Parkinson's disease(PD)is the second most prevalent neurodegenerative disorder after Alzheimer's disease(AD),and currently,no disease-modifying therapies are available[1].A key pathological hallmark of PD is t...Parkinson's disease(PD)is the second most prevalent neurodegenerative disorder after Alzheimer's disease(AD),and currently,no disease-modifying therapies are available[1].A key pathological hallmark of PD is the presence of Lewy bodies,which are primarily composed of aggregatedα-synuclein(α-syn)[2].The misfolding,self-aggregation,and inter-neuronal propagation of pathologicalα-syn,likely via a prion-like mechanism,are thought to drive the progressive degeneration of dopaminergic neurons and contribute to disease progression[3].However,the molecular mechanisms governing the neuronal uptake and inter-neuronal transmission ofα-syn remain inadequately understood.展开更多
Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also ...Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell(SC)cords migration and axons elongation.Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects,systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce.This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration,and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them,encompassing(1)in vitro prevascularization,(2)in vivo prevascularization,and(3)stimulation of neurovascularization in situ.Furthermore,we emphasize that the lack of accuracy for structure and spatiotemporal regulation,as well as the operational inconvenience and delayed connection to the host's nerve stumps,have stuck the existing neurovascularization technology in the preclinical stage.The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.展开更多
Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass （PBM）. Insulin-like growth factor type Ⅰ （IGF-1） levels correlate with the pa...Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass （PBM）. Insulin-like growth factor type Ⅰ （IGF-1） levels correlate with the pattern of bone mass accrual and many chronic illnesses are associated with low IGF-1 levels. Reduced serum levels of IGF-1 minimally affect the integrity of the skeleton, whereas recent studies suggest that skeletal IGF-I regulates PBM. To determine the role of IGF-1 in postnatal bone mass accrual regardless of source, we established an inducible type 1 Igf receptor Cre/lox knockout mouse model, in which the type 1 Igf receptor was deleted inducibely in the mesenchymal stem cells （MSCs） from 3-7 weeks of age. The size of the mouse was not affected as knockout and wild type mice had similar body weights and nasoanal and femoral lengths. However, bone volume and trabecular bone thickness were decreased in the secondary spongiosa of female knockout mice relative to wild type controls, indicating that IGF-1 is critical for bone mass. IGF-1 signaling in MSCs in vitro has been implicated to be involved in both migration to the bone surface and differentiation into bone forming osteoblasts. To clarify the exact role of IGF-1 in bone, we found by immunohistochemical analysis that a similar number of Osterix-positive osteoprogenitors were on the bone perimeter, indicating migration of MSCs was not affected. Most importantly, 56% fewer osteocalcin-positive mature osteoblasts were present on the bone perimeter in the secondary spongiosa in knockout mice versus wild type littermates. These in vivo data demonstrate that the primary role of skeletal IGF-1 is for the terminal differentiation of osteoprogenitors, but refute the role of IGF-1 in MSC migration in vivo. Additionally, these findings confirm that impaired IGF-1 signaling in bone MSCs is sufficient to impair bone mass acquisition.展开更多
Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteob...Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteoblasts. However, little is known about the signaling mechanisms that regulates the osteoblast-to-osteocyte transition. Here we report that PTH and IGF-I synergistically enhance osteoblast-to-osteocyte differentiation. We identified that a specific tyrosine residue, Y494, on the cytoplasmic domain of PTH1R can be phosphorylated by insulin-like growth factor type I receptor(IGF1R) in vitro. Phosphorylated PTH1R localized to the barbed ends of actin filaments and increased actin polymerization during morphological change of osteoblasts into osteocytes.Disruption of the phosphorylation site reduced actin polymerization and dendrite length. Mouse models with conditional ablation of PTH1R in osteoblasts demonstrated a reduction in the number of osteoctyes and dendrites per osteocyte, with complete overlap of PTH1R with phosphorylated-PTH1R positioning in osteocyte dendrites in wild-type mice. Thus, our findings reveal a novel signaling mechanism that enhances osteoblast-to-osteocyte transition by direct phosphorylation of PTH1R by IGF1R.展开更多
