Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impair...Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impairment in Parkinson's disease is essential for early diagnosis,prognostic assessments,and the development of targeted therapies.This review aims to summarize recent advancements in biofluid biomarkers for cognitive impairment in Parkinson's disease,focusing on the detection of specific proteins,metabolites,and other biomarkers in blood,cerebrospinal fluid,and saliva.These biomarkers can shed light on the multifaceted etiology of cognitive impairment in Parkinson's disease,which includes protein misfolding,neurodegeneration,inflammation,and oxidative stress.The integration of biofluid biomarkers with neuroimaging and clinical data can facilitate the development of predictive models to enhance early diagnosis and monitor the progression of cognitive impairment in patients with Parkinson's disease.This comprehensive approach can improve the existing understanding of the mechanisms driving cognitive decline and support the development of targeted therapeutic strategies aimed at modifying the course of cognitive impairment in Parkinson's disease.Despite the promise of these biomarkers in characterizing the mechanisms underlying cognitive decline in Parkinson's disease,further research is necessary to validate their clinical utility and establish a standardized framework for early detection and monitoring of cognitive impairment in Parkinson's disease.展开更多
Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protei...Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.展开更多
AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct(CBD) stones.METHODS From Ap...AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct(CBD) stones.METHODS From April 2014 to May 2016, 15 consecutive patients(6 men and 9 women) aged 45-86(mean, 69.07 ± 9.91) years suffering from CBD stones associated with gallstones were evaluated. Good gallbladder contraction function was confirmed by type B ultrasonography. Dilation of the CBD and cystic duct was detected. Percutaneous transhepatic balloon dilation of the papilla was performed, ursodeoxycholic acid was administered, and all patients had a high-fat diet. All subjects underwent repeated cholangiography, and percutaneous transhepatic removal was carried out in patients with secondary CBD stones originating from the gallbladder. RESULTS All patients underwent percutaneous transhepatic balloon dilation with a primary success rate of 100%. The combined therapy was successful in 86.7% of patients with concomitant CBD stones and gallstones. No remaining stones were detected in the gallbladder. Transient adverse events include abdominal pain(n = 1), abdominal distension(n = 1), and fever(n = 1). Complications were treated successfully via nonsurgical management without long-term complications. No procedure-related mortality occurred. CONCLUSION For patients with concomitant CBD stones and gallstones, after percutaneous transhepatic removal of primary CBD stones, oral ursodeoxycholic acid and a high-fat diet followed by percutaneous transhepatic removal of secondary CBD stones appear to be a feasible and effective option for management of gallstones.展开更多
Selective laser melting(SLM)has the advantage in preparing supersaturated solid solutions due to its unique thermal field and high solidification rate.In this study,a face-centered cubic single-phase FeCrNi medium ent...Selective laser melting(SLM)has the advantage in preparing supersaturated solid solutions due to its unique thermal field and high solidification rate.In this study,a face-centered cubic single-phase FeCrNi medium entropy alloy(MEA)with an ultrahigh Cr content(~35 at.%)was additively manufactured by SLM.The as-built MEA shows a hierarchical microstructure of coarse columnar grains and submicron dislocation cell structures,where the cell boundaries are probed segregated with Cr and C and decorated with nano carbides.The appearance of these dislocation barriers results in an excellent combination of strength(σ_(0.2)=745 MPa,σ_(UTS)=1007 MPa)and ductility(ε_(f)=31%).The current MEA also shows a superb corrosion resistance with a corrosion current density of 0.06μA cm^(−2) in 3.5 wt.%NaCl solution,which is far lower than that of 316 L.The high content of solutioned Cr in the MEA ensures sufficient Cr supply to form an integrated Cr_(2)O_(3) passive film,and the large number of cell boundaries acting as the diffusion channels lead to the fast formation of a stable passive film over the alloy surface.展开更多
In medium/high entropy alloys, their mechanical properties are strongly dependent on the chemicalelemental composition. Thus, searching for optimum elemental composition remains a critical issue to maximize the mechan...In medium/high entropy alloys, their mechanical properties are strongly dependent on the chemicalelemental composition. Thus, searching for optimum elemental composition remains a critical issue to maximize the mechanical performance. However, this issue solved by traditional optimization process via "trial and error" or experiences of domain experts is extremely difficult. Here we propose an approach based on high-throughput simulation combined machine learning to obtain medium entropy alloys with high strength and low cost. This method not only obtains a large amount of data quickly and accurately,but also helps us to determine the relationship between the composition and mechanical properties.The results reveal a vital importance of high-throughput simulation combined machine learning to find best mechanical properties in a wide range of elemental compositions for development of alloys with expected performance.展开更多
