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Hepatocellular carcinoma (HCC) is a typical highly heterogeneous solid tumor with high morbidity and mortality worldwide, especially in China; however, the immune microenvironment of HCC has not been clarified so far. Here, we employed single‐cell RNA sequencing (scRNA‐seq) on diethylnitrosamine (DEN)‐induced mouse HCC model to dissect the immune cell dynamics during tumorigenesis. Our findings reveal distinct immune profiles in both precancerous and cancerous lesions, indicating early tumor‐associated immunological alterations. Notably, specific T and B cell subpopulations are preferentially enriched in the HCC tumor microenvironment (TME). Furthermore, we identified a subpopulation of naïve B cells with high CD83 expression, correlating with improved prognosis in human HCC. These signature genes were validated in The Cancer Genome Atlas HCC RNA‐seq dataset. Moreover, cell interaction analysis revealed that subpopulations of B cells in both mouse and human samples are activated and may potentially contribute to oncogenic processes. In summary, our study provides insights into the dynamic immune microenvironment and cellular networks in HCC pathogenesis, with a specific emphasis on naïve B cells. These findings emphasize the significance of targeting TME in HCC patients to prevent HCC pathological progression, which may give a new perspective on the therapeutics for HCC. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the development of T2D and the underlain mechanism have not been fully elucidated. Methods: A Mendelian randomization (MR) was performed to estimate the causality between two diseases. Bioinformatics tools, including gene ontology and pathway enrichment analyses, were employed to analyze the common differentially expressed genes (DEGs) in periodontitis and T2D. MR and colocalization analyses were then utilized to investigate the causal associations between potential pathogenic gene expression and the risk of T2D. Single cell-type expression analysis was further performed to detect the cellular localization of these genes. Results: Genetically predicted periodontitis was associated with a higher risk of T2D (OR, 1.469; 95% CI, 1.117–1.930; P = 0.006) and insulin resistance (OR 1.034; 95%CI 1.001–1.068; P = 0.041). 79 common DEGs associated with periodontitis and T2D were then identified and demonstrated enrichment mainly in CXC receptor chemokine receptor binding and interleutin-17 signaling pathway. The integration of GWAS with the expression quantitative trait locis of these genes from the peripheral blood genetically prioritized 6 candidate genes, including 2 risk genes (RAP2A, MCUR1) and 4 protective genes (WNK1, NFIX, FOS, PANX1) in periodontitis-related T2D. Enriched in natural killer cells, RAP2A (OR 4.909; 95% CI 1.849–13.039; P = 0.001) demonstrated high risk influence on T2D, and exhibited strong genetic evidence of colocalization (coloc.abf-PPH4 = 0.632). Conclusions: This study used a multi-omics integration method to explore causality between periodontitis and T2D, and revealed molecular mechanisms using bioinformatics tools. Periodontitis was associated with a higher risk of T2D. MCUR1, RAP2A, FOS, PANX1, NFIX and WNK1 may play important roles in the pathogenesis of periodontitis-related T2D, shedding light on the development of potential drug targets. [ABSTRACT FROM AUTHOR]

Background: This study aimed to conduct a bibliometric analysis of the literature on stem cell therapy for spinal cord injury to visualize the research status, identify hotspots, and explore the development trends in this field. Methods: We searched the Web of Science Core Collection database using relevant keywords ("stem cells" and "spinal cord injury") and retrieved the published literature between 2000 and 2022. Data such as journal title, author information, institutional affiliation, country, and keywords were extracted. Afterwards, we performed bibliometric analysis of the retrieved data using Bibliometrix, VOSviewer, and CiteSpace. Results: A total of 5375 articles related to stem cell therapy for spinal cord injury were retrieved, and both the annual publication volume and the cumulative publication volume showed an upward trend. neural regeneration research was the journal with the most publications and the fastest cumulative publication growth (162 articles), Okano Hideyuki was the author with the highest number of publications and citations (114 articles), Sun Yat-sen University was the institution with the highest number of publications (420 articles), and China was the country with the highest number of publications (5357 articles). However, different authors, institutions, and countries need to enhance their cooperation in order to promote the generation of significant academic achievements. Current research in this field has focused on stem cell transplantation, neural regeneration, motor function recovery, exosomes, and tissue engineering. Meanwhile, future research directions are primarily concerned with the molecular mechanisms, safety, clinical trials, exosomes, scaffolds, hydrogels, and inflammatory responses of stem cell therapy for spinal cord injuries. Conclusion: In summary, this study provided a comprehensive analysis of the current research status and frontiers of stem cell therapy for spinal cord injury. The findings provide a foundation for future research and clinical translation efforts of stem cell therapy in this field. [ABSTRACT FROM AUTHOR]

Coxsackievirus A6 (CVA6), a member of species A enterovirus, is associated with outbreaks of hand-foot-and-mouth disease and causes a large nationwide burden of disease. However, the molecular pathogenesis of CVA6 remains unclear. In the present study, we established a suckling Institute of Cancer Research (ICR) mouse infection model to explore the neural pathogenicity of CVA6. Five-day-old mice infected with CVA6 strain F219 showed lethargy and paralysis, and died 5 or 6 days after infection via IM injection. Cerebral edema and neuronal cell swelling were observed in the infected brain tissue, and we found that the CVA6 VP1 antigen could co-localize with GFAP-positive astrocytes in infected mouse brain using an immunofluorescence assay. CVA6 strain F219 can also infect human glioma (U251) cells. Transcriptome analysis of brain tissues from infected mice and infected U251 cells showed that significantly differentially expressed genes were enriched in antiviral and immune response and neurological system processes. These results indicate that CVA6 could cause neural pathogenesis and provide basic data for exploring the mechanism of how host–cell interactions affect viral replication and pathogenesis. Importance: Coxsackievirus A6 (CVA6) surpasses the two main pathogens, enterovirus 71 (EV-A71) and coxsackievirus A16 (CVA16), which are the leading pathogens causing HFMD in many provinces of China. In our study, CVA6 infection caused neurogenic pathogenesis in a neonatal murine model, manifesting as cerebral edema and neuronal cell swelling, CVA6 VP1 antigen could co-localize with GFAP-positive astrocytes in the infected mouse brain. Based on CVA6-infected brain tissue and U251 cell transcriptome analysis, we found upregulated antiviral and immune response-related genes such as Zbp1, Usp18, Oas2, Irf7, Ddx60, Ifit3, Ddx58, and Isg15, while the neurological system process-related genes were downregulated, including Fcrls, Ebnrb, Cdk1, and Anxa5. [ABSTRACT FROM AUTHOR]

