While viral infections can disturb the host gut microbiome,the dynamic alterations in microbial composition following infection remain poorly characterized.This study identified SRV-8-infected monkeys and classified t...While viral infections can disturb the host gut microbiome,the dynamic alterations in microbial composition following infection remain poorly characterized.This study identified SRV-8-infected monkeys and classified them into five groups based on infection progression.16S rRNA amplicon sequencing revealed significant alterations in the relative and inferred absolute abundance of bacterial genera UCG-002,Agathobacter,Coprococcus,and Holdemanella during the early stage of SRV-8 infection,coinciding with provirus formation.These microbial shifts were accompanied by functional modifications in bacterial communities at the same stage.In contrast,ITS amplicon sequencing indicated no significant differences in fungal composition between healthy wild-type and SRV-8-infected monkeys.Spearman correlation analyses demonstrated close interactions between intestinal bacteria and fungi following SRV-8 infection.Additionally,SRV-8 seropositive groups exhibited significantly elevated mRNA expression levels of pro-inflammatory(TNF-α,IFN-γ,IL-1β,and IL-6)and anti-inflammatory(IL-10)cytokine genes,highlighting close associations between inflammatory cytokines and immune responses.Overall,these findings provide a comprehensive characterization of bacterial and fungal microbiota dynamics and inflammatory cytokine responses associated with SRV-8 infection,clarifying the pathobiological mechanisms underlying SRV-8 infection from the perspective of the gut microbiome.展开更多
To improve cancer pain management, the Medical Oncology Department of Sun Yat-sen University Cancer Center(SYSUCC) launched the Good Pain Management(GPM) Ward Program, which has been recognized by the Chinese Ministry...To improve cancer pain management, the Medical Oncology Department of Sun Yat-sen University Cancer Center(SYSUCC) launched the Good Pain Management(GPM) Ward Program, which has been recognized by the Chinese Ministry of Health and promoted throughout the nation. This retrospective case-control study was designed to evaluate the effectiveness of the program. Patients diagnosed with malignant solid tumors with bone metastasis were eligible. Patients who were admitted 6 months before the initiation of the GPM program were used as the control group, and patients admitted 6 months after the initiation of the program were used as the GPM group. The pain-reporting rate and pain management index(PMI) were calculated. The pain levels before and after pain management were compared. A total of 475 patients(244 in the control group and 231 in the GPM group) were analyzed. The pain-reporting rate of the GPM group was significantly higher than that of the control group(62.8% vs. 37.7%, P < 0.001). The PMI of the GPM group was significantly higher than that of the control group(0.083 vs.-0.261, P < 0.001). Therefore, the GPM Ward Program improved the pain management of cancer patients and provided experience for improving cancer pain management in the future.展开更多
Aging is closely related to physiology and disease development in animals.Gut microbiota varies with lifecycle and exerts profound influences on the host.To investigate gut microbial alterations during growth and matu...Aging is closely related to physiology and disease development in animals.Gut microbiota varies with lifecycle and exerts profound influences on the host.To investigate gut microbial alterations during growth and maturation,41 female cynomolgus monkeys(Macaca fascicularis)ranging in age from 1 month to 15 years were divided into four groups(infant,young,adult,and middle-aged).展开更多
Introduction:An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma(NPC).However,targeted therapy-related oncogenic mutations have not been fully evaluated.This study aim...Introduction:An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma(NPC).However,targeted therapy-related oncogenic mutations have not been fully evaluated.This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC.Methods:By using the SNaPshot assay,a rapid detection method,19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients.The associations between oncogenic mutations and clinicopathologic factors were analyzed.Results:Among 70 patients,12(17.1%) had mutations in 5 oncogenes:7(10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog(KIT) mutation,2(2.8%) had epidermal growth factor receptor(EGFR) mutation,1(1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase,catalytic subunit alpha(PIK3CA) mutation,1(1.4%) had Kirsten rat sarcoma viral oncogene homolog(KRAS) mutation,and 1(1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1(BRAF) mutations.No significant differences were observed between oncogenic mutations and clinicopathologic characteristics.Additionally,these oncogenic mutations were not associated with tumor recurrence or metastasis.Conclusions:Oncogenic mutations are present in NPC patients.The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.展开更多
Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, le...Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, leukemia, and lymphomas. Quantitative characterization of the interactions between CDK2 and its inhibitors at atomic level may provide a deep understanding of protein-inhibitor interactions and clues for more effective drug discovery. In this study, we have used the computational alanine scanning approach in combination with an efficient interaction entropy method to study the microscopic mechanism of binding between CDK2 and its 13 inhibitors. The total binding free energy from the method shows a correlation of 0.76?0.83 with the experimental values. The free energy component reveals two binding mode in the 13 complexes, namely van der Waals dominant, and electrostatic dominant. Decomposition of the total energy to per-residue contribution allows us to identify five hydrophobic residues as hot spots during the binding. Residues that are responsible for determining the strength of the binding were also analyzed.展开更多