African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the ...African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the disease has spread to many other countries. No commercial vaccines are available to prevent ASF. In this study, we generated a recombinant Newcastle disease virus(r NDV) expressing ASFV protein 72(p72) by reverse genetics and evaluated its humoral and cellular immunogenicity in a mouse model. The recombinant virus, r NDV/p72, replicated well in embryonated chicken eggs and was safe to use in chicks and mice. The p72 gene in r NDV/p72 was stably maintained through ten passages. Mice immunized with r NDV/p72 developed high titers of ASFV p72 specific Ig G antibody, and had higher levels of Ig G1 than IgG2 a. Immunization also elicited T-cell proliferation and secretion of IFN-γ and IL-4. Taken together, these results indicate that r NDV expressing ASFV p72 might be a potential vaccine candidate for preventing ASF.展开更多
BACKGROUND Immunoglobulin A nephropathy(IgAN)is a common form of chronic glomer-ulonephritis.Currently,IgAN is one of the main causes of chronic renal failure in China;its prognosis varies greatly between patients,wit...BACKGROUND Immunoglobulin A nephropathy(IgAN)is a common form of chronic glomer-ulonephritis.Currently,IgAN is one of the main causes of chronic renal failure in China;its prognosis varies greatly between patients,with renal function at the time of diagnosis and prognosis being strongly correlated.Mycophenolate mofetil(MMF)is a drug with a good immunomodulatory effect and is commonly used clinically.However,its effects in IgAN have not yet been clearly demonstrated.Therefore,herein,we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment.METHODS Between January 2011 and December 2020,200 patients with moderate-to-severe IgAN were included in this study,all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University.All patients underwent a renal puncture biopsy,which revealed primary IgAN with a glomerular filtration rate(GFR)of 30–60 mL/min.The patients were divided into a glucocorticoid therapy group(GTG)and an immunosuppressive therapy group(ITG)according to the different treatment regimens,with 100 patients in each group.Based on general treatments,such as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,patients in the GTG were administered prednisone 0.5–0.8 mg/(kg·d^(-1))for 4–8 wk,which was reduced by 5 mg every two weeks until the maintenance(30 mg/d)dose was reached and maintained for 12 mo.In the ITG,MMF was administered at 1.0 g/d for 6–12 mo,followed by a maintenance dosage of 0.5 g/d for 12 mo.Age,sex,blood pressure,24-h urinary egg white measurement,serum creatinine(Scr),blood uric acid,blood albumin,blood potassium(K),hemoglobin,GFR,alanine aminotransferase,total cholesterol(T-CHO),fasting blood glucose,and body mass index were recorded.The 24-h urinary protein,Scr,and GFR levels were recorded 3,6,9,and 12 mo after treatment.Follow-up data were also collected.RESULTS No discernible differences existed between the two groups in terms of age,sex,blood pressure,creatinine,24-h urinary protein level,GFR,or other biochemical indicators at the time of enrollment.Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function.Nine months after treatment,the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG.By the 12th month of treatment,the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month.In addition,the overall response rate in the ITG was significantly higher than that in the GTG.The occurrence of side effects did not vary significantly between the two regimens;however,endpoint events were significantly more common in the GTG than in the ITG.The follow-up time for the GTG was noticeably lower than that for the ITG.CONCLUSION Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.展开更多
At present,the problem of heavy metal pollution in farmland in southern China is serious. Especially,the cadmium and lead are two heavy metal elements with serious pollution and great harm to human body. This paper re...At present,the problem of heavy metal pollution in farmland in southern China is serious. Especially,the cadmium and lead are two heavy metal elements with serious pollution and great harm to human body. This paper reviewed some common methods and materials used in the control of cadmium and lead pollution in farmland soil. Then,it discussed the problems in the repair of cadmium and lead pollution in farmland soil. It came up with the future research direction,to provide references for remediation of lead and cadmium pollution in farmland soil.展开更多
Leaf economics spectrum(LES)describes the fundamental trade-offs between leaf structural,chemical,and physiological investments.Generally,structurally robust thick leaves with high leaf dry mass per unit area(LMA)exhi...Leaf economics spectrum(LES)describes the fundamental trade-offs between leaf structural,chemical,and physiological investments.Generally,structurally robust thick leaves with high leaf dry mass per unit area(LMA)exhibit lower photosynthetic capacity per dry mass(Amass).Paradoxically,“soft and thinleaved”mosses and spikemosses have very low Amass,but due to minute-size foliage elements,their LMA and its components,leaf thickness(LT)and density(LD),have not been systematically estimated.Here,we characterized LES and associated traits in cryptogams in unprecedented details,covering five evolutionarily different lineages.We found that mosses and spikemosses had the lowest LMA and LT values ever measured for terrestrial plants.Across a broad range of species from different lineages,Amass and LD were negatively correlated.In contrast,Amass was only related to LMA when LMA was greater than 14 g cm^(-2).In fact,low Amass reflected high LD and cell wall thickness in the studied cryptogams.We conclude that evolutionarily old plant lineages attained poorly differentiated,ultrathin mesophyll by increasing LD.Across plant lineages,LD,not LMA,is the trait that represents the trade-off between leaf robustness and physiology in the LES.展开更多