In recent years, bamboo has been well exploited in the pulp and paper industry. Moso bamboo (Phyllostachys edulis (Carriere) J. Houzeau; hereafter M), originated from China with a long history of cultivation as the most abundant resource with the widest distribution area among bamboo plants in China. In this study, Moso bamboo (M) and nine bamboo varieties were selected in the bamboo germplasm resources storage bank of the Anhui Taiping Experimental Station of ICBR. The characteristics of their cell structures were compared, and the differences were analyzed from a genetic perspective. The results showed that M had the highest fiber cell length, fiber cell width, length, and parenchyma width, while GJ showed the lowest of these measurements [P. edulis 'Kikko-chiku',G.H.Lai]. The fiber wall thickness of Q [P. edulis f. obliquinoda (Z.P.Wang et N.X.Ma) Ohrnberger] was the smallest, while its fiber lumen diameter was the highest in the group. The parenchyma wall thickness and parenchyma lumen diameter of Q were the smallest in the group. The fiber cells of M and Q had better flexibility, which is conducive to improving the tensile strength, break resistance, and folding resistance of paper made from these materials. SY and GJ may be more suitable for ornamental items because of their special appearances. The purpose of this study was to explore the genetic variation patterns of various cell structure indicators among Moso bamboo and its varieties, as well as to develop a strategy of bamboo growing and lumbering based on the local conditions, providing reference data for the utilization of non-woody forest resources. [ABSTRACT FROM AUTHOR]

Simple Summary: The forest musk deer is a wild animal that is endangered due to widespread hunting for its musk, which is used in medicine and perfume. Stem cells can differentiate into a variety of cells, tissues, organs, and even complete individuals, which can be used for cell therapy and germplasm preservation. Mesenchymal stem cells are the most abundant stem cells in animals and have been isolated from many animals, such as cows and dogs. In this study, to evaluate the feasibility of isolating mesenchymal stem cells from forest musk deer, bone marrow was collected from forest musk deer, and the cells were isolated and characterized. They exhibit the same stemness and differentiation capacity as other mammals studied previously. Therefore, bone marrow mesenchymal stem cells may be an important tool for forest musk deer cell therapy. The forest musk deer (Moschus berezovskii) is an endangered animal that produces musk that is utilized for medical applications worldwide, and this species primarily lives in China. Animal-derived musk can be employed as an important ingredient in Chinese medicine. To investigate the properties of bone marrow mesenchymal stem cells (MSCs) obtained from the bone marrow of forest deer for future application, MSCs were isolated and cultivated in vitro. The properties and differentiation of these cells were assessed at the cellular and gene levels. The results show that 81,533 expressed genes were detected by RNA sequencing, and marker genes of MSCs were expressed in the cells. Karyotype analysis of the cells determined the karyotype to be normal, and marker proteins of MSCs were observed to be expressed in the cell membranes. Cells were differentiated into osteoblasts, adipocytes, and chondroblasts. The expression of genes related to osteoblasts, adipocytes, and chondroblasts was observed to be increased. The results of this study demonstrate that the properties of the cells isolated from bone marrow were in keeping with the characteristics of MSCs, providing a possible basis for future research. [ABSTRACT FROM AUTHOR]

Objective(s): Esophageal cancer is one of the most common cancers with high incidence and mortality rates, especially in China. MicroRNA (miRNA) can be used as a prognostic marker for various human cancers. This study aims to detect suitable miRNA markers for esophageal squamous cell carcinoma (ESCC). Materials and Methods: Our previous gene expression data of ESCC cells and the data from GSE43732 and GSE112840 were analyzed. The expression of miR-574-5p in ESCC patients and controls was analyzed by real-time quantitative PCR. The effect of miR-574-5p on proliferation was detected by real-time cell analysis (RTCA) and EdU proliferation assay after cell transfections. The target gene small C-terminal domain phosphatase 1 (CTDSP1) of miR-574-5p was validated by luciferase reporter assay and western blotting. Results: In the current study, the bioinformatics analysis found miR-574-5p up-regulated in ESCC. The qPCR assay of 26 ESCC and 13 adjacent/ normal tissues confirmed these results. We further demonstrated that miR-574-5p overexpression promoted cell proliferation. Then the dual-luciferase reporter assay and the rescue experiment suggested that CTDSP1 was a direct target of miR-574-5p. Conclusion: MiR-574-5p played an oncological role in ESCC by interacting and negatively regulating CTDSP1. These results provided a deeper understanding of the effect of miR-574-5p on ESCC. [ABSTRACT FROM AUTHOR]

