Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-ce...Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.展开更多
Microalloying elements play a crucial role in mechanical properties and phase stability of metallic alloys.In this work,we employ first-principles calculations and atomic-scale high-angle annular dark-field scanning t...Microalloying elements play a crucial role in mechanical properties and phase stability of metallic alloys.In this work,we employ first-principles calculations and atomic-scale high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM)to find promising microalloying elements that will improve the stability and properties ofβ"/Al interface andβ"phase in Al–Mg-Si alloys.First,we define a substitution energy for evaluating the stability ofβ"phase andβ"/Al interface with microalloying elements doped.Then,experiments of HAADF-STEM imaging are carried out to verify the calculational results.Next,using the most stable structures doped with microalloying elements,the mechanical properties of theβ"bulk and theβ"/Al interface were calculated and analyzed.At last,we have figured out the effects of all considered microalloying elements and obtained a rule that the stable occupancy of solute atoms is related to their own radius and the radius of Mg,Si,and Al.These findings will provide some theoretical basis for future microalloying strategies of Al–Mg-Si alloys.展开更多
There is currently a huge worldwide demand for donor kidneys for organ transplantation.Consequently,numerous marginal donor kidneys,such as kidneys with microthrombi,are used to save patients'lives.While some stud...There is currently a huge worldwide demand for donor kidneys for organ transplantation.Consequently,numerous marginal donor kidneys,such as kidneys with microthrombi,are used to save patients'lives.While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function(DGF)(McCall et al.,2003;Gao et al.,2019),other studies have demonstrated that microthrombi negatively impact the rate of DGF(Batra et al.,2016;Hansen et al.,2018),but not graft survival rate(McCall et al.,2003;Batra et al.,2016;Gao et al.,2019).In contrast,Hansen et al.(2018)concluded that fibrin thrombi were not only associated with reduced graft function six months posttransplantation but also with increased graft loss within the first year of transplantation.On the other hand,Batra et al.(2016)found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups.To date,however,the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial,necessitating further research.展开更多
Transcription factors and phytohormones have been reported to play crucial roles to regulate leaf complexity among plant species. Using the compound-leafed species Lotus japonicus, a model legume plant with five visib...Transcription factors and phytohormones have been reported to play crucial roles to regulate leaf complexity among plant species. Using the compound-leafed species Lotus japonicus, a model legume plant with five visible leaflets, we characterized four independent mutants with reduced leaf complexity, proliferating floral meristem (pfm), proliferating floral organ-2 (pfo-2), fused leaflets1 (ful1) and umbrella leaflets (uml), which were further identified as loss-of-function mutants of Arabidopsis orthologs LEAFY (LFY ), UNUSUAL FLORAL ORGANS (UFO), CUP-SHAPED COTYLEDON 2 (CUC2) and PIN-FORMED 1 (PIN1), respectively. Comparing the leaf development of wild-type and mutants by a scanning electron microscopy approach, leaflet initiation and/or dissection were found to be affected in these mutants. Expression and phenotype analysis indicated that PFM/LjLFY and PFO/LjUFO determined the basipetal leaflet initiation manner in L. japonicus. Genetic analysis of ful1 and uml mutants and their double mutants revealed that the CUC2-like gene and auxin pathway also participated in leaflet dissection in L. japonicus, and their functions might influence cytokinin biogenesis directly or indirectly. Our results here suggest that multiple genes were interplayed and played conserved functions in controlling leaf complexity during compound leaf development in L. japonicus.展开更多
BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining...BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining is negative,because of the similarities in histopathology.This study investigated whether donor-derived cell-free DNA(ddcfDNA)can be used to differentiate BKPyVAN.Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function,22 with type I TCMR,21 with proven BKPy VAN,and 5 with possible Py VAN.We found that urinary ddcfDNA levels were upregulated in recipients with graft injury,whereas plasma ddcfDNA levels were comparable for all groups.The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients(10.4 vs.6.1 ng/mL,P<0.001 and 68.4%vs.55.3%,P=0.013,respectively).Urinary ddcfDNA fractions(not concentrations)were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup(81.30%vs.56.64%,P=0.025).With a cut-off value of 7.81 ng/m L,urinary ddcf DNA concentrations distinguished proven BKPyVAN from type I TCMR(area under the curve(AUC)=0.848,95%confidence interval(95%CI):0.734 to 0.963).These findings suggest that urinary ddcf DNA is a non-invasive biomarker which can reliably differentiate BKPy VAN from type I TCMR.展开更多
Chronic kidney disease(CKD)poses a great burden to global public health as current therapies are generally ineffective.Early detection and effective therapy are crucial for the future prevention and progression of CKD...Chronic kidney disease(CKD)poses a great burden to global public health as current therapies are generally ineffective.Early detection and effective therapy are crucial for the future prevention and progression of CKD.Nanoparticles(NPs)vary by particle size,charge,shape and the density of targeting ligands and are associated with enhancement of the pharmacokinetic properties,targetability,or the bioavailability of drugs.Thus,the emergence of NPs in medicine has provided novel solutions to the potential diagnosis and treatment of CKD.This review describes the current experimental research,clinical applications of NPs,the current challenges,and upcoming opportunities in the diagnosis and treatment of CKD.展开更多
