Antifungal resistance is the leading cause of antifungal treatment failure in invasive candidiasis.Metabolic rewiring could become a new insight to account for antifungal resistance as to find innovative clinical ther...Antifungal resistance is the leading cause of antifungal treatment failure in invasive candidiasis.Metabolic rewiring could become a new insight to account for antifungal resistance as to find innovative clinical therapies.Here,we show that dynamic surface-enhanced Raman spectroscopy is a promising tool to identify the metabolic differences between fluconazole(Diflucan)-resistant and fluconazole(Diflucan)-sensitive Candida albicans through the signatures of biochemical components and complemented with machine learning algorithms and two-dimensional correlation spectroscopy,an underlying resistance mechanism,that is,the change of purine metabolites induced the resistance of Candida albicans has been clarified yet never reported anywhere.We hope the integrated methodology introduced in this work could be beneficial for the interpretation of cellular regulation,propelling the development of targeted antifungal therapies and diagnostic tools for more efficient management of severe antifungal resistance.展开更多
Cutaneous nerve regeneration in diabetic wounds remains a challenge for current clinical treatment.Herein,a natural protein-based functional hydrogel is developed using keratin as the sole matrix,and protocatechuic al...Cutaneous nerve regeneration in diabetic wounds remains a challenge for current clinical treatment.Herein,a natural protein-based functional hydrogel is developed using keratin as the sole matrix,and protocatechuic aldehyde(PA)and zinc ions as the building blocks through dual-dynamic crosslinking reactions of thiol-aldehyde addition and catecholzinc ions coordination.The unique structural design endows the hydrogel with excellent injectability,skin adhesion,self-healing and antibacterial ability,and biocompatibility.In addition,this hydrogel acts as a drug carrier for the loading and sustained release of phellopterin(PP),a natural compound extracted from traditional Chinese medicine Angelica dahurica.Our findings demonstrate that the PP-loaded hydrogel promotes cutaneous nerve regeneration,angiogenesis and tissue remodeling in the full-thickness wounds in both db/db and streptozotocin-induced C57BL/6 diabetic mice,notably by the synergistic effect of zinc ions and PP,showing a great potential in diabetic wound therapy.展开更多
Photoacoustic imaging(PAI),renowned for its high spatial resolution and deep tissue penetration,holds great promise for disease diagnosis and molecular detection.However,the performance of commercially available PAI c...Photoacoustic imaging(PAI),renowned for its high spatial resolution and deep tissue penetration,holds great promise for disease diagnosis and molecular detection.However,the performance of commercially available PAI contrast agent is often hindered by intrinsic fluorescence,which reduces photoacoustic(PA)signal intensity and contrast,thereby limiting their applications.Herein,we rationally designed and synthesized a class of PAI contrast agents based on a phenothiazine core.By precise molecular engineering,we introduced a twisted intramolecular charge transfer(TICT)effect to suppress fluorescence,minimize radiative decay,and facilitate nonradiative energy dissipation,thereby enhancing photothermal conversion efficiency and significantly improving PA signal intensity and imaging contrast-to-noise ratio both in vitro and in vivo.Moreover,the structure facilitates the convenient incorporation of derivatization sites,allowing for further structural expansion and modification.Building upon this platform,we developed a hypochlorous acid(HOCl)-responsive PA probe,DHU-PAOCl-1,to further explore the biomedical imaging potential of these designed contrast agents.DHU-PAOCl-1 exhibited high selectivity and pH stability,with a detection limit of 11.88 nM.In a dermatitis animal model,DHU-PAOCl-1 enabled precise in situ visualization of endogenously generated HOCl at inflammatory sites,offering a powerful imaging tool for the early diagnosis and real-time monitoring of inflammation-related diseases.Collectively,this study provides an effective molecular design strategy for high-performance PAI contrast agents and expands the application potential of PAI technology in molecular diagnostics and therapeutic monitoring.展开更多
