Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone homeostasis.The hypothalamus...Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone homeostasis.The hypothalamus,located in the central nervous system(CNS),plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system,neuropeptide release,and neuroendocrine mechanisms.These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts(OBs),the activation of osteoclasts(OCs),and the functional activities of bone cells.Sensory nerves extensively innervate skeletal tissues,facilitating the transmission of interoceptive signals to the CNS.This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions.The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.展开更多
Achieving efficient hemostasis and wound management is vital to preserve life and restore health in case of extensive hemor-rhagic skin damage.Here,we develop a filter pump-like hierarchical porous-structure(HPS)dress...Achieving efficient hemostasis and wound management is vital to preserve life and restore health in case of extensive hemor-rhagic skin damage.Here,we develop a filter pump-like hierarchical porous-structure(HPS)dressing based on a non-woven substrate,konjac glucomannan(KGM)aerogel,and bi-functional microporous starch(BMS).The KGM aerogel intercalates into the non-woven network structure,forming a hydrophilic frame to stimulate the plasma permeation toward the interior in synergy with the hydrophilic pores of the BMS.The BMS surface forms a hydrophobic matrix that fills the spaces of the KGM hydrophilic frame,contributing to the isolation and aggregation of blood cells on the surface of the HPS dressing to establish rapid hemostasis.Animal model experiments suggest reliable HPS dressing hemostatic capacity,as it is able to stop ear artery and liver bleeding within 97.6±15.2 s and 67.8±5.4 s,respectively.Furthermore,the dressings exhibit antibacterial properties and enabled wound healing within 2 weeks.In vitro hemolysis and cytotoxicity tests also confirm the biocompatibility of HPS dressings.This novel“two-in-one”hemostatic dressing facilitates tissue repair of bleeding wounds over the entire recovery period,thereby providing a convenient strategy for wound management.展开更多
Efficient, precise dynamic modeling and analysis for complex weapon systems have become more and more important in their dynamic design and performance optimizing. As a new method developed in recent years, the discre...Efficient, precise dynamic modeling and analysis for complex weapon systems have become more and more important in their dynamic design and performance optimizing. As a new method developed in recent years, the discrete time transfer matrix method of multibody system is highly efficient for multibody system dynamics. In this paper, taking a shipboard gun system as an example, by deducing some new transfer equations of elements, the discrete time transfer matrix method of multibody sys- tem is used to solve the dynamics problems of complex rigid-flexible coupling weapon systems successfully. This method does not need the global dynamic equations of system and has the low order of system matrix, high computational efficiency. The proposed method has advantages for dynamic design of complex weapon systems, and can be carried over straightforwardly to other complex mechanical systems.展开更多
Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge.Therefore,we present a novel hemostatic st...Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge.Therefore,we present a novel hemostatic strategy based on magnetic field-mediated guidance.The biphasic Janus magnetic particle(MSS@Fe2O3-T)comprised aggregates ofα-Fe2O3 nanoparticles(Fe_(2)O_(3) NPs)as the motion actuator,negatively modified microporous starch(MSS)as the base hemostatic substrate,and thrombin as the loaded hemostatic drug.Before application,the particles were first wrapped using NaHCO_(3) and then doped with protonated tranexamic acid(TXA-NH_(3)^(+)),which ensured their high self-dispersibility in liquids.During application,the particles promptly self-diffused in blood by bubble propulsion and travelled to deep bleeding sites against reverse rushing blood flow under magnetic guidance.In vivo tests confirmed the superior hemostatic performance of the particles in perforating and inflected wounds(“V”-shaped femoral artery and“J”-shaped liver bleeding models).The present strategy,for the first time,extends the range of magnetically guided drug carriers to address the challenges in the hemorrhage control of perforating and inflected wounds.展开更多