Background:Erythropoietin is a glycoprotein that mainly regulates erythropoiesis.In patients with chronic renal failure with anemia,darbepoetin alfa can stimulate erythropoiesis,correct anemia,and maintain hemoglobin ...Background:Erythropoietin is a glycoprotein that mainly regulates erythropoiesis.In patients with chronic renal failure with anemia,darbepoetin alfa can stimulate erythropoiesis,correct anemia,and maintain hemoglobin levels.This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections(Recombinant Human Erythropoietin injection,rHuEPO)when maintaining hemoglobin(Hb)levels within the target range(10.0-12.0 g/dL)for the treatment of renal anemia.Methods:Ninety-five patients were enrolled in this study from April 15,2013 to April 10,2014 at 25 sites.In this study,patients(n=95)aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group(n=56)and a twice or three times per week intravenous epoetin alfa group(n=39)for 28 weeks,who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease(CKD)and were undergoing hemodialysis or hemofiltration with ESA-naive(erythropoiesis stimulating agent-naive).The primary efficacy profile was the mean Hb level(the non-inferiority margin was-1.0 g/dL,week 21-28);the secondary efficacy profiles were the Hb increase rate(week 0-4),the target Hb achievement cumulative rate and time,the change trends of the Hb levels,and the target Hb maintenance ratio.Adverse events(AEs)were observed and compared,and the efficacy and safety were analyzed between the two treatment groups.Additionally,the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group,respectively;the difference of the lower limits of the 95%confidence intervals(CI)between the two groups was 0.1 g/dL(>-1.0 g/dL),and non-inferiority was proven;the Hb levels started to increase in the first four weeks at a similar increase rate;no obvious differences were observed between the groups in the target Hb achievement cumulative rates,and the Hb levels as well as the target Hb level maintenance rate changed over time.The incidence of AEs was 62.5%in the darbepoetin alfa group and 76.9%in the epoetin alfa group.All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion:Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well,which makes it not inferior to epoetin alfa intravenously twice or three times per week.Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.展开更多
The high-manganese steels are important structural materials,owing to their excellent toughness at low temperatures.However,the microstructural causes for their unusual properties have not adequately been understood t...The high-manganese steels are important structural materials,owing to their excellent toughness at low temperatures.However,the microstructural causes for their unusual properties have not adequately been understood thus far.Here,we report a reversal relationship between impact toughness and grain size in a high-manganese steel and its unrevealed microscopic mechanisms,which result in an excellent low-temperature toughness of the steel.Our investigations show that with increasing grain size the impact toughness of the steel can be improved drastically,especially at low-temperatures.Advanced electron microscopy characterization reveals that the enhanced impact toughness of the coarse-grained steel is attributed to the twinning induced plasticity and transformation induced plasticity effects,which produce large quantities of deformation twins,ε_(hcp)-martensite andα'_(bcc)-martensite.Inversely,in the fine-grained steels,the formation of deformation twins and martensite is significantly inhibited,leading to the decrease of impact toughness.Microstructural characterizations also indicate thatε_(hcp)-martensite becomes more stable thanα'_(bcc)-martensite with decreasing temperature,resulting in characteristic microstructures in the coarse-grained samples after impact deformation at liquid nitrogen temperature.In the coarse-grained samples under impact deformation at-80℃,ε_(hcp)-martensite transformation,α'_(bcc)-martensite transformation and deformation twinning all occur simultaneously,which greatly improves the toughness of the steel.展开更多
The crystallography of phase transformation is an important issue for studying metallic alloys.Here,we demonstrate an abnormal orientation relation between face-centered cubic(fcc) and hexagonal closepacked(hcp) phase...The crystallography of phase transformation is an important issue for studying metallic alloys.Here,we demonstrate an abnormal orientation relation between face-centered cubic(fcc) and hexagonal closepacked(hcp) phases due to the intersection of two ε_(hcp)-martensite variants in a high manganese steel.The corresponding crystallogra phic cha racteristics,including invariant line,habit plane and atomic steps,have been characterized by transmission electron micro scopy and the quasi-O-line model.In addition,the models of phase transfo rmation about the intersection are proposed based on transmission mechanisms of dislocations.Our findings enrich the theories of phase transformation and implicate the possibility to fabricate stro nger and tougher steel.展开更多
Acute kidney injury(AKI),has become the focus of increasing attention due to its high risk of death.The early diagnosis and treatment of AKI significantly reduce the risk of renal tissue damage and kidney dysfunction....Acute kidney injury(AKI),has become the focus of increasing attention due to its high risk of death.The early diagnosis and treatment of AKI significantly reduce the risk of renal tissue damage and kidney dysfunction.However,the efficient early diagnosis and treatment approach for AKI remains a challenge.AKI screening via precise nanomaterial theranostics is a new alternative approach.This study summarizes the recent advances in functional nanomaterials in the early detection and treatment of AKI.The challenges and problems in the use of nanomaterials for AKI in clinical applications are also discussed.It is anticipated that highlighting these new advances will lay the foundation for further translational research on the promising application of nanomaterials for AKI.展开更多
The coarsened grain boundaries (GBs) with vein-like morphology frequently appear in the nitrogen diffusion layer of nitrocarburized carbon steels. The electron probe X-ray microanalysis shows that such vein-like GBs...The coarsened grain boundaries (GBs) with vein-like morphology frequently appear in the nitrogen diffusion layer of nitrocarburized carbon steels. The electron probe X-ray microanalysis shows that such vein-like GBs are rich in nitrogen and carbon atoms. Transmission electron microscopy and scanning electron microscopy further reveal that the coarsened GBs consist of γ'-nitrocarbide (Fe4(C,N)) and ε-nitrocarbide lamellas that are formed during nitrocarburizing due to high nitrogen concentration at GBs. It is shown that many of {111}〈112〉 micro twins exist in the γ'-phase lamellas and thin ε-phase slices prefer to nucleate at their twin boundaries with the orientation relationship of {0001}ε//{111}γ'. Upon growing large γ'-Iamellas may become faceted and thin ε-Iamellas may grow thicker and become the main portions in the vein-like GBs. The microstructure evolution occurring in the vein-like GBs can be depicted as: α + [N]/[C] → + [C,N] →ε-nitrocarbides.展开更多
Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associ...Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method:This study was a multicenter,randomized,open-label,intergroup parallel control phase III noninferiority trial from April 19,2013 to September 9,2014 at 25 sites.In this study,the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks.The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week.All subjects underwent epoetin alfa administration during the 8-week baseline period.After that,subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group.The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period(noninferiority threshold:-1.0 g/dl)was tested between the two treatments.The time-dependent hemoglobin(Hb)concentration and the maintenance rate of the target Hb concentration(the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl)were also evaluated.Iron metabolism,including changes in the serum iron,total iron-binding capacity,ferritin,transferrin saturation,and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further.Adverse events(AEs)were also observed and compared,and the safety was analyzed between the two treatment groups.The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:Four hundred and sixty-six patients were enrolled in this study,and ultimately 384 cases were analyzed for safety,including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group.There were 211 cases in the per-protocol set,including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group.The changes in the average Hb concentrations from the baseline to the end of the evaluation period were-0.07 and-0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively.The difference between the two groups was 0.08 g/dl(95%confidence interval[CI]:-0.22 to 0.39),and the lower limit of the 95%CI was-0.22>-1.0 g/dl.The average Hb concentrations of the two groups were 10.88-11.43 g/dl(darbepoetin alfa)and 10.91-11.38 g/dl(epoetin alfa)during the study period of Weeks 0-28,with the maintenance rates of the target Hb concentration ranging within 71%-87%and 78%-95%in the darbepoetin alfa group and epoetin alfa group respectively.During the period of comparison between the two groups,the incidence of AEs in the darbepoetin alfa group was 61.42%,while in the epoetin alfa group it was 56.41%.All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion:The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.展开更多
Ferroptosis plays a critical pathophysiological role in several types of acute kidney injury(AKI).The development of nanomaterials targeting iron metabolism and ferroptosis is a promising approach for AKI treatment.He...Ferroptosis plays a critical pathophysiological role in several types of acute kidney injury(AKI).The development of nanomaterials targeting iron metabolism and ferroptosis is a promising approach for AKI treatment.Herein,we synthesized gallic acid-gallium polyvinyl pyrrolidone nanoparticles(GGP NPs)as a potential iron-scavenging agent because of their nearly ionic radius and chemical similarity with iron.The results indicated that GGP NPs accumulated in tubular epithelial cells and showed good biocompatibility.GGP NPs significantly inhibited cisplatin(CP)-induced ferroptosis in HK-2 cells by reducing the accumulation of intracellular free iron and mitochondrial dysfunction,and suppressing the perturbations of ferroptosis processes,including lipid peroxidation,nicotinamide adenine dinucleotide phosphate(NADPH)and glutathione(GSH)levels,glutathione peroxidase 4(GPX4)activity,and ferritinophagy.An in vivo study demonstrated that treatment with GGP NPs significantly ameliorated the renal tubular injury and mitochondrial damage induced by CP treatment or ischemia-reperfusion injury.Our study suggests that GGP NPs may be an effective and promising candidate for AKI treatment and enable potential clinical translation.展开更多
The 2xxx series Al alloys have been widely used in aerospace industry owing to their high strength,good plasticity and superior formability.To ensure a good control of shape,the quenched alloy sheets require a small p...The 2xxx series Al alloys have been widely used in aerospace industry owing to their high strength,good plasticity and superior formability.To ensure a good control of shape,the quenched alloy sheets require a small pre-deformation before artificial aging.However,this pre-deformation considerably deteriorates the mechanical strength of the Al-3.0 Cu-1.8 Mg-0.5 Si(wt%)alloys due to the formation of unfavorable large-sized precipitates at dislocations.To tackle this issue,we designed a pre-aging process prior to the pre-deformation.The thermal-mechanical treatment,involving pre-aging,pre-deformation and subsequent aging,markedly enhanced the ultimate tensile strength up to 521 MPa compared to that(448 MPa)of the alloy without pre-aging.Microstructure characterization revealed that the fine precipitates(~2 nm)with a uniform dispersion were promoted within the Al matrix,which in turn partly suppressed the formation of the unfavorable large-sized precipitate(~100 nm).Our findings provide a new clue for designing stronger Al alloys with age-hardenability.展开更多
Background:Leukocyte telomere length shortening is a characteristic of premature senescence,a process that can be accelerated by oxidative stress.In general,patients with end-stage renal disease undergoing regular hem...Background:Leukocyte telomere length shortening is a characteristic of premature senescence,a process that can be accelerated by oxidative stress.In general,patients with end-stage renal disease undergoing regular hemodialysis(HD)are repeatedly exposed to oxidative stress.Patients undergoing HD tend to have cardiovascular diseases associated with oxidative stress and inflammation.Therefore,we assumed that telomere length is associated with HD vintage and the degree of vascular calcification.Methods:A total of 144 patients undergoing regular HD before kidney transplantation and 62 patients on hemodialysis,but not undergoing kidney transplantation,were enrolled.We measured common laboratory values,such as calcium,phosphate,and hemoglobin levels,and assessed the degree of vascular calcification in the patients.The leukocyte telomere length was measured using reverse transcription polymerase chain reaction,and Spearman correlation was used for correlation analysis.Results:The leukocyte telomere length was negatively associated with age(rho=-0.306,P<0.01);it was shorter in middle-aged patients than in young patients(13.48±4.80 vs.15.86±4.51,P<0.01).The telomere length was significantly different among patients aged 52-74 years in groups with different HD vintages.Additionally,the telomere length was positively associated with serum hemoglobin(Hb)levels in all patients(rho=0.290,P<0.01).There was a significant difference among patients divided into three groups according to the degree of anemia(17.09±5.64 vs.14.40±4.07 vs.13.99±3.95,P<0.01).Further,a significant difference was observed in the telomere length among patients with different degrees of vascular calcification(16.79±4.91 vs.13.61±2.82 vs.14.62±3.63 vs.10.71±3.74,P<0.01).The telomere length was shorter in the patients on hemodialysis who did not receive a kidney transplant than in the surgical patients(8.12±1.83 vs.14.33±4.63,P<0.01).Conclusion:This study demonstrated that the telomere length was significantly correlated with HD vintage in patients of a certain age group.The telomere length was shorter in patients on hemodialysis who matched for age and dialysis vintage with kidney transplant patients.It was also associated with vascular calcification and serum Hb levels in all patients undergoing HD.展开更多