Background: Hair follicle stem cells (HFSCs) are derived from the bulge region and are important autologous stem cell sources. Bibliometric is a statistical method that quantitatively analyses the research papers concerned about one special topic. This study aims to estimate the research status and trends of HFSCs worldwide by bibliometric analyses. Methods: Data were obtained from the Web of Science by searching keywords related to HFSCs. Publication distributions stratified by countries/regions, institutions, journals, and authors were systematically assessed. The frequency of keywords was assessed, and bibliometric mapping was employed to describe the development of HFSC research. Results: A total of 458 publications that met our screening criteria were included in this study, consisting of 423 (92.4%) articles and 35 (7.6%) reviews. The United States of America (USA) ranked first in the number of publications at 146 (31.9%), followed by China at 130 (28.4%), which is consistent with the rank of the H-index. Author keywords were classified into three clusters, namely, basic study, applied study, and biomarker; average publication time of keywords in applied study cluster is later than basic study cluster. The keywords "bulge", "nestin", and "skin" are the top three most frequent keywords in basic studies; "differentiation", "proliferation", and "alopecia" are the top three most frequent keywords in applied studies. With respect to the latest research hotspots, "apoptosis" and "tissue engineering" are relatively new keywords. Conclusions: The USA and China were the most productive countries for research on HFSCs. The focus of keywords gradually shifted from basic study to applied study. Research on the differentiation/proliferation of HFSCs and the role of HFSCs in alopecia have been recent research focuses. Apoptosis and tissue engineering are recommended as promising research hotspots. Our study provides profound insights into the research history, current status, and future trend of HFSCs. [ABSTRACT FROM AUTHOR]

Multigene family (MGF) gene products are increasingly reported to be implicated in African swine fever virus (ASFV) virulence and attenuation of host defenses, among which the MGF360-9L and MGF505-7R gene products are characterized by convergent but distinct mechanisms of immune evasion. Herein, a recombinant ASFV mutant, ASFV-D9L/D7R, bearing combinational deletions of MGF360-9L and MGF505-7R, was constructed from the highly virulent ASFV strain CN/GS/2018 of genotype II that is currently circulating in China. Pigs inoculated intramuscularly with 104 50% hemadsorption doses (HAD50) of the mutant remained clinically healthy without any serious side effects. Importantly, in a virulence challenge, all four within-pen contact pigs demonstrated clinical signs and pathological findings consistent with ASF. In contrast, vaccinated pigs (5/6) were protected and clinical indicators tended to be normal, accompanied by extensive tissue repairs. Similar to most viral infections, innate immunity and both humoral and cellular immune responses appeared to be vital for protection. Notably, transcriptome sequencing (RNA-seq) and quantitative PCR (qPCR) analysis revealed a regulatory function of the mutant in dramatic and sustained expression of type I/III interferons and inflammatory and innate immune genes in vitro. Furthermore, infection with the mutant elicited an early and robust p30-specific IgG response, which coincided and was strongly correlated with the protective efficacy. Analysis of the cellular response revealed a strong ASFV-specific interferon gamma (IFN-g) response and immunostaining of CD41 T cells coupled with a high level of CD1631 macrophage infiltration in spleens of vaccinated pigs. Our study identifies a new mechanism of immunological regulation by ASFV MGFs that rationalizes the design of live attenuated vaccine for implementation of improved control strategies to eradicate ASFV. IMPORTANCE Currently, the deficiency in commercially available vaccines or therapeutic options against African swine fever constitutes a matter of major concern in the swine industry globally. Here, we report the design and construction of a recombinant ASFV mutant harboring combinational deletions of interferon inhibitors MGF360-9L and MGF505-7R based on a genotype II ASFV CN/GS/2018 strain currently circulating in China. The mutant was completely attenuated when inoculated at a high dose of 104 HAD50. In the virulence challenge with homologous virus, sterile immunity was achieved, demonstrating the mutant's potential as a promising vaccine candidate. This sufficiency of effectiveness supports the claim that this live attenuated virus may be a viable vaccine option with which to fight ASF. [ABSTRACT FROM AUTHOR]

Suid herpesvirus 1 (SuHV-1), known as pseudorabies virus (PRV), is one of the most devastating swine pathogens in China, particularly the sudden occurrence of PRV variants in 2011. The higher pathogenicity and cross-species transmission potential of the newly emerged variants caused not only colossal economic losses, but also threatened public health. To uncover the underlying pathogenesis of PRV variants, Tandem Mass Tag (TMT)-based proteomic analysis was performed to quantitatively screen the differentially expressed cellular proteins in PRV-infected Vero cells. A total of 7072 proteins were identified and 960 proteins were significantly regulated: specifically 89 upregulated and 871 downregulated. To make it more credible, the expression of XRCC5 and XRCC6 was verified by western blot and RT-qPCR, and the results dovetailed with the proteomic data. The differentially expressed proteins were involved in various biological processes and signaling pathways, such as chaperonin-containing T-complex, NIK/NF-κB signaling pathway, DNA damage response, and negative regulation of G2/M transition of mitotic cell cycle. Taken together, our data holistically outline the interactions between PRV and host cells, and our results may shed light on the pathogenesis of PRV variants and provide clues for pseudorabies prevention. [ABSTRACT FROM AUTHOR]

Accurate forecast of citywide passenger demand helps online car-hailing service providers to better schedule driver supplies. Previous research either uses only passenger order history and fails to capture the deep dependency of passenger demand, or is restricted on grid region partition that loses physical context. Recent advance in mobile traffic analysis has fostered understanding of city functions. In this article, we propose FlowFlexDP, a demand prediction model that integrates regional crowd flow and applies to flexible region partition. Analysis on a cellular dataset covering 1.5 million users in a major city in China reveals strong correlation between passenger demand and crowd flow. FlowFlexDP extracts both order history and crowd flow from cellular data, and adopts Graph Convolutional Neural Network to adapt prediction for regions of arbitrary shapes and sizes in a city. Evaluation on a large scale data set of 6 online car-hailing applications from cellular data shows that FlowFlexDP accurately predicts passenger demand and outperforms the state-of-the-art demand prediction methods. [ABSTRACT FROM AUTHOR]

