Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underp...Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.展开更多
Wireless Sensor Network(WSNs)consists of a group of nodes that analyze the information from surrounding regions.The sensor nodes are responsible for accumulating and exchanging information.Generally,node local-ization...Wireless Sensor Network(WSNs)consists of a group of nodes that analyze the information from surrounding regions.The sensor nodes are responsible for accumulating and exchanging information.Generally,node local-ization is the process of identifying the target node’s location.In this research work,a Received Signal Strength Indicator(RSSI)-based optimal node localization approach is proposed to solve the complexities in the conventional node localization models.Initially,the RSSI value is identified using the Deep Neural Network(DNN).The RSSI is conceded as the range-based method and it does not require special hardware for the node localization process,also it consumes a very minimal amount of cost for localizing the nodes in 3D WSN.The position of the anchor nodes is fixed for detecting the location of the target.Further,the optimal position of the target node is identified using Hybrid T cell Immune with Lotus Effect Optimization algorithm(HTCI-LEO).During the node localization process,the average localization error is minimized,which is the objective of the optimal node localization.In the regular and irregular surfaces,this hybrid algorithm effectively performs the localization process.The suggested hybrid algorithm converges very fast in the three-dimensional(3D)environment.The accuracy of the proposed node localization process is 94.25%.展开更多
Objective： To study the relationship of local immunity in the female genital tract with the clinical course of Nongonococcal Urethritis （NGU）. Methods： We collected cervical secretions from patients and examined l...Objective： To study the relationship of local immunity in the female genital tract with the clinical course of Nongonococcal Urethritis （NGU）. Methods： We collected cervical secretions from patients and examined levels of SIgA and IFN- γ. Results： Levels of SIgA and IFN- γ in the infected group were lower than those in the uninfected group, P1〈0.05 and P2〈0.05. The level of SIgA and IFN- γ in C.t,UU and C.t＋UU infected groups were not significantly different. Comparing the negative-changed group with thenonnegative-changed group, the level of SIgA and IFN-γ was 39.22±20.04mg/L and 103.19±29.94pg/ml, 26.00±10.56mg/I and 88.21±15.10pg/ml, P1〉0.05 and P2〉0.05. Conclusion： SIgA and IFN-γ secreted by genital tractmucosa may help prevent and resist local NGU infection.However, the effect is limited, and is insufficient to eliminate infection completely and prevent reinfection.展开更多
Hepatocellular carcinoma(HCC)is characterized by high heterogeneity in both intratumoral and interpatient manners.While interpatient heterogeneity is related to personalized therapy,intratumoral heterogeneity(ITH)larg...Hepatocellular carcinoma(HCC)is characterized by high heterogeneity in both intratumoral and interpatient manners.While interpatient heterogeneity is related to personalized therapy,intratumoral heterogeneity(ITH)largely influences the efficacy of therapies in individuals.ITH contributes to tumor growth,metastasis,recurrence,and drug resistance and consequently limits the prognosis of patients with HCC.There is an urgent need to understand the causes,characteristics,and consequences of tumor heterogeneity in HCC for the purposes of guiding clinical practice and improving survival.Here,we summarize the studies and technologies that describe ITH in HCC to gain insight into the origin and evolutionary process of heterogeneity.In parallel,evidence is collected to delineate the dynamic relationship between ITH and the tumor ecosystem.We suggest that conducting comprehensive studies of ITH using single-cell approaches in temporal and spatial dimensions,combined with population-based clinical trials,will help to clarify the clinical implications of ITH,develop novel intervention strategies,and improve patient prognosis.展开更多
The power-law node degree distributions of peer-to-peer overlay networks make them extremely robust to random failures whereas highly vulnerable under intentional targeted attacks. To enhance attack survivability of t...The power-law node degree distributions of peer-to-peer overlay networks make them extremely robust to random failures whereas highly vulnerable under intentional targeted attacks. To enhance attack survivability of these networks, DeepCure, a novel heuristic immunization strategy, is proposed to conduct decentralized but targeted immunization. Different from existing strategies, DeepCure identifies immunization targets as not only the highly-connected nodes but also the nodes with high availability and/or high link load, with the aim of injecting immunization information into just right targets to cure. To better trade off the cost and the efficiency, DeepCure deliberately select these targets from 2-local neighborhood, as well as topologically-remote but semantically-close friends if needed. To remedy the weakness of existing strategies in case of sudden epidemic outbreak, DeepCure is also coupled with a local-hub oriented rate throttling mechanism to enforce proactive rate control. Extensive simulation results show that DeepCure outperforms its competitors, producing an arresting increase of the network attack tolerance, at a lower price of eliminating viruses or malicious attacks.展开更多
