Passivation by the inorganic-rich solid electrolyte interphase(SEI),especially the LiF-rich SEI,is highly desirable to guarantee the durable lifespan of Li metal batteries(LMBs).Here,we report a diluent with the capab...Passivation by the inorganic-rich solid electrolyte interphase(SEI),especially the LiF-rich SEI,is highly desirable to guarantee the durable lifespan of Li metal batteries(LMBs).Here,we report a diluent with the capability to facilitate the formation of LiF-rich SEI while avoiding the excess consumption of Li salts.Dissimilar to most of reported inert diluents,heptafluoro-l-methoxypropane(HM) is firstly demonstrated to cooperate with the decomposition of anions to generate LiF-rich SEI via releasing Fcontaining species near Li surface.The designed electrolyte consisting of 1.8 M LiFSI in the mixture of1,2-dimethoxyethane(DME)/HM(2:1 by vol.) achieves excellent compatibility with both Li metal anodes(Coulombic efficiency~99.8%) and high-voltage cathodes(4.4 V LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2)(NMC811) and 4.5 V LiCoO_(2)(LCO) vs Li^(+)/Li).The 4.4 V Li(20μm)‖NMC811(2.5 mA h cm^(-2)) and 4.5 V Li(20μm)‖LCO(2.5 mA h cm^(-2)) cells achieve capacity retentions of 80% over 560 cycles and 80% over 505 cycles,respectively.Meanwhile,the anode-free pouch cell delivers an energy density of~293 W h kg^(-1)initially and retains 70% of capacity after 100 deep cycles.This work highlights the critical impact of diluent on the SEI formation,and opens up a new direction for designing desirable interfacial chemistries to enable high-performance LMBs.展开更多
Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is ...Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.展开更多
Highly entangled hydrogels exhibit excellent mechanical properties,including high toughness,high stretchability,and low hysteresis.By considering the evolution of randomly distributed entanglements within the polymer ...Highly entangled hydrogels exhibit excellent mechanical properties,including high toughness,high stretchability,and low hysteresis.By considering the evolution of randomly distributed entanglements within the polymer network upon mechanical stretches,we develop a constitutive theory to describe the large stretch behaviors of these hydrogels.In the theory,we utilize a representative volume element(RVE)in the shape of a cube,within which there exists an averaged chain segment along each edge and a mobile entanglement at each corner.By employing an explicit method,we decouple the elasticity of the hydrogels from the sliding motion of their entanglements,and derive the stress-stretch relations for these hydrogels.The present theoretical analysis is in agreement with experiment,and highlights the significant influence of the entanglement distribution within the hydrogels on their elasticity.We also implement the present developed constitutive theory into a commercial finite element software,and the subsequent simulations demonstrate that the exact distribution of entanglements strongly affects the mechanical behaviors of the structures of these hydrogels.Overall,the present theory provides valuable insights into the deformation mechanism of highly entangled hydrogels,and can aid in the design of these hydrogels with enhanced performance.展开更多
Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Me...Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(P<0.001).The expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC.展开更多
Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a s...Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.展开更多
Background:The downstaging of hepatocellular carcinoma(HCC)has been confirmed to benefit liver transplantation(LT)patients whose tumors are beyond the transplantation criteria.Milan criteria(MC),a tumor size and numbe...Background:The downstaging of hepatocellular carcinoma(HCC)has been confirmed to benefit liver transplantation(LT)patients whose tumors are beyond the transplantation criteria.Milan criteria(MC),a tumor size and number-based assessment,is currently used as the endpoint in these patients.However,many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy.Hence,this study aimed to explore the feasibility of Hangzhou criteria(HC),which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number,as an endpoint of downstaging.Methods:We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy(LRT)as downstaging/bridge treatment prior to LT in three centers of China.Results:Recipients were divided into four groups:failed downstaging to the HC(group A,n=46),successful downstaging to the HC(group B,n=30),remained within the HC all the time(group C,n=113),and tumor progressed(group D,n=17).The 3-year HCC recurrence probabilities of groups B and C were not significantly different(10.3%vs.11.6%,P=0.87).The HCC recurrent rate was significantly higher in group A(52.3%)compared with that in group B/C(P<0.05).Seven patients(7/76,9.2%)whose tumor exceeded the the HC were successfully downstaged to the MC,and 39.5%(30/76)to the the HC.In group B,23 patients remained beyond the MC and their survivals were as well as those of patients within the MC.Conclusions:Compared to the MC,HC downstaging criteria can give more HCC patients access to LT and furthermore,the outcome of these patients is the same as those matching MC downstaging criteria.Hangzhou downstaging criteria therefore is applicable in clinical practice.展开更多
Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,ch...Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,chemokine receptor 4(CXCR4),are important regulators of cell migration.We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease.A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway,and then treated with 5μL of neural stem cell suspension(1.5×104/L)in the right substantia nigra.Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation.Parkinson-like behavior in rats was detected using apomorphine-induced rotation.Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Using quantitative real-time polymerase chain reaction,the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured.In addition,western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4.Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation,increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra,and enhanced the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Injection of AMD3100 inhibited the aforementioned effects.These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease.This study was approved by the Animal Care and Use Committee of Kunming Medical University,China(approval No.SYXKK2015-0002)on April 1,2014.展开更多
AIM:To investigate the impact of renal and graft function on post-transplant hyperlipidemia(PTHL) in living donor liver transplantation(LDLT).METHODS:A total of 115 adult patients undergoing LDLT from January 2007 to ...AIM:To investigate the impact of renal and graft function on post-transplant hyperlipidemia(PTHL) in living donor liver transplantation(LDLT).METHODS:A total of 115 adult patients undergoing LDLT from January 2007 to May 2009 at a single center were enrolled.Data were collected and analyzed by the China Liver Transplant Registry retrospectively.PTHL was defined as serum triglycerides ≥ 150 mg/dL or serum cholesterol ≥ 200 mg/dL or the need for pharmacologic treatment at the sixth month after LDLT.Early renal dysfunction(ERD) was defined as serum creatinine ≥ 2 mg/dL and/or the need for renal replacement therapy in the first post-transplant week.RESULTS:In 115 eligible patients,the incidence of PTHL was 24.3%.Recipients with PTHL showed a higher incidence of post-transplant cardiovascular events compared to those without PTHL(17.9% vs 4.6%,P = 0.037).Serum creatinine showed significant positive correlations with total serum triglycerides,both at posttransplant month 1 and 3(P < 0.01).Patients with ERD had much higher pre-transplant serum creatinine levels(P < 0.001) and longer duration of pre-transplant renal insufficiency(P < 0.001) than those without ERD.Pretransplant serum creatinine,graft-to-recipient weight ratio,graft volume/standard liver volume ratio,body mass index(BMI) and ERD were identified as risk factors for PTHL by univariate analysis.Furthermore,ERD [odds ratio(OR) = 9.593,P < 0.001] and BMI(OR = 6.358,P = 0.002) were identified as independent risk factors for PTHL by multivariate analysis.CONCLUSION:Renal function is closely associated with the development of PTHL in LDLT.Post-transplant renal dysfunction,which mainly results from pre-transplant renal insufficiency,contributes to PTHL.展开更多
Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not be...Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not been revealed.Methods:HCC tumor samples from 76 patients were implanted in immunodeficient mice.The molecular expression was evaluated by immunohistochemistry.Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test.The independent prediction parameters were identified by logistic regression analyses.Results:The engraftment rate for PDX models from patients with HCC was 39.47%(30/76).Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates.Tumors with poor differentiation and vascular invasion were related to engraftment success.The positive expression of CK19,CD133,glypican-3(GPC3),and Ki67 in tumor samples was associated with engraftment success.Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment.Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates,with 71.9%in GPC3^(+)/Ki67^(+)tumors,30.8%in GPC3^(-)/Ki67^(+)tumors,15.0%in GPC3^(+)/Ki67^(-)tumors,and 0 in GPC3^(-)/Ki67^(-)tumors.Conclusions:Successful engraftment of HCC PDXs was significantly related to molecular features.Tumors with the GPC3+/Ki67+phenotype were the most likely to successfully establish HCC PDXs.展开更多
