e-Health—a new form of health care service using information technology—has received a great deal of academic attention in the past. What can we learn from these prior studies? This article analyses the development ...e-Health—a new form of health care service using information technology—has received a great deal of academic attention in the past. What can we learn from these prior studies? This article analyses the development of prior work using the scientific literature related to e-Health from the Web of Science core database. Our systematic review suggest that: 1) IT adoption is the most important research topic in this field, 2) Research methods are growing in diversity, 3) Research topics are reasonably differentiated.展开更多
对民用航空器结构用碳纤维树脂基复合材料(CFRP)进行吸湿性能研究,测试其吸湿率随时间的变化规律,同时监测吸湿过程中试样电阻率的变化规律,对饱和吸湿试样再进行通电处理,获取脱湿率与通电电流的关系,之后对未处理、吸湿及吸湿/通电处...对民用航空器结构用碳纤维树脂基复合材料(CFRP)进行吸湿性能研究,测试其吸湿率随时间的变化规律,同时监测吸湿过程中试样电阻率的变化规律,对饱和吸湿试样再进行通电处理,获取脱湿率与通电电流的关系,之后对未处理、吸湿及吸湿/通电处理试样进行弯曲性能测试,通过观察弯曲断口处裂纹走向及断口形貌,分析湿热、湿热/电热作用对CFRP弯曲性能的影响。结果表明,试样吸湿率随吸湿时间延长呈先上升后趋于稳定的趋势,其电阻率呈先下降后稳定的变化规律,饱和吸湿试样经通电处理后,脱湿率随电流增加而增大,但试样湿含量不能降低为0。吸湿后小电流2~4 A(ρ=33.4~66.8 m A/mm^2)处理,试样弯曲性能较单纯吸湿试样有所提升,弯曲断裂后试样并未分离成两部分,吸湿后大电流5~6 A(ρ=83.6~100.2 m A/mm^2)处理,造成试样弯曲强度下降,弯曲断裂表现为脆性断裂。展开更多
Objective： Portal vein metastasis of hepatocellular carcinoma（HCC） results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor throm...Objective： Portal vein metastasis of hepatocellular carcinoma（HCC） results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor thrombus（PVTT） is complex and is not yet fully understood. This study was conducted to investigate the impact of portal vein blood on the proliferation, metastasis, invasion and apoptosis of PVTT cells and to explore its possible mechanisms, which was expected to lay a foundation for ascertaining the mechanism underlying the portal vein metastasis of HCC.Methods： Peripheral blood and portal vein blood were collected from patients with HCC, and the sera from these two sources were used to culture the PVTT-originated HCC cell line CSQT-2. The cells were collected after 24 h, and flow cytometry was performed to detect cell proliferation, cell cycle stages and apoptosis. Transwell migration and invasion assays were applied to detect the metastasis and invasion of the cells in each group. The changes in the expression of MMP-2 and MMP-9 in cells were detected via Western blotting. The contents of IL-12, IFN-γ, IL-1β, IL-2 and TNF-α in the two groups of sera were quantified using corresponding kits. Results： Compared with the group of cells cultured with peripheral serum, the cells cultured with portal vein serum showed significantly lower apoptosis（P〈0.01）, significantly enhanced cell metastasis and invasion（P〈0.01）, whereas cell proliferation and the stages of the cell cycle did not differ significantly（P〉0.05）. A significantly increased expression level of MMP-2 has been observed in tumor cells treated portal vein serum. In addition, compared with peripheral serum, the content of IL-12 was significantly decreased in portal vein serum（P〈0.05）, while the contents of IFN-γ, IL-1β, IL-2, and TNF-α did not differ significantly（P〈0.05）. Conclusions： Portal vein serum from HCC patients could inhibit the apoptosis of PVTT-originated HCC cells and promote cell metastasis and invasion. This effect may be related to the lower level of IL-12 in portal vein serum.展开更多
The Wnt/β-catenin signaling pathway regulates many aspects of tumor biology,and many studies have focused on the role of this signaling pathway in tumor cells.However,it is now clear that tumor development and metast...The Wnt/β-catenin signaling pathway regulates many aspects of tumor biology,and many studies have focused on the role of this signaling pathway in tumor cells.However,it is now clear that tumor development and metastasis depend on the two-way interaction between cancer cells and their environment,thereby forming a tumor microenvironment(TME).In this review,we discuss how Wnt/β-catenin signaling regulates cross-interactions among different components of the TME,including immune cells,stem cells,tumor vasculature,and noncellular components of the TME in hepatocellular carcinoma.We also investigate their preclinical and clinical insights for primary liver cancer intervention,and explore the significance of using Wnt/β-catenin mutations as a biomarker to predict resistance in immunotherapy.展开更多
Cancers of the digestive system(DS),including esophageal,gastric,colorectal,liver,and pancreatic can-cers,have a high incidence and mortality worldwide.Current cancer models cannot faithfully recapitu-late the critica...Cancers of the digestive system(DS),including esophageal,gastric,colorectal,liver,and pancreatic can-cers,have a high incidence and mortality worldwide.Current cancer models cannot faithfully recapitu-late the critical features of the original tumor,resulting in the failure of translation from basic research into clinical practice.More advanced cancer models are in urgent need of pathogenesis exploration and anticancer medicine development.Organoids are in vitro cultured three dimensional(3D)self-organizing organotypic structures derived from tissues and pluripotent stem cells,which faithfully mimic the histological features and preserve the genetic heterogeneity of the original tissues.Both normal and malignant organoids can now be efficiently established from the DS tissues of patients.In this review,we summarize the general methods to generate human DS organoids and their applications as a novel model in basic cancer research,preclinical medical practice,and precision medicine.展开更多