The Omicron variants have continued to cause severe acute respiratory syndrome coronavirus 2 infections.To better understand the anti-viral effects of vaccination on host-virus interactions during the outbreak of BA.2...The Omicron variants have continued to cause severe acute respiratory syndrome coronavirus 2 infections.To better understand the anti-viral effects of vaccination on host-virus interactions during the outbreak of BA.2.2 Omicron,we conducted RNA-seq transcriptome analysis on nasopharyngeal swabs from COVID-19 patients in Shanghai.This study was performed on selected cases from unvaccinated,fully vaccinated,and booster groups with the same founder virus infection background.We observed predominant immune cell chemotaxis and interleukin-1 production,as well as mucosal keratinization and epidermis development,in unvaccinated patients.In contrast,fully vaccinated subjects exhibited an obvious T-cell activation in the local immune response,whereas B-cell activation was higher in booster-vaccinated cases.In conclusion,our findings suggest that full or booster vaccination provides better adaptive immunity and relieve inflammation at the nasopharyngeal site,thereby reducing the risk of cytokine storm during breakthrough infection.展开更多
The rapid success of RNA vaccines in preventing SARS-CoV-2 has sparked interest in their use for cancer immunotherapy.Although many cancers originate in mucosal tissues,current RNA cancer vaccines are mainly administe...The rapid success of RNA vaccines in preventing SARS-CoV-2 has sparked interest in their use for cancer immunotherapy.Although many cancers originate in mucosal tissues,current RNA cancer vaccines are mainly administered non-mucosally.Here,we developed a non-invasive intranasal cancer vaccine utilizing circular RNA encapsulated in lipid nanoparticles to induce localized mucosal immune responses.This strategy elicited potent anti-tumor T cell responses in preclinical lung cancer models while mitigating the systemic adverse effects commonly associated with intravenous RNA vaccination.Specifically,type 1 conventional dendritic cells were indispensable for T cell priming post-vaccination,with both alveolar macrophages and type 1 conventional dendritic cells boosting antigen-specific T cell responses in lung tissues.Moreover,the vaccination facilitated the expansion of both endogenous and adoptive transferred antigen-specific T cells,resulting in robust anti-tumor efficacy.Single-cell RNA sequencing revealed that the vaccination reprograms endogenous T cells,enhancing their cytotoxicity and inducing a memory-like phenotype.Additionally,the intranasal vaccine can modulate the response of CAR-T cells to augment therapeutic efficacy against tumor cells expressing specific tumor-associated antigens.Collectively,the intranasal RNA vaccine strategy represents a novel and promising approach for developing RNA vaccines targeting mucosal malignancies.展开更多
文摘Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.
基金appreciation to King Saud University for funding this research through the Researchers Supporting Program number(RSPD2024R918),King Saud University,Riyadh,Saudi Arabia.
文摘Wireless Sensor Network(WSNs)consists of a group of nodes that analyze the information from surrounding regions.The sensor nodes are responsible for accumulating and exchanging information.Generally,node local-ization is the process of identifying the target node’s location.In this research work,a Received Signal Strength Indicator(RSSI)-based optimal node localization approach is proposed to solve the complexities in the conventional node localization models.Initially,the RSSI value is identified using the Deep Neural Network(DNN).The RSSI is conceded as the range-based method and it does not require special hardware for the node localization process,also it consumes a very minimal amount of cost for localizing the nodes in 3D WSN.The position of the anchor nodes is fixed for detecting the location of the target.Further,the optimal position of the target node is identified using Hybrid T cell Immune with Lotus Effect Optimization algorithm(HTCI-LEO).During the node localization process,the average localization error is minimized,which is the objective of the optimal node localization.In the regular and irregular surfaces,this hybrid algorithm effectively performs the localization process.The suggested hybrid algorithm converges very fast in the three-dimensional(3D)environment.The accuracy of the proposed node localization process is 94.25%.
文摘Objective： To study the relationship of local immunity in the female genital tract with the clinical course of Nongonococcal Urethritis （NGU）. Methods： We collected cervical secretions from patients and examined levels of SIgA and IFN- γ. Results： Levels of SIgA and IFN- γ in the infected group were lower than those in the uninfected group, P1〈0.05 and P2〈0.05. The level of SIgA and IFN- γ in C.t,UU and C.t＋UU infected groups were not significantly different. Comparing the negative-changed group with thenonnegative-changed group, the level of SIgA and IFN-γ was 39.22±20.04mg/L and 103.19±29.94pg/ml, 26.00±10.56mg/I and 88.21±15.10pg/ml, P1〉0.05 and P2〉0.05. Conclusion： SIgA and IFN-γ secreted by genital tractmucosa may help prevent and resist local NGU infection.However, the effect is limited, and is insufficient to eliminate infection completely and prevent reinfection.
基金National Natural Science Foundation of China,No.81871320 and No.81830089Zhejiang Provincial Natural Science Foundation of China,No.LR20H160002.