In this paper, combining the transfer matrix method and the finite element method, the modified finite element transfer matrix method is presented for high efficient dynamic modeling of laminated plates. Then, by cons...In this paper, combining the transfer matrix method and the finite element method, the modified finite element transfer matrix method is presented for high efficient dynamic modeling of laminated plates. Then, by constructing the modal filter and the disturbance force observer, and using the feedback and feedforward approaches, the H ∞ independent modal space control strategy is designed for active vibration control of laminate plates subjected to arbitrary, immeasurable disturbance forces. Compared with ordinary dynamic modeling and control methods of laminated plate structures, the proposed method has the low memory requirement, high computational efficiency and robust control performance. Formulations as well as some numerical examples are given to validate the method and the control performance.展开更多
Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature,thereby causing massive blood loss and significantly increased...Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature,thereby causing massive blood loss and significantly increased mortality.Inspired by the attack action of torpedoes,we synthesized microcluster(MC)colloidosomes equipped with magnetic-mediated navigation and“blast”systems to deliver hemostats into the cavity of vase-type wounds.CaCO_(3)/Fe_(2)O_(3)(CF)microparticles functionalized with Arg-Gly-Asp(RGD)modified polyelectrolyte multilayers were co-assembled with oppositely charged zwitterionic carbon dots(CDs)to form MC colloidosomes,which were loaded with thrombin and protonated tranexamic acid(TXA-NH_(3)^(+)).The composite microparticles moved against blood flow under magnetic mediation and simultaneously disassembled for the burst release of thrombin stimulated by TXA-NH_(3)^(+).The CO_(2) bubbles generated during disassembly produced a“blast”that propelled thrombin into the wound cavity.Severe bleeding in a vase-type hemorrhage model in the rabbit liver was rapidly controlled within~60 s.Furthermore,in vivo subcutaneous muscle and liver implantation models demonstrated excellent biodegradability of MC colloidosomes.This study is the first to propose a novel strategy based on the principle of torpedoes for transporting hemostats into vase-type wounds to achieve rapid hemostasis,creating a new paradigm for combating trauma treatment.展开更多
Background: Tuberculosis is a leading cause of morbidity and mortality in humans worldwide. There is an urgent need for new and effective drugs to treat tuberculosis and shorten the duration of tuberculosis therapy. 1...Background: Tuberculosis is a leading cause of morbidity and mortality in humans worldwide. There is an urgent need for new and effective drugs to treat tuberculosis and shorten the duration of tuberculosis therapy. 1, 25-dihydroxy vitamin D3 (1,25 (OH)2D3) has been reported to have a synergistic effect with pyrazinamide (PZA) in killing tubercle bacilli in vitro. The addition of 1,25 (OH)2D3 to standard tuberculosis treatment should benefit patients if the adjunctive drug has a synergistic effect in vivo. Thus, in this study, calcitriol (bioactive 1,25 (OH)2D3) was administered to mice undergoing treatment for Mycobacterium tuberculosis (M.tb) infection with PZA, a first-line anti-tuberculosis drug, to determine whether vitamin D3 enhances the therapeutic effect. Methods: C57BL/6 female mice were infected with the M.tb H37Rv strain through aerosol exposure. Calcitriol and PZA, either alone or in combination, were orally administered to the M.tb infected mice. The effect of calcitriol on PZA activity was determined by evaluating the bacterial burden and analyzing the histopathological lesions in the lungs and spleen. To investigate the expression of inflammatory cytokines and anti-microbial peptide genes, we determined the transcriptional levels of interferon-γ(IFN-γ), interleukin-4 (IL-4), mouse β-defensin-2 (mBD2), and cathelicidin LL-37 through real-time quantitative polymerase chain reaction. The protein levels of IFN-γ were detected by enzyme-linked immunosorbent assay. Differences between groups were analyzed with independent samples t-test or one-way analysis of variance. Results: Calcitriol alone had little effect on tuberculosis infection, whereas PZA, compared with saline control treatment, decreased the bacterial burden (spleens: PZA vs. saline, 4.82 ± 0.22 vs. 5.22 ± 0.40 Log10 colony-forming units [CFU]/gram, t = 2.13, P < 0.05;lungs: PZA vs. saline, 5.55 ± 0.15 vs. 6.83 ± 0.46 Log10 CFU/gram, t = 6.56, P < 0.01) and pathological