In recent decades, diseases concerning the gut microbiota have presented some of the most serious public health problems worldwide. The human host＇s physiological status is influenced by the intestinal microbiome, th...In recent decades, diseases concerning the gut microbiota have presented some of the most serious public health problems worldwide. The human host＇s physiological status is influenced by the intestinal microbiome, thus integrating external factors, such as diet, with genetic and immune signals. The notion that chronic inflammation drives carcinogenesis has been widely established for various tissues. It is surprising that the role of the microbiota in tumorigenesis has only recently been recognized, given that the presence of bacteria at tumor sites was first described more than a century ago. Extensive epidemiological studies have revealed that there is a strong link between the gut microbiota and some common cancers. However, the exact molecular mechanisms linking the gut microbiota and cancer are not yet fully understood. Changes to the gut microbiota are instrumental in determining the occurrence and progression of hepatocarcinoma, chronic liver diseases related to alcohol, nonalcoholic fatty liver disease （NAFLD）, and cirrhosis. To be specific, the gut milieu may play an important role in systemic inflammation, endotoxemia, and vasodilation, which leads to complications such as spontaneous bacterial peritonitis and hepatic encephalopathy. Relevant animal studies involving gut microbiota manipulations, combined with observational studies on patients with NAFLD, have provided ample evidence pointing to the contribution of dysbiosis to the pathogenesis of NAFLD. Given the poor prognosis of these clinical events, their prevention and early management are essential. Studies of the composition and function of the gut microbiota could shed some light on understanding the prognosis because the microbiota serves as an essential component of the gut milieu that can impact the aforementioned clinical events. As far as disease management is concerned, probiotics may provide a novel direction for therapeutics for hepatocellular carcinoma （HCC） and NAFLD, given that probiotics function as a type of medicine that can improve human health by regulating the immune system. Here, we provide an overview of the relationships among the gut microbiota, tumors, and liver diseases. In addition, considering the significance of bacterial homeostasis, we discuss probiotics in this article in order to guide treatments for related diseases.展开更多
Cancer is a global public health threat and a leading cause of death in China.In 2020,the number of new cancer cases around the world reached approximately 19.3 million,and about 10.0 million cancer-related deaths occ...Cancer is a global public health threat and a leading cause of death in China.In 2020,the number of new cancer cases around the world reached approximately 19.3 million,and about 10.0 million cancer-related deaths occurred.Tumor diagnosis and treatment remain a huge challenge due to the diversity of cancer etiology,the complicated mechanism and long process of tumorigenesis,and the significant heterogeneity between individuals.As cancer is a systemic disease,tumor diagnosis is multidisciplinary.Tumor treatment has evolved from the initial conventional surgery,radiotherapy,and chemotherapy to the current multimethod and multidisciplinary comprehensive treatment.With the continuous deepening and advancement of research in disease biology,we have gained a better understanding of cancer.展开更多
Crosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression.A tumor subpopulation called liver cancer stem cells(CSCs)significantly accounts for the initiation,metastasis...Crosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression.A tumor subpopulation called liver cancer stem cells(CSCs)significantly accounts for the initiation,metastasis,therapeutic resistance,and recurrence of liver cancer.Emerging evidence demonstrates that the interaction between liver CSCs and immune cells plays a crucial role in shaping an immunosuppressive microenvironment and determining immunotherapy responses.This review sheds light on the bidirectional crosstalk between liver CSCs and immune cells for liver cancer progression,as well as the underlying molecular mechanisms after presenting an overview of liver CSCs characteristic and their microenvironment.Finally,we discuss the potential application of liver CSCs-targeted immunotherapy for liver cancer treatment.展开更多
Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes.Herein,we retrospectively analyzed pancreatic lesions in autops...Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes.Herein,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients.Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans.Minor and limited phenotypic and histopathological changes were observed in adult models.Systemic proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio levels.Furthermore,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic dysfunction.In contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.展开更多
This study presents atmospheric N_(2)O mole fractions measured from discrete air samples from 2001 to 2018 at Mt.Waliguan(WLG)station(36°17′N,100°54′E,3816 m asl)in China,which is a global background stati...This study presents atmospheric N_(2)O mole fractions measured from discrete air samples from 2001 to 2018 at Mt.Waliguan(WLG)station(36°17′N,100°54′E,3816 m asl)in China,which is a global background station of the World Meteorological Organization/Global Atmosphere Watch Programme(WMO/GAW)in central Eurasia.Observed N_(2)O characteristics of annual means,interannual variability,and seasonal cycles were investigated.Our results show that N_(2)O at WLG possess a distinct increasing trend and a statistically significant seasonal cycle,with an average growth rate of 0.9±0.01 ppb yr^(−1)(1σ)(1ppb=10^(−9)),which is close to the global mean.The detrended seasonal cycle shows a trough of−0.25±0.04(1σ)ppb in June and a peak of 0.13±0.07(1σ)ppb in September,with an amplitude of 0.38 ppb.The pattern is due to combined effects of variation in surface sources,vertical convection within the boundary layer and stratosphere to troposphere transportation(STE).The interannual variability in growth rate was partly driven by quasi-biennial oscillation(QBO)of tropical zonal wind through stratospheric transport into the troposphere.According to a cluster analysis of back trajectories and the corresponding average N_(2)O load,most air masses cover arid and semi-arid areas in inner Asia with low N_(2)O emissions,indicating that the atmospheric N_(2)O at the WLG represents the background N_(2)O level in central Eurasia.展开更多
