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ObjectiveTo investigate the clinical value of WNT1 inducible signaling pathway protein 1 (WISP-1) and vascular endothelial growth factor-A (VEGF-A) as novel molecular markers of esophageal squamous cell carcinoma (ESCC) in elderly patients. MethodsElderly patients with ESCC were divided into 65-70 years old group and >70 years old group. Immunohistochemical staining and RT-PCR were used to detect the expression levels of WISP-1 and VEGF-A proteins and mRNAs, respectively. Log rank test was used to analyze correlation between clinicopathological features and prognosis of ESCC in the elderly. ResultsThe positive expression rate of WISP-1 in ESCC tissues was significantly higher than that in para-cancer tissues (53.33% vs. 35.42%, P=0.045). The positive expression rate of WISP-1 in patients over 70 years old and with lymph node metastasis was significantly higher than that in patients aged 65-70 years and without lymph node metastasis (P=0.047 and 0.032). The positive expression rate of VEGF-A protein in ESCC tissues was significantly higher than that in para-cancer tissues (50.00% vs. 20.83%, P=0.001). The positive expression rate of VEGF-A in patients with depth of infiltration T3-T4 stage, lymph node metastasis, and TNM Ⅲ-Ⅳ stage was significantly higher than that in patients with T1-T2 stage, no lymph node metastasis, and Ⅰ-Ⅱ stage (P=0.030, 0.006, and 0.010, respectively). The mRNA expression levels of these two molecules were significantly higher in ESCC tissues than in para-cancer tissues (P

Background: Ginsenoside Rg1 (Rg1) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng. Research has shown that Rg1 has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood. Methods: Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV–Vis and fluorescence spectra) techniques, potential targets and pathways for Rg1 against myocardial ischemia (MI) were screened and explored. Results: An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg1 against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg1 intervention on H9c2 cells injured by H2O2 showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg1 on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg1 was also evaluated. Conclusion: Rg1 can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg1, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.

With the incredible growth of the scale and complexity of datasets, creating proper visualizations for users becomes more and more challenging in large datasets. Though several visualization recommendation systems have been proposed, so far, the lack of practical engineering inputs is still a major concern regarding the usage of visualization recommendations in the industry. In this paper, we proposed AVA, an open-sourced web-based framework for Automated Visual Analytics. AVA contains both empiric-driven and insight-driven visualization recommendation methods to meet the demands of creating aesthetic visualizations and understanding expressible insights respectively. The code is available at https://github.com/antvis/AVA.

Abstract Artificial micro/nanomotors using active particles hold vast potential in applications such as drug delivery and microfabrication. However, upgrading them to micro/nanorobots capable of performing precise tasks with sophisticated functions remains challenging. Bubble microthruster (BMT) is introduced, a variation of the bubble‐driven microrobot, which focuses the energy from a collapsing microbubble to create an inertial impact on nearby target microparticles. Utilizing ultra‐high‐speed imaging, the microparticle mass and density is determined with sub‐nanogram resolution based on the relaxation time characterizing the microparticle's transient response. Master curves of the BMT method are shown to be dependent on the viscosity of the solution. The BMT, controlled by a gamepad with magnetic‐field guidance, precisely manipulates target microparticles, including bioparticles. Validation involves measuring the polystyrene microparticle mass and hollow glass microsphere density, and assessing the mouse embryo mass densities. The BMT technique presents a promising chip‐free, real‐time, highly maneuverable strategy that integrates bubble microrobot‐based manipulation with precise bioparticle mass and density detection, which can facilitate microscale bioparticle characterizations such as embryo growth monitoring.

Abstract Background Brain abscesses caused by Prevotella oris are rarely reported. Here, we described a case of a brain infection caused by Prevotella oris that was detected by metagenomic next-generation sequencing (mNGS). Case presentation A 63-year-old man with no medical history reported headache in the right frontotemporal region, fever, and intermittent diplopia. Magnetic resonance imaging (MRI) revealed abnormal signals and enhancement changes in the superior sellar region. mNGS testing showed that cerebrospinal fluid collected from the spine was positive for Prevotella oris. After receiving a combined treatment of antibiotic therapy, the patient recovered well. Conclusion We reviewed the relevant literature and summarized the characteristics and prognosis of this type of bacterial infection to provide ideas for clinicians to diagnose and treat this disease.

