Fusobacterium nucleatum(F.nucleatum)is an early pathogenic colonizer in periodontitis,but the host response to infection with this pathogen remains unclear.In this study,we built an F.nucleatum infectious model with h...Fusobacterium nucleatum(F.nucleatum)is an early pathogenic colonizer in periodontitis,but the host response to infection with this pathogen remains unclear.In this study,we built an F.nucleatum infectious model with human periodontal ligament stem cells(PDLSCs)and showed that F.nucleatum could inhibit proliferation,and facilitate apoptosis,ferroptosis,and inflammatory cytokine production in a dose-dependent manner.The F.nucleatum adhesin Fad A acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β,IL-6 and IL-8.Further study showed that Fad A could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways.Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F.nucleatum infection.NFκB1 and NFκB2 upregulated after 3 h of F.nucleatum-infection,and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time.Using computational drug repositioning analysis,we predicted and validated that two potential drugs(piperlongumine and fisetin)could attenuate the negative effects of F.nucleatum-infection.Collectively,this study unveils the potential pathogenic mechanisms of F.nucleatum and the host inflammatory response at the early stage of F.nucleatum infection.展开更多
Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors ...Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy;they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.展开更多
In the previous research,when the economic factor forecasting solution of Urbanization was used into practice,the users almost always ignored the effects of the lagged economic development factors.The accuracy of the ...In the previous research,when the economic factor forecasting solution of Urbanization was used into practice,the users almost always ignored the effects of the lagged economic development factors.The accuracy of the forecasting should be decreased seriously by this way.In this paper,taking Gansu province as an example,the authors try to improve the forecasting accuracy on the basis of the unrestricted PDL(Polynomial Distributed Lag)Models.In the context,the ARIMA Models and CPPS software are also applied to finish the forecasting more accurately.展开更多
基金foundation support of the National Natural Science Foundation of China(Grant No.82071122)the Program of Taishan Young from Shandong Province+3 种基金Major Innovation Projects in Shandong Province(No.2021SFGC0502)Oral Microbiome Innovation Team of Young Scientist Project of Shandong Province(Grant No.2020KJK001)and Jinan City(2021GXRC021)The National High-level Young Scientist Project Foundation(2019)Excellent Young Scientist Foundation of Shandong Province(Grant No.ZR202102230369)。
文摘Fusobacterium nucleatum(F.nucleatum)is an early pathogenic colonizer in periodontitis,but the host response to infection with this pathogen remains unclear.In this study,we built an F.nucleatum infectious model with human periodontal ligament stem cells(PDLSCs)and showed that F.nucleatum could inhibit proliferation,and facilitate apoptosis,ferroptosis,and inflammatory cytokine production in a dose-dependent manner.The F.nucleatum adhesin Fad A acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β,IL-6 and IL-8.Further study showed that Fad A could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways.Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F.nucleatum infection.NFκB1 and NFκB2 upregulated after 3 h of F.nucleatum-infection,and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time.Using computational drug repositioning analysis,we predicted and validated that two potential drugs(piperlongumine and fisetin)could attenuate the negative effects of F.nucleatum-infection.Collectively,this study unveils the potential pathogenic mechanisms of F.nucleatum and the host inflammatory response at the early stage of F.nucleatum infection.
文摘Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy;they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.
文摘In the previous research,when the economic factor forecasting solution of Urbanization was used into practice,the users almost always ignored the effects of the lagged economic development factors.The accuracy of the forecasting should be decreased seriously by this way.In this paper,taking Gansu province as an example,the authors try to improve the forecasting accuracy on the basis of the unrestricted PDL(Polynomial Distributed Lag)Models.In the context,the ARIMA Models and CPPS software are also applied to finish the forecasting more accurately.