Various material design strategies have been developed to enhance photocatalytic performance of TiO_(2).However,no report is available on applications of the photopiezocatalysis strategy on TiO_(2)due to its lack of p...Various material design strategies have been developed to enhance photocatalytic performance of TiO_(2).However,no report is available on applications of the photopiezocatalysis strategy on TiO_(2)due to its lack of piezoelectricity.Here we developed a low-temperature molten salt etching process to create rutile TiO_(2)nanoparticles by etching[MgO_(6)]octahedrons away from MgTiO_(3)by molten NH_(4)Cl,during which a lattice distortion occurred in TiO_(2).The lattice distortion broke the structure symmetry of rutile TiO_(2)and subsequently endowed these rutile TiO_(2)nanoparticles with an unusual piezoelectric response with the maximum effective piezoelectric coefficient(d_(33))of~41.6 pm/V,which had not previously been found in TiO_(2)photocatalysts.Thus,the photopiezocatalysis strategy was applied for the first time to enhance the photocatalytic performance of these TiO_(2)nanoparticles.The creation of lattice distortion to induce piezoelectricity could be extended to other photocatalysts that the photopiezocatalysis strategy has not been applied to and may generate novel functionalities for various technical applications.展开更多
The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative capacities.The hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events...The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative capacities.The hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events of cell proliferation,migration,and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription factors.Studies on liver development and diseases have revealed that SRY-related high-mobility group box 9(SOx9)plays an important role in liver embryogenesis and the progression of hepatobiliary diseases.sox9 is not only a master regulator of cell fate determination and tissue morphogenesis,but also regulates various biological features of cancer,including cancer stemness,invasion,and drug resistance,making Sox9 a potential biomarker for tumor prognosis and progression.This review systematically summarizes the latest findings of sox9 in hepatobiliary development,homeostasis,and disease.We also highlight the value of sox9 as a novel biomarker and potential target for the clinical treatment of major liverdiseases.展开更多
Auditory neuropathy spectrum disorder(ANSD)represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function,but with the preservation of outer hair ce...Auditory neuropathy spectrum disorder(ANSD)represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function,but with the preservation of outer hair cell function.ANSD represents up to 15%of individuals with hearing impairments.Through mutation screening,bioinformatic analysis and expression studies,we have previously identified several apoptosis-inducing factor(AIF)mitochondria-associated 1(AIFM1)variants in ANSD families and in some other sporadic cases.Here,to elucidate the pathogenic mechanisms underlying each AIFM1 variant,we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system and constructed AIF-wild type(WT)and AIF-mutant(mut)(p.T260A,p.R422W,and p.R451Q)stable transfection cell lines.We then analyzed AIF structure,coenzyme-binding affinity,apoptosis,and other aspects.Results revealed that these variants resulted in impaired dimerization,compromising AIF function.The reduction reaction of AIF variants had proceeded slower than that of AIF-WT.The average levels of AIF dimerization in AIF variant cells were only 34.5%-49.7%of that of AIF-WT cells,resulting in caspase-independent apoptosis.The average percentage of apoptotic cells in the variants was 12.3%-17.9%,which was significantly higher than that(6.9%-7.4%)in controls.However,nicotinamide adenine dinucleotide(NADH)treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells.Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD,and introduce NADH as a potential drug for ANSD treatment.Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.展开更多
Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods.However,these methods have their own deficienc...Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods.However,these methods have their own deficiencies that restrict the therapeutic applications of such induced hepatocytes.In this study,we present a transgene-free,highly efficient chemical-induced direct reprogramming approach to generate hepatocyte-like cells from mouse embryonic fibroblasts(MEFs).Using a small molecule cocktail(SMC)as an inducer,MEFs can be directly reprogrammed into hepatocyte-like cells,bypassing the intermediate stages of pluripotent and immature hepatoblasts.These chemical-induced hepatocyte-like cells(ciHeps)closely resemble mature primary hepatocytes in terms of morphology,biological behavior,gene expression patterns,marker expression levels,and hepatic functions.Furthermore,transplanted ciHeps can integrate into the liver,promote liver regeneration,and improve survival rates in mice with acute liver damage.ciHeps can also ameliorate liver fibrosis caused by chronic injuries and enhance liver function.Notably,ciHeps exhibit no tumorigenic potential either in vitro or in vivo.Mechanistically,SMC-induced mesenchymal-to-epithelial transition and suppression of SNAI1 contribute to the fate conversion of fibroblasts into ciHeps.These results indicate that this transgene-free,chemical-induced direct reprogramming technique has the potential to serve as a valuable means of producing alternative hepatocytes for both research and therapeutic purposes.Additionally,this method also sheds light on the direct reprogramming of other cell types under chemical induction.展开更多