Podocyte injury is an important cause of proteinuria.Angiopoietin-like protein 4(Angptl4)is a secreted glycoprotein and has a role in proteinuria.However,the exact role of Angptl4 in podocyte injury and its upstream r...Podocyte injury is an important cause of proteinuria.Angiopoietin-like protein 4(Angptl4)is a secreted glycoprotein and has a role in proteinuria.However,the exact role of Angptl4 in podocyte injury and its upstream regulators has not been clarified.In this study,we used lipopolysaccharide(LPS)-induced mice and cultured podocytes as podocyte injury models.Our results indicated that LPS increased the expression of podocyte Angptl4 in vivo and in vitro.Furthermore,we showed that Angptl4 overexpression deteriorated LPS-induced podocyte injury by inducing podocyte cytoskeleton rearrangement,reducing the expression of synaptopodin while Angptl4 knockdown alleviated LPS-induced podocyte injury.In addition,we found that inhibitors and siRNA targeting TLR4/MyD88/NF-κB signaling inhibited the upregulation of Angptl4 in LPS-induced podocytes.Moreover,inhibitors and siRNA targeting calcineurin/NFAT signaling also relieved LPS-induced Angptl4 expression and podocyte injury in vivo and in vitro.Taken together,our study has elucidated that both of the TLR4/MyD88/NF-κB and calcineurin/NFAT signaling mediate the upregulation of Angptl4 in LPS-induced podocytes,which has important implications for further understanding the molecular mechanism of LPS-induced podocyte injury.展开更多
Introducing and stabilizing twins in aluminum is a challenge for metals research due to their high formation energy.Employing first-principles calculations,we investigated the twin boundary segregation of alloying ele...Introducing and stabilizing twins in aluminum is a challenge for metals research due to their high formation energy.Employing first-principles calculations,we investigated the twin boundary segregation of alloying elements and their impact on the twin boundary energy in aluminum.Alloying elements with small solubilities but strong interaction with twin boundary would significantly reduce twin boundary energies in aluminum at low temperatures.With increasing temperature,their segregation near twin boundary weakens,leading to their influence on twin boundary energies reduced.Some elements with large solubilities may greatly reduce the twin energies not only at low temperatures but also at high temperatures.Based on careful analysis of charge density and atomic radius,it has been found that chemical difference has little influence on twin boundary energy whereas the atomic size effect plays a leading role in causing the change of twin boundary energy.展开更多
Antibody-mediated rejection(ABMR)is a major cause of dysfunction and loss of transplanted kidney.The current treatments for ABMR involve nonspecific inhibition and clearance of T/B cells or plasma cells.However,the pr...Antibody-mediated rejection(ABMR)is a major cause of dysfunction and loss of transplanted kidney.The current treatments for ABMR involve nonspecific inhibition and clearance of T/B cells or plasma cells.However,the prognosis of patients following current treatment is poor.T follicular helper cells(Tfh)play an important role in allograft-specific antibodies secreting plasma cell(PC)development.Tfh cells are therefore considered to be important therapeutic targets for the treatment of antibody hypersecretion disorders,such as transplant rejection and autoimmune diseases.Tacrolimus(Tac),the primary immunosuppressant,prevents rejection by reducing T cell activation.However,its administration should be closely monitored to avoid serious side effects.In this study,we investigated whether Tac delivery to helper T(CD4^(+))cells using functionalized mesoporous nanoparticles can block Tfh cell differentiation after alloantigen exposure.Results showed that Tac delivery ameliorated humoral rejection injury in rodent kidney graft by suppressing Tfh cell development,PC,and donor-specific antibody(DSA)generation without causing severe side effects compared with delivery through the drug administration pathway.This study provides a promising therapeutic strategy for preventing humoral rejection in solid organ transplantation.The specific and controllable drug delivery avoids multiple disorder risks and side effects observed in currently used clinical approaches.展开更多
The authors regret that some statistical errors were made in“Lipopolysaccharide-induced podocyte injury is regulated by calcineurin/NFAT and TLR4/MyD88/NF-kB signaling pathways through Angiopoietin-like protein 4”(G...The authors regret that some statistical errors were made in“Lipopolysaccharide-induced podocyte injury is regulated by calcineurin/NFAT and TLR4/MyD88/NF-kB signaling pathways through Angiopoietin-like protein 4”(Genes Dis,https://doi.org/10.1016/j.gendis.2020.07.005)at Figure 2G,Figure 3B and F,and Figure 4C and D for Angptl4 expression,Figure 5E for CaN expression.展开更多
The morphological evolution of the precipitates in Al–7.4Zn–1.7Mg–2.0Cu(wt%) alloy was studied by highresolution transmission electron microscopy(HRTEM). Statistics reveal that the hardness of the alloy changes...The morphological evolution of the precipitates in Al–7.4Zn–1.7Mg–2.0Cu(wt%) alloy was studied by highresolution transmission electron microscopy(HRTEM). Statistics reveal that the hardness of the alloy changes accordingly with the change of the average thickness–diameter ratio of precipitates. The GPII zones are mainly responsible for the first and also the highest hardness peak. They grow in diameter and keep 7-atomic-layer in thickness. Once the thickness changes, the phase transformation from GPII zone to g0 or g-precursor would occur. The resultant metastable g0 and g-precursor precipitates grow in both diameter and thickness, but much faster in the former. After the first hardness peak,the metastable g0 precipitates and g-precursor, coexisting with part of GPII zones, are counted as the main hardening precipitates.展开更多
基金supported by the National Natural Science Foundation of China(No.2022YFC82200842)the Zhejiang Provincial Natural Science Foundation of China(No.LQ22H050004).
文摘Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.
基金financially supported by the National Natural Science Foundation of China(Nos.52001119,51831004,and 52171006)the Fundamental Research Funds for the Central Universities.
