Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i...Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.展开更多
Mitochondria,the most crucial energy-generating organelles in eukaryotic cells,play a pivotal role in regulating energy metabolism.However,their significance extends beyond this,as they are also indispensable in vital...Mitochondria,the most crucial energy-generating organelles in eukaryotic cells,play a pivotal role in regulating energy metabolism.However,their significance extends beyond this,as they are also indispensable in vital life processes such as cell proliferation,differentiation,immune responses,and redox balance.In response to various physiological signals or external stimuli,a sophisticated mitochondrial quality control(MQC)mechanism has evolved,encompassing key processes like mitochondrial biogenesis,mitochondrial dynamics,and mitophagy,which have garnered increasing attention from researchers to unveil their specific molecular mechanisms.In this review,we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC.Furthermore,the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail.We also discuss agonists or antagonists targeting MQC,aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.展开更多
In this editorial,we comment on the article published in a recent issue of the World Journal of Orthopedics.Although substantial literature regarding pain management of acute musculoskeletal injury has been published ...In this editorial,we comment on the article published in a recent issue of the World Journal of Orthopedics.Although substantial literature regarding pain management of acute musculoskeletal injury has been published over the last three decades,there is still a lack of evidence-based protocol for individual and population disparities.This systematic review gives us a comprehensive view of the evidence-based use of opioid vs opioid-free analgesia.Nevertheless,there is still a need for further investigation at a high level regarding this topic.展开更多
In this article,we comment on the article by Oommen et al.Oommen et al provided a comprehensive overview of the management of hip centre restoration in total hip arthroplasty(THA)for childhood hip disorder sequelae.Gi...In this article,we comment on the article by Oommen et al.Oommen et al provided a comprehensive overview of the management of hip centre restoration in total hip arthroplasty(THA)for childhood hip disorder sequelae.Given the developmental disparity in this population,specific preoperative planning is an essential prerequisite for the success of THA procedures.In the review by Oommen et al,assessments of acetabular and femoral anatomic variations were fully described.However,spinal malalignment and stiffness are common in physical and radiological examinations and should be taken into careful consideration when planning surgical procedures.Poor outcomes of THA for patients with comorbid hip and spinopelvic pathologies have been widely reported,especially for hips with childhood disorder sequelae.Therefore,in this editorial,we would like to emphasize the need for a thorough hip-spine evaluation of patients with childhood hip disorder sequelae before THA.展开更多
With the enhancement of environmental protection awareness, the requirements on drilling fluid are increasingly strict, and the use of ordinary oil-based drilling fluid has been strictly restricted. In order to solve ...With the enhancement of environmental protection awareness, the requirements on drilling fluid are increasingly strict, and the use of ordinary oil-based drilling fluid has been strictly restricted. In order to solve the environmental protection and oil-gas reservoir protection problems of offshore oil drilling, a new synthetic basic drilling fluid system is developed. The basic formula is as follows: a basic fluid (80% Linear a-olefin + 20% Simulated seawater) + 2.5% nano organobentonite + 3.5% emulsifier RHJ-5<sup>#</sup> + 2.5% fluid loss agent SDJ-1 + 1.5% CaO + the right amount of oil wetting barite to adjust the density, and a multifunctional oil and gas formation protective agent YRZ has been developed. The performance was evaluated using a high-low-high-temperature rheometer, a high-temperature and high-pressure demulsification voltage tester, and a high-temperature and high-pressure dynamic fluid loss meter. The results show that the developed synthetic based drilling fluid has good rheological property, demulsification voltage ≥ 500 V, temperature resistance up to 160°C, high temperature and high pressure filtration loss < 3.5 mL. After adding 2% - 5% YRZ into the basic formula of synthetic based drilling fluid, the permeability recovery value exceeds 90% and the reservoir protection effect is excellent. The new synthetic deepwater drilling fluid is expected to have a good application prospect in offshore deepwater drilling.展开更多
基金supported by research grants from the Ningbo Science and Technology Plan Project,No.2022Z143hezuo(to BL)the National Natural Science Foundation of China,No.82201520(to XD)。
文摘Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.
基金supported by the National Natural Science Foundation of China(8210082163,81800343)the Fundamental Research Fund for the Central Universities(2042021kf0081)+1 种基金the Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province(2020CFA027)the Doctor of Excellence Program of the First Hospital of Jilin University(JDYY-DEP-2023043).
文摘Mitochondria,the most crucial energy-generating organelles in eukaryotic cells,play a pivotal role in regulating energy metabolism.However,their significance extends beyond this,as they are also indispensable in vital life processes such as cell proliferation,differentiation,immune responses,and redox balance.In response to various physiological signals or external stimuli,a sophisticated mitochondrial quality control(MQC)mechanism has evolved,encompassing key processes like mitochondrial biogenesis,mitochondrial dynamics,and mitophagy,which have garnered increasing attention from researchers to unveil their specific molecular mechanisms.In this review,we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC.Furthermore,the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail.We also discuss agonists or antagonists targeting MQC,aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.
基金Supported by Yuzhong District Natural Science Foundation of Chongqing,No.20240129。
文摘In this editorial,we comment on the article published in a recent issue of the World Journal of Orthopedics.Although substantial literature regarding pain management of acute musculoskeletal injury has been published over the last three decades,there is still a lack of evidence-based protocol for individual and population disparities.This systematic review gives us a comprehensive view of the evidence-based use of opioid vs opioid-free analgesia.Nevertheless,there is still a need for further investigation at a high level regarding this topic.
文摘In this article,we comment on the article by Oommen et al.Oommen et al provided a comprehensive overview of the management of hip centre restoration in total hip arthroplasty(THA)for childhood hip disorder sequelae.Given the developmental disparity in this population,specific preoperative planning is an essential prerequisite for the success of THA procedures.In the review by Oommen et al,assessments of acetabular and femoral anatomic variations were fully described.However,spinal malalignment and stiffness are common in physical and radiological examinations and should be taken into careful consideration when planning surgical procedures.Poor outcomes of THA for patients with comorbid hip and spinopelvic pathologies have been widely reported,especially for hips with childhood disorder sequelae.Therefore,in this editorial,we would like to emphasize the need for a thorough hip-spine evaluation of patients with childhood hip disorder sequelae before THA.
文摘With the enhancement of environmental protection awareness, the requirements on drilling fluid are increasingly strict, and the use of ordinary oil-based drilling fluid has been strictly restricted. In order to solve the environmental protection and oil-gas reservoir protection problems of offshore oil drilling, a new synthetic basic drilling fluid system is developed. The basic formula is as follows: a basic fluid (80% Linear a-olefin + 20% Simulated seawater) + 2.5% nano organobentonite + 3.5% emulsifier RHJ-5<sup>#</sup> + 2.5% fluid loss agent SDJ-1 + 1.5% CaO + the right amount of oil wetting barite to adjust the density, and a multifunctional oil and gas formation protective agent YRZ has been developed. The performance was evaluated using a high-low-high-temperature rheometer, a high-temperature and high-pressure demulsification voltage tester, and a high-temperature and high-pressure dynamic fluid loss meter. The results show that the developed synthetic based drilling fluid has good rheological property, demulsification voltage ≥ 500 V, temperature resistance up to 160°C, high temperature and high pressure filtration loss < 3.5 mL. After adding 2% - 5% YRZ into the basic formula of synthetic based drilling fluid, the permeability recovery value exceeds 90% and the reservoir protection effect is excellent. The new synthetic deepwater drilling fluid is expected to have a good application prospect in offshore deepwater drilling.