Recently,convolutional neural networks(CNNs)have achieved excellent performance for the recommendation system by extracting deep features and building collaborative filtering models.However,CNNs have been verified sus...Recently,convolutional neural networks(CNNs)have achieved excellent performance for the recommendation system by extracting deep features and building collaborative filtering models.However,CNNs have been verified susceptible to adversarial examples.This is because adversarial samples are subtle non-random disturbances,which indicates that machine learning models produce incorrect outputs.Therefore,we propose a novel model of Adversarial Neural Collaborative Filtering with Embedding Dimension Correlations,named ANCF in short,to address the adversarial problem of CNN-based recommendation system.In particular,the proposed ANCF model adopts the matrix factorization to train the adversarial personalized ranking in the prediction layer.This is because matrix factorization supposes that the linear interaction of the latent factors,which are captured between the user and the item,can describe the observable feedback,thus the proposed ANCF model can learn more complicated representation of their latent factors to improve the performance of recommendation.In addition,the ANCF model utilizes the outer product instead of the inner product or concatenation to learn explicitly pairwise embedding dimensional correlations and obtain the interaction map from which CNNs can utilize its strengths to learn high-order correlations.As a result,the proposed ANCF model can improve the robustness performance by the adversarial personalized ranking,and obtain more information by encoding correlations between different embedding layers.Experimental results carried out on three public datasets demonstrate that the ANCF model outperforms other existing recommendation models.展开更多
It is widely recognized that tumor immune microenvironment(TIME)plays a crucial role in tumor progression,metastasis,and therapeutic response.Despite several noninvasive strategies have emerged for cancer diagnosis an...It is widely recognized that tumor immune microenvironment(TIME)plays a crucial role in tumor progression,metastasis,and therapeutic response.Despite several noninvasive strategies have emerged for cancer diagnosis and prognosis,there are still lack of efective radiomic-based model to evaluate TIME status,let alone predict clinical outcome and immune checkpoint inhibitor(ICIs)response for hepatocellular carcinoma(HCC).In this study,we developed a radiomic model to evaluate TIME status within the tumor and predict prognosis and immunotherapy response.A total of 301 patients who underwent magnetic resonance imaging(MRI)examinations were enrolled in our study.The intra-tumoral expression of 17 immune-related molecules were evaluated using co-detection by indexing(CODEX)technology,and we construct Immunoscore(IS)with the least absolute shrinkage and selection operator(LASSO)algorithm and Cox regression method to evaluate TIME.Of 6115 features extracted from MRI,fve core features were fltered out,and the Radiomic Immunoscore(RIS)showed high accuracy in predicting TIME status in testing cohort(area under the curve=0.753).More importantly,RIS model showed the capability of predicting therapeutic response to anti-programmed cell death 1(PD-1)immunotherapy in an independent cohort with advanced HCC patients(area under the curve=0.731).In comparison with previously radiomicbased models,our integrated RIS model exhibits not only higher accuracy in predicting prognosis but also the potential guiding signifcance to HCC immunotherapy.展开更多
Objective:To make an overview of global research trends in the etiology of auditory neuropathy(AN)over the past 30 years using a bibliometric approach.Methods:Bibliometric analyses were conducted by GraphPad Prism 9.0...Objective:To make an overview of global research trends in the etiology of auditory neuropathy(AN)over the past 30 years using a bibliometric approach.Methods:Bibliometric analyses were conducted by GraphPad Prism 9.0,Citespace 6.2.R2,and an online analysis platform to analyze and visualize publications related to etiology of AN from the Web of Science Core Collection(WoSCC)database from 1996 to 2022.Additionally,genetic factors in human AN were analyzed.Results:In total,604 original articles and reviews related to the etiology of AN from the WoSCC were included for bibliometric analysis.The results showed that annual publications and trend on etiology of AN increased linearly from 2000.Among them,the United States and China published nearly 400 records(40.32%).From the 604 records,a total of 752 keywords and 10 clustered network maps were extracted by Citespace,and‘mutations’was among the top 10 keywords.Analysis of genetic factors found that more than 30 genes were related to AN,and the latest burst occurred in 2022.Conclusion:The bibliometric analysis mapped the global research trends and analyzed hotspots for future.The results indicated that the annual publications increased linearly from 2000.Notably,there was a burst in genetic factors in 2022,which identified that genetic factor would remain a focus of future research.展开更多
Age-associated changes in immune cells have been linked to an increased risk for infection.However,a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking....Age-associated changes in immune cells have been linked to an increased risk for infection.However,a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking.Here,we combined scRNA-seq,mass cytometry and sCATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19.We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector,cytotoxic,exhausted and reg-ulatory cells,along with increased late natural killer cells,age-associated B cells,inflammatory monocytes and age-associated dendritic cells.In addition,the expression of genes,which were implicated in coron-avirus susceptibility,was upregulated in a cell subtype-specific manner with age.Notably,COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senes-cence.Therefore,these findings suggest that a dysreg-ulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.展开更多
基金the National Natural Science Foundation of China(U21A20376,82102871,81988101,81903184,81790633,and 81830054)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-00-07E00065)+1 种基金the National Science Foundation of Shanghai(21XD1404600,21JC1406600,and 22140901000)the China Postdoctoral Science Foundation(2020M671007).
文摘e-Health—a new form of health care service using information technology—has received a great deal of academic attention in the past. What can we learn from these prior studies? This article analyses the development of prior work using the scientific literature related to e-Health from the Web of Science core database. Our systematic review suggest that: 1) IT adoption is the most important research topic in this field, 2) Research methods are growing in diversity, 3) Research topics are reasonably differentiated.