lesions in the lungs. Simultaneous administration of calcitriol with PZA, compared with PZA alone, decreased the bacterial load (spleen: calcitriol + PZA vs. PZA, 4.37 ± 0.13 vs. 4.82 ± 0.22 Log10 CFU/gram, t = 4.36, P < 0.01;lung: calcitriol + PZA vs. PZA, 5.03 ± 0.32 vs. 5.55 ± 0.15 Log10 CFU/gram, t = 3.58, P < 0.01) and attenuated the lung lesions (gross pathological score: calcitriol + PZA vs. PZA, 3.25 ± 0.50 vs. 2.50 ± 0.58, t = 1.96, P < 0.05;affected area of total lung area: calcitriol + PZA vs. PZA, 30.75%± 6.50% vs. 21.55%± 2.99%, t = 2.66, P < 0.05). Further studies demonstrated calcitriol significantly increased the expression of anti-inflammatory cytokine IL-4 but suppressed production of the pro-inflammatory cytokine IFN-γ(IL-4: calcitriol vs. saline, 5.69 ± 0.50 vs. 2.80 ± 0.56 fold of control, t= 6.74, P < 0.01;IFN-γ: calcitriol vs. saline, 1.36 ± 0.11 vs. 4.13 ± 0.83 fold of control, t= 5.77, P < 0.01). In addition, calcitriol alone or in combination with PZA significantly enhanced the transcriptional level of anti-microbial peptides (cathelicidin LL-37: calcitriol vs. saline, 10.59 ± 1.03 vs. 2.80 ± 0.90 fold of control, t = 9.85, P < 0.01;mBD2: calcitriol vs. saline, 7.92 ± 0.62 vs. 1.79 ± 0.45 fold of control, t = 13.82, P < 0.01), whereas PZA exerted a negative effect on anti-microbial peptide gene expression. Conclusions: Calcitriol as adjunctive treatment can result in beneficial treatment outcomes in M.tb infection by suppressing the inflammatory response and up-regulating the expression of anti-microbial peptides. These results indicate the feasibility of using calcitriol adjunctively with standard chemotherapy for the treatment of M.tb infection.展开更多
基金supported by the National Natural Science Foundation of China (No.82172408,81902234,81772314,and 81922045)the Original Exploration project (22ZR1480300)+4 种基金Outstanding Academic Leaders (Youth)project (21XD1422900)of Shanghai Science and Technology Innovation Action PlanPrinciple Investigator Innovation Team of Both Shanghai Sixth People’s Hospital and Shanghai Institute of Nutrition and Health,Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program (No.20191829)The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang (No.SHDC2020CR4032)Shanghai Excellent Academic Leader ProgramShanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration (No.20DZ2254100)。
文摘Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue,a process known as skeletal interoception,which is crucial for maintaining bone homeostasis.The hypothalamus,located in the central nervous system(CNS),plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system,neuropeptide release,and neuroendocrine mechanisms.These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts(OBs),the activation of osteoclasts(OCs),and the functional activities of bone cells.Sensory nerves extensively innervate skeletal tissues,facilitating the transmission of interoceptive signals to the CNS.This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions.The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.
基金National Natural Science Foundation of China(No.52103096)Natural Science Foundation of Chongqing,China(Nos.cstb2022nscq-msx0555 and cstc2020jcyj-msxmX0024)Fundamental Research Funds for Central Universities(Nos.SWU-XDPY22010,XDJK2019AC003,and XDJK2020B017).
文摘Achieving efficient hemostasis and wound management is vital to preserve life and restore health in case of extensive hemor-rhagic skin damage.Here,we develop a filter pump-like hierarchical porous-structure(HPS)dressing based on a non-woven substrate,konjac glucomannan(KGM)aerogel,and bi-functional microporous starch(BMS).The KGM aerogel intercalates into the non-woven network structure,forming a hydrophilic frame to stimulate the plasma permeation toward the interior in synergy with the hydrophilic pores of the BMS.The BMS surface forms a hydrophobic matrix that fills the spaces of the KGM hydrophilic frame,contributing to the isolation and aggregation of blood cells on the surface of the HPS dressing to establish rapid hemostasis.Animal model experiments suggest reliable HPS dressing hemostatic capacity,as it is able to stop ear artery and liver bleeding within 97.6±15.2 s and 67.8±5.4 s,respectively.Furthermore,the dressings exhibit antibacterial properties and enabled wound healing within 2 weeks.In vitro hemolysis and cytotoxicity tests also confirm the biocompatibility of HPS dressings.This novel“two-in-one”hemostatic dressing facilitates tissue repair of bleeding wounds over the entire recovery period,thereby providing a convenient strategy for wound management.
