral activity against various viruses. However, the effect of viperin on human enteroviruses and the interaction mechanism between EVA71 and viperin remains elusive. Here, we confirmed the EVA71-induced expression of viperin in a mouse model and cell lines and showed that viperin upregulation by EVA71 infection occurred on both the mRNA and protein level. Viperin knockdown and overexpression in EVA71-infected cells indicated that this protein can markedly inhibit EVA71 infection. Interestingly, immunofluorescent confocal microscopy and co-immunoprecipitation assays indicated that viperin interacts and colocalizes with the EVA71 protein 2C in the endoplasmic reticulum. Furthermore, amino acids 50–60 in the N-terminal domain of viperin were the key residues responsible for viperin interaction with 2C. More importantly, the N-terminal domain of viperin was found responsible for inhibiting EVA71 replication. Our findings can potentially aid future research on the prevention and treatment of nervous system damage caused by EVA71 and may provide a potential target for antiviral therapy.

In the context of the COVID-19 pandemic, this research aimed to explore the relationship between dormitory environment, learning engagement, and mental health among college students, with a special focus on college students of different gender groups. We conducted a cross-sectional survey of students from 45 universities in China. For mental health, we tested students for depression using the 5-Item WHO Well-Being Index (WHO-5). The dormitory environment is exemplified by a typical four-person dormitory layout in China, which is assessed in four main areas: site location, functional layout, maintenance management, and view from the window. Meanwhile, we examined the relationship between mental health and the dormitory environment using learning engagement as a mediating variable. We found that the dormitory environment positively influences college students’ mental health through the mediating role of learning engagement. We found gender differences in mental health among Chinese college students. The mental health of male students was better than that of female students. More importantly, we found differences in the influence of dormitory environment on the mental health of college students in different gender groups. In the dormitory environment-learning engagement pathway, the influence was more pronounced for male students. In the learning engagement— mental health pathway, the total and indirect effects were more substantial for women than for men. As our study took place during the epidemic, the examination of the relationship between dormitory environment and college students’ mental health in this study will also inspire college administrators to pay more attention to the dormitory environment and support the development of public health policies to promote college students’ mental health. We encourage further research on the relationship between dormitory environment and college students’ mental health, which will promote the greening of college dormitories and improve college students’ mental health. [ABSTRACT FROM AUTHOR]