Despite the diverse roles of tripartite motif(Trim)-containing proteins in the regulation of autophagy,the innate immune response,and cell differentiation,their roles in skeletal diseases are largely unknown.We recent...Despite the diverse roles of tripartite motif(Trim)-containing proteins in the regulation of autophagy,the innate immune response,and cell differentiation,their roles in skeletal diseases are largely unknown.We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast(OB)differentiation in osteosarcoma.However,how Trim21 contributes to skeletal degenerative disorders,including osteoporosis,remains unknown.First,human and mouse bone specimens were evaluated,and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients.Next,we found that global knockout of the Trim21 gene(KO,Trim2^(1-/-))resulted in higher bone mass compared to that of the control littermates.We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and elevating the activity of OBs;moreover,Trim21 depletion suppressed osteoclast(OC)formation of RAW264.7 cells.In addition,the differentiation of OCs from bone marrow-derived macrophages(BMMs)isolated from Trim21^(-/-)and Ctsk-cre;Trim21^(f/f)mice was largely compromised compared to that of the littermate control mice.Mechanistically,YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs.More importantly,the loss of Trim21 prevented ovariectomy(OVX)-and lipopolysaccharide(LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling.Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption,thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.展开更多
BACKGROUND There is no consensus on the usage of extended criteria donor(ECD)grafts in liver transplantation(LT)for acute-on-chronic liver failure(ACLF)patients.AIM To summarize the experience of using ECD livers in A...BACKGROUND There is no consensus on the usage of extended criteria donor(ECD)grafts in liver transplantation(LT)for acute-on-chronic liver failure(ACLF)patients.AIM To summarize the experience of using ECD livers in ACLF-LT.METHODS A retrospective cohort study was conducted,enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021.The patients were divided into ECD and non-ECD groups for analysis.RESULTS A total of 145 recipients were enrolled in this study,of which ECD and non-ECD recipients accounted for 53.8%and 46.2%,respectively.Donation after cardiac death(DCD)recipients accounted for the minority compared with donation after brain death(DBD)recipients(16.6%vs 83.4%).Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients.ECD grafts were associated with a significantly higher incidence of early allograft dysfunction(EAD)than non-ECD grafts(67.9%vs 41.8%,P=0.002).Postoperative outcomes between DCD and DBD recipients were comparable(P>0.05).ECD graft(P=0.009),anhepatic phase(P=0.034)and recipient gamma glutamyltransferase(P=0.016)were independent risk factors for EAD.Recipient preoperative number of extrahepatic organ failures>2(P=0.015)and intraoperative blood loss(P=0.000)were independent predictors of poor post-LT survival.CONCLUSION Although related to a higher risk of EAD,ECD grafts can be safely used in ACLF-LT.The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.展开更多
Red mud produced in the Bayer process is a hazardous solid waste because of its high alkalinity; however, it is rich in valuable components such as titanium, iron, and aluminum. In this study, a novel calcification–c...Red mud produced in the Bayer process is a hazardous solid waste because of its high alkalinity; however, it is rich in valuable components such as titanium, iron, and aluminum. In this study, a novel calcification–carbonation method was developed to recover alkali and alumina from Bayer red mud under mild reaction conditions. Batch experiments were performed to evaluate the potential effects of important parameters such as temperature, amount of CaO added, and CO_2 partial pressure on the recovery of alkali and alumina. The results showed that 95.2% alkali and 75.0% alumina were recovered from red mud with decreases in the mass ratios of Na_2 O to Fe_2O_3 and of Al_2O_3 to Fe_2O_3 from 0.42 and 0.89 to 0.02 and 0.22, respectively. The processed red mud with less than 0.5wt% Na_2 O can potentially be used as a construction material.展开更多
Although the anti-malaria drug chloroquine(CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials,the potential mechanisms underlying this enhancement are still unclear.Here,we examine...Although the anti-malaria drug chloroquine(CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials,the potential mechanisms underlying this enhancement are still unclear.Here,we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan(TPT).The lung cancer cell line A549 was treated with TPT alone or TPT combined with CQ at non-cytotoxic concentrations.Cell viability was assessed using the MTT assay.The percentage of apoptotic cells and the presence of a side population of cells were both determined by flow cytometry.Autophagy and the expression of Bcl-2 family proteins were examined by Western blotting.The accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles were examined by confocal microscopy.CQ sensitized A549 cells to TPT and enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion.CQ inhibited TPT-induced autophagy,which modified the cytotoxicity of TPT.However,CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did not increase lysosomal permeability.This study showed that CQ at non-cytotoxic concentrations potentiated the cytotoxicity of TPT by interfering with autophagy,implying that CQ has significant potential as a chemotherapeutic enhancer.展开更多
BACKGROUND: In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.METHODS: From July 2011 to August 2012, our ce...BACKGROUND: In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.METHODS: From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively.RESULTS: Among the 29 donors, 24 were China Category II donors(organ donation after cardiac death), and five were China Category III donors(organ donation after brain death followed by cardiac death). The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422(2-696) days. Among the five mortalities during the follow-up,three died of tumor recurrence. In terms of post-transplant complications, 9 recipients(34.6%) experienced early allograft dysfunction, 1(3.8%) had non-anastomotic biliary stricture,and 1(3.8%) was complicated with hepatic arterial thrombosis.None of these complications resulted in patient death. Notably,primary non-function was not observed in any of the grafts.CONCLUSION: With careful donor selection, liver transplant from deceased donors can be performed safely and plays acritical role in overcoming the extreme organ shortage in China.展开更多
Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports s...Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC.展开更多
Our previous study has shown that the transcription factor Krüppel-like factor 7(KLF7) promotes peripheral nerve regeneration and motor function recovery after spinal cord injury.KLF7 also participates in traumat...Our previous study has shown that the transcription factor Krüppel-like factor 7(KLF7) promotes peripheral nerve regeneration and motor function recovery after spinal cord injury.KLF7 also participates in traumatic brain injury,but its regulatory mechanisms remain poorly understood.In the present study,an HT22 cell model of traumatic brain injury was established by stretch injury and oxygenglucose deprivation.These cells were then transfected with an adeno-associated virus carrying KLF7(AAV-KLF7).The results revealed that,after stretch injury and oxygen-glucose deprivation,KLF7 greatly reduced apoptosis,activated caspase-3 and lactate dehydrogenase,downregulated the expression of the apoptotic markers B-cell lymphoma 2(Bcl-2)-associated X protein(Bax) and cleaved caspase-3,and increased the expression of βIII-tubulin and the antiapoptotic marker Bcl-2.Furthermore,KLF7 overexpression upregulated Janus kinase 2(JAK2) and signal transducer and activator of transcription 3(STAT3) phosphorylation in HT22 cells treated by stretch injury and oxygenglucose deprivation.Immunoprecipitation assays revealed that KLF7 directly participated in the phosphorylation of STAT3.In addition,treatment with AG490,a selective inhibitor of JAK2/STAT3,weakened the protective effects of KLF7.A mouse controlled cortical impact model of traumatic brain injury was then established.At 30 minutes before modeling,AAV-KLF7 was injected into the ipsilateral lateral ventricle.The protein and m RNA levels of KLF7 in the hippocampus were increased at 1 day after injury and recovered to normal levels at 3 days after injury.KLF7 reduced ipsilateral hippocampal atrophy,decreased the injured cortex volume,downregulated Bax and cleaved caspase-3 expression,and increased the number of 5-bromo-2'-deoxyuridine-positive neurons and Bcl-2 protein expression.Moreover,KLF7 transfection greatly enhanced the phosphorylation of JAK2 and STAT3 in the ipsilateral hippocampus.These results suggest that KLF7 may protect hippocampal neurons after traumatic brain injury through activation of the JAK2/STAT3 signaling pathway.The study was approved by the Institutional Review Board of Mudanjiang Medical University,China(approval No.mdjyxy-2018-0012) on March 6,2018.展开更多
Carbonated decomposition of hydrogarnet is one of the vital reactions of the calcification–carbonation method,which is designed to dispose of low-grade bauxite and Bayer red mud and is a novel eco-friendly method.In ...Carbonated decomposition of hydrogarnet is one of the vital reactions of the calcification–carbonation method,which is designed to dispose of low-grade bauxite and Bayer red mud and is a novel eco-friendly method.In this study,the effect of the silica saturation coefficient(x)on the carbonation of hydrogarnet was investigated from the kinetic perspective.The results indicated that the carbonation of hydrogarnets with different x values(x=0.27,0.36,0.70,and 0.73)underwent two stages with significantly different rates,and the kinetic mechanisms of the two stages can be described by the kinetic functions R3 and D3.The apparent activation energies at Stages 1 and 2 were 41.96–81.64 and 14.80–34.84 kJ/mol,respectively.Moreover,the corresponding limiting steps of the two stages were interfacial chemical reaction and diffusion.展开更多
BACKGROUND: The deficiency of liver regeneration needs to be addressed in the fields of liver surgery, split liver transplantation and living donor liver transplantation. Researches of micro RNAs would broaden our und...BACKGROUND: The deficiency of liver regeneration needs to be addressed in the fields of liver surgery, split liver transplantation and living donor liver transplantation. Researches of micro RNAs would broaden our understandings on the mechanisms of various diseases. Our previous research confirmed that mi R-26 a regulated liver regeneration in mice; however, the relationship between mi R-26 a and its target, directly or indirectly, remains unclear. Therefore, the present study further investigated the mechanism of mi R-26 a in regulating mouse hepatocyte proliferation.METHODS: An established mouse liver cell line, Nctc-1469, was transfected with Ad5-mi R-26a-EGFP, Ad5-anti-mi R-26 aEGFP or Ad5-EGFP vector. Cell proliferation was assessed by MTS, cell apoptosis and cell cycle by flow cytometry, and gene expression by Western blotting and quantitative real-time PCR. Dual-luciferase reporter assays were used to test targets of mi R-26 a.RESULTS: Compared with the Ad5-EGFP group, Ad5-antimi R-26a-EGFP down-regulated mi R-26 a and increased proliferation of hepatocytes, with more cells entering the G1 phase of cell cycle(82.70%±1.45% vs 75.80%±3.92%), and decreased apoptosis(5.50%±0.35% vs 6.73%±0.42%). CCND2 and CCNE2 were the direct targeted genes of mi R-26 a. mi R-26 a downregulation up-regulated CCND2 and CCNE2 expressions and down-regulated p53 expression in Nctc-1469 cells. On the contrary, mi R-26 a over-expression showed the opposite results.CONCLUSIONS: mi R-26 a regulated mouse hepatocyte proliferation by directly targeting the 3' untranslated regions of cyclin D2/cyclin E2; mi R-26 a also regulated p53-mediated apoptosis. Our data suggested that mi R-26 a may be a promising regulator in liver regeneration.展开更多
BACKGROUND Parathyroid adenoma is a benign parathyroid tumor,with serum parathyroid hormone and calcium ion concentrations as the typical basis for diagnosis.Its clinical manifestations are complex and changeable;thus...BACKGROUND Parathyroid adenoma is a benign parathyroid tumor,with serum parathyroid hormone and calcium ion concentrations as the typical basis for diagnosis.Its clinical manifestations are complex and changeable;thus it is easily missed or misdiagnosed.Approximately 85%of patients with parathyroid adenoma develop primary hyperparathyroidism,and abnormalities in bones,kidneys and other organs can occur.Brown tumors are rare.CASE SUMMARY We report a rare case of fibrocystic osteitis associated with a parathyroid adenoma,which was discovered by chance due to a rib tumor.Abnormally elevated serum parathyroid hormone and calcium ion were found before surgery.We suspected primary hyperparathyroidism,and color Doppler ultrasound suggested the presence of a thyroid mass.With informed consent by the patient and her family,we first removed the rib tumor,and one week later,resection of the parathyroid adenoma and thyroid mass was performed on both sides,and the patient recovered well after surgery.CONCLUSION In the case of parathyroid adenoma combined with brown tumor,the bone cyst will gradually decrease in size with time without treatment.If not,surgery should be performed as soon as possible.展开更多