文摘Microalloying elements play a crucial role in mechanical properties and phase stability of metallic alloys.In this work,we employ first-principles calculations and atomic-scale high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM)to find promising microalloying elements that will improve the stability and properties ofβ"/Al interface andβ"phase in Al–Mg-Si alloys.First,we define a substitution energy for evaluating the stability ofβ"phase andβ"/Al interface with microalloying elements doped.Then,experiments of HAADF-STEM imaging are carried out to verify the calculational results.Next,using the most stable structures doped with microalloying elements,the mechanical properties of theβ"bulk and theβ"/Al interface were calculated and analyzed.At last,we have figured out the effects of all considered microalloying elements and obtained a rule that the stable occupancy of solute atoms is related to their own radius and the radius of Mg,Si,and Al.These findings will provide some theoretical basis for future microalloying strategies of Al–Mg-Si alloys.
基金supported by the Science and Technology Department of Zhejiang Province(No.2019C03029)the National Natural Science Foundation of China(Nos.82070766,81870510,and U21A20350)the Bethune Charitable Foundation(No.GX2019010112),China.
文摘There is currently a huge worldwide demand for donor kidneys for organ transplantation.Consequently,numerous marginal donor kidneys,such as kidneys with microthrombi,are used to save patients'lives.While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function(DGF)(McCall et al.,2003;Gao et al.,2019),other studies have demonstrated that microthrombi negatively impact the rate of DGF(Batra et al.,2016;Hansen et al.,2018),but not graft survival rate(McCall et al.,2003;Batra et al.,2016;Gao et al.,2019).In contrast,Hansen et al.(2018)concluded that fibrin thrombi were not only associated with reduced graft function six months posttransplantation but also with increased graft loss within the first year of transplantation.On the other hand,Batra et al.(2016)found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups.To date,however,the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial,necessitating further research.
基金supported by the National Natural Science Foundation of China(30930009)the Ministry of Agriculture of China for Transgenic Research(2011ZX08009-003)the Foundation from the Institute of Plant Physiology and Ecology,SIBS
文摘Transcription factors and phytohormones have been reported to play crucial roles to regulate leaf complexity among plant species. Using the compound-leafed species Lotus japonicus, a model legume plant with five visible leaflets, we characterized four independent mutants with reduced leaf complexity, proliferating floral meristem (pfm), proliferating floral organ-2 (pfo-2), fused leaflets1 (ful1) and umbrella leaflets (uml), which were further identified as loss-of-function mutants of Arabidopsis orthologs LEAFY (LFY ), UNUSUAL FLORAL ORGANS (UFO), CUP-SHAPED COTYLEDON 2 (CUC2) and PIN-FORMED 1 (PIN1), respectively. Comparing the leaf development of wild-type and mutants by a scanning electron microscopy approach, leaflet initiation and/or dissection were found to be affected in these mutants. Expression and phenotype analysis indicated that PFM/LjLFY and PFO/LjUFO determined the basipetal leaflet initiation manner in L. japonicus. Genetic analysis of ful1 and uml mutants and their double mutants revealed that the CUC2-like gene and auxin pathway also participated in leaflet dissection in L. japonicus, and their functions might influence cytokinin biogenesis directly or indirectly. Our results here suggest that multiple genes were interplayed and played conserved functions in controlling leaf complexity during compound leaf development in L. japonicus.
基金the Science and Technology Department of Zhejiang Province(No.2019C03029)the Bethune Charitable Foundation(No.G-X-2019-0101-12)+1 种基金the National Natural Science Foundation of China(Nos.81870510,81770719,81770752,and 81370851)the Zhejiang Provincial Natural Science Foundation of China(No.LQ18H050002)。
文摘BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining is negative,because of the similarities in histopathology.This study investigated whether donor-derived cell-free DNA(ddcfDNA)can be used to differentiate BKPyVAN.Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function,22 with type I TCMR,21 with proven BKPy VAN,and 5 with possible Py VAN.We found that urinary ddcfDNA levels were upregulated in recipients with graft injury,whereas plasma ddcfDNA levels were comparable for all groups.The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients(10.4 vs.6.1 ng/mL,P<0.001 and 68.4%vs.55.3%,P=0.013,respectively).Urinary ddcfDNA fractions(not concentrations)were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup(81.30%vs.56.64%,P=0.025).With a cut-off value of 7.81 ng/m L,urinary ddcf DNA concentrations distinguished proven BKPyVAN from type I TCMR(area under the curve(AUC)=0.848,95%confidence interval(95%CI):0.734 to 0.963).These findings suggest that urinary ddcf DNA is a non-invasive biomarker which can reliably differentiate BKPy VAN from type I TCMR.
基金supported by grants from the National Key R&D Program of China(2018YFC2000400)National Natural Science Foundation of China(81570605,81770674,81670651,and 81970573).
文摘Chronic kidney disease(CKD)poses a great burden to global public health as current therapies are generally ineffective.Early detection and effective therapy are crucial for the future prevention and progression of CKD.Nanoparticles(NPs)vary by particle size,charge,shape and the density of targeting ligands and are associated with enhancement of the pharmacokinetic properties,targetability,or the bioavailability of drugs.Thus,the emergence of NPs in medicine has provided novel solutions to the potential diagnosis and treatment of CKD.This review describes the current experimental research,clinical applications of NPs,the current challenges,and upcoming opportunities in the diagnosis and treatment of CKD.