Objective:To investigate the application of heparin-binding protein along with albumin(HBP+ALB)in evaluating the severity of community-acquired pneumonia(CAP)and compares it with single HBP,white blood cells(WBCs),C-r...Objective:To investigate the application of heparin-binding protein along with albumin(HBP+ALB)in evaluating the severity of community-acquired pneumonia(CAP)and compares it with single HBP,white blood cells(WBCs),C-reactive protein(CRP),and procalcitonin(PCT).Methods:A total of 226 patients with CAP admitted to the Emergency Department of Zhujiang Hospital,Southern Medical University,Guangdong,China,between March 1,2021,and March 1,2022,were enrolled.The patients were grouped into two groups:mild CAP(n=175)and severe CAP(sCAP)(n=51).Patients'characteristics and laboratory data were obtained.ROC curve and the value of the area under the curve(AUC)were used to evaluate the predictive values of HBP,ALB,WBC,CRP,and PCT.Results:WBC count,CRP,PCT,HBP,creatinine,and D-dimer were higher in the sCAP group,while ALB was lower in the sCAP group(P<0.05)than those in the mild CAP group.The AUCs of WBC,CRP,PCT,HBP,and HBP+ALB were 0.633(95%CI:0.545-0.722,P<0.05),0.635(95%CI:0.542-0.729,P<0.05),0.705(95%CI:0.619-0.791,P<0.05),0.809(95%CI:0.736-0.883,P<0.05),and 0.889(95%CI:0.842-0.936,P<0.05),respectively.Conclusions:HBP+ALB has a higher predictive value than single HBP,PCT,CRP and WBC used alone for the early assessment of CAP.展开更多
Objective:To investigate the clinical effect of microecological preparation combined with bicyclol on nonalcoholic fatty liver (NAFLD) and its effect on liver fibrosis, serum inflammatory factors and transforming grow...Objective:To investigate the clinical effect of microecological preparation combined with bicyclol on nonalcoholic fatty liver (NAFLD) and its effect on liver fibrosis, serum inflammatory factors and transforming growth factorβ1 (TGF-β1).Methods:106 patients with NAFLD were randomly divided into control group (53 cases) and case group (53 cases). The control group was given routine liver protection and bicyclol, and the case group was given Bifidobacterium triple viable probiotics based on the treatment of the control group. The two groups were treated for 6 weeks. The clinical effect, liver fibrosis, serum inflammatory factors, TGF-β1 and other changes were observed in the two groups after treatment.Results:The total effective rate of the case group was significantly higher than that of the control group (96.22% vs 83.02%), (χ2=4.970,P=0.026). After treatment, the ALB and HDL levels of the two groups of patients were higher than before. ALT, AST, and TBIL, LN, HA, PCIII, CIV, TC, TG, LDL, IL-6, TNF-a, hs-CRP, TGF-β1 were lower, compared with before and after treatment;and the improvement of liver function, liver fibrosis, blood lipid levels, serum inflammatory factors, and TGF-β1 in the case group was better than that in the control group, and the differences were statistically significant (P <0.05). The incidence of adverse reactions in the case group was lower than that in the control group (5.66% vs 11.32%). The difference was not statistically significant (χ2=1.093,P=0.296).Conclusion: Microecological preparations combined with bicyclol in the treatment of NAFLD have exact clinical effects, can significantly improve liver function, regulate blood lipid levels, reduce inflammation and liver fibrosis, and have good safety, which deserves further clinical research and promotion.展开更多
The asymmetric α-amination of 1,3-dicarbonyl compounds with dialkyl azodicarboxylates has been achieved by C2-symmetric BINOL-squaramide bearing multiple hydrogen bond donors to provide the desired products in excell...The asymmetric α-amination of 1,3-dicarbonyl compounds with dialkyl azodicarboxylates has been achieved by C2-symmetric BINOL-squaramide bearing multiple hydrogen bond donors to provide the desired products in excellent yields and enantioselectivities （up to 99% yield and 98% ee）.展开更多
Objective:To investigate the effect of Fuzheng Huayu Capsule combined with nucleoside antiviral drugs on liver and kidney function,serum inflammatory factors,Toll-like receptor 4(TLR-4),transforming growth factorβ1(T...Objective:To investigate the effect of Fuzheng Huayu Capsule combined with nucleoside antiviral drugs on liver and kidney function,serum inflammatory factors,Toll-like receptor 4(TLR-4),transforming growth factorβ1(TGF-β1)And aspartate aminotransferase-platelet ratio index(APRI).Methods:A total of 144 patients with HBV infection and decompensated cirrhosis were selected.All patients were divided into control group and case group by random number table method,with 72 cases in each group.The control group was given conventional liver protection and antiviral therapy;the case group was supplemented with Fuzheng Huayu Capsule on the basis of treatment in the control group.The changes of liver and kidney function,serum inflammatory factors,TLR-4,TGF-β1 and APRI in the two groups were observed.Results:The total effective rate of the case group was 93.06%,higher than 76.32%of the control group(P<0.05).Case group HBV DNA negative rate,negative rate of hepatitis B virus surface antigen(HBsAg),negative rate of hepatitis B virus e antigen(HBeAg)were significantly higher than the control group(76.39%vs 59.72%,55.56%vs 31.94%,51.39%vs 29.17%),the difference was statistically significant(P<0.05).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),hyaluronic acid(HA),laminin(LN),typeⅢprocollagen after treatment(PCⅢ),typeⅣcollagen(CⅣ),inner diameter of portal vein,inner diameter of splenic vein,spleen thickness,resistance index,urea nitrogen(BUN),creatinine(Cr),interleukin-6(IL-6),interleukin-8(IL-8),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),TLR-4,TGF-β1,APRI are lower than before treatment,albumin(ALB)and renal blood The flow rate was higher than before treatment;liver function indicators,liver fibrosis indicators,liver and spleen imaging indicators,renal hemodynamic indicators,serum inflammatory factors,TLR-4 in the case group The improvement of TGF-β1 and APRI.Conclusion:Fuzheng Huayu Capsules combined with nucleoside antiviral drugs have a clear clinical effect on patients with HBV infection and decompensated liver cirrhosis,significantly improve the clinical symptoms of patients,improve liver and kidney function,reduce inflammatory factor production,and can effectively inhibit HBV replication.Certain promotion value is worthy of further clinical research.展开更多