Small nucleolar RNAs (snoRNAs) are non-coding RNA (ncRNA) molecules,which are associated with specific proteins to form small nucleolar ribonucleoparticles.However,the function of snoRNAs in cancer still remains elusi...Small nucleolar RNAs (snoRNAs) are non-coding RNA (ncRNA) molecules,which are associated with specific proteins to form small nucleolar ribonucleoparticles.However,the function of snoRNAs in cancer still remains elusive.Recently,several independent lines of evidence have indicated that these ncRNAs might have crucial roles in controlling tumorigenesis,and snoRNAs could be potential biomarkers for cancer.展开更多
From 2011 to 2012, we collected Scutellonema commune from the rhizosphere soil of coconut(cocos nucifera L.) and Scutellonema magniphasma from the rhizosphere soil of Rosa chinensis in Shenyang, China. S. commune was ...From 2011 to 2012, we collected Scutellonema commune from the rhizosphere soil of coconut(cocos nucifera L.) and Scutellonema magniphasma from the rhizosphere soil of Rosa chinensis in Shenyang, China. S. commune was characterized by rounded scutella, which was varied from two annules anterior to the anus and five annules posterior. The lateral field was not areolated at the level of scutella. S. magniphasma was characterized by varying scutellum, about 7.0 μm in diameter, in position from four annules posterior to four annules anterior to the anus, and areolated at the level of the scutellum.展开更多
Objective To observe the effects of repetitive transcranial magnetic stimulation(rTMS)and cognitive behavioral therapy(CBT)on cognitive function in alcohol-dependent patients.Methods Data from 285 alcohol-dependent pa...Objective To observe the effects of repetitive transcranial magnetic stimulation(rTMS)and cognitive behavioral therapy(CBT)on cognitive function in alcohol-dependent patients.Methods Data from 285 alcohol-dependent patients were collected from Mudanjiang Medical University and Sun Yat-sen Memorial Hospital at Sun Yat-sen University between 2019 and 2021.The patients were divided into groups depending on alcohol abstinence and non-abstinence.There were 43 patients in the alcohol consumption(AC)group.The patients in the abstinence group were randomly assigned to treatment regimens with different combinations of rTMS and CBT using the Elton system.There were 49 patients in the TB+C0 group,36 in the TB+C1 group,44 in the TL+C0 group,36 in the TL+C1 group,37 in the TR+C0 group,and 40 in the TR+C1 group.Cognitive function was assessed by using the Montreal Cognitive Assessment Scale(MoCA).Results The proportion of patients with cognitive impairment in the AC group at 24 weeks was higher than that at baseline(P<0.05),whereas the proportion of cognitive impairment in the other groups did not differ significantly over time.The percentage of patients with cognitive impairment at 24 weeks was 52.3%in the TL+C0 group and 47.2%in the TL+C1 group,which was significantly lower than that in the AC group(P<0.05).MoCA scores at different time points in the AC group were significantly higher than those in the TB+C0,TL+C0,TL+C1,TR+C0,and TR+C1 groups,respectively.MoCA scores were significantly higher at 12 weeks compared with the baseline in the TB+C0,TL+C0,TL+C1,TR+C0,and TR+C1 groups(P<0.05),and similar changes were observed at 24 weeks.The MoCA scores in the TL+C1 and TL+C0 groups were higher than those in the TR+C0 group at 12 weeks after the intervention(P<0.05).Furthermore,MoCA scores in each of the TB+C1,TL+C1,TL+C0,TR+C1,and TR+C0 groups were higher than those in the AC group at 24 weeks(P<0.05).Conclusion Alcohol consumption impairs cognitive function,as evidenced by a significantly higher proportion of cognitive impairment after 24 weeks of non-abstinence.Most of the tested treatment regimens improved cognitive function.High frequency rTMS of the left dorsolateral prefrontal cortex(DLPFC)was associated with a greater improvement in cognitive function than that of the right DLPFC in alcohol-dependent patients at 12 weeks of abstinence.There does not appear to be a therapeutic advantage of CBT for cognitive impairment in alcohol-dependent patients.Screening for impaired cognitive function should be seriously considered for patients who engage in heavy drinking,and measures should be taken to reduce the risk of dementia induced by alcohol dependence.展开更多
Synthesis of diverse polythioimidocarbonates via ring-opening copolymerization of epoxides and isothiocyanates catalyzed by organoboron catalyst was reported herein.Both aromatic and aliphatic isothiocyanates underwen...Synthesis of diverse polythioimidocarbonates via ring-opening copolymerization of epoxides and isothiocyanates catalyzed by organoboron catalyst was reported herein.Both aromatic and aliphatic isothiocyanates underwent successful copolymerization with terminal and internal epoxides,allowing for the precise tuning of the performance of the resultant copolymers over a broad range.The wide scope of available isothiocyanates and epoxides enables the direct construction of sulfur-containing functional polymers featuring both high glass transition temperature and refractive index.Additionally,it was observed that aromatic isothiocyanates polymerize much faster than aliphatic ones,and the reactivity difference facilitated the one-step synthesis of block polymers from mixed aromatic isothiocyanates,aliphatic isothiocyanates and epoxides due to the preferential incorporation of aromatic isothiocyanates over the aliphatic analogues during their alternating copolymerization with epoxides.The produced polythioimidocarbonates can be used as positive resists for electron beam lithography(sensitivity of 130μC/cm^(2) and contrast of 1.53 for poly(CHO-alt-EITC)).Coupling with their high refractive index(1.58—1.68),polythioimidocarbonates might find functional applications in optics.These results render ring-opening copolymerization of epoxides and isothiocyanates a facile route to enrich functional polymer library.展开更多