Background: There is a need to identify the asthma inflammatory phenotypes of patients to facilitate personalized asthma treatment. Sputum induction is time-consuming and requires expert clinical technique. This study aimed to assess the distribution and characteristics of asthma inflammatory phenotypes in Jilin Province, China; it also aimed to identify an easier method for characterization of an asthma phenotype, rather than sputum cellular analysis. Methods: In this study, 232 asthma patients underwent sputum induction following clinical assessment and blood collection. Inflammatory cell counts in sputum were used to classify asthma inflammatory phenotypes. Receiver operating characteristic curve and Spearman correlation coefficient analyses were used to identify correlations between clinical parameters. Results: Among the included patients, there had 52.1% paucigranulocytic, 38.4% eosinophilic, 4.3% neutrophilic, and 5.2% mixed granulocytic asthma phenotypes, respectively. In total, 129 (55.6%) patients had asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO); these patients had higher proportion of smokers, higher sputum neutrophil count, worse lung function, and worse asthma control, compared with patients who had asthma alone (p < 0.05). Sputum eosinophil/neutrophil counts were positively correlated with blood eosinophil/neutrophil counts (p < 0.01). To identify the presence of sputum eosinophil proportion ≥ 3%, optimal cut-off values for blood eosinophil count and fractional exhaled nitric oxide (FeNO) were 0.2 × 109/L and 30.25 ppd (area under the curve (AUC) = 0.744; AUC = 0.653, p < 0.001). AUCs did not significantly differ between FeNO and blood eosinophil count (p = 0.162), but both exhibited poor specificity (57% and 49%, respectively). To identify the presence of sputum neutrophil proportion ≥ 61%, the optimal cut-off value for blood neutrophil proportion was 69.3% (AUC = 0.691, p = 0.0003); however, this exhibited poor sensitivity (50%). Conclusions: Paucigranulocytic asthma was the most common phenotype, followed by eosinophilic asthma. Higher proportion of smokers, poor patient compliance, insufficient treatment, and poor asthma control may have been the main causes of high ACO proportion among patients in this study. Blood eosinophil/neutrophil counts exhibited poor specificity and sensitivity for prediction of airway eosinophilic/neutrophilic inflammation. [ABSTRACT FROM AUTHOR]

Accurate forecast of citywide crowd flows on flexible region partition benefits urban planning, traffic management, and public safety. Previous research either fails to capture the complex spatiotemporal dependencies of crowd flows or is restricted on grid region partition that loses semantic context. In this paper, we propose DeepFlowFlex, a graph-based model to jointly predict inflows and outflows for each region of arbitrary shape and size in a city. Analysis on cellular datasets covering 2.4 million users in China reveals dependencies and distinctive patterns of crowd flows in not only the conventional space and time domains, but also the speed domain, due to the diverse transportation modes in the mobility data. DeepFlowFlex explicitly groups crowd flows with respect to speed and time, and combines graph convolutional long short-term memory networks and graph convolutional neural networks to extract complex spatiotemporal dependencies, especially long-term and long-distance inter-region dependencies. Evaluations on two big cellular datasets and public GPS trace datasets show that DeepFlowFlex outperforms the state-of-the-art deep learning and big-data-based methods on both grid and non-grid city map partition. [ABSTRACT FROM AUTHOR]

Yang, Wei, Song Zhao, Dan Liu, Guangming Su, Dongwei Zhang, Gui La, Yu Deng, Pian Ni, and Xiuru Guan. Establishment of reference intervals for blood cell analysis of adult Tibetan farmers and herdsmen over 4100 meters above sea level in Tibet based on a health survey. High Alt Med Biol. 21:223–231, 2020. Background: High altitude has substantial influence on reference intervals (RIs) for blood cell analysis. However, the currently used RIs for blood cell analysis in China have not been investigated in people from high-altitude areas, which may potentially cause confusion regarding disease diagnosis and treatment of Tibetan farmers and herdsmen from high-altitude areas. Therefore, it is necessary to establish blood cell analysis RIs that are suitable for people in high-altitude areas. Methods: In total, 1145 healthy Tibetan farmers and herdsmen were recruited who have lived at an altitude from 4100 to 5280 m in Kangma, Tibet, for a long time. The C28-A3 guideline from the Clinical and Laboratory Standards Institute was used to establish the RIs for hemoglobin (HGB) concentrations and red blood cell (RBC), white blood cell (WBC), and platelet (PLT) counts from the blood results of Tibetan participants. Results: There were significant gender differences in blood cell RIs for Tibetan farmers and herdsmen who lived above 4100 m above sea level in Kangma, Tibet. Compared with currently used RIs in China, RIs for HGB concentrations and RBCs in Kangma were significantly higher, whereas WBCs were similar and PLT count was lower. Conclusions: The currently used RIs in China may not be applicable to adult Tibetan farmers and herdsmen above 4100 m in Tibet. The newly obtained RIs can supplement the currently used RIs. [ABSTRACT FROM AUTHOR]