Microarc oxidation(MAO)is an effective surface treatment method for Ti alloys to allow their application in extreme environments.Here,binary electrolytes consisting of different amounts of sodium phosphate and sodium ...Microarc oxidation(MAO)is an effective surface treatment method for Ti alloys to allow their application in extreme environments.Here,binary electrolytes consisting of different amounts of sodium phosphate and sodium silicate were designed for MAO.The surface morphology,composition,and properties of MAO coatings on Ti-6Al-4V alloy treated in 0.10 mol/L electrolyte were investigated to reveal the effect of PO_(4)^(3-)and SiO_(3)^(2-)ray diffraction,and potentiodynamic polarization.The results showed that PO_(4)^(3-)is beneficial for generating microarcs and forming pores within the coating,resulting in a thick but porous coating.SiO_(3)^(2-)eration of microarcs,resulting in a thin dense coating.The thickness,density,phases content,and polarization resistance of the MAO coatings are primarily affected by the intensity of microarcs for low SiO_(3)^(2-)ciently high.The thickness of MAO coatings obtained in P/Si electrolytes shows a piecewise linear increase with increasing process time during the three stages of microarc discharge.SiO_(3)^(2-)discharge,but slows down the growth of the coating formed in the next stage.展开更多
A novel 4H-Si C trench insulated gate bipolar transistor(IGBT)with a controllable hole-extracting(CHE)path is proposed and investigated in this paper.The CHE path is controlled by metal semiconductor gate(MES gate)and...A novel 4H-Si C trench insulated gate bipolar transistor(IGBT)with a controllable hole-extracting(CHE)path is proposed and investigated in this paper.The CHE path is controlled by metal semiconductor gate(MES gate)and metal oxide semiconductor gate(MOS gate)in the p-shield region.The grounded p-shield region can significantly suppress the high electric field around gate oxide in Si C devices,but it weakens the conductivity modulation in the Si C trench IGBT by rapidly sweeping out holes.This effect can be eliminated by introducing the CHE path.The CHE path is pinched off by the high gate bias voltage at on-state to maintain high conductivity modulation and obtain a comparatively low on-state voltage(VON).During the turn-off transient,the CHE path is formed,which contributes to a decreased turn-off loss(EOFF).Based on numerical simulation,the EOFFof the proposed IGBT is reduced by 89%compared with the conventional IGBT at the same VONand the VONof the proposed IGBT is reduced by 50%compared to the grounded p-shield IGBT at the same EOFF.In addition,the average power reduction for the proposed device can be 51.0%to 81.7%and 58.2%to 72.1%with its counterparts at a wide frequency range of 500 Hz to 10 k Hz,revealing a great improvement of frequency characteristics.展开更多
BACKGROUND Subclavian artery stenosis refers to the stenosis in the lumen caused by the presence of plaque or thrombus in the subclavian artery.It is a common problem in endovascular interventions.In fact,conventional...BACKGROUND Subclavian artery stenosis refers to the stenosis in the lumen caused by the presence of plaque or thrombus in the subclavian artery.It is a common problem in endovascular interventions.In fact,conventional subclavian artery stenting via the femoral artery approach is effective and safe.Nevertheless,because femoral artery puncture is not easy to stop bleeding,it requires longer femoral artery compression or more expensive hemostatic materials,such as staplers.Patients need to be catheterized and bedridden for a longer time,which may lead to many complications,such as pseudoaneurysm.CASE SUMMARY Herein,we reported a new interventional therapy of subclavian artery.From March 1,2020 to August 31,2021,we operated on four patients with subclavian artery stenting via bilateral radial artery access.CONCLUSION After reviewing four cases of successful placement of clavicular artery stents via bilateral radial arteries,we concluded that bilateral radial artery approach is feasible.Clavicular artery stenting is safe,effective,and timesaving.It is an excellent alternative to the traditional femoral artery procedure,with few complications and high comfort degree.展开更多
OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was esta...OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was established by azoxymethane(AOM)combined and dextran sulfate sodium salt(DSS),accompanied by treatment with various dosages of UA and concomitant appraisal of body weight,stool and physical state of the mice.After the sacrifice of the mice,the tumor and length of the colorectum were measured,followed by retrieval of the liver,spleen,thymus and tumor tissue for downstream assays.The levels of inflammatory factors interleukin-6(IL-6),IL^(-1)βand C-reactive protein(CRP)in the tumor and serum were examined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of colorectal tissues were observed by HE staining.The levels in tumors of Wnt/β-catenin signaling pathway-related proteins Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry(IHC).The mRNA expressions of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,Bax,caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR(RT-qPCR).The protein levels of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,phospho-β-catenin,phospho-GSK-3β,Bcl-2 and Bax in tumors were probed by analyzed by Western blotting(WB).Also,RNA-seq was employed to assess the gut microbiota in the mice.RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC,evidenced by improved physical state,body weight,survival rate,colorectal length,the mass of liver,thymus,spleen,and decreased CAC load and colorectal mass.UA attenuated the levels of IL-6,IL^(-1)βand CRP in the mouse serum and colorectal tumor in a dose-dependent manner.HE staining showed that UA lessened carcinogenesis in the colorectum,with lower infiltration of lymphocytes,versus the control.IHC indicated that UA mitigated the expression of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and promoted the GSK-3βexpression,compared with the control.Furthermore,UA diminished the mRNA expressions of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and heightened the mRNA levels of GSK-3β,caspase-3,capase-9 and Bax in CAC.The results of mRNA expressions were verified by WB analysis,which revealed that UA impeded the protein expression of Wnt4,β-catenin,c-Myc,cyclin D1,Bcl-2,TCF4,LEF1,and elevated the protein levels of GSK-3βand Bax,phospho-β-catenin in mouse CAC.In addition,UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC.CONCLUSION Ursolic acid may protect against CAC,potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.展开更多
The development,progression,and curative efficacy of head and neck squamous cell carcinoma(HNSCC)are influenced by complex interactions between epithelial and immune cells.Nevertheless,the specific changes in the natu...The development,progression,and curative efficacy of head and neck squamous cell carcinoma(HNSCC)are influenced by complex interactions between epithelial and immune cells.Nevertheless,the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood.Cuproptosis,a form of programmed cell death that is dependent on copper,has been implicated in cancer pathogenesis.However,the understanding of cuproptosis in the context of HNSCC remains limited.In this study,we have discovered that cuproptosis-related long noncoding RNAs(CRLs)known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator(PLAU)by competitively binding to miR-193b-3p in HNSCC.The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation,migration,and invasion in HNSCC.Moreover,the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR,predominantly expressed on macrophages,thereby influencing the abnormal epithelial–immune interactome in HNSCC.Notably,the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial–immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor(EGFR)and cyclin-dependent kinase(CDK4/6)for the treatment of HNSCC.展开更多
A new welding flexible manufacturing cell (WFMC) with intelligent welding sensors was investigated. Based on the analysis of information flow in WFMC, automation Petri net control model has been studied, Which can be...A new welding flexible manufacturing cell (WFMC) with intelligent welding sensors was investigated. Based on the analysis of information flow in WFMC, automation Petri net control model has been studied, Which can be extended to complex welding flexible manufacturing system in the future.展开更多
Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecul...Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.展开更多
肾移植作为终末期肾病的有效治疗手段,已在世界范围内得到广泛开展。然而,部分患者自身因素可导致移植物功能恢复不佳,甚至导致移植物早期失功。供者特异性抗体(donor specific antibody,DSA)所致抗体介导的排斥反应(antibody-mediated ...肾移植作为终末期肾病的有效治疗手段,已在世界范围内得到广泛开展。然而,部分患者自身因素可导致移植物功能恢复不佳,甚至导致移植物早期失功。供者特异性抗体(donor specific antibody,DSA)所致抗体介导的排斥反应(antibody-mediated rejection,AMR)是移植肾失功的重要原因。DSA主要包括预存DSA和移植后新生DSA,均会影响移植物功能恢复,其中预存DSA是术后超急性排斥反应发生的重要原因,曾被认为是肾移植禁忌证之一,部分尿毒症患者因此失去了肾移植机会。近年来,随着研究的深入和临床经验的积累,很多移植中心对术前DSA阳性受者进行预处理后(如利妥昔单抗清除B细胞、血浆置换清除预存DSA和丙种球蛋白封闭抗体等)再行移植,取得了良好的临床效果[1,2]。本文回顾性分析武汉大学人民医院开展的4例预存DSA阳性肾移植受者资料,并结合相关文献探讨DSA阳性肾移植可行性及处理策略。展开更多