文摘Background:Erythropoietin is a glycoprotein that mainly regulates erythropoiesis.In patients with chronic renal failure with anemia,darbepoetin alfa can stimulate erythropoiesis,correct anemia,and maintain hemoglobin levels.This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections(Recombinant Human Erythropoietin injection,rHuEPO)when maintaining hemoglobin(Hb)levels within the target range(10.0-12.0 g/dL)for the treatment of renal anemia.Methods:Ninety-five patients were enrolled in this study from April 15,2013 to April 10,2014 at 25 sites.In this study,patients(n=95)aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group(n=56)and a twice or three times per week intravenous epoetin alfa group(n=39)for 28 weeks,who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease(CKD)and were undergoing hemodialysis or hemofiltration with ESA-naive(erythropoiesis stimulating agent-naive).The primary efficacy profile was the mean Hb level(the non-inferiority margin was-1.0 g/dL,week 21-28);the secondary efficacy profiles were the Hb increase rate(week 0-4),the target Hb achievement cumulative rate and time,the change trends of the Hb levels,and the target Hb maintenance ratio.Adverse events(AEs)were observed and compared,and the efficacy and safety were analyzed between the two treatment groups.Additionally,the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group,respectively;the difference of the lower limits of the 95%confidence intervals(CI)between the two groups was 0.1 g/dL(>-1.0 g/dL),and non-inferiority was proven;the Hb levels started to increase in the first four weeks at a similar increase rate;no obvious differences were observed between the groups in the target Hb achievement cumulative rates,and the Hb levels as well as the target Hb level maintenance rate changed over time.The incidence of AEs was 62.5%in the darbepoetin alfa group and 76.9%in the epoetin alfa group.All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion:Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well,which makes it not inferior to epoetin alfa intravenously twice or three times per week.Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.
基金supported by the National Natural Science Foundation of China[Grant Nos.5180106051831004+6 种基金1142780651671082]the China Postdoctoral Science Foundation(grant number 2019M652756)the National Key Research and Development Program of China(grant number 2016YFB0300801)the China Scholarship Council(grant number 201606130008)the financial support from Austrain Science Fund(FWF)(grant number P 32378-N37)BMBWF(grant number KR 06/2020)。
文摘The high-manganese steels are important structural materials,owing to their excellent toughness at low temperatures.However,the microstructural causes for their unusual properties have not adequately been understood thus far.Here,we report a reversal relationship between impact toughness and grain size in a high-manganese steel and its unrevealed microscopic mechanisms,which result in an excellent low-temperature toughness of the steel.Our investigations show that with increasing grain size the impact toughness of the steel can be improved drastically,especially at low-temperatures.Advanced electron microscopy characterization reveals that the enhanced impact toughness of the coarse-grained steel is attributed to the twinning induced plasticity and transformation induced plasticity effects,which produce large quantities of deformation twins,ε_(hcp)-martensite andα'_(bcc)-martensite.Inversely,in the fine-grained steels,the formation of deformation twins and martensite is significantly inhibited,leading to the decrease of impact toughness.Microstructural characterizations also indicate thatε_(hcp)-martensite becomes more stable thanα'_(bcc)-martensite with decreasing temperature,resulting in characteristic microstructures in the coarse-grained samples after impact deformation at liquid nitrogen temperature.In the coarse-grained samples under impact deformation at-80℃,ε_(hcp)-martensite transformation,α'_(bcc)-martensite transformation and deformation twinning all occur simultaneously,which greatly improves the toughness of the steel.
基金supported financially by the National Natural Science Foundation of China(Nos.51801060,51831004,11427806 and 51671082)the China Postdoctoral Science Foundation(No.2019M652756)+1 种基金the National Key Research and Development Program of China(No.2016YFB0300801)the China Scholarship Council(No.201606130008)。
文摘The crystallography of phase transformation is an important issue for studying metallic alloys.Here,we demonstrate an abnormal orientation relation between face-centered cubic(fcc) and hexagonal closepacked(hcp) phases due to the intersection of two ε_(hcp)-martensite variants in a high manganese steel.The corresponding crystallogra phic cha racteristics,including invariant line,habit plane and atomic steps,have been characterized by transmission electron micro scopy and the quasi-O-line model.In addition,the models of phase transfo rmation about the intersection are proposed based on transmission mechanisms of dislocations.Our findings enrich the theories of phase transformation and implicate the possibility to fabricate stro nger and tougher steel.
基金the National Key R&D Program of China(No.2018YFC2000400)the National Natural Science Foundation of China(Nos.31470776,81670651,81770752,81970573).
文摘Acute kidney injury(AKI),has become the focus of increasing attention due to its high risk of death.The early diagnosis and treatment of AKI significantly reduce the risk of renal tissue damage and kidney dysfunction.However,the efficient early diagnosis and treatment approach for AKI remains a challenge.AKI screening via precise nanomaterial theranostics is a new alternative approach.This study summarizes the recent advances in functional nanomaterials in the early detection and treatment of AKI.The challenges and problems in the use of nanomaterials for AKI in clinical applications are also discussed.It is anticipated that highlighting these new advances will lay the foundation for further translational research on the promising application of nanomaterials for AKI.
基金supported by the National Basic Research Program of China(No.2009CB623704)the National Natural Science Foundation of China(Nos.51071064 and 51171063)+2 种基金the Nature Science Foundation of Hunan Province(Grant No. 09JJ6002)Instrumental Innovation Foundation of Hunan Province(No.2011TT1003)the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province
文摘The coarsened grain boundaries (GBs) with vein-like morphology frequently appear in the nitrogen diffusion layer of nitrocarburized carbon steels. The electron probe X-ray microanalysis shows that such vein-like GBs are rich in nitrogen and carbon atoms. Transmission electron microscopy and scanning electron microscopy further reveal that the coarsened GBs consist of γ'-nitrocarbide (Fe4(C,N)) and ε-nitrocarbide lamellas that are formed during nitrocarburizing due to high nitrogen concentration at GBs. It is shown that many of {111}〈112〉 micro twins exist in the γ'-phase lamellas and thin ε-phase slices prefer to nucleate at their twin boundaries with the orientation relationship of {0001}ε//{111}γ'. Upon growing large γ'-Iamellas may become faceted and thin ε-Iamellas may grow thicker and become the main portions in the vein-like GBs. The microstructure evolution occurring in the vein-like GBs can be depicted as: α + [N]/[C] → + [C,N] →ε-nitrocarbides.