[Objectives]To study the remediation methods of secondary salinization and cadmium pollution in facility soil.[Methods]Two kinds of soil amendments,potassium fulvic acid and limestone powder,were selected to be applie...[Objectives]To study the remediation methods of secondary salinization and cadmium pollution in facility soil.[Methods]Two kinds of soil amendments,potassium fulvic acid and limestone powder,were selected to be applied alone or combined together to plant maize to carry out field experiments.Their effects on watermelon yield,watermelon cadmium content,soil available nitrogen,phosphorus,potassium and water-soluble salts were studied.[Results]The application of potassium fulvic acid,limestone powder and their combined application increased the yield and soluble solids of watermelon to different degrees.The contents of seven heavy metals including cadmium,copper,zinc,arsenic,lead,mercury and chromium in the watermelon of all treatments were all lower than the food safety limit stipulated in the national standard.During the harvest period of maize seedlings,all treatments could increase soil pH and decrease soil cadmium availability.In particular,3000 kg/ha of limestone powder and 1500 kg/ha of potassium fulvic acid had the best effect on reducing soil available cadmium content.In reducing soil available cadmium content,there were significant differences between single application of amendment and combined application treatments.In addition,compared with the control CK,all treatments decreased soil available nitrogen,phosphorus,potassium and water-soluble salt content.[Conclusions]Potassium fulvic acid,limestone powder and their combined application can increase the yield of watermelon,and can significantly reduce the available cadmium,nitrogen,phosphorus,potassium and water-soluble salt content in the facility soil of maize cultivation.展开更多
Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV...Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection.Methods: 136 patients with decompensated cirrhosis of HBV infection who were hospitalized in Linxi Hospital of Kailuan General Hospital, Tangshan Infectious Disease Hospital and North China University of Technology Hospital from January to February 2018, 2017 were selected. All patients were divided into control group and case group by random number table method, 68 cases in each group. The control group was treated with routine liver protection and antiviral therapy, while the case group was treated with alprostadil on the basis of the control group. The changes of liver function, liver fibrosis, liver and spleen imaging indexes, anti-virus related indexes and inflammatory factors were observed before and after treatment in the two groups.Results: The total effective rate of the case group was 97.06%, which was significantly higher than that of the control group (85.29%), and the difference was statistically significant. The ALT, AST, TBIL, LN, HA, PCIII, CIV, portal vein diameter, spleen vein diameter, spleen thickness, IL-6, hs-CRP, TNF-α and TGF-β1 were significantly lower in the case group than in the control group. ALB, HBV DNA conversion rate, HBsAg negative rate, and HBeAg negative rate were significantly higher than the control group, the difference was statistically significant. Conclusion: Alprostadil combined with nucleoside antiviral drugs can significantly improve the decompensation of HBV infection Liver function in patients with cirrhosis, reduce the degree of liver fibrosis, inhibit the production of serum inflammatory factors, and can effectively inhibit HBV replication, clinical efficacy is significant, with certain clinical application value.展开更多
Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture....Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture.In this study,we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM.Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM.Mechanistically,SIRT3 suppression results in hyperacetylation of FOXO3,hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria.Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3,thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM.Collectively,our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control,crucial for maintaining bone homeostasis in T2DM.These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.展开更多
Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which mi...Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.展开更多
基金supported by Applied Basic Research Foundation of Yunnan Province,Nos.202301AS070045,202101AY070001-115(to XY and BL)National Natural Science Foundation of China,No.81960242(to XY)。
文摘Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impairment in Parkinson's disease is essential for early diagnosis,prognostic assessments,and the development of targeted therapies.This review aims to summarize recent advancements in biofluid biomarkers for cognitive impairment in Parkinson's disease,focusing on the detection of specific proteins,metabolites,and other biomarkers in blood,cerebrospinal fluid,and saliva.These biomarkers can shed light on the multifaceted etiology of cognitive impairment in Parkinson's disease,which includes protein misfolding,neurodegeneration,inflammation,and oxidative stress.The integration of biofluid biomarkers with neuroimaging and clinical data can facilitate the development of predictive models to enhance early diagnosis and monitor the progression of cognitive impairment in patients with Parkinson's disease.This comprehensive approach can improve the existing understanding of the mechanisms driving cognitive decline and support the development of targeted therapeutic strategies aimed at modifying the course of cognitive impairment in Parkinson's disease.Despite the promise of these biomarkers in characterizing the mechanisms underlying cognitive decline in Parkinson's disease,further research is necessary to validate their clinical utility and establish a standardized framework for early detection and monitoring of cognitive impairment in Parkinson's disease.