Study Question: What is the role of pigment epithelium-derived factor (PEDF) from decidual natural killer (dNK) cells during early pregnancy?Summary Answer: PEDF from dNK cells limits the lipopolysaccharide (LPS)-induced apoptosis and inflammation of decidual stromal cells (DSCs) to maintain DSCs homoeostasis and immune balance at the maternal-foetal interface during early pregnancy.What Is Known Already: dNK cells, which secrete PEDF, play critical roles during pregnancy via a series of key regulators. PEDF, a multifunctional endogenous glycoprotein, exhibits a wide range of biological actions upon angiogenesis, inflammation, metabolic homoeostasis, immunomodulation etc., providing potential clinical applications.Study Design, Size, Duration: Natural killer (NK) cells from decidua and peripheral blood as well as DSCs isolated from normal pregnancy (NP) during the first trimester (6-10 weeks) and the matched patients suffering recurrent miscarriage (RM) were studied. RNA-sequencing analysis of dNK cells was performed to screen for potential key genes involved in RM. The expression of PEDF in dNK cells in NP and RM was examined. A coculture system with LPS-stimulated DSCs and NK cell supernatants derived from NP or RM was established to explore the regulatory mechanisms of PEDF at the maternal-foetal interface.Participants/materials, Setting, Methods: Peripheral blood and decidual tissues were obtained from women with NP (n = 61) and RM (n = 21). The expression levels of PEDF in NK cells and its receptor (PEDFR) on DSCs were analysed using flow cytometry, western blot and immunohistochemistry. Purified peripheral natural killer (pNK) cells were cocultured with DSCs or trophoblast cells or a combination of both cell types, and PEDF expression in pNK cells was then examined by flow cytometry. DSCs were treated with LPS, an outer-membrane component of Gram-negative bacteria, thereby mimicking an enhanced inflammatory status within decidua, and were cocultured with dNK cell supernatants from NP or RM. In the coculture system, plasmids expressing short hairpin RNA were used to silence PEDFR on DSCs and block the PEDF/PEDFR interaction. Inflammatory cytokines and apoptosis of DSCs treated as described above were assessed by flow cytometry. Western blotting was performed, and the specific signal pathway inhibitors were used to determine downstream PEDF/PEDFR signalling in early decidua.Main Results and the Role Of Chance: Markedly higher RNA (P < 0.001) and protein expression of PEDF (P < 0.01) was detected in normal dNK cells when compared with pNK cells. Compared with pNK cells cultured alone, PEDF expression in pNK cells was elevated after coculture with DSCs (P < 0.01) or trophoblast cells (P < 0.001). The increased pro-inflammatory cytokine, tumour necrosis factor-α and apoptosis of DSCs following LPS stimulation were suppressed by recombinant human PEDF (P < 0.001) or the supernatant of dNK cells derived from NP (P < 0.001). However, these effects were somewhat abrogated when the PEDF/PEDFR interaction was blocked with PEDFR short hairpin sRNA (P < 0.01). Furthermore, dNK cell-derived PEDF protected DSCs from LPS-induced inflammation via inhibition of nuclear factor kappa-B activation, while also protecting DSCs from LPS-induced apoptosis via promotion of extracellular signal-regulated kinase expression. Compared with NP, both significantly decreased PEDF RNA (P < 0.001) and protein expression (P < 0.001) in dNK cells, but not in pNK cells (P > 0.05), were detected in women with RM. PEDFR on DSCs was also decreased within RM compared with that within NP (P < 0.001). As a result, dNK cell-mediated anti-inflammation (P < 0.01) and anti-apoptosis (P < 0.05) for protection of LPS-treated DSCs was attenuated in patients suffering from RM.Large Scale Data: N/A.Limitations, Reasons For Caution: We cannot exclude the possibility that the differences in amounts of PEDF and its receptor in tissue from NP versus RM women could be caused by the miscarriage event in women with RM. Our experiments only involved human samples investigated in vitro. Experiments in animal models and human study cohorts are still needed to confirm these findings and further clarify the role of PEDF-PEDFR in NP and/or RM.Wider Implications Of the Findings: To the best of our knowledge, this is the first study to demonstrate PEDF expression and function at the maternal-foetal interface in the first trimester, providing further evidence that PEDF exhibits functional diversity and has great potential for clinical application(s). The findings of selectively high expression of PEDF in normal dNK cells and the PEDF-mediated role of dNK cells during NP and RM help to further elucidate the immune mechanisms behind RM.Study Funding/competing Interest(s): This work was supported by the National Basic Research Programme of China (2017YFC1001403 and 2015CB943300), Nature Science Foundation from National Nature Science Foundation of China (NSFC; 31970859, 81630036, 81501334, 91542116, 31570920, 81490744 and 31171437), the Innovation-oriented Science and Technology Grant from NHC Key Laboratory of Reproduction Regulation (CX2017-2), the Programme of Shanghai Academic/Technology Research Leader (17XD1400900) and the Key Project of Shanghai Basic Research from Shanghai Municipal Science and Technology Commission (STCSM; 12JC1401600). None of the authors has any conflict of interest to declare. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is one of the most malignant tumors in Southern China and southeast Asia, which is characterized by a dense lymphocyte infiltration and a poor prognosis. The emergence of single-cell sequencing represents a powerful tool to resolve tumor heterogeneity and delineate the complex communication among the tumor cells with neighboring stromal and immune cells in the tumor microenvironment (TME). Here, we performed single cell RNA-seq and analyzed tumor cells together with the infiltrating immune cells from three NPC tumor tissues. In our study, the malignant cells display the intra- and inter-tumoral heterogeneity among the individual patients. Analysis of the immune cells reveal the heterogeneous composition of the distinct immune cells and the various functional states of T cells in NPC tumors. Additionally, coupled with the reconstruct of the T cell receptor (TCR) sequences from immune cells full-length single-cell sequence data, we identify the diverse T cell clonotypes and expansion distribution in individual tumors. Overall, we firstly reveal the landscape of tumor and infiltrating immune cells in nasopharyngeal cancer. These results provide deeper insights on the mechanisms of tumor clearance by immune cells in the surrounding microenvironment, which will be helpful in improving the targeted and immune therapies for NPC. [ABSTRACT FROM AUTHOR]