文摘Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method:This study was a multicenter,randomized,open-label,intergroup parallel control phase III noninferiority trial from April 19,2013 to September 9,2014 at 25 sites.In this study,the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks.The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week.All subjects underwent epoetin alfa administration during the 8-week baseline period.After that,subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group.The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period(noninferiority threshold:-1.0 g/dl)was tested between the two treatments.The time-dependent hemoglobin(Hb)concentration and the maintenance rate of the target Hb concentration(the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl)were also evaluated.Iron metabolism,including changes in the serum iron,total iron-binding capacity,ferritin,transferrin saturation,and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further.Adverse events(AEs)were also observed and compared,and the safety was analyzed between the two treatment groups.The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:Four hundred and sixty-six patients were enrolled in this study,and ultimately 384 cases were analyzed for safety,including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group.There were 211 cases in the per-protocol set,including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group.The changes in the average Hb concentrations from the baseline to the end of the evaluation period were-0.07 and-0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively.The difference between the two groups was 0.08 g/dl(95%confidence interval[CI]:-0.22 to 0.39),and the lower limit of the 95%CI was-0.22>-1.0 g/dl.The average Hb concentrations of the two groups were 10.88-11.43 g/dl(darbepoetin alfa)and 10.91-11.38 g/dl(epoetin alfa)during the study period of Weeks 0-28,with the maintenance rates of the target Hb concentration ranging within 71%-87%and 78%-95%in the darbepoetin alfa group and epoetin alfa group respectively.During the period of comparison between the two groups,the incidence of AEs in the darbepoetin alfa group was 61.42%,while in the epoetin alfa group it was 56.41%.All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion:The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.
基金supported by grants from the National Key R&D Program of China(No.2018YFC2000400)Zhejiang Provincial Natural Science Foundation of China(No.LZ22H050001)+1 种基金the National Natural Science Foundation of China(Nos.81970573,81670651,and 82000637)Zhejiang provincial program for the Cultivation of High-level Innovative Health talents,and Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2020KY538).
文摘Ferroptosis plays a critical pathophysiological role in several types of acute kidney injury(AKI).The development of nanomaterials targeting iron metabolism and ferroptosis is a promising approach for AKI treatment.Herein,we synthesized gallic acid-gallium polyvinyl pyrrolidone nanoparticles(GGP NPs)as a potential iron-scavenging agent because of their nearly ionic radius and chemical similarity with iron.The results indicated that GGP NPs accumulated in tubular epithelial cells and showed good biocompatibility.GGP NPs significantly inhibited cisplatin(CP)-induced ferroptosis in HK-2 cells by reducing the accumulation of intracellular free iron and mitochondrial dysfunction,and suppressing the perturbations of ferroptosis processes,including lipid peroxidation,nicotinamide adenine dinucleotide phosphate(NADPH)and glutathione(GSH)levels,glutathione peroxidase 4(GPX4)activity,and ferritinophagy.An in vivo study demonstrated that treatment with GGP NPs significantly ameliorated the renal tubular injury and mitochondrial damage induced by CP treatment or ischemia-reperfusion injury.Our study suggests that GGP NPs may be an effective and promising candidate for AKI treatment and enable potential clinical translation.
基金supported by the National Natural Science Foundation of China(Nos.51671082,51831004,11427806,51801060,51471067)the National Key Research and Development Program of China(No.2016YFB0300801)。
文摘The 2xxx series Al alloys have been widely used in aerospace industry owing to their high strength,good plasticity and superior formability.To ensure a good control of shape,the quenched alloy sheets require a small pre-deformation before artificial aging.However,this pre-deformation considerably deteriorates the mechanical strength of the Al-3.0 Cu-1.8 Mg-0.5 Si(wt%)alloys due to the formation of unfavorable large-sized precipitates at dislocations.To tackle this issue,we designed a pre-aging process prior to the pre-deformation.The thermal-mechanical treatment,involving pre-aging,pre-deformation and subsequent aging,markedly enhanced the ultimate tensile strength up to 521 MPa compared to that(448 MPa)of the alloy without pre-aging.Microstructure characterization revealed that the fine precipitates(~2 nm)with a uniform dispersion were promoted within the Al matrix,which in turn partly suppressed the formation of the unfavorable large-sized precipitate(~100 nm).Our findings provide a new clue for designing stronger Al alloys with age-hardenability.
文摘Background:Leukocyte telomere length shortening is a characteristic of premature senescence,a process that can be accelerated by oxidative stress.In general,patients with end-stage renal disease undergoing regular hemodialysis(HD)are repeatedly exposed to oxidative stress.Patients undergoing HD tend to have cardiovascular diseases associated with oxidative stress and inflammation.Therefore,we assumed that telomere length is associated with HD vintage and the degree of vascular calcification.Methods:A total of 144 patients undergoing regular HD before kidney transplantation and 62 patients on hemodialysis,but not undergoing kidney transplantation,were enrolled.We measured common laboratory values,such as calcium,phosphate,and hemoglobin levels,and assessed the degree of vascular calcification in the patients.The leukocyte telomere length was measured using reverse transcription polymerase chain reaction,and Spearman correlation was used for correlation analysis.Results:The leukocyte telomere length was negatively associated with age(rho=-0.306,P<0.01);it was shorter in middle-aged patients than in young patients(13.48±4.80 vs.15.86±4.51,P<0.01).The telomere length was significantly different among patients aged 52-74 years in groups with different HD vintages.Additionally,the telomere length was positively associated with serum hemoglobin(Hb)levels in all patients(rho=0.290,P<0.01).There was a significant difference among patients divided into three groups according to the degree of anemia(17.09±5.64 vs.14.40±4.07 vs.13.99±3.95,P<0.01).Further,a significant difference was observed in the telomere length among patients with different degrees of vascular calcification(16.79±4.91 vs.13.61±2.82 vs.14.62±3.63 vs.10.71±3.74,P<0.01).The telomere length was shorter in the patients on hemodialysis who did not receive a kidney transplant than in the surgical patients(8.12±1.83 vs.14.33±4.63,P<0.01).Conclusion:This study demonstrated that the telomere length was significantly correlated with HD vintage in patients of a certain age group.The telomere length was shorter in patients on hemodialysis who matched for age and dialysis vintage with kidney transplant patients.It was also associated with vascular calcification and serum Hb levels in all patients undergoing HD.