Nickel-rich LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)is regarded as the promising cathode for lithium-ion batteries(LIBs).However,the challenges such as safety issues and poor cycling performance have seriously hindered...Nickel-rich LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)is regarded as the promising cathode for lithium-ion batteries(LIBs).However,the challenges such as safety issues and poor cycling performance have seriously hindered its commercial applications.In order to overcome these difficulties,there has been extensive research and development of electrolyte modifications for high-energy-density LIBs with Ni-rich cathodes.Herein,this review introduces the research progress based on solvent additives,salt type additives and other electrolytes for LIBs with NCM811cathode materials and discusses how they control the interface stability.In particular,some recommendations for further modification of enhancing electrolyte stability and improving NCM811 electrochemical properties are summarized and proposed,which put forward new design rules for the screening and customizing ideal electrolyte additives for high performance NCM811 cathode-based LIBs.展开更多
A previous study has indicated that Krüppel-like factor 7(KLF7), a transcription factor that stimulates Schwann cell(SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therape...A previous study has indicated that Krüppel-like factor 7(KLF7), a transcription factor that stimulates Schwann cell(SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of micro RNA-146 b(mi R-146 b)affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with mi RNA lentivirus, mi RNA inhibitor lentivirus, or KLF7 si RNA lentivirus in vitro. The expression of mi R146 b and KLF7,as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft(ANA) followed by injection of GFP control vector or a lentiviral vector encoding an mi R-146 b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. mi R-146 b directly targeted KLF7 by binding to the 30-UTR, suppressing KLF7. Up-regulation of mi R-146 b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing mi R-146 b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which mi R-146 b was expressed in vivo.Similarly, 4 weeks after the ANA, anti-mi R-146 b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0(anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by mi R-146 b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.展开更多
Titanium has a great effect on the digestion of bauxite in the Bayer process because it reacts readily at high temperatures in alkaline sodium aluminate solution.Under this consideration, the hydrothermal conversion o...Titanium has a great effect on the digestion of bauxite in the Bayer process because it reacts readily at high temperatures in alkaline sodium aluminate solution.Under this consideration, the hydrothermal conversion of Ti-containing minerals in the system of Na_2O–Al_2O_3–Si O_2–Ca O–Ti O_2–H_2O with increased temperatures was studied based on the thermodynamic analysis and systematic experiments. The results show that anatase converts to Al_4Ti_2 SiO_(12) at low temperatures(60–120 °C), which is similar to anatase in crystal structure. As the temperature continues to rise, Al4Ti2 Si O12decomposes gradually and converts to Ca_3 Ti Si_2(Al_2Si_(0.5)Ti_(0.5)O_(14) at 200 °C. When the temperature reaches 260 °C, Ca Ti O_3 forms as the most stable titanate species for its hexagonal closest packing with O_2-and Ca_2?. The findings enhance the understanding of titanate scaling in the Bayer process and clarify the mechanism of how additive lime improves the digestion of diaspore.展开更多
Met tyrosine kinase,a receptor for a hepatocyte growth factor(HGF),plays a critical role in tumor growth,metastasis,and drug resistance.Mitochondria are highly dynamic and undergo fission and fusion to maintain a func...Met tyrosine kinase,a receptor for a hepatocyte growth factor(HGF),plays a critical role in tumor growth,metastasis,and drug resistance.Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network.Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers.Here,using structured illumination microscopy(SIM)and high spatial and temporal resolution live cell imaging,we identified mitochondrial trafficking of receptor tyrosine kinase Met.The ton tacts betwee n activated Met kinase and mitochondria formed dramatically,and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements.Mechanically,we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38(Fisl pY38).Fisl pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein・1(Drp1)to mitochondria.Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma(HCC)cells both in vitro and in vivo.These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities,which may provide a therapeutic target for metastatic HCC.展开更多
基金supported by the Natural Science Foundation with grants from the National Key R&D Program of China(2018YFC2002500)National Natural Science Foundation of China(81602360,82072470,82350003,92049201)+6 种基金Key Laboratory Construction Project of Guangzhou Science and Technology Bureau(202102100007)supported by the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(No.JNU1AF-CFTP-2022-a01221)Natural Science Foundation of Guangdong Province(2021A1515012154,2019A1515011082,2017A030313665,2018A030313544,2020B1515120038)Science and Technology Projects in Guangzhou(201707010493,202102010069)Macao Foundation for Development of Science and Technology(0029/2019/A)Youth Talent Support Project of Guangzhou Association for Science&Technology(X20200301018)pilot project of clinical collaboration from National Administration of Traditional Chinese Medicine and National Health Commission of the People’s Republic of China and Logistics Support Department of the Central Military Commission。
文摘Despite the diverse roles of tripartite motif(Trim)-containing proteins in the regulation of autophagy,the innate immune response,and cell differentiation,their roles in skeletal diseases are largely unknown.We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast(OB)differentiation in osteosarcoma.However,how Trim21 contributes to skeletal degenerative disorders,including osteoporosis,remains unknown.First,human and mouse bone specimens were evaluated,and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients.Next,we found that global knockout of the Trim21 gene(KO,Trim2^(1-/-))resulted in higher bone mass compared to that of the control littermates.We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and elevating the activity of OBs;moreover,Trim21 depletion suppressed osteoclast(OC)formation of RAW264.7 cells.In addition,the differentiation of OCs from bone marrow-derived macrophages(BMMs)isolated from Trim21^(-/-)and Ctsk-cre;Trim21^(f/f)mice was largely compromised compared to that of the littermate control mice.Mechanistically,YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs.More importantly,the loss of Trim21 prevented ovariectomy(OVX)-and lipopolysaccharide(LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling.Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption,thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.