Background: Platinum-based dual-drug first-line chemotherapy is commonly employed in the treatment of patients with advanced non-small cell lung cancer (NSCLC), although its clinical efficacy is limited. Bevacizumab can antagonize vascular endothelial cell growth factor (VEGF), which inhibit tumor angiogenesis and prevent tumor invasion and development. However, a comprehensive meta-analysis evaluating the effectiveness and safety of combining bevacizumab with platinum-based chemotherapy in advanced NSCLC patients is lacking.Methods: Randomized controlled trials (RCTs) investigating the combination therapy of bevacizumab and platinum-based chemotherapy for treating advanced NSCLC were searched across six databases. Data on objective response rate (ORR), disease control rate (DCR), 1-year survival rate, 2-year survival rate, 3-year survival rate, VEGF levels, and side effects were synthesized. Relative risk degree (RR) along with 95% confidence interval (CI) was used as statistical analysis measures for binary outcomes while continuous variables were analyzed using mean difference (MD) along with 95% CI. Heterogeneity was evaluated by Chi-squared and I2 tests. If there was heterogeneity, subgroup analysis was performed. Sensitivity analysis of the main outcome measures and assessment of publication bias were also performed.Results: According to our screening criteria, a total of Forty-nine RCTs were included, involving data from 4268 patients. The results of this analysis showed that compared with platinum-containing chemotherapy alone, bevacizumab combined with platinum-containing chemotherapy significantly improved ORR (RR [95% CI], 1.53 [1.44, 1.63], p < 0.00001), DCR (RR [95% CI], 1.24 [1.19, 1.29], p < 0.0001), 1-year survival rate (RR [95% CI], 1.34 [1.15, 1.57], p = 0.0003), 2-year survival rate (RR [95% CI], 2.16 [1.35, 3.43], p = 0.001), 3-year survival rate (RR [95% CI], 2.00 [1.21, 3.30], p = 0.007). In addition, bevacizumab with platinum-containing chemotherapy observably decreased the VEGF levels (RR [95% CI], −67.35 [−91.46, −43.25], p < 0.00001).Conclusion: Combination therapy involving bevacizumab demonstrated improved antitumor effects compared to chemotherapy alone in terms of ORR, DCR, 1-year survival rate, 2-year survival rate, 3-year survival rate, and VEGF levels without an increased incidence of adverse reactions. These analyses’ results can provide clinicians guidance when selecting appropriate treatments for patients diagnosed with advanced non-small cell lung cancer.

Ecosystem services (ESs) have been widely used in the management and protection of regional ecosystems. Among the numerous influencing factors, climate and vegetation are important factors affecting ESs. Nevertheless, unraveling the intricate and non-linear relationship between ESs and the fluctuations in climate and fractional vegetation cover (FVC) remains an elusive task, particularly within the intricate and dynamic context of mountainous terrains. Therefore, the Qinling Mountains (QL) was selected as the study area, four major ESs (habitat quality, water yield, carbon sequestration and soil conservation) were quantified, and two key points (threshold point and critical point of high ESs supply) were determined by elastic analysis and constraint line respectively. The results showed that the influence thresholds of temperature and FVC on ESs were 13.2 °C and 57%, respectively. The results of constraint line showed that ESs is maintained at a high level when the temperature 840 mm, and the FVC > 57%. According to the threshold points and critical points of high ESs supply, sensitive areas and high ESs supply areas were divided respectively. In addition, based on the above two regional divisions, we obtained an ecosystem management planning map of the study area and put forward corresponding practical suggestions for different regions. This study satisfies the docking of the research results and practical decision-making requirements and provides a theoretical scientific basis for the restoration and sustainable management of ecological environments.

The black-odor water body restoration is an unfinished business in protecting and maintaining the ecological functions of natural water systems in China. Magnetic coagulation (MC) had found a vast application prospect for its high-efficient separation. In this work, the performance of MC was analyzed to explore its role in natural water protection, with a focus on identification and removal mechanisms of the dissolved organic matters (DOM) by absorption and fluorescence spectroscopy in terms of the spectroscopic indices, two-dimensional correlation spectroscopy (2D-COS), and parallel factor analysis (PARAFAC) methods. MC presented an excellent performance for suspended and colloidal matters, phosphorus, and DOMs, and showed high adaptability in pollution interception and water restoration. Tryptophan-like, tyrosine-like, and humics were identified as the key components in the wastewater, which were mainly recently produced or microbial-derived. The targeted pollutants were DOMs with high molecular weight, hydrophobicity, polarity, and aromaticity for the high affinity with the hydrolyzed Al species. Polyaluminum chloride (PAC) was the key in dissolved pollutants removal, while the mix stage is crucial for DOMs with low MW or humic-like substances as PAM facilitated the flocs formation and the absorption process. However, the residual PAM and the redissolved DOMs from the recycled magnetic seeds also act as the DOM source. This work identified the DOM composition and removal mechanism in MC, which would promote its application in natural water protection.

Abstract Human cystic echinococcosis (CE) is a parasitic disease caused by tapeworms from the Echinococcus granulosus genus, potentially affected by the environment and host animals. West China is one of the most endemic areas of human CE nation and worldwide. The current study identifies the crucial environmental and host factors of human CE prevalence in the Qinghai‐Tibet Plateau and non‐Qinghai‐Tibet Plateau regions. An optimal county‐level model was used to analyze the association between key factors and human CE prevalence within the Qinghai‐Tibet Plateau. Geodetector analysis and multicollinearity tests identify key factors, and an optimal model is developed through generalized additive models. In the Qinghai‐Tibet Plateau, four key factors were identified from the 88 variables, such as maximum annual precipitation (Pre), maximum summer normalized difference vegetation index (NDVI), Tibetan population rate (TibetanR), and positive rates of Echinococcus coproantigen in dogs (DogR). Based on the optimal model, a significant positive linear relationship was observed between maximum annual Pre and human CE prevalence. A probable U‐shaped curve depicts the non‐linear relationship between maximum summer NDVI and the human CE prevalence. Human CE prevalence possesses significant positive non‐linear relationships with TibetanR and DogR. Human CE transmission is integrally affected by environmental and host factors. This explains the mechanism of human CE transmission based on the pathogen, host, and transmission framework. Therefore, the current study provides references and innovative ideas for preventing and controlling human CE in western China.