Importance The prevalence and characteristics of short stature(SS)among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies.Thus far,there have...Importance The prevalence and characteristics of short stature(SS)among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies.Thus far,there have been no accurate estimates of the prevalence of SS in China.Objective To analyze the prevalence of SS among children in China and to explore the influences of sex,area,age,study year,and study site on prevalence rates.Methods Relevant literature was identified by searching the following databases:PubMed,Embase,The Cochrane Library,Chinese Biomedical Literature,China Knowledge Resource Integrated,WeiPu,and WanFang databases.Meta-analysis was carried out using STATA 11.2.Results This meta-analysis included 39 studies with 348326 Chinese participants;the studies covered 20 provinces,municipalities,and autonomous regions.The pooled prevalence of SS was 3.2%(95%confidence interval[CI],2.6%–3.7%;I2=99.8%).The prevalence of SS in boys and girls were 3.1%(95%CI,2.5%–3.7%)and 3.2%(95%CI,2.6%–3.9%),respectively.The sex difference was not statistically significant(P>0.05).The prevalence of SS was higher in rural areas than in urban areas(4.7%[95%CI,3.6%–5.8%]vs.2.8%[95%CI,2.2%–3.4%];P<0.001).The prevalence of SS was higher in West China(5.2%;95%CI,4.4%–6.0%)than in Northeast China(0.6%;95%CI,0.3%–0.8%),East China(2.3%;95%CI,1.9%–2.8%),or Central China(2.9%;95%CI,1.9%–3.9%).Interpretation The prevalence of SS among children was higher in western and rural areas of China.Close attention to children’s growth and development is needed to prevent the occurrence of SS.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.22074015 and 82074428)Youth Talent Cultivation Initiation Fund of Zhongda Hospital,Southeast University(No.CZXM-GSP-RC110)to Hao Li+1 种基金Evidence-Based Capacity Building for TCM Specialty Therapies for Skin Diseases of National Administration of TCMInnovative Team Projects of Shanghai Municipal Commission of Health(No.2022CX011)to Fulun Li.
文摘Antifungal resistance is the leading cause of antifungal treatment failure in invasive candidiasis.Metabolic rewiring could become a new insight to account for antifungal resistance as to find innovative clinical therapies.Here,we show that dynamic surface-enhanced Raman spectroscopy is a promising tool to identify the metabolic differences between fluconazole(Diflucan)-resistant and fluconazole(Diflucan)-sensitive Candida albicans through the signatures of biochemical components and complemented with machine learning algorithms and two-dimensional correlation spectroscopy,an underlying resistance mechanism,that is,the change of purine metabolites induced the resistance of Candida albicans has been clarified yet never reported anywhere.We hope the integrated methodology introduced in this work could be beneficial for the interpretation of cellular regulation,propelling the development of targeted antifungal therapies and diagnostic tools for more efficient management of severe antifungal resistance.
基金supported by grants from the National Natural Science Foundation of China(Nos.82474515 and 82074428)Highlevel Chinese Medicine Key Discipline Construction Project(Integrative Chinese and Western Medicine Clinic)of National Administration of TCM(No.zyyzdxk-2023065)+1 种基金Young Qi-Huang Scholar of National Administration of Traditional Chinese Medicine,Evidence-Based Capacity Building for TCM Specialty Therapies for Skin Diseases of National Administration of TCM,and Innovative Team Projects of Shanghai Municipal Commission of Health(No.2022CX011)to Fulun Lithe National Natural Science Foundation of China(No.32371413)to Guang Yang.