文摘对民用航空器结构用碳纤维树脂基复合材料(CFRP)进行吸湿性能研究,测试其吸湿率随时间的变化规律,同时监测吸湿过程中试样电阻率的变化规律,对饱和吸湿试样再进行通电处理,获取脱湿率与通电电流的关系,之后对未处理、吸湿及吸湿/通电处理试样进行弯曲性能测试,通过观察弯曲断口处裂纹走向及断口形貌,分析湿热、湿热/电热作用对CFRP弯曲性能的影响。结果表明,试样吸湿率随吸湿时间延长呈先上升后趋于稳定的趋势,其电阻率呈先下降后稳定的变化规律,饱和吸湿试样经通电处理后,脱湿率随电流增加而增大,但试样湿含量不能降低为0。吸湿后小电流2~4 A(ρ=33.4~66.8 m A/mm^2)处理,试样弯曲性能较单纯吸湿试样有所提升,弯曲断裂后试样并未分离成两部分,吸湿后大电流5~6 A(ρ=83.6~100.2 m A/mm^2)处理,造成试样弯曲强度下降,弯曲断裂表现为脆性断裂。
基金supported by the China National Funds for the Science Fund for Creative Research Groups (No: 81221061)The State Key Project on Infections Diseases of China (2012zx10002016016003)+4 种基金China National Funds for the Distinguished Young Scientists (No: 81125018)National Natural Science Foundation(No: 81071750, 81101831, 81101511)New Excellent Talents Program of Shanghai Municipal Health Bureau (No:XBR2011025)Shanghai Scienceand Technology Committee (No. 134119a020010JC1417600)
文摘Objective： Portal vein metastasis of hepatocellular carcinoma（HCC） results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor thrombus（PVTT） is complex and is not yet fully understood. This study was conducted to investigate the impact of portal vein blood on the proliferation, metastasis, invasion and apoptosis of PVTT cells and to explore its possible mechanisms, which was expected to lay a foundation for ascertaining the mechanism underlying the portal vein metastasis of HCC.Methods： Peripheral blood and portal vein blood were collected from patients with HCC, and the sera from these two sources were used to culture the PVTT-originated HCC cell line CSQT-2. The cells were collected after 24 h, and flow cytometry was performed to detect cell proliferation, cell cycle stages and apoptosis. Transwell migration and invasion assays were applied to detect the metastasis and invasion of the cells in each group. The changes in the expression of MMP-2 and MMP-9 in cells were detected via Western blotting. The contents of IL-12, IFN-γ, IL-1β, IL-2 and TNF-α in the two groups of sera were quantified using corresponding kits. Results： Compared with the group of cells cultured with peripheral serum, the cells cultured with portal vein serum showed significantly lower apoptosis（P〈0.01）, significantly enhanced cell metastasis and invasion（P〈0.01）, whereas cell proliferation and the stages of the cell cycle did not differ significantly（P〉0.05）. A significantly increased expression level of MMP-2 has been observed in tumor cells treated portal vein serum. In addition, compared with peripheral serum, the content of IL-12 was significantly decreased in portal vein serum（P〈0.05）, while the contents of IFN-γ, IL-1β, IL-2, and TNF-α did not differ significantly（P〈0.05）. Conclusions： Portal vein serum from HCC patients could inhibit the apoptosis of PVTT-originated HCC cells and promote cell metastasis and invasion. This effect may be related to the lower level of IL-12 in portal vein serum.
基金supported by the National Research Program of China(Grant Nos.2017YFA0505803 and 2017YFC0908100)the State Key Project for Infectious Diseases(Grant Nos.2018ZX10732202-001 and 2018ZX10302207-004)the National Natural Science Foundation of China(Grant Nos.81790633,61922047,and 81902412).
文摘The Wnt/β-catenin signaling pathway regulates many aspects of tumor biology,and many studies have focused on the role of this signaling pathway in tumor cells.However,it is now clear that tumor development and metastasis depend on the two-way interaction between cancer cells and their environment,thereby forming a tumor microenvironment(TME).In this review,we discuss how Wnt/β-catenin signaling regulates cross-interactions among different components of the TME,including immune cells,stem cells,tumor vasculature,and noncellular components of the TME in hepatocellular carcinoma.We also investigate their preclinical and clinical insights for primary liver cancer intervention,and explore the significance of using Wnt/β-catenin mutations as a biomarker to predict resistance in immunotherapy.
基金supported by the National Natural Science Foundation of China (81902904, 82073411, 81830054, and 81988101)the China Postdoctoral Science Foundation (2019M661373)
文摘Cancers of the digestive system(DS),including esophageal,gastric,colorectal,liver,and pancreatic can-cers,have a high incidence and mortality worldwide.Current cancer models cannot faithfully recapitu-late the critical features of the original tumor,resulting in the failure of translation from basic research into clinical practice.More advanced cancer models are in urgent need of pathogenesis exploration and anticancer medicine development.Organoids are in vitro cultured three dimensional(3D)self-organizing organotypic structures derived from tissues and pluripotent stem cells,which faithfully mimic the histological features and preserve the genetic heterogeneity of the original tissues.Both normal and malignant organoids can now be efficiently established from the DS tissues of patients.In this review,we summarize the general methods to generate human DS organoids and their applications as a novel model in basic cancer research,preclinical medical practice,and precision medicine.
基金This research was supported by grants from National Natural Science Foundation of China （81521091）, the Shanghai Key Laboratory of Hepatobiliary Tumor Biology, and the Ministry of Education （MOE） Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer.