基金supported by the National Natural Science Foundation of China (Grant No: 10902051)the Natural Science Foundation of Jiangsu Province (Grant No: BK2008046)
文摘Efficient, precise dynamic modeling and analysis for complex weapon systems have become more and more important in their dynamic design and performance optimizing. As a new method developed in recent years, the discrete time transfer matrix method of multibody system is highly efficient for multibody system dynamics. In this paper, taking a shipboard gun system as an example, by deducing some new transfer equations of elements, the discrete time transfer matrix method of multibody sys- tem is used to solve the dynamics problems of complex rigid-flexible coupling weapon systems successfully. This method does not need the global dynamic equations of system and has the low order of system matrix, high computational efficiency. The proposed method has advantages for dynamic design of complex weapon systems, and can be carried over straightforwardly to other complex mechanical systems.
基金This work was supported by the National Natural Science Foundation of China(No.51703185,51803170,and 51803171)the Fundamental Research Funds for the Central Universities(nos.XDJK2019AC003 and XDJK2020B017).
文摘Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge.Therefore,we present a novel hemostatic strategy based on magnetic field-mediated guidance.The biphasic Janus magnetic particle(MSS@Fe2O3-T)comprised aggregates ofα-Fe2O3 nanoparticles(Fe_(2)O_(3) NPs)as the motion actuator,negatively modified microporous starch(MSS)as the base hemostatic substrate,and thrombin as the loaded hemostatic drug.Before application,the particles were first wrapped using NaHCO_(3) and then doped with protonated tranexamic acid(TXA-NH_(3)^(+)),which ensured their high self-dispersibility in liquids.During application,the particles promptly self-diffused in blood by bubble propulsion and travelled to deep bleeding sites against reverse rushing blood flow under magnetic guidance.In vivo tests confirmed the superior hemostatic performance of the particles in perforating and inflected wounds(“V”-shaped femoral artery and“J”-shaped liver bleeding models).The present strategy,for the first time,extends the range of magnetically guided drug carriers to address the challenges in the hemorrhage control of perforating and inflected wounds.
基金supported by the National Natural Science Foundation of China (Grant No. 10902051)the Natural Science Foundation of Jiangsu Province (Grant No. BK2008046)
文摘In this paper, combining the transfer matrix method and the finite element method, the modified finite element transfer matrix method is presented for high efficient dynamic modeling of laminated plates. Then, by constructing the modal filter and the disturbance force observer, and using the feedback and feedforward approaches, the H ∞ independent modal space control strategy is designed for active vibration control of laminate plates subjected to arbitrary, immeasurable disturbance forces. Compared with ordinary dynamic modeling and control methods of laminated plate structures, the proposed method has the low memory requirement, high computational efficiency and robust control performance. Formulations as well as some numerical examples are given to validate the method and the control performance.
基金supported by the China Agriculture Research System(No.CARS-18-ZJ0102)National Natural Science Foundation of China(Nos.52103096,51803170,51803171,and 81703424)+1 种基金Natural Science Foundation of Chongqing,China(grant number cstc2020jcyj-msxmX0383)Fundamental Research Funds for the Central Universities(2020CDJQY-A041).
文摘Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature,thereby causing massive blood loss and significantly increased mortality.Inspired by the attack action of torpedoes,we synthesized microcluster(MC)colloidosomes equipped with magnetic-mediated navigation and“blast”systems to deliver hemostats into the cavity of vase-type wounds.CaCO_(3)/Fe_(2)O_(3)(CF)microparticles functionalized with Arg-Gly-Asp(RGD)modified polyelectrolyte multilayers were co-assembled with oppositely charged zwitterionic carbon dots(CDs)to form MC colloidosomes,which were loaded with thrombin and protonated tranexamic acid(TXA-NH_(3)^(+)).The composite microparticles moved against blood flow under magnetic mediation and simultaneously disassembled for the burst release of thrombin stimulated by TXA-NH_(3)^(+).The CO_(2) bubbles generated during disassembly produced a“blast”that propelled thrombin into the wound cavity.Severe bleeding in a vase-type hemorrhage model in the rabbit liver was rapidly controlled within~60 s.Furthermore,in vivo subcutaneous muscle and liver implantation models demonstrated excellent biodegradability of MC colloidosomes.This study is the first to propose a novel strategy based on the principle of torpedoes for transporting hemostats into vase-type wounds to achieve rapid hemostasis,creating a new paradigm for combating trauma treatment.