BACKGROUND: C-terminus of the amelogenin peptide (AMG-CP) is a small molecular endogenous peptide that is highly conserved among species. It is involved in important physiological processes during tooth development. Some studies have shown that AMG-CP can regulate the proliferation and differentiation of cementoblasts, bone marrow mesenchymal stem cells and periodontal ligament fibroblasts, but the biological function of AMG-CP on ameloblasts has not been elucidated. OBJECTIVE: To investigate the effects of different concentrations of AMG-CP on the proliferation of ALC ameloblasts and its underlying mechanisms. METHODS: AMG-CP was successfully synthesized and determinated by liquid chromatography and mass spectrometry. The effects of AMG-CP at 0, 0.5, 1, 2 mg/L on the proliferation of ALC ameloblasts were observed by xCELLigence RTCA cell analysis system in real time. The effect of AMG-CP at 0, 1, 2 mg/L on cell cycle of ALC was detected by flow cytometry. Real-time PCR was used to detect the expression of cyclin D1, CDK4, MCM2, MCM5 mRNA in ALC cells treated with AMG-CP at 0, 1, 2 mg/L. Western blot was carried out to evaluate the effect of AGM-CP at 0, 1 mg/L on MAPK-ERK1/2 pathway by detecting the expression of phosphorylated ERK1/2 and total ERK1/2 in ALC cells. Pathway blockade assay was performed by using ERK1/2 blocker U0126 to pretreat ALC cells. Then cell proliferation ability as well as phosphorylated ERK1/2 expression was analyzed by xCELLigence RTCA cell analysis system and western blot. RESULTS AND CONCLUSION: Compared with the control group, AMG-CP promoted the proliferation of ALC cells, and decreased the population doubling time in a dose-depending manner. Flow cytometry detected the acceleration of cell cycle after treatment with AMG-CP. The results of Real-time PCR showed that AMG-CP upregulated cell cycle-related genes (cyclin D1, CDK4, MCM2, MCM5) expression. Western blot results showed that AMG-CP could upregulate the expression of phosphorylated ERK1/2 and activate MAPK-ERK1/2 signaling pathway in ALC cells. After U0126 was used to inhibit the MAPK-ERK1/2 pathway, the ability of AMG-CP promoting ALC proliferation was inhibited. These results suggest that AMG-CP has a potential to activate MAPK-ERK1/2 pathway, accelerate the process of cell cycle, and then promote the proliferation of ALC cells, all of which indicate that AMG-CP has the potential to promote the proliferation of ameloblasts. [ABSTRACT FROM AUTHOR]

Interviewee first talked about the important role of scientific instruments, pointing out that the scientific instruments is a powerful tool for original scientific research and innovation. The urgency and suggestions for the development of original scientific instrument research in China are put forward. Then, the connotation and ways of innovation are discussed in combination with instrument research. Finally, the scientific significance and creative achievements of the major scientific instrument development project ' Single Cell Spatio-temporal Resolution Molecular Dynamic Analysis System' undertaken by Academician Chen are introduced. [ABSTRACT FROM AUTHOR]

Understanding and predicting cellular traffic at large-scale and fine-granularity is beneficial and valuable to mobile users, wireless carriers, and city authorities. Predicting cellular traffic in modern metropolis is particularly challenging because of the tremendous temporal and spatial dynamics introduced by diverse user Internet behaviors and frequent user mobility citywide. In this paper, we characterize and investigate the root causes of such dynamics in cellular traffic through a big cellular usage dataset covering 1.5 million users and 5,929 cell towers in a major city of China. We reveal intensive spatio-temporal dependency even among distant cell towers, which is largely overlooked in previous works. To explicitly characterize and effectively model the spatio-temporal dependency of urban cellular traffic, we propose a novel decomposition of in-cell and inter-cell data traffic, and apply a graph-based deep learning approach to accurate cellular traffic prediction. Experimental results demonstrate that our method consistently outperforms the state-of-the-art time-series based approaches and we also show through an example study how the decomposition of cellular traffic can be used for event inference. [ABSTRACT FROM AUTHOR]

The deployment of fuel cell vehicles (FCVs) is very important for the decarbonization of the transportation sector. While the energy infrastructure is regarded as a critical factor for the deployment of FCVs, it is still unclear which hydrogen pathway of FCVs has the highest environmental efficiency and should be prioritized, thus restricting the development of related energy infrastructures. Therefore, 17 major hydrogen pathways of FCVs in China are designed in this study, and their environmental impacts, economic costs, and environmental efficiencies are evaluated and compared with those of the energy pathway for battery electric vehicles (BEVs). The results show that the pathways with electrolysis hydrogen from renewables have lower emissions and higher economic costs, which is contrary to the pathways with fossil-based hydrogen. Among the 17 pathways, the pathway with hydrogen from coke oven gas has the most life-cycle environmental efficiency and should be prioritized; however, it is still lower than that of the energy pathway for BEVs. As a higher share of renewables in the total electricity generation would lead to a higher environmental efficiency of hydrogen electrolysis, the hydrogen pathway with renewables could potentially be the most cost-efficient pathway with a decrease in the cost of renewables. • We design 17 hydrogen pathways of FCVs and evaluate their environmental efficiencies. • The DEA model is integrated with the techno-economic model and GREET model. • Pathways with hydrogen from coke oven gas is the most cost-efficient. • We compare the pathway efficiencies under different DEA models and electricity mixes. [ABSTRACT FROM AUTHOR]

In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged) monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes. [ABSTRACT FROM AUTHOR]

Background: Interleukin-1α (IL-1α) is thought to play a major role in renal cell carcinoma (RCC), but the specific mechanism is unclear. In this study, we explored the potential mechanism of the role of IL-1α in RCC.Methods: Two cohorts were included in this study: The Cancer Genome Atlas (TCGA) cohort (n=521) and Fudan University Shanghai Cancer Center (FUSCC) cohort (n=198). These cohorts were used for cell infiltration-related analyses.Results: In TCGA cohort, expression of IL-1α was significantly increased in patients with RCC. High IL-1α mRNA expression and intratumoral IL-1α+ cells were correlated with poor OS, which remained significant after adjustment for confounders. Elevated IL-1α mRNA expression and increased intratumoral IL-1α+ cell infiltration were associated with less mast cell infiltration in RCC. Among the relationships between IL-1α and cytotoxic factors, IL-1α was correlated with IFN-γ, TNFSF11, and GZMA. Among the relationships between IL-1α and immunosuppressive factors, we found that IL-1α was correlated with PDCD1, CD274, CTL1A4, LAG3, and BTLA.Conclusion: Expression of IL-1α was significantly correlated with the prognosis of RCC patients. IL-1α may participate in the development and progression of renal cancer through interactions with immune infiltrating mast cells. Our data demonstrate that IL-1α is a prognostic factor and potential therapeutic target for RCC. [ABSTRACT FROM AUTHOR]