Abstract Background Human echinococcosis is affected by natural environmental factors, and its prevalence shows a distinct geographical distribution. Western China has the highest endemicity of human echinococcosis worldwide, but the spatial pattern and environmental determinants of echinococcosis are still unclear. Methods Hot/cold spot analysis was used to investigate the spatial distribution of human echinococcosis prevalence. Geodetector was used to identify key natural factors, and a structured additive regression model was used to analyse the relationship between natural factors and human echinococcosis prevalence and spatially predict echinococcosis epidemics. Results Hot spots for human echinococcosis prevalence include western and southeastern parts of Tibet Autonomous Region (henceforth Tibet) and the border areas between Tibet and the provinces of Qinghai and Sichuan. Spatial effects are crucial when modelling epidemics, and relative humidity, altitude and grassland area ratio were found to have the most evident effects on echinococcosis epidemics. The relationship between these three factors and echinococcosis prevalence was non-linear, and echinococcosis risk was higher in areas with high relative humidity, high altitude, and a high ratio of grassland to other land use types. The prevalence that was predicted from the investigated environmental factors was generally higher than the actual prevalence, and more epidemic hot spots were predicted for the Qinghai-Tibet Plateau, Inner Mongolia Autonomous Region, and the provinces of Yunnan and Sichuan than the rest of western China. These results indicate that prevention and control measures may effectively reduce echinococcosis prevalence. Conclusions We suggest that the prevention and control of human echinococcosis should be prioritized in the hot spots identified here, through the rational allocation of limited medical resources to where they are most needed. Furthermore, the spatial epidemiological modelling methods used in this study can be employed in future studies on echinococcosis and similar diseases. Graphical abstract

Stomach adenocarcinoma (STAD) is always characterized by high mortality and poor prognosis with drug resistance and recrudescence due to individual genetic heterogeneity. Adenosine-to-Inosine RNA editing (ATIRE) has been reported associated with multiple tumors but the potential connection between ATIRE-related signatures and STAD remains unclear. In this study, we comprehensively elevated the genetic characteristics of ATIRE in STAD patients and first screened five vital survival-related ATIRE sites to identify a novel ATIRE-Risk score. Based on the risk scores, we further divided the patients into two different subtypes with diverse clinical characteristics and immune landscapes including immune cell infiltration (ICI), tumor microenvironment (TME), and immune checkpoint expression analysis. The low-risk subgroups, associated with better survival prognosis, were characterized by activated immune-cells, higher immune scores in TME, and down-expression of immunotherapy checkpoints. Moreover, different expressional genes (DEGs) between the above subtypes were further identified and the activation of immune-related pathways were found in low-risk patients. The stratified survival analysis further indicated patients with low-risk and high-tumor mutation burden (TMB) exhibited the best prognosis outcomes, implying the role of TMB and ATIRE-Risk scores was synergistic for the prognosis of STAD. Interestingly, anti-tumor chemotherapeutic drugs all exhibited lower IC50 values in low-risk subgroups, suggesting these patients might obtain a better curative response from the combined chemotherapy of STAD. Finally, combined with classical clinical features and ATIRE-Risk scores, we successfully established a promising nomogram system to accurately predict the 1/3/5-years survival ratio of STAD and this model was also estimated with high diagnostic efficiency and stable C-index with calibration curves. These significant ATIRE sites are promising to be further explored and might serve as a novel therapeutic target for STAD treatment.

Abstract Background Non-small cell lung cancer (NSCLC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable biomarkers, especially immunotherapy-associated biomarkers, that can predict outcomes of these patients. Methods Gene expression profiles of 1026 NSCLC patients were collected from The Cancer Genome Atlas (TCGA) datasets with their corresponding clinical and somatic mutation data. Based on immune infiltration scores, molecular clustering classification was performed to identify immune subtypes in NSCLC. After the functional enrichment analysis of subtypes, hub genes were further screened using univariate Cox, Lasso, and multivariate Cox regression analysis, and the risk score was defined to construct the prognostic model. Other microarray data and corresponding clinical information of 603 NSCLC patients from the GEO datasets were applied to conduct random forest models for the prognosis of NSCLC with 100 runs of cross-validation. Finally, external datasets with immunotherapy and chemotherapy were further applied to explore the significance of risk-scores in clinical immunotherapy response for NSCLC patients. Results Compared with Subtype-B, the Subtype-A, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration scores and up-regulation of immunotherapy markers. In addition, we found and validated an eleven -gene signatures for better application of distinguishing high- and low-risk NSCLC patients and predict patients’ prognosis and therapeutical response to immunotherapy. Furthermore, combined with other clinical characteristics based on multivariate Cox regression analysis, we successfully constructed and validated a nomogram to effectively predict the survival rate of NSCLC patients. External immunotherapy and chemotherapy cohorts validated the patients with higher risk-scores exhibited significant therapeutic response and clinical benefits. Conclusion These results demonstrated the immunological and prognostic heterogeneity within NSCLC and provided a new clinical application in predicting the prognosis and benefits of immunotherapy for the disease.