基金This study was supported by the National Natural Science Foundation of China(No.81400716)the Zhejiang Provincial Natural Science Foundation of China(No.LY20H050007,LY19H050005)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2020383770).
文摘Podocyte injury is an important cause of proteinuria.Angiopoietin-like protein 4(Angptl4)is a secreted glycoprotein and has a role in proteinuria.However,the exact role of Angptl4 in podocyte injury and its upstream regulators has not been clarified.In this study,we used lipopolysaccharide(LPS)-induced mice and cultured podocytes as podocyte injury models.Our results indicated that LPS increased the expression of podocyte Angptl4 in vivo and in vitro.Furthermore,we showed that Angptl4 overexpression deteriorated LPS-induced podocyte injury by inducing podocyte cytoskeleton rearrangement,reducing the expression of synaptopodin while Angptl4 knockdown alleviated LPS-induced podocyte injury.In addition,we found that inhibitors and siRNA targeting TLR4/MyD88/NF-κB signaling inhibited the upregulation of Angptl4 in LPS-induced podocytes.Moreover,inhibitors and siRNA targeting calcineurin/NFAT signaling also relieved LPS-induced Angptl4 expression and podocyte injury in vivo and in vitro.Taken together,our study has elucidated that both of the TLR4/MyD88/NF-κB and calcineurin/NFAT signaling mediate the upregulation of Angptl4 in LPS-induced podocytes,which has important implications for further understanding the molecular mechanism of LPS-induced podocyte injury.
基金supported financially by the National Natural Science Foundation of China (Nos.51701243,11427806,51471067 and 51371081)the Hunan Provincial Natural Science Foundation of China (No.2019JJ40544)+3 种基金the Specialized Research Found for the Doctoral Program of Higher Education of China (No. 20120161110036)the National Basic Research (973) Program of China (No.2009CB623704)the PhD Research Startup Foundation of Central South University of Forestry and Technology (No. 2017YJ020)the supercomputer TH-1A installed at Hunan University
文摘Introducing and stabilizing twins in aluminum is a challenge for metals research due to their high formation energy.Employing first-principles calculations,we investigated the twin boundary segregation of alloying elements and their impact on the twin boundary energy in aluminum.Alloying elements with small solubilities but strong interaction with twin boundary would significantly reduce twin boundary energies in aluminum at low temperatures.With increasing temperature,their segregation near twin boundary weakens,leading to their influence on twin boundary energies reduced.Some elements with large solubilities may greatly reduce the twin energies not only at low temperatures but also at high temperatures.Based on careful analysis of charge density and atomic radius,it has been found that chemical difference has little influence on twin boundary energy whereas the atomic size effect plays a leading role in causing the change of twin boundary energy.
基金the National Natural Science Foundation of China(82070766,81770719,82070767,and 81970651)Research Fellow(Grant No.328933)+1 种基金Solutions for Health Profile(336355)InFLAMES Flagship(337531)projects from the Academy of Finland,the Science and Technology Department of Zhejiang Province(2019C03029),the Finland China Food and Health Interna tional Pilot Project funded by the Finnish Ministry of Education and Culture,and the Sigrid Jusélius Foundation.
文摘Antibody-mediated rejection(ABMR)is a major cause of dysfunction and loss of transplanted kidney.The current treatments for ABMR involve nonspecific inhibition and clearance of T/B cells or plasma cells.However,the prognosis of patients following current treatment is poor.T follicular helper cells(Tfh)play an important role in allograft-specific antibodies secreting plasma cell(PC)development.Tfh cells are therefore considered to be important therapeutic targets for the treatment of antibody hypersecretion disorders,such as transplant rejection and autoimmune diseases.Tacrolimus(Tac),the primary immunosuppressant,prevents rejection by reducing T cell activation.However,its administration should be closely monitored to avoid serious side effects.In this study,we investigated whether Tac delivery to helper T(CD4^(+))cells using functionalized mesoporous nanoparticles can block Tfh cell differentiation after alloantigen exposure.Results showed that Tac delivery ameliorated humoral rejection injury in rodent kidney graft by suppressing Tfh cell development,PC,and donor-specific antibody(DSA)generation without causing severe side effects compared with delivery through the drug administration pathway.This study provides a promising therapeutic strategy for preventing humoral rejection in solid organ transplantation.The specific and controllable drug delivery avoids multiple disorder risks and side effects observed in currently used clinical approaches.
文摘The authors regret that some statistical errors were made in“Lipopolysaccharide-induced podocyte injury is regulated by calcineurin/NFAT and TLR4/MyD88/NF-kB signaling pathways through Angiopoietin-like protein 4”(Genes Dis,https://doi.org/10.1016/j.gendis.2020.07.005)at Figure 2G,Figure 3B and F,and Figure 4C and D for Angptl4 expression,Figure 5E for CaN expression.
基金financially supported by the National Basic Research Program of China (No. 2009CB623704)the National Natural Science Foundation of China (Nos. 51171063, 10904034, 51071064 and 51301064)+1 种基金Instrumental Innovation Foundation of Hunan Province (No. 2011TT1003)the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province and the Aid Program for Young Teachers (No. 531107040548)
文摘The morphological evolution of the precipitates in Al–7.4Zn–1.7Mg–2.0Cu(wt%) alloy was studied by highresolution transmission electron microscopy(HRTEM). Statistics reveal that the hardness of the alloy changes accordingly with the change of the average thickness–diameter ratio of precipitates. The GPII zones are mainly responsible for the first and also the highest hardness peak. They grow in diameter and keep 7-atomic-layer in thickness. Once the thickness changes, the phase transformation from GPII zone to g0 or g-precursor would occur. The resultant metastable g0 and g-precursor precipitates grow in both diameter and thickness, but much faster in the former. After the first hardness peak,the metastable g0 precipitates and g-precursor, coexisting with part of GPII zones, are counted as the main hardening precipitates.