文摘Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.
基金Supported by the Natural Science Foundation of Shandong Province,No.ZR2014HM050the Youth Foundation of the Second Hospital of Shandong University,No.Y2014010047+1 种基金the Nature Science Foundation of Shandong Province,No.ZR2018PH032 and No.ZR2018PH033the National Natural Science Foundation of China,No.61671276
文摘AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct(CBD) stones.METHODS From April 2014 to May 2016, 15 consecutive patients(6 men and 9 women) aged 45-86(mean, 69.07 ± 9.91) years suffering from CBD stones associated with gallstones were evaluated. Good gallbladder contraction function was confirmed by type B ultrasonography. Dilation of the CBD and cystic duct was detected. Percutaneous transhepatic balloon dilation of the papilla was performed, ursodeoxycholic acid was administered, and all patients had a high-fat diet. All subjects underwent repeated cholangiography, and percutaneous transhepatic removal was carried out in patients with secondary CBD stones originating from the gallbladder. RESULTS All patients underwent percutaneous transhepatic balloon dilation with a primary success rate of 100%. The combined therapy was successful in 86.7% of patients with concomitant CBD stones and gallstones. No remaining stones were detected in the gallbladder. Transient adverse events include abdominal pain(n = 1), abdominal distension(n = 1), and fever(n = 1). Complications were treated successfully via nonsurgical management without long-term complications. No procedure-related mortality occurred. CONCLUSION For patients with concomitant CBD stones and gallstones, after percutaneous transhepatic removal of primary CBD stones, oral ursodeoxycholic acid and a high-fat diet followed by percutaneous transhepatic removal of secondary CBD stones appear to be a feasible and effective option for management of gallstones.
基金supported by the National Natural Science Foundation of China(Nos.52020105013 and 51771232)the National Key Research and Development Plan of China(No.2016YFB0700302)
文摘Selective laser melting(SLM)has the advantage in preparing supersaturated solid solutions due to its unique thermal field and high solidification rate.In this study,a face-centered cubic single-phase FeCrNi medium entropy alloy(MEA)with an ultrahigh Cr content(~35 at.%)was additively manufactured by SLM.The as-built MEA shows a hierarchical microstructure of coarse columnar grains and submicron dislocation cell structures,where the cell boundaries are probed segregated with Cr and C and decorated with nano carbides.The appearance of these dislocation barriers results in an excellent combination of strength(σ_(0.2)=745 MPa,σ_(UTS)=1007 MPa)and ductility(ε_(f)=31%).The current MEA also shows a superb corrosion resistance with a corrosion current density of 0.06μA cm^(−2) in 3.5 wt.%NaCl solution,which is far lower than that of 316 L.The high content of solutioned Cr in the MEA ensures sufficient Cr supply to form an integrated Cr_(2)O_(3) passive film,and the large number of cell boundaries acting as the diffusion channels lead to the fast formation of a stable passive film over the alloy surface.
基金supported financially by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 51621004)the National Natural Science Foundation of China (Nos. 51871092, 11772122, 51625404, 51771232+5 种基金51671217)the State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body (No. 71865015)the State Key Laboratory of Powder Metallurgythe National Key Research and Development Program of China (Nos. 2016YFB0700300 and 2016YFB1100103)support of the U.S. Army Research Office Project (Nos. W911NF-13-1-0438 and W911NF-19-2-0049) with the program managers,Drs. M.P. Bakas,S.N. Mathaudhusupport from the National Science Foundation (Nos. DMR-1611180 and 1809640)with the program directors,Drs. J. Yang,J.G. Shiflet,and D. Farkas。
文摘In medium/high entropy alloys, their mechanical properties are strongly dependent on the chemicalelemental composition. Thus, searching for optimum elemental composition remains a critical issue to maximize the mechanical performance. However, this issue solved by traditional optimization process via "trial and error" or experiences of domain experts is extremely difficult. Here we propose an approach based on high-throughput simulation combined machine learning to obtain medium entropy alloys with high strength and low cost. This method not only obtains a large amount of data quickly and accurately,but also helps us to determine the relationship between the composition and mechanical properties.The results reveal a vital importance of high-throughput simulation combined machine learning to find best mechanical properties in a wide range of elemental compositions for development of alloys with expected performance.
基金financially supported by the National Supporting Program(2013BAD12B05)Natural Science Foundation of China(NSFC)(no.31101839 and no.31302117)+1 种基金the key program of Gansu Province(no.1013JHTA008)Jiangsu Co-innovation Center program for Prevention and Control of Important Animal Infectious Diseases and Zoonoses
文摘African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the disease has spread to many other countries. No commercial vaccines are available to prevent ASF. In this study, we generated a recombinant Newcastle disease virus(r NDV) expressing ASFV protein 72(p72) by reverse genetics and evaluated its humoral and cellular immunogenicity in a mouse model. The recombinant virus, r NDV/p72, replicated well in embryonated chicken eggs and was safe to use in chicks and mice. The p72 gene in r NDV/p72 was stably maintained through ten passages. Mice immunized with r NDV/p72 developed high titers of ASFV p72 specific Ig G antibody, and had higher levels of Ig G1 than IgG2 a. Immunization also elicited T-cell proliferation and secretion of IFN-γ and IL-4. Taken together, these results indicate that r NDV expressing ASFV p72 might be a potential vaccine candidate for preventing ASF.