The Rayleigh-Taylor instability at the weakly nonlinear(WN)stage in spherical geometry is studied by numerical simulation.The mode coupling processes are revealed.The results are consistent with the WN model based on ...The Rayleigh-Taylor instability at the weakly nonlinear(WN)stage in spherical geometry is studied by numerical simulation.The mode coupling processes are revealed.The results are consistent with the WN model based on parameter expansion,while higher order effects are found to be non-negligible.For Legendre mode perturbation Pn(cos B),the nonlinear saturation amplitude(NSA)of the fundamental mode decreases with the mode number n.When n is large,the spherical NSA is lower than the corresponding planar one.However,for large n,the planar NSA can be recovered by applying Fourier transformation to the bubble/spike near the equator and calculating the NSA of the converted trigonometric harmonic.展开更多
Interface width effect on the spherical Rayleigh–Taylor instability in the weakly nonlinear regime is studied by numerical simulations.For Legendre perturbation mode Pn with wave number Kn and interface half-width L,...Interface width effect on the spherical Rayleigh–Taylor instability in the weakly nonlinear regime is studied by numerical simulations.For Legendre perturbation mode Pn with wave number Kn and interface half-width L,the commonly adopted empirical linear growth rate formulaγnem(L)=γn/√1+KnL is found to be sufficient in spherical geometry.At the weakly nonlinear stage,the interface width affects the mode coupling processes.The development of the mode P2n is substantially influenced by the interface width.Moreover,the nonlinear saturation amplitude increases with the interface width.展开更多
The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing,delayed healing,susceptibility to infection,and elevated risk of reopening,highlighting the need for eff...The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing,delayed healing,susceptibility to infection,and elevated risk of reopening,highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels.Here,we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III(rhCol)by oxidative coupling of the catechol group using the H_(2)O_(2)/HRP catalytic system.The post-reactive hydrogel has a good porous structure,swelling rate,reasonable degradation,rheological and mechanical properties,and the catechol group and dopamine impart to the hydrogel tissue adhesiveness,antioxidant capacity,and excellent photothermal effects leading to superior in vitro antimicrobial activity.In addition,the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated.Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel.Wound closure,collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing.In summary,the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.展开更多
基金supported by the National Science and Technology Innovation 2030 Major Program(2021ZD0200900)National Key Research and Development Program of China(2022YFF0710901)+3 种基金National Natural Science Foundation of China(82021001,31825018)Biological Resources Program of the Chinese Academy of Sciences(KFJBRP-005)111 Project D18007a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘While viral infections can disturb the host gut microbiome,the dynamic alterations in microbial composition following infection remain poorly characterized.This study identified SRV-8-infected monkeys and classified them into five groups based on infection progression.16S rRNA amplicon sequencing revealed significant alterations in the relative and inferred absolute abundance of bacterial genera UCG-002,Agathobacter,Coprococcus,and Holdemanella during the early stage of SRV-8 infection,coinciding with provirus formation.These microbial shifts were accompanied by functional modifications in bacterial communities at the same stage.In contrast,ITS amplicon sequencing indicated no significant differences in fungal composition between healthy wild-type and SRV-8-infected monkeys.Spearman correlation analyses demonstrated close interactions between intestinal bacteria and fungi following SRV-8 infection.Additionally,SRV-8 seropositive groups exhibited significantly elevated mRNA expression levels of pro-inflammatory(TNF-α,IFN-γ,IL-1β,and IL-6)and anti-inflammatory(IL-10)cytokine genes,highlighting close associations between inflammatory cytokines and immune responses.Overall,these findings provide a comprehensive characterization of bacterial and fungal microbiota dynamics and inflammatory cytokine responses associated with SRV-8 infection,clarifying the pathobiological mechanisms underlying SRV-8 infection from the perspective of the gut microbiome.
文摘To improve cancer pain management, the Medical Oncology Department of Sun Yat-sen University Cancer Center(SYSUCC) launched the Good Pain Management(GPM) Ward Program, which has been recognized by the Chinese Ministry of Health and promoted throughout the nation. This retrospective case-control study was designed to evaluate the effectiveness of the program. Patients diagnosed with malignant solid tumors with bone metastasis were eligible. Patients who were admitted 6 months before the initiation of the GPM program were used as the control group, and patients admitted 6 months after the initiation of the program were used as the GPM group. The pain-reporting rate and pain management index(PMI) were calculated. The pain levels before and after pain management were compared. A total of 475 patients(244 in the control group and 231 in the GPM group) were analyzed. The pain-reporting rate of the GPM group was significantly higher than that of the control group(62.8% vs. 37.7%, P < 0.001). The PMI of the GPM group was significantly higher than that of the control group(0.083 vs.-0.261, P < 0.001). Therefore, the GPM Ward Program improved the pain management of cancer patients and provided experience for improving cancer pain management in the future.