The thyroid hormone disrupting activities of drinking water sources from the lower reaches of Yangtze River were examined using a reporter gene assay based on African green monkey kidney fibroblast (CV-1) cells. None of the eleven tested samples showed thyroid receptor (TR) agonist activity. Nine water samples exhibited TR antagonist activities with the equivalents referring to Di-n-butyl phthalate (DNBP) (TR antagonist activity equivalents, ATR-EQ50s) ranging from 6.92 × 101 to 2.85 × 102 μg DNBP/L. The ATR-EQ50s and TR antagonist equivalent ranges (ATR-EQ30–80 ranges) for TR antagonist activities indicated that the water sample from site WX-8 posed the greatest health risks. The ATR-EQ80s of the water samples ranging from 1.56 × 103 to 6.14 × 103 μg DNBP/L were higher than the NOEC of DNBP. The results from instrumental analysis showed that DNBP might be responsible for the TR antagonist activities in these water samples. Water sources along Yangtze River had thyroid hormone disrupting potential. [Copyright &y& Elsevier]

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for the treatment of cancer, because it preferentially induces apoptosis in numerous cancer cells with little or no effect on normal cells. 5,7-Dihydroxyflavone is a dietary flavonoid commonly found in many plants. Here we show that the combined treatment with 5,7-dihydroxyflavone and TRAIL at subtoxic concentrations induced strong apoptotic response in human hepatocarcinoma HepG2 cells, acute leukemia Jurkat T cells, and cervical carcinoma HeLa cells. We further investigated the mechanisms by which 5,7-dihydroxyflavone augments TRAIL-induced apoptosis in HepG2 cells. 5,7-Dihydroxyflavone up-regulated the expression of pro-apoptotic protein Bax, attenuated the expression of anti-apoptotic proteins Bcl-2, Mcl-1, and IAPs, and reduced the phosphorylation levels of Akt and STAT3, weakening the anti-apoptotic signals thus facilitating the process of apoptosis. Moreover, 5,7-dihydroxyflavone and TRAIL were well tolerated in mice, and the combination of 5,7-dihydroxyflavone and TRAIL reduced tumor burden in vivo in a HepG2 tumor xenograft model. Interestingly, 5,7-dihydroxyflavone-mediated sensitization to TRAIL-induced cell death was not observed in normal human hepatocytes L-O2. These results suggest that the 5,7-dihydroxyflavone in combination with TRAIL might be used for cancer prevention and/or therapy. [ABSTRACT FROM AUTHOR]

In 2018, African swine fever broke out in China, and the death rate after infection was close to 100%. There is no effective and safe vaccine in the world. In order to better characterize and understand the virus–host-cell interaction, quantitative proteomics was performed on porcine alveolar macrophages (PAM) infected with ASFV through tandem mass spectrometry (TMT) technology, high-performance liquid chromatography (HPLC), and mass spectrometry (MS). The proteome difference between the simulated group and the ASFV-infected group was found at 24 h. A total of 4218 proteins were identified, including 306 up-regulated differentially expressed proteins and 238 down-regulated differentially expressed proteins. Western blot analysis confirmed changes in the expression level of the selected protein. Pathway analysis is used to reveal the regulation of protein and interaction pathways after ASFV infection. Functional network and pathway analysis can provide an insight into the complexity and dynamics of virus–host cell interactions. Further study combined with proteomics data found that ARG1 has a very important effect on ASFV replication. It should be noted that the host metabolic pathway of ARG1-polyamine is important for virus replication, revealing that the virus may facilitate its own replication by regulating the level of small molecules in the host cell. [ABSTRACT FROM AUTHOR]

• Brucella vaccine strain A19 shows a reduced virulence at chronic infection. • A19 defects in invasion, survival and trafficking within cells. • A19 is sensitive to natural bactericidal components. • A19 exhibits differential expression of LPS and OMPs. Brucella vaccination is one of the most important strategies for controlling brucellosis in livestock. The A19 strain was the effective vaccine used to control brucellosis in China. However, the characteristics of physiological and attenuated virulence of the A19 strain are not investigated in detail. In this study, we compared the phenotypic characteristics of the A19 to the wild-type strain S2308. Virulence test showed that the A19 was significantly attenuated at chronic infection stage in infected mouse model. In growth analysis, the A19 exhibited a quick growth at exponential phase and premature at stationary phase. The inflammatory response of macrophages infected by the A19 was detected using TaqMan qPCR assay, indicating that the inflammatory level of the A19-infected macrophages was higher than that of the S2308 infection. Cell death analysis showed that the A19 was not cytotoxic for macrophages. Cell infection showed that the A19 reduced its ability to invade, survive and traffic within host cells, and the intracellular A19 hardly excludes lysosome-associated marker LAMP-1, suggesting that the A19 can't escape the lysosome degradation within host cells. In further study, the sensitivity test exhibited that the A19 is more sensitive to stress and bactericidal factors than the S2308 strain, Western blot and silver staining analysis exhibited that the A19 has a different expression pattern of OMPs and reduces LPS O-antigen expression relative to the S2308 strain. Those data give us a more detailed understanding about the A19 vaccine strain, which will be beneficial for improvement of current Brucella vaccine and overcoming its defects. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) 1 and PRRSV 2 have coexisted in China for a very long time. In this study, the complete genomic characterization of a PRRSV 1 strain named KZ2018 was conducted. The results showed that it shared 88.6% identity with Lelystad virus and 81.9–90.8% identities with other Chinese PRRSV 1 strains. Further study showed that its nsp2 protein had a unique discontinuous 6-amino acid (aa) deletion (aa357-360+aa411+aa449). Additionally, its GP3 and GP4 contained a long continuous 18-aa deletion in their overlapped region, which has never been described in other Chinese PRRSV 1 isolates. Amino acid analysis of cell epitopes revealed that GP3 245-256 and GP4 57-68 were the most variable epitopes among different Chinese PRRSV 1 isolates. The results might enrich our knowledge of PRRSV 1 strains in China. • Chinese PRRSV 1 strain KZ2018 had a unique discontinuous 6-aa deletion in nsp2. • KZ2018 strain had the longest 18-aa deletion in overlapping region of GP3 and GP4. • GP3 245-256 and GP4 57-68 were most variable epitopes among Chinese PRRSV 1 strains. [ABSTRACT FROM AUTHOR]