基金This study was approved by the Ethics Committee of Wuxi People's Hospital affiliated with Nanjing Medical University(approval no.KY23117).
文摘BACKGROUND Immunoglobulin A nephropathy(IgAN)is a common form of chronic glomer-ulonephritis.Currently,IgAN is one of the main causes of chronic renal failure in China;its prognosis varies greatly between patients,with renal function at the time of diagnosis and prognosis being strongly correlated.Mycophenolate mofetil(MMF)is a drug with a good immunomodulatory effect and is commonly used clinically.However,its effects in IgAN have not yet been clearly demonstrated.Therefore,herein,we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment.METHODS Between January 2011 and December 2020,200 patients with moderate-to-severe IgAN were included in this study,all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University.All patients underwent a renal puncture biopsy,which revealed primary IgAN with a glomerular filtration rate(GFR)of 30–60 mL/min.The patients were divided into a glucocorticoid therapy group(GTG)and an immunosuppressive therapy group(ITG)according to the different treatment regimens,with 100 patients in each group.Based on general treatments,such as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,patients in the GTG were administered prednisone 0.5–0.8 mg/(kg·d^(-1))for 4–8 wk,which was reduced by 5 mg every two weeks until the maintenance(30 mg/d)dose was reached and maintained for 12 mo.In the ITG,MMF was administered at 1.0 g/d for 6–12 mo,followed by a maintenance dosage of 0.5 g/d for 12 mo.Age,sex,blood pressure,24-h urinary egg white measurement,serum creatinine(Scr),blood uric acid,blood albumin,blood potassium(K),hemoglobin,GFR,alanine aminotransferase,total cholesterol(T-CHO),fasting blood glucose,and body mass index were recorded.The 24-h urinary protein,Scr,and GFR levels were recorded 3,6,9,and 12 mo after treatment.Follow-up data were also collected.RESULTS No discernible differences existed between the two groups in terms of age,sex,blood pressure,creatinine,24-h urinary protein level,GFR,or other biochemical indicators at the time of enrollment.Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function.Nine months after treatment,the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG.By the 12th month of treatment,the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month.In addition,the overall response rate in the ITG was significantly higher than that in the GTG.The occurrence of side effects did not vary significantly between the two regimens;however,endpoint events were significantly more common in the GTG than in the ITG.The follow-up time for the GTG was noticeably lower than that for the ITG.CONCLUSION Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.
基金Supported by National Key Research and Development Program(2016YED0800705-01)Key Research and Development Program of Guangxi(AB16380084+2 种基金AB16380164)Scientific Research and Technological Development Program Project of Nanning City(20162105)Scientific Development Fund Project of Guangxi Academy of Agricultural Sciences(2017JM06)
文摘At present,the problem of heavy metal pollution in farmland in southern China is serious. Especially,the cadmium and lead are two heavy metal elements with serious pollution and great harm to human body. This paper reviewed some common methods and materials used in the control of cadmium and lead pollution in farmland soil. Then,it discussed the problems in the repair of cadmium and lead pollution in farmland soil. It came up with the future research direction,to provide references for remediation of lead and cadmium pollution in farmland soil.
基金funded by the EU Regional Development Fund within the framework of the Centre of Excellence EcolChange(2014-2020.4.01.15-0002),the European Commission through the European Research Council(advanced grant 322603,SIPVOL+),the Estonian Research Council(personal grant PSG884)base funding nr 190200,the National Natural Science foundation of China(31711530648)+2 种基金the Personnel Startup Project of the Scientific Research and Development Foundation of Zhejiang A&F University(2021FR041)the study was partly purchased from funding by the EU Regional Development Fund(AnaEE Estonia,2014-2020.4.01.20-0285,and the project“Plant Biology Infrastructure-TAIM”,2014-2020.4.01.20-0282)the Estonian Research Council(“Plant Biology Infrastructure-TAIM”,TT5).
文摘Leaf economics spectrum(LES)describes the fundamental trade-offs between leaf structural,chemical,and physiological investments.Generally,structurally robust thick leaves with high leaf dry mass per unit area(LMA)exhibit lower photosynthetic capacity per dry mass(Amass).Paradoxically,“soft and thinleaved”mosses and spikemosses have very low Amass,but due to minute-size foliage elements,their LMA and its components,leaf thickness(LT)and density(LD),have not been systematically estimated.Here,we characterized LES and associated traits in cryptogams in unprecedented details,covering five evolutionarily different lineages.We found that mosses and spikemosses had the lowest LMA and LT values ever measured for terrestrial plants.Across a broad range of species from different lineages,Amass and LD were negatively correlated.In contrast,Amass was only related to LMA when LMA was greater than 14 g cm^(-2).In fact,low Amass reflected high LD and cell wall thickness in the studied cryptogams.We conclude that evolutionarily old plant lineages attained poorly differentiated,ultrathin mesophyll by increasing LD.Across plant lineages,LD,not LMA,is the trait that represents the trade-off between leaf robustness and physiology in the LES.