文摘BACKGROUND There is no consensus on the usage of extended criteria donor(ECD)grafts in liver transplantation(LT)for acute-on-chronic liver failure(ACLF)patients.AIM To summarize the experience of using ECD livers in ACLF-LT.METHODS A retrospective cohort study was conducted,enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021.The patients were divided into ECD and non-ECD groups for analysis.RESULTS A total of 145 recipients were enrolled in this study,of which ECD and non-ECD recipients accounted for 53.8%and 46.2%,respectively.Donation after cardiac death(DCD)recipients accounted for the minority compared with donation after brain death(DBD)recipients(16.6%vs 83.4%).Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients.ECD grafts were associated with a significantly higher incidence of early allograft dysfunction(EAD)than non-ECD grafts(67.9%vs 41.8%,P=0.002).Postoperative outcomes between DCD and DBD recipients were comparable(P>0.05).ECD graft(P=0.009),anhepatic phase(P=0.034)and recipient gamma glutamyltransferase(P=0.016)were independent risk factors for EAD.Recipient preoperative number of extrahepatic organ failures>2(P=0.015)and intraoperative blood loss(P=0.000)were independent predictors of poor post-LT survival.CONCLUSION Although related to a higher risk of EAD,ECD grafts can be safely used in ACLF-LT.The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.
基金financially supported by the Joint Funds of the National Natural Science Foundation of China(No.U1202274)the National Natural Science Foundation of China(No.51204040)+1 种基金the Research Fund for the Doctoral Program of Higher Education of China(No.20120042110011)the Fundamental Research Funds for the Central Universities(No.N140204015)
文摘Red mud produced in the Bayer process is a hazardous solid waste because of its high alkalinity; however, it is rich in valuable components such as titanium, iron, and aluminum. In this study, a novel calcification–carbonation method was developed to recover alkali and alumina from Bayer red mud under mild reaction conditions. Batch experiments were performed to evaluate the potential effects of important parameters such as temperature, amount of CaO added, and CO_2 partial pressure on the recovery of alkali and alumina. The results showed that 95.2% alkali and 75.0% alumina were recovered from red mud with decreases in the mass ratios of Na_2 O to Fe_2O_3 and of Al_2O_3 to Fe_2O_3 from 0.42 and 0.89 to 0.02 and 0.22, respectively. The processed red mud with less than 0.5wt% Na_2 O can potentially be used as a construction material.
基金supported by research grants from the National Natural Science Foundation of China(No.30972882)the Natural Science Foundation of Guangdong Province,China(No.9151008901000149)
文摘Although the anti-malaria drug chloroquine(CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials,the potential mechanisms underlying this enhancement are still unclear.Here,we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan(TPT).The lung cancer cell line A549 was treated with TPT alone or TPT combined with CQ at non-cytotoxic concentrations.Cell viability was assessed using the MTT assay.The percentage of apoptotic cells and the presence of a side population of cells were both determined by flow cytometry.Autophagy and the expression of Bcl-2 family proteins were examined by Western blotting.The accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles were examined by confocal microscopy.CQ sensitized A549 cells to TPT and enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion.CQ inhibited TPT-induced autophagy,which modified the cytotoxicity of TPT.However,CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did not increase lysosomal permeability.This study showed that CQ at non-cytotoxic concentrations potentiated the cytotoxicity of TPT by interfering with autophagy,implying that CQ has significant potential as a chemotherapeutic enhancer.
基金supported by grants from the National High Technology Research and Development Program of China(863 Program)(2012AA021008)the Special Fund for Science Research by Ministry of Health(201302009)
文摘BACKGROUND: In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.METHODS: From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively.RESULTS: Among the 29 donors, 24 were China Category II donors(organ donation after cardiac death), and five were China Category III donors(organ donation after brain death followed by cardiac death). The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422(2-696) days. Among the five mortalities during the follow-up,three died of tumor recurrence. In terms of post-transplant complications, 9 recipients(34.6%) experienced early allograft dysfunction, 1(3.8%) had non-anastomotic biliary stricture,and 1(3.8%) was complicated with hepatic arterial thrombosis.None of these complications resulted in patient death. Notably,primary non-function was not observed in any of the grafts.CONCLUSION: With careful donor selection, liver transplant from deceased donors can be performed safely and plays acritical role in overcoming the extreme organ shortage in China.