文摘In recent decades, diseases concerning the gut microbiota have presented some of the most serious public health problems worldwide. The human host＇s physiological status is influenced by the intestinal microbiome, thus integrating external factors, such as diet, with genetic and immune signals. The notion that chronic inflammation drives carcinogenesis has been widely established for various tissues. It is surprising that the role of the microbiota in tumorigenesis has only recently been recognized, given that the presence of bacteria at tumor sites was first described more than a century ago. Extensive epidemiological studies have revealed that there is a strong link between the gut microbiota and some common cancers. However, the exact molecular mechanisms linking the gut microbiota and cancer are not yet fully understood. Changes to the gut microbiota are instrumental in determining the occurrence and progression of hepatocarcinoma, chronic liver diseases related to alcohol, nonalcoholic fatty liver disease （NAFLD）, and cirrhosis. To be specific, the gut milieu may play an important role in systemic inflammation, endotoxemia, and vasodilation, which leads to complications such as spontaneous bacterial peritonitis and hepatic encephalopathy. Relevant animal studies involving gut microbiota manipulations, combined with observational studies on patients with NAFLD, have provided ample evidence pointing to the contribution of dysbiosis to the pathogenesis of NAFLD. Given the poor prognosis of these clinical events, their prevention and early management are essential. Studies of the composition and function of the gut microbiota could shed some light on understanding the prognosis because the microbiota serves as an essential component of the gut milieu that can impact the aforementioned clinical events. As far as disease management is concerned, probiotics may provide a novel direction for therapeutics for hepatocellular carcinoma （HCC） and NAFLD, given that probiotics function as a type of medicine that can improve human health by regulating the immune system. Here, we provide an overview of the relationships among the gut microbiota, tumors, and liver diseases. In addition, considering the significance of bacterial homeostasis, we discuss probiotics in this article in order to guide treatments for related diseases.
文摘Cancer is a global public health threat and a leading cause of death in China.In 2020,the number of new cancer cases around the world reached approximately 19.3 million,and about 10.0 million cancer-related deaths occurred.Tumor diagnosis and treatment remain a huge challenge due to the diversity of cancer etiology,the complicated mechanism and long process of tumorigenesis,and the significant heterogeneity between individuals.As cancer is a systemic disease,tumor diagnosis is multidisciplinary.Tumor treatment has evolved from the initial conventional surgery,radiotherapy,and chemotherapy to the current multimethod and multidisciplinary comprehensive treatment.With the continuous deepening and advancement of research in disease biology,we have gained a better understanding of cancer.
基金supported by the National Natural Science Foundation of China(Nos.82273176,81902894,81972779,81903036,81622039,81830054,91859205,and 81988101)Chinese National Key Project(No.2018ZX10723204-006-003)+1 种基金Shanghai Municipal Commission of Education Project(No.201901070007E00065)Program of Shanghai Academic Research Leader(No.23XD1404800).
文摘Crosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression.A tumor subpopulation called liver cancer stem cells(CSCs)significantly accounts for the initiation,metastasis,therapeutic resistance,and recurrence of liver cancer.Emerging evidence demonstrates that the interaction between liver CSCs and immune cells plays a crucial role in shaping an immunosuppressive microenvironment and determining immunotherapy responses.This review sheds light on the bidirectional crosstalk between liver CSCs and immune cells for liver cancer progression,as well as the underlying molecular mechanisms after presenting an overview of liver CSCs characteristic and their microenvironment.Finally,we discuss the potential application of liver CSCs-targeted immunotherapy for liver cancer treatment.
基金supported by the Institute of Basic Medical Sciences,the Chinese Academy of Medical Sciences,the Neuroscience Center,the China Human Brain Banking Consortium,the ALS Brain Bank Initiative in China,and Home for Heal and Help for their assistance in this paper.This work was supported by the National Natural Science Foundation of China(82141204,82061138007,82221004,82041008)the National Key Research and Development Project of China(2020YFA0707803)+2 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)grant(2021-1-I2M-035,2021-1-I2M-034 and 2021-CAMS-JZ002)Bill&Melinda Gates Foundation(INV-006371)Key-Area Research and Development Program of Guangdong Province(2022B1111020005).
文摘Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes.Herein,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients.Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans.Minor and limited phenotypic and histopathological changes were observed in adult models.Systemic proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio levels.Furthermore,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic dysfunction.In contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.41730103&41805129).
文摘This study presents atmospheric N_(2)O mole fractions measured from discrete air samples from 2001 to 2018 at Mt.Waliguan(WLG)station(36°17′N,100°54′E,3816 m asl)in China,which is a global background station of the World Meteorological Organization/Global Atmosphere Watch Programme(WMO/GAW)in central Eurasia.Observed N_(2)O characteristics of annual means,interannual variability,and seasonal cycles were investigated.Our results show that N_(2)O at WLG possess a distinct increasing trend and a statistically significant seasonal cycle,with an average growth rate of 0.9±0.01 ppb yr^(−1)(1σ)(1ppb=10^(−9)),which is close to the global mean.The detrended seasonal cycle shows a trough of−0.25±0.04(1σ)ppb in June and a peak of 0.13±0.07(1σ)ppb in September,with an amplitude of 0.38 ppb.The pattern is due to combined effects of variation in surface sources,vertical convection within the boundary layer and stratosphere to troposphere transportation(STE).The interannual variability in growth rate was partly driven by quasi-biennial oscillation(QBO)of tropical zonal wind through stratospheric transport into the troposphere.According to a cluster analysis of back trajectories and the corresponding average N_(2)O load,most air masses cover arid and semi-arid areas in inner Asia with low N_(2)O emissions,indicating that the atmospheric N_(2)O at the WLG represents the background N_(2)O level in central Eurasia.