文摘Objective:To investigate the application of heparin-binding protein along with albumin(HBP+ALB)in evaluating the severity of community-acquired pneumonia(CAP)and compares it with single HBP,white blood cells(WBCs),C-reactive protein(CRP),and procalcitonin(PCT).Methods:A total of 226 patients with CAP admitted to the Emergency Department of Zhujiang Hospital,Southern Medical University,Guangdong,China,between March 1,2021,and March 1,2022,were enrolled.The patients were grouped into two groups:mild CAP(n=175)and severe CAP(sCAP)(n=51).Patients'characteristics and laboratory data were obtained.ROC curve and the value of the area under the curve(AUC)were used to evaluate the predictive values of HBP,ALB,WBC,CRP,and PCT.Results:WBC count,CRP,PCT,HBP,creatinine,and D-dimer were higher in the sCAP group,while ALB was lower in the sCAP group(P<0.05)than those in the mild CAP group.The AUCs of WBC,CRP,PCT,HBP,and HBP+ALB were 0.633(95%CI:0.545-0.722,P<0.05),0.635(95%CI:0.542-0.729,P<0.05),0.705(95%CI:0.619-0.791,P<0.05),0.809(95%CI:0.736-0.883,P<0.05),and 0.889(95%CI:0.842-0.936,P<0.05),respectively.Conclusions:HBP+ALB has a higher predictive value than single HBP,PCT,CRP and WBC used alone for the early assessment of CAP.
基金China Hepatitis Prevention Fund Project(tqgb20170015)Hebei medical science research key project(20170933)+1 种基金Hebei medical science research key project(20150842)Hebei Science and Technology Department funded project(162777133)
文摘Objective:To investigate the clinical effect of microecological preparation combined with bicyclol on nonalcoholic fatty liver (NAFLD) and its effect on liver fibrosis, serum inflammatory factors and transforming growth factorβ1 (TGF-β1).Methods:106 patients with NAFLD were randomly divided into control group (53 cases) and case group (53 cases). The control group was given routine liver protection and bicyclol, and the case group was given Bifidobacterium triple viable probiotics based on the treatment of the control group. The two groups were treated for 6 weeks. The clinical effect, liver fibrosis, serum inflammatory factors, TGF-β1 and other changes were observed in the two groups after treatment.Results:The total effective rate of the case group was significantly higher than that of the control group (96.22% vs 83.02%), (χ2=4.970,P=0.026). After treatment, the ALB and HDL levels of the two groups of patients were higher than before. ALT, AST, and TBIL, LN, HA, PCIII, CIV, TC, TG, LDL, IL-6, TNF-a, hs-CRP, TGF-β1 were lower, compared with before and after treatment;and the improvement of liver function, liver fibrosis, blood lipid levels, serum inflammatory factors, and TGF-β1 in the case group was better than that in the control group, and the differences were statistically significant (P <0.05). The incidence of adverse reactions in the case group was lower than that in the control group (5.66% vs 11.32%). The difference was not statistically significant (χ2=1.093,P=0.296).Conclusion: Microecological preparations combined with bicyclol in the treatment of NAFLD have exact clinical effects, can significantly improve liver function, regulate blood lipid levels, reduce inflammation and liver fibrosis, and have good safety, which deserves further clinical research and promotion.
基金the Fundamental Research Funds for the Central Universities (No.2042014kf0248) for support of this research
文摘The asymmetric α-amination of 1,3-dicarbonyl compounds with dialkyl azodicarboxylates has been achieved by C2-symmetric BINOL-squaramide bearing multiple hydrogen bond donors to provide the desired products in excellent yields and enantioselectivities （up to 99% yield and 98% ee）.
基金China Hepatitis Prevention Fund Project(No.tqgb20170015)Hebei medical science research key project(No.20170933)+1 种基金Hebei medical science research key project(No.20150842)Hebei Science and Technology Department funded project(No.162777133).
