In the modern economy,startups are not only significant drivers of innovation and technological progress but also key players in addressing employment issues and promoting economic diversification.However,startups oft...In the modern economy,startups are not only significant drivers of innovation and technological progress but also key players in addressing employment issues and promoting economic diversification.However,startups often face substantial operational risks and uncertainties in their early stages,especially regarding financing.To uncover the impact of different resource allocations and strategic choices on financing success,this study proposes a predictive method based on the latent Dirichlet allocation(LDA)topic model and deep neural networks through an in-depth analysis of startup financing cases.We systematically collected description text data from 2,000 startups and extracted text features from these descriptions using the LDA topic model.These features,combined with several traditional numerical indicators such as industry,product type,technology type,number of employees,and company size,were used to train a deep neural network to predict startup financing outcomes.The experimental results show that the prediction performance based on the LDA topic model is significantly better than that of traditional models relying solely on numerical data.This highlights the importance of text features in predicting the success of startup financing.展开更多
Understanding mercury(Hg)metabolism and exposure pathways in pregnant women is essential for protecting fetal health.However,most previous studies have relied primarily on Hg concentrations in single biomarkers,limiti...Understanding mercury(Hg)metabolism and exposure pathways in pregnant women is essential for protecting fetal health.However,most previous studies have relied primarily on Hg concentrations in single biomarkers,limiting insight into in vivo metabolic differences and maternal-fetal transfer,especially regarding source-specific MeHg metabolism.This study applies compound-specific stable isotope analysis to investigate total Hg(THg)and methylmercury(MeHg)concentrations and isotopic signatures in rice and maternal biomarkers from the Wanshan Hg mining area,China.Widespread mass-dependent fractionation(MDF)was observed across different biomarkers.The MDF of THg was driven by internal redistribution and demethylation of MeHg,while the MDF of MeHg specifically reflected metabolic demethylation processes in the gut and brain.In contrast,no mass-independent fractionation(MIF)was observed during maternal or transplacental THg transfer,suggesting thatΔ199Hg values in maternal biomarkers reflect food-source signals.This study identifies the biomarker-specific contribution of dietary sources:MeHg isotope mixing models revealed that rice contributed a higher proportion of Hg in maternal blood than in hair,comparable to that in placenta and cord blood.Comparisons with previously reported fish-derived MeHg isotopes suggest that rice-derived MeHg undergoes preferential demethylation and elimination,highlighting the complexity of in vivo Hg dynamics.The use of both THg and MeHg isotopes in biomarkers enables more precise tracing of dietary Hg sources.These findings highlight the value of multi-biomarker isotope analysis for tracing Hg sources and improving exposure assessments.展开更多
The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumo...The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels(DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful antitumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.展开更多
Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response.However,single blockade of these pathways is usually ineffective because of the complex crosstalk a...Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response.However,single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways.The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications.To circumvent this issue,we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle(PNM)for cancer therapy.PNM was engineered by integrating the PI3K/m TOR inhibitor PF-04691502(PF)and the broad spectrum CDK inhibitor flavopiridol(Flav)into a single nanoplatform,which showed tumor-specific accumulation,activation and deep penetration in response to the high glutathione(GSH)tumoral microenvironment.The codelivery of PF and Flav could trigger gasdermin E(GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response.Furthermore,the combination of PNM-induced immunogenic pyroptosis with antiprogrammed cell death-1(a PD-1)immunotherapy further boosted the antitumor effect and prolonged the survival time of mice.Collectively,these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/m TOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.展开更多
基金Supported by Suzhou Key Laboratory of Artificial Intelligence and Social Governance Technologies(SZS2023007)Smart Social Governance Technology and Innovative Application Platform(YZCXPT2023101)the Innovation System of the Integration between Industry and Education for Smart Governance(CJRH2024101)。
文摘In the modern economy,startups are not only significant drivers of innovation and technological progress but also key players in addressing employment issues and promoting economic diversification.However,startups often face substantial operational risks and uncertainties in their early stages,especially regarding financing.To uncover the impact of different resource allocations and strategic choices on financing success,this study proposes a predictive method based on the latent Dirichlet allocation(LDA)topic model and deep neural networks through an in-depth analysis of startup financing cases.We systematically collected description text data from 2,000 startups and extracted text features from these descriptions using the LDA topic model.These features,combined with several traditional numerical indicators such as industry,product type,technology type,number of employees,and company size,were used to train a deep neural network to predict startup financing outcomes.The experimental results show that the prediction performance based on the LDA topic model is significantly better than that of traditional models relying solely on numerical data.This highlights the importance of text features in predicting the success of startup financing.