基金This study was supported by the National Natural Science Foundation of China(Grant Nos.52272125 and 51902271)the Fundamental Research Funds for the Central Universities(Grant Nos.2682021CX116,2682020CX07,and 2682020CX08)Sichuan Science and Technology Program(Grant Nos.2020YJ0259,2020YJ0072,and 2021YFH0163).We would like to thank Analysis and Testing Center of Southwest Jiaotong University for the assistance on material characterization.
文摘Various material design strategies have been developed to enhance photocatalytic performance of TiO_(2).However,no report is available on applications of the photopiezocatalysis strategy on TiO_(2)due to its lack of piezoelectricity.Here we developed a low-temperature molten salt etching process to create rutile TiO_(2)nanoparticles by etching[MgO_(6)]octahedrons away from MgTiO_(3)by molten NH_(4)Cl,during which a lattice distortion occurred in TiO_(2).The lattice distortion broke the structure symmetry of rutile TiO_(2)and subsequently endowed these rutile TiO_(2)nanoparticles with an unusual piezoelectric response with the maximum effective piezoelectric coefficient(d_(33))of~41.6 pm/V,which had not previously been found in TiO_(2)photocatalysts.Thus,the photopiezocatalysis strategy was applied for the first time to enhance the photocatalytic performance of these TiO_(2)nanoparticles.The creation of lattice distortion to induce piezoelectricity could be extended to other photocatalysts that the photopiezocatalysis strategy has not been applied to and may generate novel functionalities for various technical applications.
基金supported by grants from the National Natural Science Foundation of China(No.82172895,81670516)the Funds for CreativeResearch Groups of China(No.81521091)the Clinical Research Plan of Shanghai Hospital Development Center(SHDC,China)(No.SHDC2020CR2011A).
文摘The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative capacities.The hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events of cell proliferation,migration,and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription factors.Studies on liver development and diseases have revealed that SRY-related high-mobility group box 9(SOx9)plays an important role in liver embryogenesis and the progression of hepatobiliary diseases.sox9 is not only a master regulator of cell fate determination and tissue morphogenesis,but also regulates various biological features of cancer,including cancer stemness,invasion,and drug resistance,making Sox9 a potential biomarker for tumor prognosis and progression.This review systematically summarizes the latest findings of sox9 in hepatobiliary development,homeostasis,and disease.We also highlight the value of sox9 as a novel biomarker and potential target for the clinical treatment of major liverdiseases.
基金the National Natural Science Foundation of China(Nos.32070584,81830028,31771398,82222016,and 8207040100)the Zhejiang Provincial Natural Science Foundation of China(No.LZ19C060001)the Fundamental Research Funds for the Central Universities(No.2019QNA6001)。
文摘Auditory neuropathy spectrum disorder(ANSD)represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function,but with the preservation of outer hair cell function.ANSD represents up to 15%of individuals with hearing impairments.Through mutation screening,bioinformatic analysis and expression studies,we have previously identified several apoptosis-inducing factor(AIF)mitochondria-associated 1(AIFM1)variants in ANSD families and in some other sporadic cases.Here,to elucidate the pathogenic mechanisms underlying each AIFM1 variant,we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system and constructed AIF-wild type(WT)and AIF-mutant(mut)(p.T260A,p.R422W,and p.R451Q)stable transfection cell lines.We then analyzed AIF structure,coenzyme-binding affinity,apoptosis,and other aspects.Results revealed that these variants resulted in impaired dimerization,compromising AIF function.The reduction reaction of AIF variants had proceeded slower than that of AIF-WT.The average levels of AIF dimerization in AIF variant cells were only 34.5%-49.7%of that of AIF-WT cells,resulting in caspase-independent apoptosis.The average percentage of apoptotic cells in the variants was 12.3%-17.9%,which was significantly higher than that(6.9%-7.4%)in controls.However,nicotinamide adenine dinucleotide(NADH)treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells.Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD,and introduce NADH as a potential drug for ANSD treatment.Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
基金supported by the National Natural Science Foundation of China(81472772)the Natural Science Foundation of Shanghai(14ZR1408900)the Major National Science and Technology Projects(2018ZX10302207).
文摘Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods.However,these methods have their own deficiencies that restrict the therapeutic applications of such induced hepatocytes.In this study,we present a transgene-free,highly efficient chemical-induced direct reprogramming approach to generate hepatocyte-like cells from mouse embryonic fibroblasts(MEFs).Using a small molecule cocktail(SMC)as an inducer,MEFs can be directly reprogrammed into hepatocyte-like cells,bypassing the intermediate stages of pluripotent and immature hepatoblasts.These chemical-induced hepatocyte-like cells(ciHeps)closely resemble mature primary hepatocytes in terms of morphology,biological behavior,gene expression patterns,marker expression levels,and hepatic functions.Furthermore,transplanted ciHeps can integrate into the liver,promote liver regeneration,and improve survival rates in mice with acute liver damage.ciHeps can also ameliorate liver fibrosis caused by chronic injuries and enhance liver function.Notably,ciHeps exhibit no tumorigenic potential either in vitro or in vivo.Mechanistically,SMC-induced mesenchymal-to-epithelial transition and suppression of SNAI1 contribute to the fate conversion of fibroblasts into ciHeps.These results indicate that this transgene-free,chemical-induced direct reprogramming technique has the potential to serve as a valuable means of producing alternative hepatocytes for both research and therapeutic purposes.Additionally,this method also sheds light on the direct reprogramming of other cell types under chemical induction.
基金supported by National Natural Science Foundation of China(61902116).