Triple-negative breast cancer (TNBC) is associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. There is an urgent need to screen for reliable indices, especially immunotherapy-associated biomarkers that can predict patient outcomes. Pyroptosis, as an inflammation-induced type of programmed cell death, is shown to create a tumor-suppressive environment and improve the chemotherapeutic response in multiple tumors. However, the specific therapeutic effect of pyroptosis in TNBC remains unclear. In this study, we present a consensus clustering by pyroptosis-related signatures of 119 patients with TNBC into two subtypes (clusterA and clusterB) with distinct immunological and prognostic characteristics. First, clusterB, associated with better outcomes, was characterized by a significantly higher pyroptosis-related signature expression, tumor microenvironment prognostic score, and upregulation of immunotherapy checkpoints. A total of 262 differentially expressed genes between the subtypes were further identified and the Ps-score was built using LASSO and COX regression analyses. The external GEO data set demonstrated that cohorts with low Ps-scores consistently had higher expression of pyroptosis-related signatures, immunocyte infiltration levels, and better prognosis. In addition, external immunotherapy and chemotherapy cohorts validated that patients with lower Ps-scores exhibited significant therapeutic response and clinical benefit. Combined with other clinical characteristics, we successfully constructed a nomogram to effectively predict the survival rate of patients with TNBC. Finally, using the scRNA-seq data sets, we validated the landscape of cellular subtypes of TNBC and successfully constructed an miRNA-Ps-score gene interaction network. These findings indicated that the systematic assessment of tumor pyroptosis and identification of Ps-scores has potential clinical implications and facilitates tailoring optimal immunotherapeutic strategies for TNBC.

Abstract Background Pulmonary arterial hypertension (PAH) is a life-threatening condition. The aim of this study was to explore potential crucial genes and pathways associated with PAH based on integrative analyses of gene expression and to shed light on the identification of biomarker for PAH. Methods Gene expression profile of pulmonary tissues from 27 PAH patients and 22 normal controls were downloaded from public database (GSE53408 and GSE113439). After the identification of differentially expressed genes (DEGs), hub pathways and genes were identified based on the comprehensive evaluation of protein-protein interaction (PPI) network analysis, modular analysis and cytohubba’s analysis, and further validated in another PAH transcriptomic dataset (GSE33463). Potentially associated micro-RNAs (miRNAs) were also predicted. Results A total of 521 DEGs were found between PAH and normal controls, including 432 up-regulated DEGs and 89 down-regulated DEGs. Functional enrichment analysis showed that these DEGs were mainly enriched in mitotic cell cycle process, mitotic cell cycle and microtubule cytoskeleton organization. Moreover, five key genes (CDK1, SMC2, SMC4, KIF23, and CENPE) were identified and then further validated in another transcriptomic dataset associated with special phenotypes of PAH. Furthermore, these hub genes were mainly enriched in promoting mitotic cell cycle process, which may be closely associated with the pathogenesis of PAH. We also found that the predicted miRNAs targeting these hub genes were found to be enriched in TGF-β and Hippo signaling pathway. Conclusion These findings are expected to gain a further insight into the development of PAH and provide a promising index for the detection of PAH.

Background: Gastric cancer (GC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable indices especially immunotherapy-associated parameters that can predict the therapeutic responses to immunotherapy of GC patients.Methods: Gene expression profile of 854 GC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE84433) with their corresponding clinical and somatic mutation data. Based on immune cell infiltration (ICI) levels, molecular clustering classification was performed to identify subtypes and ICI scores in GC patients. After functional enrichment analysis of subtypes, we further explored the correlation between ICI scores and Tumor Mutation Burden (TMB) and the significance in clinical immunotherapy response.Results: Three subtypes were identified based on ICI scores with distinct immunological and prognostic characteristics. The ICI-cluster C, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration and up-regulation of PD-L1. ICI scores were identified through using principal component analysis (PCA) and the low ICI scores were consistent with the increased TMB and the immune-activating signaling pathways. Contrarily, the high-ICI score cluster was involved in the immunosuppressive pathways, such as TGF-beta, MAPK and WNT signaling pathways, which might be responsible for poor prognosis of GC. External immunotherapy and chemotherapy cohorts validated the patients with lower ICI scores exhibited significant therapeutic responses and clinical benefits.Conclusion: This study elucidated that ICI score could sever as an effective prognostic and predictive indicator for immunotherapy in GC. These findings indicated that the systematic assessment of tumor ICI landscapes and identification of ICI scores have crucial clinical implications and facilitate tailoring optimal immunotherapeutic strategies.