The Chang＇e-3 panoramic camera, which is composed of two cameras with identical functions, performances and interfaces, is installed on the lunar rover mast. It can acquire 3D images of the lunar surface based on the...The Chang＇e-3 panoramic camera, which is composed of two cameras with identical functions, performances and interfaces, is installed on the lunar rover mast. It can acquire 3D images of the lunar surface based on the principle of binocular stereo vision. By rotating and pitching the mast, it can take several photographs of the patrol area. After stitching these images, panoramic images of the scenes will be obtained.Thus the topography and geomorphology of the patrol area and the impact crater, as well as the geological structure of the lunar surface, will be analyzed and studied.In addition, it can take color photographs of the lander using the Bayer color coding principle. It can observe the working status of the lander by switching between static image mode and dynamic video mode with automatic exposure time. The focal length of the lens on the panoramic camera is 50 mm and the field of view is 19.7？umination and viewing conditions, the largest signal-to-no×14.5？.Under the best illise ratio of the panoramic camera is 44 d B. Its static modulation transfer function is 0.33. A large number of ground testing experiments and on-orbit imaging results show that the functional interface of the panoramic camera works normally. The image quality of the panoramic camera is satisfactory. All the performance parameters of the panoramic camera satisfy the design requirements.展开更多
Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squ...Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.展开更多
Aiming at the problem of long time-consuming and low accuracy of existing age estimation approaches,a new age estimation method using Gabor feature fusion,and an improved atomic search algorithm for feature selection ...Aiming at the problem of long time-consuming and low accuracy of existing age estimation approaches,a new age estimation method using Gabor feature fusion,and an improved atomic search algorithm for feature selection is proposed.Firstly,texture features of five scales and eight directions in the face region are extracted by Gabor wavelet transform.The statistical histogram is introduced to encode and fuse the directional index with the largest feature value on Gabor scales.Secondly,a new hybrid feature selection algorithm chaotic improved atom search optimisation with simulated annealing(CIASO-SA)is presented,which is based on an improved atomic search algorithm and the simulated annealing algorithm.Besides,the CIASO-SA algorithm introduces a chaos mechanism during atomic initialisation,significantly improving the convergence speed and accuracy of the algorithm.Finally,a support vector machine(SVM)is used to get classification results of the age group.To verify the performance of the proposed algorithm,face images with three resolutions in the Adience dataset are tested.Using the Gabor real part fusion feature at 48�48 resolution,the average accuracy and 1-off accuracy of age classification exhibit a maximum of 60.4%and 85.9%,respectively.Obtained results prove the superiority of the proposed algorithm over the state-of-the-art methods,which is of great referential value for application to the mobile terminals.展开更多
Two-dimensional van der Waals magnetic materials are of great current interest for their promising applications in spintronics.Using density functional theory calculations in combination with the maximally localized W...Two-dimensional van der Waals magnetic materials are of great current interest for their promising applications in spintronics.Using density functional theory calculations in combination with the maximally localized Wannier functions method and the magnetic anisotropy analyses,we study the electronic and magnetic properties of MnPSe_(3)monolayer.Our results show that it is a charge transfer antiferromagnetic(AF)insulator.For this Mn^(2)+3d^(5)system,although it seems straightforward to explain the AF ground state using the direct exchange,we find that the nearly 90oMn-Se-Mn charge transfer type superexchange plays a dominant role in stabilizing the AF ground state.Moreover,our results indicate that,although the shape anisotropy favors an out-of-plane spin orientation,the spin-orbit coupling(SOC)leads to the experimentally observed in-plane spin orientation.We prove that the actual dominant contribution to the magnetic anisotropy comes from the second-order perturbation of the SOC,by analyzing its distribution over the reciprocal space.Using the AF exchange and anisotropy parameters obtained from our calculations,our Monte Carlo simulations give the Néel temperature T_(N)=47 K for MnPSe_(3)monolayer,which agrees with the experimental 40 K.Furthermore,our calculations show that under a uniaxial tensile(compressive)strain,Néel vector would be parallel(perpendicular)to the strain direction,which well reproduces the recent experiments.We also predict that T_(N)would be increased by a compressive strain.展开更多
Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum stress.The exact interplay between stress and liver diseases remains unclear.Autophagy plays an essential ro...Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum stress.The exact interplay between stress and liver diseases remains unclear.Autophagy plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver diseases.Once the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain homeostasis.In recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much attention.FGF21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to stress.Also,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal role.This review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.展开更多
基金supported by the National Natural Science Foundation of China(22072134,22161142017,and U21A2081)the Natural Science Foundation of Zhejiang Province(LZ21B030002)+2 种基金the Fundamental Research Funds for the Zhejiang Provincial Universities(2021XZZX010)the Fundamental Research Funds for the Central Universities(2021FZZX001-09)“Hundred Talents Program” of Zhejiang University。
文摘Passivation by the inorganic-rich solid electrolyte interphase(SEI),especially the LiF-rich SEI,is highly desirable to guarantee the durable lifespan of Li metal batteries(LMBs).Here,we report a diluent with the capability to facilitate the formation of LiF-rich SEI while avoiding the excess consumption of Li salts.Dissimilar to most of reported inert diluents,heptafluoro-l-methoxypropane(HM) is firstly demonstrated to cooperate with the decomposition of anions to generate LiF-rich SEI via releasing Fcontaining species near Li surface.The designed electrolyte consisting of 1.8 M LiFSI in the mixture of1,2-dimethoxyethane(DME)/HM(2:1 by vol.) achieves excellent compatibility with both Li metal anodes(Coulombic efficiency~99.8%) and high-voltage cathodes(4.4 V LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2)(NMC811) and 4.5 V LiCoO_(2)(LCO) vs Li^(+)/Li).The 4.4 V Li(20μm)‖NMC811(2.5 mA h cm^(-2)) and 4.5 V Li(20μm)‖LCO(2.5 mA h cm^(-2)) cells achieve capacity retentions of 80% over 560 cycles and 80% over 505 cycles,respectively.Meanwhile,the anode-free pouch cell delivers an energy density of~293 W h kg^(-1)initially and retains 70% of capacity after 100 deep cycles.This work highlights the critical impact of diluent on the SEI formation,and opens up a new direction for designing desirable interfacial chemistries to enable high-performance LMBs.
基金supported by funding from the National Key Research and Development Program of China(Grant No.2021 YFA1100500)The Major Research Plan of the National Natural Science Foundation of China(Grant No.92159202)+3 种基金Key Program,National Natural Science Foundation of China(Grant No.81930016)National Natural Science Foundation of China(Grant No.82300743)Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ23H160044)Key Research&Development Program of Zhejiang Province(Grant Nos.2019C03050,2022C03108,and 2021C03118)。
文摘Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.
基金Project supported by the Key Research Project of Zhejiang Laboratory (No.K2022NB0AC03)the National Natural Science Foundation of China (No.11872334)the National Natural Science Foundation of Zhejiang Province of China (No.LZ23A020004)。
文摘Highly entangled hydrogels exhibit excellent mechanical properties,including high toughness,high stretchability,and low hysteresis.By considering the evolution of randomly distributed entanglements within the polymer network upon mechanical stretches,we develop a constitutive theory to describe the large stretch behaviors of these hydrogels.In the theory,we utilize a representative volume element(RVE)in the shape of a cube,within which there exists an averaged chain segment along each edge and a mobile entanglement at each corner.By employing an explicit method,we decouple the elasticity of the hydrogels from the sliding motion of their entanglements,and derive the stress-stretch relations for these hydrogels.The present theoretical analysis is in agreement with experiment,and highlights the significant influence of the entanglement distribution within the hydrogels on their elasticity.We also implement the present developed constitutive theory into a commercial finite element software,and the subsequent simulations demonstrate that the exact distribution of entanglements strongly affects the mechanical behaviors of the structures of these hydrogels.Overall,the present theory provides valuable insights into the deformation mechanism of highly entangled hydrogels,and can aid in the design of these hydrogels with enhanced performance.