Stem cell senescence and exhaustion,a hallmark of aging,lead to declines in tissue repair and regeneration in aged individuals.Emerging evidence has revealed that epigenetic regulation plays critical roles in the self...Stem cell senescence and exhaustion,a hallmark of aging,lead to declines in tissue repair and regeneration in aged individuals.Emerging evidence has revealed that epigenetic regulation plays critical roles in the self-renew,lineage-commitment,survival,and function of stem cells.Moreover,epigenetic alterations are considered important drivers of stem cell dysfunction during aging.In this review,we focused on current knowledge of the histone modifications in the aging of mesenchymal stem cells(MSCs).The aberrant epigenetic modifications on histones,including methylation and acetylation,have been found in aging MSCs.By disturbing the expression of specific genes,these epigenetic modifications affect the self-renew,survival,and differentiation of MSCs.A set of epigenetic enzymes that write or erase these modifications are critical in regulating the aging of MSCs.Furthermore,we discussed the rejuvenation strategies based on epigenetics to prevent stem cell aging and/or rejuvenate senescent MSCs.展开更多
基金supported by the Natural Science Foundation of Liaoning Province,China(2023-MSLH-029).
文摘Parkinson's disease(PD)is the second most prevalent neurodegenerative disorder after Alzheimer's disease(AD),and currently,no disease-modifying therapies are available[1].A key pathological hallmark of PD is the presence of Lewy bodies,which are primarily composed of aggregatedα-synuclein(α-syn)[2].The misfolding,self-aggregation,and inter-neuronal propagation of pathologicalα-syn,likely via a prion-like mechanism,are thought to drive the progressive degeneration of dopaminergic neurons and contribute to disease progression[3].However,the molecular mechanisms governing the neuronal uptake and inter-neuronal transmission ofα-syn remain inadequately understood.
基金financially supported by the following programs:National Key Research and Development Program of China(No.2023YFB3813003)National Natural Science Foundation of China(Nos.82430031,82122014,82071085)+1 种基金Zhejiang Provincial Natural Science Foundation of China(No.LR21H140001)the Central Universities(No.2022FZZX01-33)。
文摘Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell(SC)cords migration and axons elongation.Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects,systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce.This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration,and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them,encompassing(1)in vitro prevascularization,(2)in vivo prevascularization,and(3)stimulation of neurovascularization in situ.Furthermore,we emphasize that the lack of accuracy for structure and spatiotemporal regulation,as well as the operational inconvenience and delayed connection to the host's nerve stumps,have stuck the existing neurovascularization technology in the preclinical stage.The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.
基金supported in part by the grants from the United States National Institute of Health NIDDK including T32DK07751 (JLC)the Diabetes Research and Training Center grant P60DK079637(JSF),and DK057501 and DK08098 (XC)
文摘Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass （PBM）. Insulin-like growth factor type Ⅰ （IGF-1） levels correlate with the pattern of bone mass accrual and many chronic illnesses are associated with low IGF-1 levels. Reduced serum levels of IGF-1 minimally affect the integrity of the skeleton, whereas recent studies suggest that skeletal IGF-I regulates PBM. To determine the role of IGF-1 in postnatal bone mass accrual regardless of source, we established an inducible type 1 Igf receptor Cre/lox knockout mouse model, in which the type 1 Igf receptor was deleted inducibely in the mesenchymal stem cells （MSCs） from 3-7 weeks of age. The size of the mouse was not affected as knockout and wild type mice had similar body weights and nasoanal and femoral lengths. However, bone volume and trabecular bone thickness were decreased in the secondary spongiosa of female knockout mice relative to wild type controls, indicating that IGF-1 is critical for bone mass. IGF-1 signaling in MSCs in vitro has been implicated to be involved in both migration to the bone surface and differentiation into bone forming osteoblasts. To clarify the exact role of IGF-1 in bone, we found by immunohistochemical analysis that a similar number of Osterix-positive osteoprogenitors were on the bone perimeter, indicating migration of MSCs was not affected. Most importantly, 56% fewer osteocalcin-positive mature osteoblasts were present on the bone perimeter in the secondary spongiosa in knockout mice versus wild type littermates. These in vivo data demonstrate that the primary role of skeletal IGF-1 is for the terminal differentiation of osteoprogenitors, but refute the role of IGF-1 in MSC migration in vivo. Additionally, these findings confirm that impaired IGF-1 signaling in bone MSCs is sufficient to impair bone mass acquisition.