Huang-Lian-Jie-Du decoction (HLJDD) has been widely applied to treat inflammation-associated diseases for thousands of years in China. However, the concrete molecular mechanism of HLJDD in the treatment of rheumatoid arthritis (RA) remains unclear. In this work, network pharmacology and molecular docking were applied to preliminarily analyze the potential active ingredients, drug targets, and related pathways of HLJDD on treating RA. A total of 102 active compounds with corresponding 189 targets were identified from HLJDD, and 41 common targets were further identified by intersecting with RA-related targets. Functional enrichment analysis was performed to screen the biological pathways associated with RA. Ten hub targets were further identified through constructing the protein–protein interaction (PPI) network of common targets, which were mainly enriched in the interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and Toll-like receptor signaling pathway. Furthermore, a complex botanical drugs-ingredients-hub-targets-disease network was successfully constructed. The molecular docking results exhibited that these vital ingredients of HLJDD had a stable binding to the hub targets. Among these ingredients, quercetin (MOL000098) was the most common molecule with stable binding to all the targets, and PTGS2 was considered the most important target with multiple regulations by the most active ingredients. In vitro, we successfully validated the inhibitory role of quercetin in the cellular proliferation of human RA fibroblast-like synoviocyte cell line (MH7A cells). These findings indicated that the potential mechanisms of HLJDD for RA treatment might be attributed to inhibiting the immune-inflammatory response, reducing the release of chemokines, and alleviating the destruction of extracellular matrix (ECM) in the synovial compartment.

Transmission of dengue virus is a complex process with interactions between virus, mosquitoes and humans, influenced by multiple factors simultaneously. Studies have examined the impact of climate or socio-ecological factors on dengue, or only analyzed the individual effects of each single factor on dengue transmission. However, little research has addressed the interactive effects by multiple factors on dengue incidence. This study uses the geographical detector method to investigate the interactive effect of climate and socio-ecological factors on dengue incidence from two perspectives: over a long-time series and during outbreak periods; and surmised on the possibility of dengue outbreaks in the future. Results suggest that the temperature plays a dominant role in the long-time series of dengue transmission, while socio-ecological factors have great explanatory power for dengue outbreaks. The interactive effect of any two factors is greater than the impact of single factor on dengue transmission, and the interactions of pairs of climate and socio-ecological factors have more significant impact on dengue. Increasing temperature and surge in travel could cause dengue outbreaks in the future. Based on these results, three recommendations are offered regarding the prevention of dengue outbreaks: mitigating the urban heat island effect, adjusting the time and frequency of vector control intervention, and providing targeted health education to travelers at the border points. This study hopes to provide meaningful clues and a scientific basis for policymakers regarding effective interventions against dengue transmission, even during outbreaks.

Beijing–Tianjin–Hebei (BTH) region in China suffers frequent and heavy pollution from particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5). Despite the extensive studies conducted in this region, there are insufficient data on the chemical composition, formation mechanism, potential sources, and regional transport contribution of PM2.5 in Zhangjiakou, Hebei province. In this study, the chemical and spatiotemporal variation in PM2.5 in Zhangjiakou were investigated at four urban sites in Zhangjiakou in 2019. The mean (± standard deviation, SD) observed PM2.5 concentration was 43.0 ± 34.2 μg/m3. The concentrations of PM2.5 and its major components were generally higher in the south than in the north, and in winter than in summer. The major chemical components were organic matter (OM, 31.8%), secondary inorganic ions (SIA, 25.7%), and mineral dust (14.7%). Higher NO3−/EC, SO42−/EC, sulphur oxidation ratios (SOR), and nitrogen oxidation ratios (NOR) were observed on pollution days, implying intense secondary production of nitrate during pollution periods. Heterogeneous reactions were important contributors to secondary sulphate formation. Secondary organic carbon (SOC) proportions (i.e., SOC/OC and SOC/EC ratios) decreased markedly from clean days to heavy pollution days in response to enhanced primary organic carbon (POC) emissions on pollution days. The source contributions varied among sites, seasons, and pollution levels according to positive matrix factorization (PMF) model; combustion and SIA sources were the key factors for air pollutant emission reduction. Small-scale and short-distance air mass transport from the northwestern and southern regions greatly impacted PM2.5 pollution according to potential source analysis. Weather Research and Forecast model (WRF) was coupled with Comprehensive Air Quality Model with Extensions (CAMx), and found that regional transport contributed significantly to PM2.5 pollution in Zhangjiakou (74.6%). The results of this study indicate that joint prevention and control of regional air pollution would meaningfully improve air quality in the BTH region.

A 60-day study was conducted to evaluate the growth performance, nutritional quality of edible tissues (muscle and hepatopancreas) of red swamp crayfish (Procambarus clarkii) cultivated using commercial diet feeding (diet group) and biofloc technology (biofloc group). The commercial diet used in the biofloc group was only 60 % of that in the diet group. Glucose and wheat bran were used as additional carbon sources in the biofloc group. The results showed bioflocs was characterized by sufficient protein content but lower lipid content, however, the growth performance of crayfish in the biofloc group were significantly better at the end of the experiment. Besides, the total lipid content in hepatopancreas of crayfish in the biofloc group was higher. Moreover, saturated fatty acid (STA) content in hepatopancreas and monounsaturated fatty acid (MUFA) content in muscle were higher in the biofloc group, while MUFA content in muscle was significantly lower. No significant difference was observed in total amino acid (TAA), essential amino acid (EAA) and essential amino acids index (EAAI) in muscle in both groups. In conclusion, crayfish could be better cultivated using biofloc technology. However, the lipid deficiency and nutritional imbalance of bioflocs would affect the lipid nutritional composition in edible tissues of crayfish.