基金the National Key Research and Development Program of China(No.2021YFA1100500)the Major Research Plan of the National Natural Science Foundation of China(No.92159202)+2 种基金the Key Research&Development Plan of Zhejiang Province(No.2019C03050),the Key Research&Development Plan of Zhejiang Province(No.2021C03118)National S&T Major Project(No.2017ZX10203205)the Health Science&Technology Plan of Zhejiang Province(No.2022RC060)。
文摘Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(P<0.001).The expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(P<0.001).TNF and TNFR1 showed no relationship with patients’outcomes,whereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,P<0.001).Notably,elevated TNFR2 levels were also associated with an increased risk of post-transplant lung metastasis(hazard ratio:1.146;P<0.001).Cox regression analysis revealed that TNFR2,Hangzhou criteria,age,and hepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC.
基金supported by the Key Research Projects of Universities of Henan Province,No.21A320064 (to XS)the National Key Research and Development Program of China,No.2021YFA1201504 (to LZ)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Science,No.XDB36000000 (to CW)the National Natural Science Foundation of China,Nos.31971295,12374406 (both to LZ)。
文摘Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.
基金grants from the National Science and Technology Major Project of China(No.2017ZX10203205)the National Natural Science Founds for Distinguished Young Scholar of China(No.81625003)+1 种基金the State Key Program of National Natural Science Foundation of China(No.81930016)the National Natural Science Foundation of China(No.81902407).
文摘Background:The downstaging of hepatocellular carcinoma(HCC)has been confirmed to benefit liver transplantation(LT)patients whose tumors are beyond the transplantation criteria.Milan criteria(MC),a tumor size and number-based assessment,is currently used as the endpoint in these patients.However,many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy.Hence,this study aimed to explore the feasibility of Hangzhou criteria(HC),which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number,as an endpoint of downstaging.Methods:We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy(LRT)as downstaging/bridge treatment prior to LT in three centers of China.Results:Recipients were divided into four groups:failed downstaging to the HC(group A,n=46),successful downstaging to the HC(group B,n=30),remained within the HC all the time(group C,n=113),and tumor progressed(group D,n=17).The 3-year HCC recurrence probabilities of groups B and C were not significantly different(10.3%vs.11.6%,P=0.87).The HCC recurrent rate was significantly higher in group A(52.3%)compared with that in group B/C(P<0.05).Seven patients(7/76,9.2%)whose tumor exceeded the the HC were successfully downstaged to the MC,and 39.5%(30/76)to the the HC.In group B,23 patients remained beyond the MC and their survivals were as well as those of patients within the MC.Conclusions:Compared to the MC,HC downstaging criteria can give more HCC patients access to LT and furthermore,the outcome of these patients is the same as those matching MC downstaging criteria.Hangzhou downstaging criteria therefore is applicable in clinical practice.
基金supported by the National Natural Science Foundation of China,No.81241126(to XLD)and 81360197(to XLD)a grant from the Department of Science and Technology of Kunming Medical University in China,No.2013C227(to XLD)the Joint Special Fund for the Department of Science and Technology of Kunming Medical University in China,No.2014FB041(to XBS)
文摘Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,chemokine receptor 4(CXCR4),are important regulators of cell migration.We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease.A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway,and then treated with 5μL of neural stem cell suspension(1.5×104/L)in the right substantia nigra.Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation.Parkinson-like behavior in rats was detected using apomorphine-induced rotation.Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Using quantitative real-time polymerase chain reaction,the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured.In addition,western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4.Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation,increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra,and enhanced the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Injection of AMD3100 inhibited the aforementioned effects.These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease.This study was approved by the Animal Care and Use Committee of Kunming Medical University,China(approval No.SYXKK2015-0002)on April 1,2014.