基金provided by K01-AR060433 (T.Q.)K08-AR064833 (J.C)R01-AR063943 (X.C)
文摘Parathyroid hormone(PTH) regulates bone remodeling by activating PTH type 1 receptor(PTH1R) in osteoblasts/osteocytes. Insulinlike growth factor type 1(IGF-1) stimulates mesenchymal stem cell differentiation to osteoblasts. However, little is known about the signaling mechanisms that regulates the osteoblast-to-osteocyte transition. Here we report that PTH and IGF-I synergistically enhance osteoblast-to-osteocyte differentiation. We identified that a specific tyrosine residue, Y494, on the cytoplasmic domain of PTH1R can be phosphorylated by insulin-like growth factor type I receptor(IGF1R) in vitro. Phosphorylated PTH1R localized to the barbed ends of actin filaments and increased actin polymerization during morphological change of osteoblasts into osteocytes.Disruption of the phosphorylation site reduced actin polymerization and dendrite length. Mouse models with conditional ablation of PTH1R in osteoblasts demonstrated a reduction in the number of osteoctyes and dendrites per osteocyte, with complete overlap of PTH1R with phosphorylated-PTH1R positioning in osteocyte dendrites in wild-type mice. Thus, our findings reveal a novel signaling mechanism that enhances osteoblast-to-osteocyte transition by direct phosphorylation of PTH1R by IGF1R.
基金financially supported by China Postdoctoral Science Foundation (No.2021M700569)Chongqing Postdoctoral Science Foundation (No.cstc2021jcyj-bsh0133)
文摘Microarc oxidation(MAO)is an effective surface treatment method for Ti alloys to allow their application in extreme environments.Here,binary electrolytes consisting of different amounts of sodium phosphate and sodium silicate were designed for MAO.The surface morphology,composition,and properties of MAO coatings on Ti-6Al-4V alloy treated in 0.10 mol/L electrolyte were investigated to reveal the effect of PO_(4)^(3-)and SiO_(3)^(2-)ray diffraction,and potentiodynamic polarization.The results showed that PO_(4)^(3-)is beneficial for generating microarcs and forming pores within the coating,resulting in a thick but porous coating.SiO_(3)^(2-)eration of microarcs,resulting in a thin dense coating.The thickness,density,phases content,and polarization resistance of the MAO coatings are primarily affected by the intensity of microarcs for low SiO_(3)^(2-)ciently high.The thickness of MAO coatings obtained in P/Si electrolytes shows a piecewise linear increase with increasing process time during the three stages of microarc discharge.SiO_(3)^(2-)discharge,but slows down the growth of the coating formed in the next stage.
基金Project supported by the Hunan Provincial Natural Science Foundation of China(Grant No.2021JJ30738)Scientific Research Fund of Hunan Provincial Education Department(Grant No.19K001)Hunan Provincial Key Laboratory of Flexible Electronic Materials Genome Engineering’s Open Fund Project-2020(Grant No.202016)。
文摘A novel 4H-Si C trench insulated gate bipolar transistor(IGBT)with a controllable hole-extracting(CHE)path is proposed and investigated in this paper.The CHE path is controlled by metal semiconductor gate(MES gate)and metal oxide semiconductor gate(MOS gate)in the p-shield region.The grounded p-shield region can significantly suppress the high electric field around gate oxide in Si C devices,but it weakens the conductivity modulation in the Si C trench IGBT by rapidly sweeping out holes.This effect can be eliminated by introducing the CHE path.The CHE path is pinched off by the high gate bias voltage at on-state to maintain high conductivity modulation and obtain a comparatively low on-state voltage(VON).During the turn-off transient,the CHE path is formed,which contributes to a decreased turn-off loss(EOFF).Based on numerical simulation,the EOFFof the proposed IGBT is reduced by 89%compared with the conventional IGBT at the same VONand the VONof the proposed IGBT is reduced by 50%compared to the grounded p-shield IGBT at the same EOFF.In addition,the average power reduction for the proposed device can be 51.0%to 81.7%and 58.2%to 72.1%with its counterparts at a wide frequency range of 500 Hz to 10 k Hz,revealing a great improvement of frequency characteristics.