The endoplasmic reticulum (ER) forms direct membrane contact sites with the plasma membrane (PM) in eukaryotic cells. These ER-PM contact sites play essential roles in lipid homeostasis, ion dynamics, and cell signaling, which are carried out by protein-protein or protein-lipid interactions. Distinct tethering factors dynamically control the architecture of ER-PM junctions in response to intracellular signals or external stimuli. The physiological roles of ER-PM contact sites are dependent on a variety of regulators that individually or cooperatively perform functions in diverse cellular processes. This review focuses on proteins functioning at ER-PM contact sites and highlights the recent progress in their mechanisms and physiological roles.

Background Conceptualising comorbidity is complex and the term is used variously. Here, it is the coexistence of two or more diagnoses which might be defined as ‘chronic’ and, although they may be pathologically related, they may also act independently. Of interest here is the comorbidity of common psychiatric disorders and impaired cognition.Objectives To examine whether anxiety and/or depression are/is important longitudinal predictors of cognitive change.Methods UK Biobank participants used at three time points (n=502 664): baseline, first follow-up (n=20 257) and first imaging study (n=40 199). Participants with no missing data were 1175 participants aged 40–70 years, 41% women. Machine learning was applied and the main outcome measure of reaction time intraindividual variability (cognition) was used.Findings Using the area under the receiver operating characteristic curve, the anxiety model achieves the best performance with an area under the curve (AUC) of 0.68, followed by the depression model with an AUC of 0.63. The cardiovascular and diabetes model, and the covariates model have weaker performance in predicting cognition, with an AUC of 0.60 and 0.56, respectively.Conclusions Outcomes suggest that psychiatric disorders are more important comorbidities of long-term cognitive change than diabetes and cardiovascular disease, and demographic factors. Findings suggest that psychiatric disorders (anxiety and depression) may have a deleterious effect on long-term cognition and should be considered as an important comorbid disorder of cognitive decline.Clinical implications Important predictive effects of poor mental health on longitudinal cognitive decline should be considered in secondary and also primary care.

With the development of cities and the explosion of information, vast amounts of geo-tagged textural data about Points of Interests (POIs) have been generated. Extracting useful information and discovering text spatial distributions from the data are challenging and meaningful. Also, the huge numbers of POIs in modern cities make it important to have efficient approaches to retrieve and choose a destination. This paper provides a visual design combing metro map and wordles to meet the needs. In this visualization, metro lines serve as the divider lines splitting the city into several subareas and the boundaries to constrain wordles within each subarea. The wordles are generated from keywords extracted from the text about POIs (including reviews, descriptions, etc.) and embedded into the subareas based on their geographical locations. By generating intuitive results and providing an interactive visualization to support exploring text distribution patterns, our strategy can guide the users to explore urban spatial characteristics and retrieve a location efficiently. Finally, we implement a visual analysis of the restaurants data in Shanghai, China as a case study to evaluate our strategy. Keywords: Text visualization, Location retrieval, Urban data, Metro map, Word cloud

Urinary exosomes containing specific biomarkers have recently been considered as novel potential non-invasive candidates for renal disease diagnosis. However, the development of urinary exosomes in basic research and their subsequent diagnostic application are impeded by the lack of an efficient isolation method. One of the main challenges during urinary exosomes isolation is how to remove a large number of Tamm Horsfall proteins (around 92 kDa) and other biological components from exosome enrichment mixture. Herein, we report a facile and low-cost isolation method for highlypurified human urinary exosomes based on dialysis. The key protocol for exosome isolation includes only two steps: (1) Healthy person urines were collected. 10 mL urine in 300 kDa dialysis tubes was firstly dialyzed in phosphate-buffered saline solution three times for sequential nine hours; (2) The dialysis suspension was concentrated to 200 μL by using 100 kDa ultracentrifuge tubes to achieve urinary exosome isolation. For verification, the concentrated solution was examined by western blot, transmission electronic microscopy, atomic force microscopy and qNano, which demonstrated the highly-purified urinary exosomes were present. Furthermore, a total of 359 proteins were identified by the proteomic analysis of purified urinary exosomes from healthy persons. Those results demonstrated that highly-purified urinary exosomes could be achieved by our isolation method; 359 proteins were identified from healthy persons. Further works will focus on screening and identifying disease-related biomarkers from human urine exosomes for clinical diagnosis.