文摘Objective:To investigate the effect of Fuzheng Huayu Capsule combined with nucleoside antiviral drugs on liver and kidney function,serum inflammatory factors,Toll-like receptor 4(TLR-4),transforming growth factorβ1(TGF-β1)And aspartate aminotransferase-platelet ratio index(APRI).Methods:A total of 144 patients with HBV infection and decompensated cirrhosis were selected.All patients were divided into control group and case group by random number table method,with 72 cases in each group.The control group was given conventional liver protection and antiviral therapy;the case group was supplemented with Fuzheng Huayu Capsule on the basis of treatment in the control group.The changes of liver and kidney function,serum inflammatory factors,TLR-4,TGF-β1 and APRI in the two groups were observed.Results:The total effective rate of the case group was 93.06%,higher than 76.32%of the control group(P<0.05).Case group HBV DNA negative rate,negative rate of hepatitis B virus surface antigen(HBsAg),negative rate of hepatitis B virus e antigen(HBeAg)were significantly higher than the control group(76.39%vs 59.72%,55.56%vs 31.94%,51.39%vs 29.17%),the difference was statistically significant(P<0.05).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),hyaluronic acid(HA),laminin(LN),typeⅢprocollagen after treatment(PCⅢ),typeⅣcollagen(CⅣ),inner diameter of portal vein,inner diameter of splenic vein,spleen thickness,resistance index,urea nitrogen(BUN),creatinine(Cr),interleukin-6(IL-6),interleukin-8(IL-8),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),TLR-4,TGF-β1,APRI are lower than before treatment,albumin(ALB)and renal blood The flow rate was higher than before treatment;liver function indicators,liver fibrosis indicators,liver and spleen imaging indicators,renal hemodynamic indicators,serum inflammatory factors,TLR-4 in the case group The improvement of TGF-β1 and APRI.Conclusion:Fuzheng Huayu Capsules combined with nucleoside antiviral drugs have a clear clinical effect on patients with HBV infection and decompensated liver cirrhosis,significantly improve the clinical symptoms of patients,improve liver and kidney function,reduce inflammatory factor production,and can effectively inhibit HBV replication.Certain promotion value is worthy of further clinical research.
基金Supported by Guangxi Science and Technology Plan Project(Gui Ke AB18221096&Gui Ke AB 21196019)。
文摘[Objectives]To study the remediation methods of secondary salinization and cadmium pollution in facility soil.[Methods]Two kinds of soil amendments,potassium fulvic acid and limestone powder,were selected to be applied alone or combined together to plant maize to carry out field experiments.Their effects on watermelon yield,watermelon cadmium content,soil available nitrogen,phosphorus,potassium and water-soluble salts were studied.[Results]The application of potassium fulvic acid,limestone powder and their combined application increased the yield and soluble solids of watermelon to different degrees.The contents of seven heavy metals including cadmium,copper,zinc,arsenic,lead,mercury and chromium in the watermelon of all treatments were all lower than the food safety limit stipulated in the national standard.During the harvest period of maize seedlings,all treatments could increase soil pH and decrease soil cadmium availability.In particular,3000 kg/ha of limestone powder and 1500 kg/ha of potassium fulvic acid had the best effect on reducing soil available cadmium content.In reducing soil available cadmium content,there were significant differences between single application of amendment and combined application treatments.In addition,compared with the control CK,all treatments decreased soil available nitrogen,phosphorus,potassium and water-soluble salt content.[Conclusions]Potassium fulvic acid,limestone powder and their combined application can increase the yield of watermelon,and can significantly reduce the available cadmium,nitrogen,phosphorus,potassium and water-soluble salt content in the facility soil of maize cultivation.
文摘Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection.Methods: 136 patients with decompensated cirrhosis of HBV infection who were hospitalized in Linxi Hospital of Kailuan General Hospital, Tangshan Infectious Disease Hospital and North China University of Technology Hospital from January to February 2018, 2017 were selected. All patients were divided into control group and case group by random number table method, 68 cases in each group. The control group was treated with routine liver protection and antiviral therapy, while the case group was treated with alprostadil on the basis of the control group. The changes of liver function, liver fibrosis, liver and spleen imaging indexes, anti-virus related indexes and inflammatory factors were observed before and after treatment in the two groups.Results: The total effective rate of the case group was 97.06%, which was significantly higher than that of the control group (85.29%), and the difference was statistically significant. The ALT, AST, TBIL, LN, HA, PCIII, CIV, portal vein diameter, spleen vein diameter, spleen thickness, IL-6, hs-CRP, TNF-α and TGF-β1 were significantly lower in the case group than in the control group. ALB, HBV DNA conversion rate, HBsAg negative rate, and HBeAg negative rate were significantly higher than the control group, the difference was statistically significant. Conclusion: Alprostadil combined with nucleoside antiviral drugs can significantly improve the decompensation of HBV infection Liver function in patients with cirrhosis, reduce the degree of liver fibrosis, inhibit the production of serum inflammatory factors, and can effectively inhibit HBV replication, clinical efficacy is significant, with certain clinical application value.
基金supported by the National Key Research and Development Project (2021YFA1201404)National Natural Science Foundation of China Major Project (81991514)+6 种基金General Project (82272530, 82372459)Jiangsu Province Medical Innovation Center of Orthopedic Surgery (CXZX202214)Jiangsu Provincial Key Medical Center FoundationJiangsu Provincial Medical Outstanding Talent FoundationJiangsu Provincial Medical Youth Talent FoundationJiangsu Provincial Key Medical Talent Foundationthe Fundamental Research Funds for the Central Universities (14380493, 14380494)
文摘Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture.In this study,we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM.Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM.Mechanistically,SIRT3 suppression results in hyperacetylation of FOXO3,hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria.Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3,thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM.Collectively,our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control,crucial for maintaining bone homeostasis in T2DM.These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.
基金supported by grants from the National Key Research and Development Program of China,No.2017YFA0105400(to LR)the Key Research and Development Program of Guangdong Province,No.2019B020236002(to LR)the National Natural Science Foundation of China,Nos.81972111(to LZ),81772349(to BL).
文摘Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.