文摘BACKGROUND Subclavian artery stenosis refers to the stenosis in the lumen caused by the presence of plaque or thrombus in the subclavian artery.It is a common problem in endovascular interventions.In fact,conventional subclavian artery stenting via the femoral artery approach is effective and safe.Nevertheless,because femoral artery puncture is not easy to stop bleeding,it requires longer femoral artery compression or more expensive hemostatic materials,such as staplers.Patients need to be catheterized and bedridden for a longer time,which may lead to many complications,such as pseudoaneurysm.CASE SUMMARY Herein,we reported a new interventional therapy of subclavian artery.From March 1,2020 to August 31,2021,we operated on four patients with subclavian artery stenting via bilateral radial artery access.CONCLUSION After reviewing four cases of successful placement of clavicular artery stents via bilateral radial arteries,we concluded that bilateral radial artery approach is feasible.Clavicular artery stenting is safe,effective,and timesaving.It is an excellent alternative to the traditional femoral artery procedure,with few complications and high comfort degree.
基金National Natural Science Foundation of China(81573813,81173598)Sichuan Provincial Admin⁃istration of Traditional Chinese Medicine of China(2021MS447)+1 种基金Excellent Talent Program of Chengdu University of Tra⁃ditional Chinese Medicine of China(YXRC2019002,ZRYY1917)Open Research Fund of the State Key Laboratory of Southwestern Chinese Medicine Resources of China(2020XSGG006)。
文摘OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was established by azoxymethane(AOM)combined and dextran sulfate sodium salt(DSS),accompanied by treatment with various dosages of UA and concomitant appraisal of body weight,stool and physical state of the mice.After the sacrifice of the mice,the tumor and length of the colorectum were measured,followed by retrieval of the liver,spleen,thymus and tumor tissue for downstream assays.The levels of inflammatory factors interleukin-6(IL-6),IL^(-1)βand C-reactive protein(CRP)in the tumor and serum were examined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of colorectal tissues were observed by HE staining.The levels in tumors of Wnt/β-catenin signaling pathway-related proteins Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry(IHC).The mRNA expressions of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,Bax,caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR(RT-qPCR).The protein levels of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,phospho-β-catenin,phospho-GSK-3β,Bcl-2 and Bax in tumors were probed by analyzed by Western blotting(WB).Also,RNA-seq was employed to assess the gut microbiota in the mice.RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC,evidenced by improved physical state,body weight,survival rate,colorectal length,the mass of liver,thymus,spleen,and decreased CAC load and colorectal mass.UA attenuated the levels of IL-6,IL^(-1)βand CRP in the mouse serum and colorectal tumor in a dose-dependent manner.HE staining showed that UA lessened carcinogenesis in the colorectum,with lower infiltration of lymphocytes,versus the control.IHC indicated that UA mitigated the expression of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and promoted the GSK-3βexpression,compared with the control.Furthermore,UA diminished the mRNA expressions of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and heightened the mRNA levels of GSK-3β,caspase-3,capase-9 and Bax in CAC.The results of mRNA expressions were verified by WB analysis,which revealed that UA impeded the protein expression of Wnt4,β-catenin,c-Myc,cyclin D1,Bcl-2,TCF4,LEF1,and elevated the protein levels of GSK-3βand Bax,phospho-β-catenin in mouse CAC.In addition,UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC.CONCLUSION Ursolic acid may protect against CAC,potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.