文摘Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC.
基金supported by the National Natural Science Foundation of China,No.81870977 (to YW)the Natural Science Foundation of Heilongjiang of China,No.H2018068 (to WYL)+3 种基金the Basic Research Operating Expenses Program of Heilongjiang Provincial Universities of China,No.2019-KYYWFMY-0018 (to WYL)the Graduate Innovative Research Projects of Mudanjiang Medical College of China,No.YJSCX-MY22 (to DM)Key projects of Education Department of Hebei Province of China,No.ZD2020178 (to XMF)Hebei Key Laboratory of Nerve Injury and Repair of China (to XMF)。
文摘Our previous study has shown that the transcription factor Krüppel-like factor 7(KLF7) promotes peripheral nerve regeneration and motor function recovery after spinal cord injury.KLF7 also participates in traumatic brain injury,but its regulatory mechanisms remain poorly understood.In the present study,an HT22 cell model of traumatic brain injury was established by stretch injury and oxygenglucose deprivation.These cells were then transfected with an adeno-associated virus carrying KLF7(AAV-KLF7).The results revealed that,after stretch injury and oxygen-glucose deprivation,KLF7 greatly reduced apoptosis,activated caspase-3 and lactate dehydrogenase,downregulated the expression of the apoptotic markers B-cell lymphoma 2(Bcl-2)-associated X protein(Bax) and cleaved caspase-3,and increased the expression of βIII-tubulin and the antiapoptotic marker Bcl-2.Furthermore,KLF7 overexpression upregulated Janus kinase 2(JAK2) and signal transducer and activator of transcription 3(STAT3) phosphorylation in HT22 cells treated by stretch injury and oxygenglucose deprivation.Immunoprecipitation assays revealed that KLF7 directly participated in the phosphorylation of STAT3.In addition,treatment with AG490,a selective inhibitor of JAK2/STAT3,weakened the protective effects of KLF7.A mouse controlled cortical impact model of traumatic brain injury was then established.At 30 minutes before modeling,AAV-KLF7 was injected into the ipsilateral lateral ventricle.The protein and m RNA levels of KLF7 in the hippocampus were increased at 1 day after injury and recovered to normal levels at 3 days after injury.KLF7 reduced ipsilateral hippocampal atrophy,decreased the injured cortex volume,downregulated Bax and cleaved caspase-3 expression,and increased the number of 5-bromo-2'-deoxyuridine-positive neurons and Bcl-2 protein expression.Moreover,KLF7 transfection greatly enhanced the phosphorylation of JAK2 and STAT3 in the ipsilateral hippocampus.These results suggest that KLF7 may protect hippocampal neurons after traumatic brain injury through activation of the JAK2/STAT3 signaling pathway.The study was approved by the Institutional Review Board of Mudanjiang Medical University,China(approval No.mdjyxy-2018-0012) on March 6,2018.
基金the National Natural Science Foundation of China(Nos.51874078,U1710257,U1202274,and 51764039)the Open Fund of Key Laboratory for Ecological Metallurgy of Multimetallic Mineral(Ministry of Education)Northeastern University,China(No.NEMM2019004).
文摘Carbonated decomposition of hydrogarnet is one of the vital reactions of the calcification–carbonation method,which is designed to dispose of low-grade bauxite and Bayer red mud and is a novel eco-friendly method.In this study,the effect of the silica saturation coefficient(x)on the carbonation of hydrogarnet was investigated from the kinetic perspective.The results indicated that the carbonation of hydrogarnets with different x values(x=0.27,0.36,0.70,and 0.73)underwent two stages with significantly different rates,and the kinetic mechanisms of the two stages can be described by the kinetic functions R3 and D3.The apparent activation energies at Stages 1 and 2 were 41.96–81.64 and 14.80–34.84 kJ/mol,respectively.Moreover,the corresponding limiting steps of the two stages were interfacial chemical reaction and diffusion.
基金supported by grants from the Key Clinical Project from the Ministry of Health(159)the National Natural Science Foundation of China(30972951 and 81170448)+1 种基金Special Fund for Science Research by Ministry of Health(201002004)the PhD Programs Foundation of Ministry of Education of China(20130171120076)
文摘BACKGROUND: The deficiency of liver regeneration needs to be addressed in the fields of liver surgery, split liver transplantation and living donor liver transplantation. Researches of micro RNAs would broaden our understandings on the mechanisms of various diseases. Our previous research confirmed that mi R-26 a regulated liver regeneration in mice; however, the relationship between mi R-26 a and its target, directly or indirectly, remains unclear. Therefore, the present study further investigated the mechanism of mi R-26 a in regulating mouse hepatocyte proliferation.METHODS: An established mouse liver cell line, Nctc-1469, was transfected with Ad5-mi R-26a-EGFP, Ad5-anti-mi R-26 aEGFP or Ad5-EGFP vector. Cell proliferation was assessed by MTS, cell apoptosis and cell cycle by flow cytometry, and gene expression by Western blotting and quantitative real-time PCR. Dual-luciferase reporter assays were used to test targets of mi R-26 a.RESULTS: Compared with the Ad5-EGFP group, Ad5-antimi R-26a-EGFP down-regulated mi R-26 a and increased proliferation of hepatocytes, with more cells entering the G1 phase of cell cycle(82.70%±1.45% vs 75.80%±3.92%), and decreased apoptosis(5.50%±0.35% vs 6.73%±0.42%). CCND2 and CCNE2 were the direct targeted genes of mi R-26 a. mi R-26 a downregulation up-regulated CCND2 and CCNE2 expressions and down-regulated p53 expression in Nctc-1469 cells. On the contrary, mi R-26 a over-expression showed the opposite results.CONCLUSIONS: mi R-26 a regulated mouse hepatocyte proliferation by directly targeting the 3' untranslated regions of cyclin D2/cyclin E2; mi R-26 a also regulated p53-mediated apoptosis. Our data suggested that mi R-26 a may be a promising regulator in liver regeneration.