Gold nanorod-based gene delivery system potentially represents a powerful nanotechnology for cancer therapy. Here we for the first time reported the use of polyamidoamine (PAMAM) dendrimer modified-gold nanorods (dGNR) as a high efficient gene delivery system for the targeted silencing of survivin via RNA interference for breast cancer therapy. Gold nanorods were functionalized with thiol-terminated polyamidoamine dendrimer; survivin shRNA plasmid was constructed and conjugated with dGNR. The resultant survivin-shRNA-GNR nanocomposites were incubated with human breast cancer MCF-7 cells, irradiated with 140 mJ/pulse of laser light of 1,064 nm for 15 s, and then continued to culture for 1 to 3 days. These cells were collected and analyzed by MTT, quantitative reverse transcription-PCR, Western blotting, fluorescent microscopy, and high-resolution transmission electron microscopy. 25 nude mice models with breast cancer were established; the nanocomposites of survivin-shRNA-dGNR were injected into the tumor tissues at gradually increased dose, and then were irradiated with 140 mJ/pulse of laser light of 1,064 nm for 15 s one time per week. The nude mice were raised for two months, and then were sacrificed. The tumor tissues were picked out, and their sizes were measured. Results showed that PAMAM dendrimer-functionalized gold nanorods were successfully synthesized; they could enter into MCF-7 cells within 30 min, release survivin shRNA plasmids with high efficiency, enhance the expression of transferred survivin genes in tumor cells under near-IR laser irradiation, and cause remarkable down-regulation of survivin gene and protein, inhibite cell growth in dose-and time-dependent means, and induce cell apoptosis. EGFP fluorescent signals in the tumor localization of nude mice. The tumor sizes in nude mice became smaller and smaller as the dose of the injected nanocomposites increased. In conclusion, PAMAM dendrimer-functionalized gold nanorods may be a high efficient gene delivery release system for survivin-shRNA vector under near-infrared light irradiation; the constructed survivin-shRNA-dGNR composites can effectively inhibit the growth of breast cancer cells, and have potential applications in breast cancer therapy and molecular imaging.

The subcellular localization of proteins is a fundamental aspect of protein functions. Determining the subcellular localization is important for understanding the biological functions of proteins. Here, we developed a set of rice organelle marker lines, in which the expressing fluorescent organelle markers could be used as comparative standards in determining the subcellular localization of the protein of interest. We constructed green fluorescent protein (GFP)- and/or Discosoma sp. red fluorescent protein (DsRed)-tagged organelle markers targeted to the endoplasmic reticulum (ER), mitochondria, Golgi apparatus, peroxisome, actin cytoskeleton, plastid, tonoplast, plasma membrane, and nucleus, respectively. The utility of the rice marker lines for protein subcellular localization studies was demonstrated by detecting a nucleus-localized OsWRKY45 and a mitochondria-associated NbHxk1 in protoplasts of the GFP-OsH2B and the ScCOX4-DsRed lines, respectively. Using a sheath-inoculation method, followed by a live-cell imaging, we detected co-localization of a Magnaporthe oryzae PWL2:mCherry : NLS fusion with the nucleus marker in the GFP-OsH2B rice epidermal cells, confirming the translocation of the M. oryzae effector PWL2 into host cells, and further demonstrating the feasibility of using the organelle marker lines for studying dynamics of proteins in rice cells in the interactions between rice and pathogens. The set of organelle marker lines developed in the present study, provides a valuable resource for protein subcellular localization studies in rice.

AimsResearch demonstrates a negative relationship between alcohol use and affect, but the value of deprecation is unknown and thus cannot be included in estimates of the cost of alcohol to society. This paper aims to examine this relationship and develop econometric techniques to value the loss in affect attributable to alcohol consumption.MethodsCross-sectional (n = 129,437) and longitudinal (n = 11,352) analyses of alcohol consumers in UK Biobank data were undertaken, with depression and neuroticism as proxies of negative affect. The cross-sectional relationship between household income, negative affect and alcohol consumption were analysed using regression models, controlling for confounding variables, and using within-between random models that are robust to unobserved heterogeneity. The differential in household income required to offset alcohol's detriment to affect was derived.ResultsA consistent relationship between depression and alcohol consumption (β = 0.001, z = 7.64) and neuroticism and alcohol consumption (β = 0.001, z = 9.24) was observed in cross-sectional analyses, replicated in within-between models (depression β = 0.001, z = 2.32; neuroticism β = 0.001, z = 2.33). Significant associations were found between household income and depression (cross sectional β = -0.157, z = -23.86, within-between β = -0.146, z = -9.51) and household income and neuroticism (cross sectional β = -0.166, z = -32.02, within-between β = -0.158, z = -7.44). The value of reducing alcohol consumption by one gram/day was pooled and estimated to be £209.06 (95% CI £171.84 to £246.27).ConclusionsThere was a robust relationship between alcohol consumption and negative affect. Econometric methods can value the intangible effects of alcohol use and may, therefore, facilitate the fiscal determination of benefit.

Cellular immunotherapy has become a potential therapeutic method for different diseases. Herein, we reported clinical trial results of Cytokine-induced killer (CIK) cells used for patients with hepatitis B, cirrhosis and liver cancers from 2000 to 2015. Results showed CIK cell therapeutic effects were closely positively associated with CIK cell numbers, treated times and HBV genotypes. Different stages of HBV patients treated with > 1010 CIK cells per time for more than ten times exhibited remarkable decrease of HBV DNA numbers (P < 0.01), ALT and AST gradually recovered to normal scope, cytokine factors such as IFN-γ, IL-1b, IL-2, IL-4, IL-6, IL-10, IL-22 and IL-27 exhibited obvious increase, lifespan of patients with cirrhosis and hepatocellular carcinoma were extended, and that all the patients felt better in sleep, diet and pain during the period of CIK therapy. In conclusion, CIK cell therapy is a good alternative therapeutic method and can be effectively used for treatment of different stages of HBV patients.