基金Supported by The National Natural Science Foundation of China,No.81100321Science Fund for Creative Research Groups of the National Natural Science Foundation of China,No. 81121002Science and Technology Department of Zhejiang Province,2009R50038
文摘AIM:To investigate the impact of renal and graft function on post-transplant hyperlipidemia(PTHL) in living donor liver transplantation(LDLT).METHODS:A total of 115 adult patients undergoing LDLT from January 2007 to May 2009 at a single center were enrolled.Data were collected and analyzed by the China Liver Transplant Registry retrospectively.PTHL was defined as serum triglycerides ≥ 150 mg/dL or serum cholesterol ≥ 200 mg/dL or the need for pharmacologic treatment at the sixth month after LDLT.Early renal dysfunction(ERD) was defined as serum creatinine ≥ 2 mg/dL and/or the need for renal replacement therapy in the first post-transplant week.RESULTS:In 115 eligible patients,the incidence of PTHL was 24.3%.Recipients with PTHL showed a higher incidence of post-transplant cardiovascular events compared to those without PTHL(17.9% vs 4.6%,P = 0.037).Serum creatinine showed significant positive correlations with total serum triglycerides,both at posttransplant month 1 and 3(P < 0.01).Patients with ERD had much higher pre-transplant serum creatinine levels(P < 0.001) and longer duration of pre-transplant renal insufficiency(P < 0.001) than those without ERD.Pretransplant serum creatinine,graft-to-recipient weight ratio,graft volume/standard liver volume ratio,body mass index(BMI) and ERD were identified as risk factors for PTHL by univariate analysis.Furthermore,ERD [odds ratio(OR) = 9.593,P < 0.001] and BMI(OR = 6.358,P = 0.002) were identified as independent risk factors for PTHL by multivariate analysis.CONCLUSION:Renal function is closely associated with the development of PTHL in LDLT.Post-transplant renal dysfunction,which mainly results from pre-transplant renal insufficiency,contributes to PTHL.
基金supported by grants from the National Science and Technology Major Project of China(No.2017ZX10203205)the National Natural Science Funds for Distinguished Young Scholar of China(No.81625003)+1 种基金Key Program National Natural Science Foundation of China(No.81930016)Key Research&Development Plan of Zhejiang Province(No.2019C03050)。
文摘Objective:Patient-derived xenograft(PDX)models provide a promising preclinical platform for hepatocellular carcinoma(HCC).However,the molecular features associated with successful engraftment of PDX models have not been revealed.Methods:HCC tumor samples from 76 patients were implanted in immunodeficient mice.The molecular expression was evaluated by immunohistochemistry.Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test.The independent prediction parameters were identified by logistic regression analyses.Results:The engraftment rate for PDX models from patients with HCC was 39.47%(30/76).Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates.Tumors with poor differentiation and vascular invasion were related to engraftment success.The positive expression of CK19,CD133,glypican-3(GPC3),and Ki67 in tumor samples was associated with engraftment success.Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment.Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates,with 71.9%in GPC3^(+)/Ki67^(+)tumors,30.8%in GPC3^(-)/Ki67^(+)tumors,15.0%in GPC3^(+)/Ki67^(-)tumors,and 0 in GPC3^(-)/Ki67^(-)tumors.Conclusions:Successful engraftment of HCC PDXs was significantly related to molecular features.Tumors with the GPC3+/Ki67+phenotype were the most likely to successfully establish HCC PDXs.