文摘Recently,convolutional neural networks(CNNs)have achieved excellent performance for the recommendation system by extracting deep features and building collaborative filtering models.However,CNNs have been verified susceptible to adversarial examples.This is because adversarial samples are subtle non-random disturbances,which indicates that machine learning models produce incorrect outputs.Therefore,we propose a novel model of Adversarial Neural Collaborative Filtering with Embedding Dimension Correlations,named ANCF in short,to address the adversarial problem of CNN-based recommendation system.In particular,the proposed ANCF model adopts the matrix factorization to train the adversarial personalized ranking in the prediction layer.This is because matrix factorization supposes that the linear interaction of the latent factors,which are captured between the user and the item,can describe the observable feedback,thus the proposed ANCF model can learn more complicated representation of their latent factors to improve the performance of recommendation.In addition,the ANCF model utilizes the outer product instead of the inner product or concatenation to learn explicitly pairwise embedding dimensional correlations and obtain the interaction map from which CNNs can utilize its strengths to learn high-order correlations.As a result,the proposed ANCF model can improve the robustness performance by the adversarial personalized ranking,and obtain more information by encoding correlations between different embedding layers.Experimental results carried out on three public datasets demonstrate that the ANCF model outperforms other existing recommendation models.
基金National Natural Science Foundation of China(U21A20376,81988101,81790633 and 81830054)National Science Foundation of Shanghai(21XD1404600,17ZR143800,21JC1406600 and 22140901000)Project of Shanghai Municipal Commission of Health(2022LJ024).
文摘It is widely recognized that tumor immune microenvironment(TIME)plays a crucial role in tumor progression,metastasis,and therapeutic response.Despite several noninvasive strategies have emerged for cancer diagnosis and prognosis,there are still lack of efective radiomic-based model to evaluate TIME status,let alone predict clinical outcome and immune checkpoint inhibitor(ICIs)response for hepatocellular carcinoma(HCC).In this study,we developed a radiomic model to evaluate TIME status within the tumor and predict prognosis and immunotherapy response.A total of 301 patients who underwent magnetic resonance imaging(MRI)examinations were enrolled in our study.The intra-tumoral expression of 17 immune-related molecules were evaluated using co-detection by indexing(CODEX)technology,and we construct Immunoscore(IS)with the least absolute shrinkage and selection operator(LASSO)algorithm and Cox regression method to evaluate TIME.Of 6115 features extracted from MRI,fve core features were fltered out,and the Radiomic Immunoscore(RIS)showed high accuracy in predicting TIME status in testing cohort(area under the curve=0.753).More importantly,RIS model showed the capability of predicting therapeutic response to anti-programmed cell death 1(PD-1)immunotherapy in an independent cohort with advanced HCC patients(area under the curve=0.731).In comparison with previously radiomicbased models,our integrated RIS model exhibits not only higher accuracy in predicting prognosis but also the potential guiding signifcance to HCC immunotherapy.
基金supported by the grants of the National Natural Science Foundation of China(82222016,8235005,82271189).
文摘Objective:To make an overview of global research trends in the etiology of auditory neuropathy(AN)over the past 30 years using a bibliometric approach.Methods:Bibliometric analyses were conducted by GraphPad Prism 9.0,Citespace 6.2.R2,and an online analysis platform to analyze and visualize publications related to etiology of AN from the Web of Science Core Collection(WoSCC)database from 1996 to 2022.Additionally,genetic factors in human AN were analyzed.Results:In total,604 original articles and reviews related to the etiology of AN from the WoSCC were included for bibliometric analysis.The results showed that annual publications and trend on etiology of AN increased linearly from 2000.Among them,the United States and China published nearly 400 records(40.32%).From the 604 records,a total of 752 keywords and 10 clustered network maps were extracted by Citespace,and‘mutations’was among the top 10 keywords.Analysis of genetic factors found that more than 30 genes were related to AN,and the latest burst occurred in 2022.Conclusion:The bibliometric analysis mapped the global research trends and analyzed hotspots for future.The results indicated that the annual publications increased linearly from 2000.Notably,there was a burst in genetic factors in 2022,which identified that genetic factor would remain a focus of future research.
基金This work was supported by the National Key Research and Development Program of China(2017YFA0105804)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010000)+8 种基金the National Key Research and Development Program of China(2018YFC2000100,2017YFA0103304,2017YFA0102802,2018YFA0107203)the National Natural Science Foundation of China(81670897,81625009,91749202.81861168034,81921006,31671429,91949209,91749123,81671377,81822018,81870228,81922027,81701388,81601233)the Program of the Beijing Municipal Science and Technology Commission(Z191100001519005)Bejing Natural Science Foun-dation(Z190019)Bejing Municipal Commission of Health and Family Planning(PXM2018026283_000002)Advanced Innovation Center for Human Brain Protection(3500-1192012)the Key Research Program of the Chinese Academy of Sciences(KFZD-SW-221)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08),Youth Innovation Promotion Association of CAS(2016093)the State Key Laboratory of Membrane Biology and the State Key Laboratory of Stem Cell and Reproductive Biology.
文摘Age-associated changes in immune cells have been linked to an increased risk for infection.However,a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking.Here,we combined scRNA-seq,mass cytometry and sCATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19.We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector,cytotoxic,exhausted and reg-ulatory cells,along with increased late natural killer cells,age-associated B cells,inflammatory monocytes and age-associated dendritic cells.In addition,the expression of genes,which were implicated in coron-avirus susceptibility,was upregulated in a cell subtype-specific manner with age.Notably,COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senes-cence.Therefore,these findings suggest that a dysreg-ulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