Understanding the spatiotemporal dynamics of bamboo forests is of critical importance as it characterizes the interaction between forest and agricultural ecosystems and provides essential information for sustainable ecosystem management and decision-making. Thus far, the specific dynamics of moso bamboo (Phyllostachys edulis) and other bamboo are still unknown. In this study, we used temporal information extracted from Landsat time series stacks with Google Earth Engine (GEE) to characterize the spatiotemporal dynamics of bamboo forests, including moso bamboo and other bamboo, in Lin’an County, China, from 2000 to 2019. The bamboo forests were mapped in four periods: the early 2000s (2000–2004), the late 2000s (2005–2009), the early 2010s (2010–2014), and the late 2010s (2015–2019). The overall accuracy of these maps ranged from 97% to 99%. We then analyzed the spatiotemporal dynamics of the bamboo forests at the county and subdistrict/township scales, and probed the bamboo forest gain and loss with respect to the terrain features. Our findings show that bamboo forests increased by 4% from 2000 to 2014, followed by a sharp decrease of 13% in the late 2010s. The decrease was mainly caused by the loss of other bamboo. Approximately 69% of the bamboo forest gain occurred in non-bamboo forest areas, and the rest occupied non-forest areas. Bamboo forest loss was mainly due to conversion into orchard (59%) and forest plantation (22%). Compared to bamboo forest gain, bamboo forest loss was typically observed in areas with lower elevations and steeper slopes. Our study offers spatially explicit and timely insight into bamboo forest changes at the regional scale. The derived maps can be applied to study the drivers, consequences, and future trends of bamboo forest dynamics, which will contribute to sustainable ecosystem management.

Dysentery, an acute infectious disease still prevalent in many parts of the world, especially in developing counties, is caused by a group of bacteria known as Shigella . Because of the sensitivity of dysentery to climate change, the relationship between dysentery incidence and climate factors has become a growing research interest. Previous studies have mainly focused on identifying key climate factors and examining the relationship between dysentery incidence and climate change. However, there has been little research on modeling and projecting the occurrence of dysentery based on key climate factors. Here we selected Binyang County in China, a subtropical monsoon climate region where epidemics are typical, as the study area. We used heat maps to extract climate risk windows (with minimum temperatures of 24 °C–26 °C, precipitation amounts of 160–380 mm, and relative humidities of 69%–85%) for dysentery transmission. We then developed a climate-dysentery model and validated its reliability. Finally, based on climate risk windows and the developed model, three earth system models (BNU-ESM, IPSL-CM5A-MR, and MIROC-ESM) were used to project future occurrence periods and incidence of dysentery under future climate condition. The projected results showed that May to August were high-incidence periods, and the occurrence of dysentery exhibited an upward trend in the future. Accordingly, we provided two practical recommendations for defeating dysentery: seasonal control in the study area, and advocacy of prevention in potentially pandemic regions. This study hopes to provide a theoretical basis for developing a dysentery warning system from the perspective of climate change.

This paper presents a compact, highly isolated tri-band MIMO antenna for 5G and X-band communication applications. The overall dimensions of the antenna are 43 mm × 30 mm × 1.6 mm. It consists of two monopole radiating units and a metal base with branches and slit slots. The antenna achieves tri-band characteristics by improving the shape of the radiating patch. The isolation of the antenna is enhanced by slotting the floor and loading I- and T-shaped branches to absorb coupling currents. S12 > 15 dB is achieved in the frequency ranges of 3.3 GHz–4.06 GHz, 4.62 GHz–5.28 GHz, and 8.14 GHz–9.28 GHz. Measurement results show that the measured S-parameters do not change significantly compared with the simulation. It also has a low envelope correlation coefficient and good radiation performance. [ABSTRACT FROM AUTHOR]

In this paper, a novel measurement matrix construction method based on adaptive cross-approximation (ACA) is proposed to improve the performance of the compressive sensing-based method of moments (CS-MoM) for analyzing electromagnetic scattering problems. ACA is based on a weight scheme and is able to recognize the rows and columns that contribute significantly to the matrix. Thus, the object is divided into multiple blocks, and the impedance matrix is partitioned into near-field and far-field groups to establish the condition for applying ACA. Then, the row indexes are extracted from the group with the highest number of ACA recognized rows in the far-field groups of each block. Finally, by combining all row indexes to extract the impedance matrix, a lower-dimensional and deterministic measurement matrix is constructed, thereby improving computational efficiency. Numerical simulation results validate the accuracy and effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

This paper introduces a 12-element asymmetric mirror-coupled loop antenna for integration into 5G smartphones. The proposed antenna includes six identical asymmetrically mirrored (AM)-coupled building blocks, each consisting of two gap-coupled loop antennas, with each building block dimensioning a mere 12 × 7 mm2. The unique architecture of the proposed antenna yields an isolation performance exceeding 14 dB without the necessity for ancillary decoupling elements and effectively covers the dual-band 5G mobile frequency bands of 3.3-3.6 GHz and 4.8-5.0 GHz. The antenna was optimized using simulation software HFSS, and the results indicate an antenna's envelope correlation coefficient of less than 0.016 and an efficiency range of 72%-81%. Finally, the performance of single-hand and double-hand handset smartphone modes is discussed, which still exhibit good radiation and MIMO performance under both modes, demonstrating their stability in practical applications. Simulation and measurement results indicate that the proposed 12-element MIMO antenna holds great promise for 5G smartphone applications. [ABSTRACT FROM AUTHOR]