文摘The Chang＇e-3 panoramic camera, which is composed of two cameras with identical functions, performances and interfaces, is installed on the lunar rover mast. It can acquire 3D images of the lunar surface based on the principle of binocular stereo vision. By rotating and pitching the mast, it can take several photographs of the patrol area. After stitching these images, panoramic images of the scenes will be obtained.Thus the topography and geomorphology of the patrol area and the impact crater, as well as the geological structure of the lunar surface, will be analyzed and studied.In addition, it can take color photographs of the lander using the Bayer color coding principle. It can observe the working status of the lander by switching between static image mode and dynamic video mode with automatic exposure time. The focal length of the lens on the panoramic camera is 50 mm and the field of view is 19.7？umination and viewing conditions, the largest signal-to-no×14.5？.Under the best illise ratio of the panoramic camera is 44 d B. Its static modulation transfer function is 0.33. A large number of ground testing experiments and on-orbit imaging results show that the functional interface of the panoramic camera works normally. The image quality of the panoramic camera is satisfactory. All the performance parameters of the panoramic camera satisfy the design requirements.
基金supported by the National Natural Science Foundation of China (82103508, 81871866, 82173252, 81672996)the Natural Science Foundation of Shaanxi Province (2022JQ?862)。
文摘Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.
文摘Aiming at the problem of long time-consuming and low accuracy of existing age estimation approaches,a new age estimation method using Gabor feature fusion,and an improved atomic search algorithm for feature selection is proposed.Firstly,texture features of five scales and eight directions in the face region are extracted by Gabor wavelet transform.The statistical histogram is introduced to encode and fuse the directional index with the largest feature value on Gabor scales.Secondly,a new hybrid feature selection algorithm chaotic improved atom search optimisation with simulated annealing(CIASO-SA)is presented,which is based on an improved atomic search algorithm and the simulated annealing algorithm.Besides,the CIASO-SA algorithm introduces a chaos mechanism during atomic initialisation,significantly improving the convergence speed and accuracy of the algorithm.Finally,a support vector machine(SVM)is used to get classification results of the age group.To verify the performance of the proposed algorithm,face images with three resolutions in the Adience dataset are tested.Using the Gabor real part fusion feature at 48�48 resolution,the average accuracy and 1-off accuracy of age classification exhibit a maximum of 60.4%and 85.9%,respectively.Obtained results prove the superiority of the proposed algorithm over the state-of-the-art methods,which is of great referential value for application to the mobile terminals.
基金supported by the National Natural Science Foundation of China(Grant Nos.12174062,12241402,and 12104307)。
文摘Two-dimensional van der Waals magnetic materials are of great current interest for their promising applications in spintronics.Using density functional theory calculations in combination with the maximally localized Wannier functions method and the magnetic anisotropy analyses,we study the electronic and magnetic properties of MnPSe_(3)monolayer.Our results show that it is a charge transfer antiferromagnetic(AF)insulator.For this Mn^(2)+3d^(5)system,although it seems straightforward to explain the AF ground state using the direct exchange,we find that the nearly 90oMn-Se-Mn charge transfer type superexchange plays a dominant role in stabilizing the AF ground state.Moreover,our results indicate that,although the shape anisotropy favors an out-of-plane spin orientation,the spin-orbit coupling(SOC)leads to the experimentally observed in-plane spin orientation.We prove that the actual dominant contribution to the magnetic anisotropy comes from the second-order perturbation of the SOC,by analyzing its distribution over the reciprocal space.Using the AF exchange and anisotropy parameters obtained from our calculations,our Monte Carlo simulations give the Néel temperature T_(N)=47 K for MnPSe_(3)monolayer,which agrees with the experimental 40 K.Furthermore,our calculations show that under a uniaxial tensile(compressive)strain,Néel vector would be parallel(perpendicular)to the strain direction,which well reproduces the recent experiments.We also predict that T_(N)would be increased by a compressive strain.
基金supported by the National Key Research and Development Program of China(No.2021YFA1100500)the Major Research Plan of the National Natural Science Foundation of China(No.92159202)+2 种基金the Key Program,National Natural Science Foundation of China(No.81930016)the Young Program of National Natural Science Funds(China)(No.82000617)A Project Supported by Scientific Research Fund of Zhejiang Provincial Education Department(China)(No.Y202250784).
文摘Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum stress.The exact interplay between stress and liver diseases remains unclear.Autophagy plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver diseases.Once the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain homeostasis.In recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much attention.FGF21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to stress.Also,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal role.This review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.