基金supported by the National Natural Science Foundation of China(42207487,U1812403)the Guizhou Provincial Major Scientific and Technological Program([2025]002)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Y2021106).
文摘Understanding mercury(Hg)metabolism and exposure pathways in pregnant women is essential for protecting fetal health.However,most previous studies have relied primarily on Hg concentrations in single biomarkers,limiting insight into in vivo metabolic differences and maternal-fetal transfer,especially regarding source-specific MeHg metabolism.This study applies compound-specific stable isotope analysis to investigate total Hg(THg)and methylmercury(MeHg)concentrations and isotopic signatures in rice and maternal biomarkers from the Wanshan Hg mining area,China.Widespread mass-dependent fractionation(MDF)was observed across different biomarkers.The MDF of THg was driven by internal redistribution and demethylation of MeHg,while the MDF of MeHg specifically reflected metabolic demethylation processes in the gut and brain.In contrast,no mass-independent fractionation(MIF)was observed during maternal or transplacental THg transfer,suggesting thatΔ199Hg values in maternal biomarkers reflect food-source signals.This study identifies the biomarker-specific contribution of dietary sources:MeHg isotope mixing models revealed that rice contributed a higher proportion of Hg in maternal blood than in hair,comparable to that in placenta and cord blood.Comparisons with previously reported fish-derived MeHg isotopes suggest that rice-derived MeHg undergoes preferential demethylation and elimination,highlighting the complexity of in vivo Hg dynamics.The use of both THg and MeHg isotopes in biomarkers enables more precise tracing of dietary Hg sources.These findings highlight the value of multi-biomarker isotope analysis for tracing Hg sources and improving exposure assessments.
基金financially supported by National Natural Science Foundation of China(51703187,81874131,and 81672668)the Chongqing Talent Plan for Young Top Notch Talents(CQYC202005029,China)+2 种基金Major State Basic Research Development Program of China(2017YFA0205201 and 2018YFA0107301)National Key Research and Development Program(2017YFSF090107,China)the Hubei Province Natural Science Funds for Distinguished Young Scholar 2017CFA062。
文摘The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels(DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful antitumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.
基金financially supported by National Natural Science Foundation of China(82072996,81874131,51703187)the National Key Research and Development Program(2017YFSF090107,China)+3 种基金the Hubei Province Natural Science Funds for Distinguished Young Scholar(2017CFA062,China)Innovative research team of high-level local universities in Shanghai(ZLCX20180500,China)Chongqing Talents of Exceptional Young Talents Project(CQYC202005029 and cstc2021ycjh-bgzxm0061,China)the Venture&Innovation Support Program for Chongqing Overseas Returnees(cx2021017)。
文摘Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response.However,single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways.The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications.To circumvent this issue,we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle(PNM)for cancer therapy.PNM was engineered by integrating the PI3K/m TOR inhibitor PF-04691502(PF)and the broad spectrum CDK inhibitor flavopiridol(Flav)into a single nanoplatform,which showed tumor-specific accumulation,activation and deep penetration in response to the high glutathione(GSH)tumoral microenvironment.The codelivery of PF and Flav could trigger gasdermin E(GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response.Furthermore,the combination of PNM-induced immunogenic pyroptosis with antiprogrammed cell death-1(a PD-1)immunotherapy further boosted the antitumor effect and prolonged the survival time of mice.Collectively,these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/m TOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.