文摘Cutaneous nerve regeneration in diabetic wounds remains a challenge for current clinical treatment.Herein,a natural protein-based functional hydrogel is developed using keratin as the sole matrix,and protocatechuic aldehyde(PA)and zinc ions as the building blocks through dual-dynamic crosslinking reactions of thiol-aldehyde addition and catecholzinc ions coordination.The unique structural design endows the hydrogel with excellent injectability,skin adhesion,self-healing and antibacterial ability,and biocompatibility.In addition,this hydrogel acts as a drug carrier for the loading and sustained release of phellopterin(PP),a natural compound extracted from traditional Chinese medicine Angelica dahurica.Our findings demonstrate that the PP-loaded hydrogel promotes cutaneous nerve regeneration,angiogenesis and tissue remodeling in the full-thickness wounds in both db/db and streptozotocin-induced C57BL/6 diabetic mice,notably by the synergistic effect of zinc ions and PP,showing a great potential in diabetic wound therapy.
基金support from the National Key R&D Program of China(2023YFC3605700),NNSFC(22371038,22377010,82202326,82474515)Shanghai Municipal Commission of Science and Technology(23Y31920300).
文摘Photoacoustic imaging(PAI),renowned for its high spatial resolution and deep tissue penetration,holds great promise for disease diagnosis and molecular detection.However,the performance of commercially available PAI contrast agent is often hindered by intrinsic fluorescence,which reduces photoacoustic(PA)signal intensity and contrast,thereby limiting their applications.Herein,we rationally designed and synthesized a class of PAI contrast agents based on a phenothiazine core.By precise molecular engineering,we introduced a twisted intramolecular charge transfer(TICT)effect to suppress fluorescence,minimize radiative decay,and facilitate nonradiative energy dissipation,thereby enhancing photothermal conversion efficiency and significantly improving PA signal intensity and imaging contrast-to-noise ratio both in vitro and in vivo.Moreover,the structure facilitates the convenient incorporation of derivatization sites,allowing for further structural expansion and modification.Building upon this platform,we developed a hypochlorous acid(HOCl)-responsive PA probe,DHU-PAOCl-1,to further explore the biomedical imaging potential of these designed contrast agents.DHU-PAOCl-1 exhibited high selectivity and pH stability,with a detection limit of 11.88 nM.In a dermatitis animal model,DHU-PAOCl-1 enabled precise in situ visualization of endogenously generated HOCl at inflammatory sites,offering a powerful imaging tool for the early diagnosis and real-time monitoring of inflammation-related diseases.Collectively,this study provides an effective molecular design strategy for high-performance PAI contrast agents and expands the application potential of PAI technology in molecular diagnostics and therapeutic monitoring.
文摘Importance The prevalence and characteristics of short stature(SS)among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies.Thus far,there have been no accurate estimates of the prevalence of SS in China.Objective To analyze the prevalence of SS among children in China and to explore the influences of sex,area,age,study year,and study site on prevalence rates.Methods Relevant literature was identified by searching the following databases:PubMed,Embase,The Cochrane Library,Chinese Biomedical Literature,China Knowledge Resource Integrated,WeiPu,and WanFang databases.Meta-analysis was carried out using STATA 11.2.Results This meta-analysis included 39 studies with 348326 Chinese participants;the studies covered 20 provinces,municipalities,and autonomous regions.The pooled prevalence of SS was 3.2%(95%confidence interval[CI],2.6%–3.7%;I2=99.8%).The prevalence of SS in boys and girls were 3.1%(95%CI,2.5%–3.7%)and 3.2%(95%CI,2.6%–3.9%),respectively.The sex difference was not statistically significant(P>0.05).The prevalence of SS was higher in rural areas than in urban areas(4.7%[95%CI,3.6%–5.8%]vs.2.8%[95%CI,2.2%–3.4%];P<0.001).The prevalence of SS was higher in West China(5.2%;95%CI,4.4%–6.0%)than in Northeast China(0.6%;95%CI,0.3%–0.8%),East China(2.3%;95%CI,1.9%–2.8%),or Central China(2.9%;95%CI,1.9%–3.9%).Interpretation The prevalence of SS among children was higher in western and rural areas of China.Close attention to children’s growth and development is needed to prevent the occurrence of SS.
