Hepatocellular carcinoma(HCC)is a highly heterogenous dis-ease in histology,genetic aberrations,and protein expression.Over the past decade,the development of new omics techniques has fa-cilitated significant advances...Hepatocellular carcinoma(HCC)is a highly heterogenous dis-ease in histology,genetic aberrations,and protein expression.Over the past decade,the development of new omics techniques has fa-cilitated significant advances in the field of molecular typing stud-ies of HCC.In the era of precision medicine,it is of great signif-icance to improve the efficacy of HCC treatment based on tumor molecular subtyping.Cytokeratin(CK)19-positive HCC has gained increasing atten-tion.Although CK19 is a marker of biliary epithelial cells,10%−30%of HCCs are observed to be CK19 positive[1].Differing from com-bined hepatocellular and cholangiocarcinoma,CK19-positive HCC displays typical HCC morphological features,exhibiting strong co-express of both hepatocyte and cholangiocyte markers within the same tumor cells.Consequently,CK19-positive HCC is also referred to as dual-phenotype HCC,with displaying cholangiolar differenti-ation.展开更多
Alcohol consumption poses an escalating public health challenge.However,the impact of alcoholic liver disease(ALD)on post-transplant hepatitis B virus(HBV)reactivation and surgical outcomes remains inadequately charac...Alcohol consumption poses an escalating public health challenge.However,the impact of alcoholic liver disease(ALD)on post-transplant hepatitis B virus(HBV)reactivation and surgical outcomes remains inadequately characterized.Herein,we retrospectively analyzed our cohort(NCT06114251)comprising 453 patients with an HBV background.Propensity score matching(PSM)and sensitivity analyses were employed to assess the influence of ALD on surgical outcomes.Benchmark analysis compared the predictive performance of 21 models for post-transplant HBV reactivation.The Shapley additive explanation(SHAP)algorithm facilitated feature ranking and model interpretation.Patients were stratified into three subgroups based on the alcohol-modified HBV reactivation index(AMBRI).Among the cohort,113 patients(24.9%)had concurrent pre-transplant diagnoses of ALD and HBV infection,while 340(75.1%)had HBV infection alone.The presence of ALD was associated with an elevated risk of HBV reactivation and liver metastasis.PSM and sensitivity analyses revealed significantly lower five-year HBV reactivation-free survival(74.9%vs 85.4%),overall survival(OS,56.2%vs 70.5%),and tumor recurrence-free survival(RFS,47.8%vs 63.3%)in the ALD cohort.In recipients without HBV reactivation,hepatocellular carcinomas(HCCs)arising from both ALD and HBV exhibited inferior RFS(log-rank P=0.026)and OS beyond one year(landmark P=0.032)compared to HBV-related HCC alone.Benchmark analysis identified the surv.cforest model as the optimal predictor,achieving an area under the receiver operating characteristic(AUC)curve of 0.914 in internal validation and 0.884 in external validation,outperforming the published Cox model(AUC=0.78).AMBRI-based stratification delineated three distinct risk subgroups,with the intermediate-and high-risk groups exhibiting significantly worse OS and RFS than the low-risk group.In this study,stratification by AMBRI identified intermediate-and high-risk groups with poorer post-transplant outcomes,underscoring the necessity for intensified surveillance and enhanced HBV treatment regimens,particularly in recipients with pre-transplant ALD.展开更多
The introduction of two-dimensional(2D)perovskite layers on top of three-dimensional(3D)perovskite films enhances the performance and stability of perovskite solar cells(PSCs).However,the electronic effect of the spac...The introduction of two-dimensional(2D)perovskite layers on top of three-dimensional(3D)perovskite films enhances the performance and stability of perovskite solar cells(PSCs).However,the electronic effect of the spacer cation and the quality of the 2D capping layer are critical factors in achieving the required results.In this study,we compared two fluorinated salts:4-(trifluoromethyl)benzamidine hydrochloride(4TF-BA·HCl)and 4-fluorobenzamidine hydrochloride(4F-BA·HCl)to engineer the 3D/2D perovskite films.Surprisingly,4F-BA formed a high-performance 3D/2D heterojunction,while4TF-BA produced an amorphous layer on the perovskite films.Our findings indicate that the balanced intramolecular charge polarization,which leads to effective hydrogen bonding,is more favorable in 4F-BA than in 4TF-BA,promoting the formation of a crystalline 2D perovskite.Nevertheless,4TF-BA managed to improve efficiency to 24%,surpassing the control device,primarily due to the natural passivation capabilities of benzamidine.Interestingly,the devices based on 4F-BA demonstrated an efficiency exceeding 25%with greater longevity under various storage conditions compared to 4TF-BA-based and the control devices.展开更多
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
Intervertebral disc degeneration(IDD),osteoarthritis(OA),and osteoporosis(OP)are common musculoskeletal disorders(MSDs)with similar age-related risk factors,representing the leading causes of disability.However,succes...Intervertebral disc degeneration(IDD),osteoarthritis(OA),and osteoporosis(OP)are common musculoskeletal disorders(MSDs)with similar age-related risk factors,representing the leading causes of disability.However,successful therapeutic development and translation have been hampered by the lack of clinically-relevant animal models.In this study,we investigated the potential suitability of the tree shrew,a small mammal with a close genetic relationship to primates,as a new animal model for MSDs.Age-related spontaneous IDD in parallel with a gradual disappearance of notochordal cells were commonly observed in tree shrews upon skeletal maturity with no sex differences,while age-related osteoporotic changes including bone loss in the metaphyses were primarily presented in aged females,similar to observations in humans.Moreover,in the osteochondral defect model,tree shrew cartilage exhibited behavior similar to that of humans,characterized by a more restricted self-healing capacity compared to the rapid spontaneous healing of joint surfaces observed in rats.The induced OA model in tree shrews was highly efficient and reproducible,characterized by gradual deterioration of articular cartilage,recapitulating the human OA phenotype to some degree.Surgery-induced IDD models were successfully established in tree shrews,in which the lumbar spine instability model developed slow progressive disc degeneration with more similarity to the clinical state,whereas the needle puncture model led to the rapid development of IDD with more severe symptoms.Taken together,our findings pave the way for the development of the tree shrew as a new animal model for the study of MSDs and aging.展开更多