文摘Hepatocellular carcinoma(HCC)is characterized by high heterogeneity in both intratumoral and interpatient manners.While interpatient heterogeneity is related to personalized therapy,intratumoral heterogeneity(ITH)largely influences the efficacy of therapies in individuals.ITH contributes to tumor growth,metastasis,recurrence,and drug resistance and consequently limits the prognosis of patients with HCC.There is an urgent need to understand the causes,characteristics,and consequences of tumor heterogeneity in HCC for the purposes of guiding clinical practice and improving survival.Here,we summarize the studies and technologies that describe ITH in HCC to gain insight into the origin and evolutionary process of heterogeneity.In parallel,evidence is collected to delineate the dynamic relationship between ITH and the tumor ecosystem.We suggest that conducting comprehensive studies of ITH using single-cell approaches in temporal and spatial dimensions,combined with population-based clinical trials,will help to clarify the clinical implications of ITH,develop novel intervention strategies,and improve patient prognosis.
基金This research work is supported in part by the National High Technology Research and Development 863 Program of China under Grant No.2004AA104270.
文摘The power-law node degree distributions of peer-to-peer overlay networks make them extremely robust to random failures whereas highly vulnerable under intentional targeted attacks. To enhance attack survivability of these networks, DeepCure, a novel heuristic immunization strategy, is proposed to conduct decentralized but targeted immunization. Different from existing strategies, DeepCure identifies immunization targets as not only the highly-connected nodes but also the nodes with high availability and/or high link load, with the aim of injecting immunization information into just right targets to cure. To better trade off the cost and the efficiency, DeepCure deliberately select these targets from 2-local neighborhood, as well as topologically-remote but semantically-close friends if needed. To remedy the weakness of existing strategies in case of sudden epidemic outbreak, DeepCure is also coupled with a local-hub oriented rate throttling mechanism to enforce proactive rate control. Extensive simulation results show that DeepCure outperforms its competitors, producing an arresting increase of the network attack tolerance, at a lower price of eliminating viruses or malicious attacks.
基金supported by the National Natural Science Foundation of China(Nos 92169212 and 82161138018)Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response(20dz2260100)+1 种基金Key Discipline Construction Plan fromShanghaiMunicipalHealth Commission(GWV-10.1-XK01)ShanghaiMunicipal Science and Technology Major Project(HS2021SHZX001).
文摘The Omicron variants have continued to cause severe acute respiratory syndrome coronavirus 2 infections.To better understand the anti-viral effects of vaccination on host-virus interactions during the outbreak of BA.2.2 Omicron,we conducted RNA-seq transcriptome analysis on nasopharyngeal swabs from COVID-19 patients in Shanghai.This study was performed on selected cases from unvaccinated,fully vaccinated,and booster groups with the same founder virus infection background.We observed predominant immune cell chemotaxis and interleukin-1 production,as well as mucosal keratinization and epidermis development,in unvaccinated patients.In contrast,fully vaccinated subjects exhibited an obvious T-cell activation in the local immune response,whereas B-cell activation was higher in booster-vaccinated cases.In conclusion,our findings suggest that full or booster vaccination provides better adaptive immunity and relieve inflammation at the nasopharyngeal site,thereby reducing the risk of cytokine storm during breakthrough infection.
基金supported by the National Natural Science Foundation of China(82294366062 to X.L.)Beijing Municipal Science and Technology Commission(Z231100007223007 to G.C.Y.and X.L.)Shandong Provincial Natural Science Foundation(ZR2023LSW006toX.L.).
文摘The rapid success of RNA vaccines in preventing SARS-CoV-2 has sparked interest in their use for cancer immunotherapy.Although many cancers originate in mucosal tissues,current RNA cancer vaccines are mainly administered non-mucosally.Here,we developed a non-invasive intranasal cancer vaccine utilizing circular RNA encapsulated in lipid nanoparticles to induce localized mucosal immune responses.This strategy elicited potent anti-tumor T cell responses in preclinical lung cancer models while mitigating the systemic adverse effects commonly associated with intravenous RNA vaccination.Specifically,type 1 conventional dendritic cells were indispensable for T cell priming post-vaccination,with both alveolar macrophages and type 1 conventional dendritic cells boosting antigen-specific T cell responses in lung tissues.Moreover,the vaccination facilitated the expansion of both endogenous and adoptive transferred antigen-specific T cells,resulting in robust anti-tumor efficacy.Single-cell RNA sequencing revealed that the vaccination reprograms endogenous T cells,enhancing their cytotoxicity and inducing a memory-like phenotype.Additionally,the intranasal vaccine can modulate the response of CAR-T cells to augment therapeutic efficacy against tumor cells expressing specific tumor-associated antigens.Collectively,the intranasal RNA vaccine strategy represents a novel and promising approach for developing RNA vaccines targeting mucosal malignancies.
