Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health problem1.Extensive evidence h...Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health problem1.Extensive evidence has indicated that screening can decrease cancer mortality,particularly among high-risk groups,and several representative national and regional cancer screening programs have been launched in China to cope with the increasing burden of cancer.展开更多
There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as ...There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as a promising target pathway for developing novel bone anabolic drugs. Although neutralizing antibodies against the Wnt antagonist sclerostin have been tested,Wnt ligands themselves have not been fully explored as a potential therapy. Previous work has demonstrated Wnt7b as an endogenous ligand upregulated during osteoblast differentiation, and that Wnt7b overexpression potently stimulates bone accrual in the mouse. The earlier studies however did not address whether Wnt7b could promote bone formation when specifically applied to aged or fractured bones. Here we have developed a doxycycline-inducible strategy where Wnt7b is temporally induced in the bones of aged mice or during fracture healing. We report that forced expression of Wnt7b for 1 month starting at 15 months of age greatly stimulated trabecular and endosteal bone formation, resulting in a marked increase in bone mass. We further tested the effect of Wnt7b on bone healing in a murine closed femur fracture model. Induced expression of Wnt7b at the onset of fracture did not affect the initial cartilage formation but promoted mineralization of the subsequent bone callus. Thus, targeted delivery of Wnt7b to aged bones or fracture sites may be explored as a potential therapy.展开更多
Windborne debris is one of the most important causes of the envelop destruction according to the postdamage investigations.The problem of windborne debris damage could be summarized as three parts,including windborne ...Windborne debris is one of the most important causes of the envelop destruction according to the postdamage investigations.The problem of windborne debris damage could be summarized as three parts,including windborne debris risk analysis,debris flying trajectories,and impact resistance of envelope analysis.The method of debris distribution is developed.The flying trajectories of compact and plate-like debris are solved by using a numerical method according to the different aerodynamic characteristics.The impact resistance of the envelopes is also analyzed.Besides,the process of windborne debris damage analysis is described in detail.An example of industrial building is given to demonstrate the whole method by using the observed data of typhoon Chanchu(2006).The method developed in this paper could be applied to risk assessment of windborne debris for structures in wind hazard.展开更多
P-N and P=N bonds play important roles in the design and synthesis of functional molecules such as bioactive compounds and organic ligands for catalysis.Existing methods for P-N coupling mostly rely on Staudinger cond...P-N and P=N bonds play important roles in the design and synthesis of functional molecules such as bioactive compounds and organic ligands for catalysis.Existing methods for P-N coupling mostly rely on Staudinger condensation or nucleophilic substitution between phosphorus electrophiles and amine nucleo philes.Herein,we report a nitrene-mediated intermolecular P-N coupling reaction between various phos phorus nucleophiles and dioxazolones under simp le iron-catalyzed conditions.These reactions offer an efficient,versatile,and broadly applicable method for synthesis of a range of N-P compounds,including amidophosphines,iminophosphonamides,phosphinamides,aminophosphines,and iminophospho ranes,from readily available precursors under mild conditions.展开更多
基金supported by grants from the National Key Research and Development Program of China(Grant No.2021YFC2500400)the National Natural Science Foundation of China(Grant Nos.81974439&82204121)+2 种基金the Beijing-Tianjin-Hebei Basic Research Cooperation Special Project(20JCZXJC00090)the Tianjin Health Committee Foundation(Grant No.TJWJ2021MS008)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health problem1.Extensive evidence has indicated that screening can decrease cancer mortality,particularly among high-risk groups,and several representative national and regional cancer screening programs have been launched in China to cope with the increasing burden of cancer.
基金supported by AR060456 (F.L.), AR047867 (M.J.S.)the Washington University Musculoskeletal Research Center (NIH P30 AR057235)
文摘There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as a promising target pathway for developing novel bone anabolic drugs. Although neutralizing antibodies against the Wnt antagonist sclerostin have been tested,Wnt ligands themselves have not been fully explored as a potential therapy. Previous work has demonstrated Wnt7b as an endogenous ligand upregulated during osteoblast differentiation, and that Wnt7b overexpression potently stimulates bone accrual in the mouse. The earlier studies however did not address whether Wnt7b could promote bone formation when specifically applied to aged or fractured bones. Here we have developed a doxycycline-inducible strategy where Wnt7b is temporally induced in the bones of aged mice or during fracture healing. We report that forced expression of Wnt7b for 1 month starting at 15 months of age greatly stimulated trabecular and endosteal bone formation, resulting in a marked increase in bone mass. We further tested the effect of Wnt7b on bone healing in a murine closed femur fracture model. Induced expression of Wnt7b at the onset of fracture did not affect the initial cartilage formation but promoted mineralization of the subsequent bone callus. Thus, targeted delivery of Wnt7b to aged bones or fracture sites may be explored as a potential therapy.
文摘Windborne debris is one of the most important causes of the envelop destruction according to the postdamage investigations.The problem of windborne debris damage could be summarized as three parts,including windborne debris risk analysis,debris flying trajectories,and impact resistance of envelope analysis.The method of debris distribution is developed.The flying trajectories of compact and plate-like debris are solved by using a numerical method according to the different aerodynamic characteristics.The impact resistance of the envelopes is also analyzed.Besides,the process of windborne debris damage analysis is described in detail.An example of industrial building is given to demonstrate the whole method by using the observed data of typhoon Chanchu(2006).The method developed in this paper could be applied to risk assessment of windborne debris for structures in wind hazard.
基金the Natural Science Foundation of China(nos.21421062 and 21901127)the China Postdoctoral Science Foundation(nos.2018M640225 and 2019T120179)Nankai-Cangzhou Green Chemistry Institute(no.NCC2020FH02)for financial support of this work.
文摘P-N and P=N bonds play important roles in the design and synthesis of functional molecules such as bioactive compounds and organic ligands for catalysis.Existing methods for P-N coupling mostly rely on Staudinger condensation or nucleophilic substitution between phosphorus electrophiles and amine nucleo philes.Herein,we report a nitrene-mediated intermolecular P-N coupling reaction between various phos phorus nucleophiles and dioxazolones under simp le iron-catalyzed conditions.These reactions offer an efficient,versatile,and broadly applicable method for synthesis of a range of N-P compounds,including amidophosphines,iminophosphonamides,phosphinamides,aminophosphines,and iminophospho ranes,from readily available precursors under mild conditions.