文摘BACKGROUND Parathyroid adenoma is a benign parathyroid tumor,with serum parathyroid hormone and calcium ion concentrations as the typical basis for diagnosis.Its clinical manifestations are complex and changeable;thus it is easily missed or misdiagnosed.Approximately 85%of patients with parathyroid adenoma develop primary hyperparathyroidism,and abnormalities in bones,kidneys and other organs can occur.Brown tumors are rare.CASE SUMMARY We report a rare case of fibrocystic osteitis associated with a parathyroid adenoma,which was discovered by chance due to a rib tumor.Abnormally elevated serum parathyroid hormone and calcium ion were found before surgery.We suspected primary hyperparathyroidism,and color Doppler ultrasound suggested the presence of a thyroid mass.With informed consent by the patient and her family,we first removed the rib tumor,and one week later,resection of the parathyroid adenoma and thyroid mass was performed on both sides,and the patient recovered well after surgery.CONCLUSION In the case of parathyroid adenoma combined with brown tumor,the bone cyst will gradually decrease in size with time without treatment.If not,surgery should be performed as soon as possible.
文摘Small nucleolar RNAs (snoRNAs) are non-coding RNA (ncRNA) molecules,which are associated with specific proteins to form small nucleolar ribonucleoparticles.However,the function of snoRNAs in cancer still remains elusive.Recently,several independent lines of evidence have indicated that these ncRNAs might have crucial roles in controlling tumorigenesis,and snoRNAs could be potential biomarkers for cancer.
基金supported by the National Natural Science Foundation of China(31171823)
文摘From 2011 to 2012, we collected Scutellonema commune from the rhizosphere soil of coconut(cocos nucifera L.) and Scutellonema magniphasma from the rhizosphere soil of Rosa chinensis in Shenyang, China. S. commune was characterized by rounded scutella, which was varied from two annules anterior to the anus and five annules posterior. The lateral field was not areolated at the level of scutella. S. magniphasma was characterized by varying scutellum, about 7.0 μm in diameter, in position from four annules posterior to four annules anterior to the anus, and areolated at the level of the scutellum.
基金National Key Research and Development Program(2018YFC1314400)Key R&D plan of Heilongjiang Province(GA21C010)。
文摘Objective To observe the effects of repetitive transcranial magnetic stimulation(rTMS)and cognitive behavioral therapy(CBT)on cognitive function in alcohol-dependent patients.Methods Data from 285 alcohol-dependent patients were collected from Mudanjiang Medical University and Sun Yat-sen Memorial Hospital at Sun Yat-sen University between 2019 and 2021.The patients were divided into groups depending on alcohol abstinence and non-abstinence.There were 43 patients in the alcohol consumption(AC)group.The patients in the abstinence group were randomly assigned to treatment regimens with different combinations of rTMS and CBT using the Elton system.There were 49 patients in the TB+C0 group,36 in the TB+C1 group,44 in the TL+C0 group,36 in the TL+C1 group,37 in the TR+C0 group,and 40 in the TR+C1 group.Cognitive function was assessed by using the Montreal Cognitive Assessment Scale(MoCA).Results The proportion of patients with cognitive impairment in the AC group at 24 weeks was higher than that at baseline(P<0.05),whereas the proportion of cognitive impairment in the other groups did not differ significantly over time.The percentage of patients with cognitive impairment at 24 weeks was 52.3%in the TL+C0 group and 47.2%in the TL+C1 group,which was significantly lower than that in the AC group(P<0.05).MoCA scores at different time points in the AC group were significantly higher than those in the TB+C0,TL+C0,TL+C1,TR+C0,and TR+C1 groups,respectively.MoCA scores were significantly higher at 12 weeks compared with the baseline in the TB+C0,TL+C0,TL+C1,TR+C0,and TR+C1 groups(P<0.05),and similar changes were observed at 24 weeks.The MoCA scores in the TL+C1 and TL+C0 groups were higher than those in the TR+C0 group at 12 weeks after the intervention(P<0.05).Furthermore,MoCA scores in each of the TB+C1,TL+C1,TL+C0,TR+C1,and TR+C0 groups were higher than those in the AC group at 24 weeks(P<0.05).Conclusion Alcohol consumption impairs cognitive function,as evidenced by a significantly higher proportion of cognitive impairment after 24 weeks of non-abstinence.Most of the tested treatment regimens improved cognitive function.High frequency rTMS of the left dorsolateral prefrontal cortex(DLPFC)was associated with a greater improvement in cognitive function than that of the right DLPFC in alcohol-dependent patients at 12 weeks of abstinence.There does not appear to be a therapeutic advantage of CBT for cognitive impairment in alcohol-dependent patients.Screening for impaired cognitive function should be seriously considered for patients who engage in heavy drinking,and measures should be taken to reduce the risk of dementia induced by alcohol dependence.
基金supported by the National Natural Science Foundation of China(Grants 51973186 and 22101253)the National Science Fund for Distinguished Young Scholars(No.T2225004).