基金financially supported by the following programs:National Natural Science Foundation of China(82122014,82071085,82001045,82201122,82020108011)National Key Research and Development Program of China(2018YFA0703000)+6 种基金China Postdoctoral Science Foundation(2023M743009)Zhejiang Provincial Natural Science Foundation of China(LR21H140001,LQ21H140002,LR22H140005)Zhejiang Basic Public Welfare Research Project(LGF22H140007)Medical Technology and Education of Zhejiang Province of China(2018KY501)Foundation of Zhejiang University(2022QZJH55)Zhejiang University of Stomatology Postdoctoral Scientific Research Foundation(2023PDF013)Foundation of Stomatology Hospital Affiliated to Zhejiang University School of Medicine(RD2022JCXK01)。
文摘The development,progression,and curative efficacy of head and neck squamous cell carcinoma(HNSCC)are influenced by complex interactions between epithelial and immune cells.Nevertheless,the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood.Cuproptosis,a form of programmed cell death that is dependent on copper,has been implicated in cancer pathogenesis.However,the understanding of cuproptosis in the context of HNSCC remains limited.In this study,we have discovered that cuproptosis-related long noncoding RNAs(CRLs)known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator(PLAU)by competitively binding to miR-193b-3p in HNSCC.The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation,migration,and invasion in HNSCC.Moreover,the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR,predominantly expressed on macrophages,thereby influencing the abnormal epithelial–immune interactome in HNSCC.Notably,the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial–immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor(EGFR)and cyclin-dependent kinase(CDK4/6)for the treatment of HNSCC.
基金The National Natural Science FOundation of China under grant No.59635160 supports this work.
文摘A new welding flexible manufacturing cell (WFMC) with intelligent welding sensors was investigated. Based on the analysis of information flow in WFMC, automation Petri net control model has been studied, Which can be extended to complex welding flexible manufacturing system in the future.
基金supported by grants from the National Natural Science Foundation of China(Nos.81870067 and 82170664).
文摘Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
文摘肾移植作为终末期肾病的有效治疗手段,已在世界范围内得到广泛开展。然而,部分患者自身因素可导致移植物功能恢复不佳,甚至导致移植物早期失功。供者特异性抗体(donor specific antibody,DSA)所致抗体介导的排斥反应(antibody-mediated rejection,AMR)是移植肾失功的重要原因。DSA主要包括预存DSA和移植后新生DSA,均会影响移植物功能恢复,其中预存DSA是术后超急性排斥反应发生的重要原因,曾被认为是肾移植禁忌证之一,部分尿毒症患者因此失去了肾移植机会。近年来,随着研究的深入和临床经验的积累,很多移植中心对术前DSA阳性受者进行预处理后(如利妥昔单抗清除B细胞、血浆置换清除预存DSA和丙种球蛋白封闭抗体等)再行移植,取得了良好的临床效果[1,2]。本文回顾性分析武汉大学人民医院开展的4例预存DSA阳性肾移植受者资料,并结合相关文献探讨DSA阳性肾移植可行性及处理策略。
基金supported by grants from the National Key Research and Development Program of China(No.2021YFA1100603)the National Natural Science Foundation of China(No.32271365,81600912 and 82071092)+2 种基金the Technology Innovation Research and Development Project of Chengdu,China(2022-YF05-01388-SN)the Key Project of Sichuan province,China(No.2020YFS0177 and 2019YFS0311)the Fundamental Research Funds for the Central Universities(China)(No.YJ201878).
文摘Stem cell senescence and exhaustion,a hallmark of aging,lead to declines in tissue repair and regeneration in aged individuals.Emerging evidence has revealed that epigenetic regulation plays critical roles in the self-renew,lineage-commitment,survival,and function of stem cells.Moreover,epigenetic alterations are considered important drivers of stem cell dysfunction during aging.In this review,we focused on current knowledge of the histone modifications in the aging of mesenchymal stem cells(MSCs).The aberrant epigenetic modifications on histones,including methylation and acetylation,have been found in aging MSCs.By disturbing the expression of specific genes,these epigenetic modifications affect the self-renew,survival,and differentiation of MSCs.A set of epigenetic enzymes that write or erase these modifications are critical in regulating the aging of MSCs.Furthermore,we discussed the rejuvenation strategies based on epigenetics to prevent stem cell aging and/or rejuvenate senescent MSCs.