基金supported by the National Key Research and Development Program of China(2018YFC1003000)National Natural Science Foundation of China(31825018)+2 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32060100)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)Shanghai Municipal Government Bureau of Science and Technology(18JC1410100)。
文摘Aging is closely related to physiology and disease development in animals.Gut microbiota varies with lifecycle and exerts profound influences on the host.To investigate gut microbial alterations during growth and maturation,41 female cynomolgus monkeys(Macaca fascicularis)ranging in age from 1 month to 15 years were divided into four groups(infant,young,adult,and middle-aged).
基金supported in part by a grant from the National High Technology Research and Development Program of China(No.2012AA02A501)
文摘Introduction:An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma(NPC).However,targeted therapy-related oncogenic mutations have not been fully evaluated.This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC.Methods:By using the SNaPshot assay,a rapid detection method,19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients.The associations between oncogenic mutations and clinicopathologic factors were analyzed.Results:Among 70 patients,12(17.1%) had mutations in 5 oncogenes:7(10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog(KIT) mutation,2(2.8%) had epidermal growth factor receptor(EGFR) mutation,1(1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase,catalytic subunit alpha(PIK3CA) mutation,1(1.4%) had Kirsten rat sarcoma viral oncogene homolog(KRAS) mutation,and 1(1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1(BRAF) mutations.No significant differences were observed between oncogenic mutations and clinicopathologic characteristics.Additionally,these oncogenic mutations were not associated with tumor recurrence or metastasis.Conclusions:Oncogenic mutations are present in NPC patients.The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.
基金supported by National Key R&D Program of China (No.2016YFA0501700)National Natural Science Foundation of China (No.21433004, No.31700646, No.91753103)+1 种基金Innovation Program of Shanghai Municipal Education Commission (201701070005E00020)NYU Global Seed Grant
文摘Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, leukemia, and lymphomas. Quantitative characterization of the interactions between CDK2 and its inhibitors at atomic level may provide a deep understanding of protein-inhibitor interactions and clues for more effective drug discovery. In this study, we have used the computational alanine scanning approach in combination with an efficient interaction entropy method to study the microscopic mechanism of binding between CDK2 and its 13 inhibitors. The total binding free energy from the method shows a correlation of 0.76?0.83 with the experimental values. The free energy component reveals two binding mode in the 13 complexes, namely van der Waals dominant, and electrostatic dominant. Decomposition of the total energy to per-residue contribution allows us to identify five hydrophobic residues as hot spots during the binding. Residues that are responsible for determining the strength of the binding were also analyzed.
基金National Natural Science Foundation of China under Grant Nos.11575033,11675026,and 11975053.
文摘The Rayleigh-Taylor instability at the weakly nonlinear(WN)stage in spherical geometry is studied by numerical simulation.The mode coupling processes are revealed.The results are consistent with the WN model based on parameter expansion,while higher order effects are found to be non-negligible.For Legendre mode perturbation Pn(cos B),the nonlinear saturation amplitude(NSA)of the fundamental mode decreases with the mode number n.When n is large,the spherical NSA is lower than the corresponding planar one.However,for large n,the planar NSA can be recovered by applying Fourier transformation to the bubble/spike near the equator and calculating the NSA of the converted trigonometric harmonic.
基金Supported by the National Natural Science Foundation of China(Grant Nos.11575033,11675026,and 11975053)。
文摘Interface width effect on the spherical Rayleigh–Taylor instability in the weakly nonlinear regime is studied by numerical simulations.For Legendre perturbation mode Pn with wave number Kn and interface half-width L,the commonly adopted empirical linear growth rate formulaγnem(L)=γn/√1+KnL is found to be sufficient in spherical geometry.At the weakly nonlinear stage,the interface width affects the mode coupling processes.The development of the mode P2n is substantially influenced by the interface width.Moreover,the nonlinear saturation amplitude increases with the interface width.
基金supported by grants from National Natural Science Foundation of China No.82172206Zhejiang Provincial Medical and Healthy Science Foundation of China(No.2023RC183 and 2024KY110).
文摘The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing,delayed healing,susceptibility to infection,and elevated risk of reopening,highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels.Here,we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III(rhCol)by oxidative coupling of the catechol group using the H_(2)O_(2)/HRP catalytic system.The post-reactive hydrogel has a good porous structure,swelling rate,reasonable degradation,rheological and mechanical properties,and the catechol group and dopamine impart to the hydrogel tissue adhesiveness,antioxidant capacity,and excellent photothermal effects leading to superior in vitro antimicrobial activity.In addition,the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated.Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel.Wound closure,collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing.In summary,the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.