Background: To explore the molecular genetic cause of a four-generation autosomal dominant congenital cataract family in China.Methods: Targeted region sequencing was performed to screen for the potential mutation, and Sanger sequencing was used to confirm the mutation. The homology model was constructed to identify the protein structural change, PolyPhen-2 and Provean were used to predict the mutation impact. Functional and cellular analysis of the wild and mutant GJA8 were performed in DF-1 cells by western blotting, dye uptake assay, immunofluorescence, Annexin V-FITC staining.Results: A novel heterozygous mutation (c.205G > A; p.Ala69Thr) was identified within GJA8, which cosegregated with congenital cataract phenotype in this family. Bioinformatics analysis showed the mutation was located in a highly conserved region, and the mutation was predicted to be pathogenic. Function analysis indicated that the mutation inhibited GJA8 hemichannel activity, reduced cell tolerance to oxidative stress, changed the protein distribution pattern and inhibited the cell growth.Conclusions: We have identified a novel missense mutation in GJA8 (c.205G > A, p.Ala69Thr) in a four-generation Chinese family and our results will further broaden the gene mutation spectrum of GJA8. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is common in Southern China. The molecular mechanism underlying NPC genesis and progression has been comprehensively investigated, but the key gene (s) or pathway (s) pertaining to NPC are unidentified. We explored some key genes and pathways involved in NPC through using meta-analysis of deposited expression of microarray data of NPC. The expression of proliferating cell nuclear antigen clamp associated factor (PCLAF) was determined by real-time PCR and western blots. CCK-8 assay, colony formation assay, transwell migration assay, cell wound healing assay, cell cycle analysis and cell apoptosis were carried out to assess biological behaviors caused by downregulation and overexpression of PCLAF in vitro. CHIP was utilized to determine the direct upstream regulatory transcription factors of PCLAF. PCLAF was the key gene of NPC, which was significantly up-regulated in NPC cell line compared to the normal nasopharyngeal cell line. Additionally, in vitro assay has demonstrated the down-regulation and overexpression of PCLAF, resulted in significantly suppressed and enhanced NPC proliferation, metastasis and invasion respectively. Furthermore, the up-regulation of PCLAF in NPC is induced by direct binding of dysregulated NF-κB p50/RelB complex to the promoter of PCLAF. Our results offer a strategy for re-using the deposited data to find the key genes and pathways involved in pathogenesis of cancer. Our study has provided evidence of supporting the role of PCLAF in NPC genesis and progression. [ABSTRACT FROM AUTHOR]

In response to extreme environmental conditions, Bactrian camels with largest population in China have evolved with the unique and extraordinary stress-tolerant mechanism in the bodies, in which the most abundantly secreted serum albumins contribute to an important role in diverse physiological activities such as maintaining osmotic pressure and transporting endogenous/exogenous molecules. In this study, we have for the first time purified Chinese Bactrian camel serum albumins (CSA) aimed at exploring their biomedical application. The mass spectrometric as well as structural analysis of CSA have revealed the sequence consensus and alpha-helix abundant structures among its heterologous proteins. Using desolvation methods, CSA-based nanoparticles have been prepared to encapsulate two substrate molecules including Doxorubicin (Dox) and hemin, which confers the versatility of nanocomposite. As drug delivery matrix, the Dox-loaded CSA nanoparticles displayed sustained release behaviors of DOX with the decreased cytotoxicity detected by both CCK-8 assay and real-time cell analysis. The CSA-hemin nanoparticles exhibited superior catalytic activities in the oxidation of Orange II comparable with horse radish peroxidase following a ping-pong mechanism. Furthermore, the constructed CSA-hemin nanoparticles were applied for the spectroscopic detection of H 2 O 2 resulting in a wide linear calibration curve ranging from 5 to 400 μM with a detection limit of 3.32 μM. Unlabelled Image • Chinese Bactrian camel serum albumins (CSA) was purified for biomedical use. • The amino acid sequence of CSA was solved for the first time. • A versatile biocargo of CSA was built for biocatalysis and bioanalysis. [ABSTRACT FROM AUTHOR]

As a health-care food and traditional Chinese medicine, E'jiao, from the skin of Equus animus L, has been used to nourish blood in China for more than 2000 years. In modern medicine, there are also evidences indicate it has a beneficial effect on chemotherapy-caused blood deficiency. However, its mechanism of action for blood invigoration remains unclear. In the present study, we investigated the hematopoietic effect of E'jiao in 5-Fluorouracil-treated mice. In addition to the counting of bone marrow nucleated cells (BMNCs), flow cytometry was used to detect the population of hematopoietic stem cells (HSCs), and colony-forming unit (CFU) was used to assay the differentiation ability of hematopoietic progenitor cells (HPCs). Gene expression profiles of bone marrow cells were obtained from RNA sequencing (RNA-seq) and differentially expressed genes (DEGs) were analyzed with an emphasis on hematopoiesis-related pathways. The results show that E'jiao promotes the proliferation of both BMNCs and HSCs, as well as the differentiation of HPCs. By providing a hematopoiesis-related molecular regulatory network of E'jiao, we point out that the mechanism of E'jiao is associated with pathways including ECM-receptor interaction, Wnt signaling pathway, PI3K-Akt signaling pathway, TGF-beta signaling pathway, Hematopoietic cell lineage and Osteoclast differentiation, in which Ibsp, Col1a1, Col1a2, Notum, Sost, Dkk1, Irx5, Irx3 and Dcn are the key regulatory molecules. These findings provide valuable molecular basis for the mechanism of action of E'jiao. [ABSTRACT FROM AUTHOR]