文摘Synthesis of diverse polythioimidocarbonates via ring-opening copolymerization of epoxides and isothiocyanates catalyzed by organoboron catalyst was reported herein.Both aromatic and aliphatic isothiocyanates underwent successful copolymerization with terminal and internal epoxides,allowing for the precise tuning of the performance of the resultant copolymers over a broad range.The wide scope of available isothiocyanates and epoxides enables the direct construction of sulfur-containing functional polymers featuring both high glass transition temperature and refractive index.Additionally,it was observed that aromatic isothiocyanates polymerize much faster than aliphatic ones,and the reactivity difference facilitated the one-step synthesis of block polymers from mixed aromatic isothiocyanates,aliphatic isothiocyanates and epoxides due to the preferential incorporation of aromatic isothiocyanates over the aliphatic analogues during their alternating copolymerization with epoxides.The produced polythioimidocarbonates can be used as positive resists for electron beam lithography(sensitivity of 130μC/cm^(2) and contrast of 1.53 for poly(CHO-alt-EITC)).Coupling with their high refractive index(1.58—1.68),polythioimidocarbonates might find functional applications in optics.These results render ring-opening copolymerization of epoxides and isothiocyanates a facile route to enrich functional polymer library.
基金financially supported by the National Natural Science Foundation of China(Nos.51971090,U21A20311)。
文摘Nickel-rich LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)is regarded as the promising cathode for lithium-ion batteries(LIBs).However,the challenges such as safety issues and poor cycling performance have seriously hindered its commercial applications.In order to overcome these difficulties,there has been extensive research and development of electrolyte modifications for high-energy-density LIBs with Ni-rich cathodes.Herein,this review introduces the research progress based on solvent additives,salt type additives and other electrolytes for LIBs with NCM811cathode materials and discusses how they control the interface stability.In particular,some recommendations for further modification of enhancing electrolyte stability and improving NCM811 electrochemical properties are summarized and proposed,which put forward new design rules for the screening and customizing ideal electrolyte additives for high performance NCM811 cathode-based LIBs.
基金supported by the National Natural Science Foundation of China (81371362, 81641125, and 81500629)the Scientific Research Foundation of Heilongjiang Province, China (LC2017040)+1 种基金the Science Fund of Heilongjiang Provincial Health and Family Planning Commission, China (2016357 and 2016385)the Basic Research Operating Expenses Program of Heilongjiang Provincial Universities, China (2017- KYYWFMY0661)
文摘A previous study has indicated that Krüppel-like factor 7(KLF7), a transcription factor that stimulates Schwann cell(SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of micro RNA-146 b(mi R-146 b)affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with mi RNA lentivirus, mi RNA inhibitor lentivirus, or KLF7 si RNA lentivirus in vitro. The expression of mi R146 b and KLF7,as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft(ANA) followed by injection of GFP control vector or a lentiviral vector encoding an mi R-146 b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. mi R-146 b directly targeted KLF7 by binding to the 30-UTR, suppressing KLF7. Up-regulation of mi R-146 b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing mi R-146 b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which mi R-146 b was expressed in vivo.Similarly, 4 weeks after the ANA, anti-mi R-146 b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0(anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by mi R-146 b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.
基金financially supported by the National Natural Science Foundation of China(Nos.U1202274 and51504059)China Postdoctoral Science Foundation Funded Project(No.2015M581352)the Fundamental Research Funds for the Central Universities of China(Nos.N140203005 and N140204015)
文摘Titanium has a great effect on the digestion of bauxite in the Bayer process because it reacts readily at high temperatures in alkaline sodium aluminate solution.Under this consideration, the hydrothermal conversion of Ti-containing minerals in the system of Na_2O–Al_2O_3–Si O_2–Ca O–Ti O_2–H_2O with increased temperatures was studied based on the thermodynamic analysis and systematic experiments. The results show that anatase converts to Al_4Ti_2 SiO_(12) at low temperatures(60–120 °C), which is similar to anatase in crystal structure. As the temperature continues to rise, Al4Ti2 Si O12decomposes gradually and converts to Ca_3 Ti Si_2(Al_2Si_(0.5)Ti_(0.5)O_(14) at 200 °C. When the temperature reaches 260 °C, Ca Ti O_3 forms as the most stable titanate species for its hexagonal closest packing with O_2-and Ca_2?. The findings enhance the understanding of titanate scaling in the Bayer process and clarify the mechanism of how additive lime improves the digestion of diaspore.
基金This study was supported by the Natural Science Foundation of China(81772624,81972855,81630079,and 81972442)the Science and Technology Project of Guangzhou(201803010007)+4 种基金the Natural Science Foundation of Guangdong Province(2017A030313481,2021 Al 515010092)the National Postdoctoral Program for Innovative Talents(BX2021391)the Fundamental Research Funds for the Central Universities(17ykjc25)the National Key R&D Program of China(2017YFC0908501)the Open Funds of State Key Laboratory of Oncology in South China(KY013714).
文摘Met tyrosine kinase,a receptor for a hepatocyte growth factor(HGF),plays a critical role in tumor growth,metastasis,and drug resistance.Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network.Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers.Here,using structured illumination microscopy(SIM)and high spatial and temporal resolution live cell imaging,we identified mitochondrial trafficking of receptor tyrosine kinase Met.The ton tacts betwee n activated Met kinase and mitochondria formed dramatically,and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements.Mechanically,we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38(Fisl pY38).Fisl pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein・1(Drp1)to mitochondria.Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma(HCC)cells both in vitro and in vivo.These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities,which may provide a therapeutic target for metastatic HCC.