文摘Background: Tuberculosis is a leading cause of morbidity and mortality in humans worldwide. There is an urgent need for new and effective drugs to treat tuberculosis and shorten the duration of tuberculosis therapy. 1, 25-dihydroxy vitamin D3 (1,25 (OH)2D3) has been reported to have a synergistic effect with pyrazinamide (PZA) in killing tubercle bacilli in vitro. The addition of 1,25 (OH)2D3 to standard tuberculosis treatment should benefit patients if the adjunctive drug has a synergistic effect in vivo. Thus, in this study, calcitriol (bioactive 1,25 (OH)2D3) was administered to mice undergoing treatment for Mycobacterium tuberculosis (M.tb) infection with PZA, a first-line anti-tuberculosis drug, to determine whether vitamin D3 enhances the therapeutic effect. Methods: C57BL/6 female mice were infected with the M.tb H37Rv strain through aerosol exposure. Calcitriol and PZA, either alone or in combination, were orally administered to the M.tb infected mice. The effect of calcitriol on PZA activity was determined by evaluating the bacterial burden and analyzing the histopathological lesions in the lungs and spleen. To investigate the expression of inflammatory cytokines and anti-microbial peptide genes, we determined the transcriptional levels of interferon-γ(IFN-γ), interleukin-4 (IL-4), mouse β-defensin-2 (mBD2), and cathelicidin LL-37 through real-time quantitative polymerase chain reaction. The protein levels of IFN-γ were detected by enzyme-linked immunosorbent assay. Differences between groups were analyzed with independent samples t-test or one-way analysis of variance. Results: Calcitriol alone had little effect on tuberculosis infection, whereas PZA, compared with saline control treatment, decreased the bacterial burden (spleens: PZA vs. saline, 4.82 ± 0.22 vs. 5.22 ± 0.40 Log10 colony-forming units [CFU]/gram, t = 2.13, P < 0.05;lungs: PZA vs. saline, 5.55 ± 0.15 vs. 6.83 ± 0.46 Log10 CFU/gram, t = 6.56, P < 0.01) and pathological lesions in the lungs. Simultaneous administration of calcitriol with PZA, compared with PZA alone, decreased the bacterial load (spleen: calcitriol + PZA vs. PZA, 4.37 ± 0.13 vs. 4.82 ± 0.22 Log10 CFU/gram, t = 4.36, P < 0.01;lung: calcitriol + PZA vs. PZA, 5.03 ± 0.32 vs. 5.55 ± 0.15 Log10 CFU/gram, t = 3.58, P < 0.01) and attenuated the lung lesions (gross pathological score: calcitriol + PZA vs. PZA, 3.25 ± 0.50 vs. 2.50 ± 0.58, t = 1.96, P < 0.05;affected area of total lung area: calcitriol + PZA vs. PZA, 30.75%± 6.50% vs. 21.55%± 2.99%, t = 2.66, P < 0.05). Further studies demonstrated calcitriol significantly increased the expression of anti-inflammatory cytokine IL-4 but suppressed production of the pro-inflammatory cytokine IFN-γ(IL-4: calcitriol vs. saline, 5.69 ± 0.50 vs. 2.80 ± 0.56 fold of control, t= 6.74, P < 0.01;IFN-γ: calcitriol vs. saline, 1.36 ± 0.11 vs. 4.13 ± 0.83 fold of control, t= 5.77, P < 0.01). In addition, calcitriol alone or in combination with PZA significantly enhanced the transcriptional level of anti-microbial peptides (cathelicidin LL-37: calcitriol vs. saline, 10.59 ± 1.03 vs. 2.80 ± 0.90 fold of control, t = 9.85, P < 0.01;mBD2: calcitriol vs. saline, 7.92 ± 0.62 vs. 1.79 ± 0.45 fold of control, t = 13.82, P < 0.01), whereas PZA exerted a negative effect on anti-microbial peptide gene expression. Conclusions: Calcitriol as adjunctive treatment can result in beneficial treatment outcomes in M.tb infection by suppressing the inflammatory response and up-regulating the expression of anti-microbial peptides. These results indicate the feasibility of using calcitriol adjunctively with standard chemotherapy for the treatment of M.tb infection.