Objective:The role of non-alcoholic steatohepatitis(NASH)in hepatitis B virus(HBV)reactivation following liver transplantation for hepatocellular carcinoma(HCC)remains unclear,and the metabolic differences between pat...Objective:The role of non-alcoholic steatohepatitis(NASH)in hepatitis B virus(HBV)reactivation following liver transplantation for hepatocellular carcinoma(HCC)remains unclear,and the metabolic differences between patients with NASH and those with HBV reactivation are also yet to be elucidated.This study is to investigate the impact of NASH on HBV reactivation risk and prognosis following liver transplantation for HCC,and to develop a predictive model and identify therapeutic targets.Methods:This study included 274 patients who underwent liver transplantation for HCC.The HBV reactivation status of patients with NASH was analyzed,and the metabolic characteristics of peripheral blood were examined to compare NASH and non-NASH patients with or without HBV reactivation.Results:The HBV reactivation free survival was better in non-NASH patients(P<0.0001).Furthermore,NASH patients with HBV reactivation had worse recurrence-free survival(RFS)than non-NASH patients with HBV reactivation(P=0.016).In contrast,the RFS of NASH patients without HBV reactivation was comparable to that of non-NASH patients without HBV reactivation(P=0.810).Subsequently,we constructed a model to predict HBV reactivation by incorporating 7 clinical indicators using the Least Absolute Shrinkage and Selection Operator-Cox(LASSO-Cox)approach.The area under the receiver operating characteristic curve(AUROC)values for predictions at 500,1,000,and 1,500 d were 0.759,0.809,and 0.814,respectively.Finally,metabolic pathway analysis identified key pathways involved in HBV reactivation,and glutamine was found to be an independent protective factor against HBV reactivation following liver transplantation for HCC.Conclusions:NASH patients are more prone to HBV reactivation following liver transplantation for HCC and exhibit worse recurrence-free survival.Glutamine may serve as a potential therapeutic target or predictive biomarker for HBV reactivation.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
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
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: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
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
Electrical additive manufacturing can improve manufacturing efficiency and reduce the cost of 16MND5 reactor pres-sure vessel steel. Impact tests were conducted to compare the impact toughness of 16MND5 steels manufac...Electrical additive manufacturing can improve manufacturing efficiency and reduce the cost of 16MND5 reactor pres-sure vessel steel. Impact tests were conducted to compare the impact toughness of 16MND5 steels manufactured by the electrical additive manufacturing and conventional forging, respectively. It is found that the impact toughness of electrical additive manufacturing specimen was slightly higher than that of conventional forging specimen. The characterizations of microstructure show that there were large ferrites and carbides in electrical additive manufacturing specimen. The fracture mechanisms of electrical additive manufacturing specimen were that microvoids or microcracks were prone to nucleate at the large ferrite/bainite interface and large carbide/bainitic ferrite interface, where the stress concentration was high. In addi-tion, the block size and high-angle grain boundaries played a vital role in hindering crack propagation of electrical additive manufacturing specimen, helping to improve the impact energy and leading to a low ductile–brittle transition temperature. The results suggest that the electrical additive manufacturing technology was an effective method to enhance the impact toughness of 16MND5 steel.展开更多
Toward understanding the macroscopic mechanical behaviors of responsive deoxyribonucleic acid(DNA)hydrogels integrated with DNA motors,here we construct the state map for the translocation process of a single C-termin...Toward understanding the macroscopic mechanical behaviors of responsive deoxyribonucleic acid(DNA)hydrogels integrated with DNA motors,here we construct the state map for the translocation process of a single C-terminal translocase domain(FtsKC)on a single DNA chain at the molecular level and then investigate the movement of single or multiple FtsKC motors on DNA chains with varied branch topology.Our studies indicate that multiple FtsKC motors can have coordinated motion,which is mainly due to the force responsive behavior of individual FtsKC motor.We further suggest the potential application of motors of FtsKC,together with DNA chains of specific branch topology,to serve as strain sensors in hydrogels.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
Pulmonary metastasis is a life-threatening complication for patients with hepatocellular carcinoma(HCC)undergoing liver transplantation(LT).In addition to the common mechanisms underlying tumor metastasis,another inev...Pulmonary metastasis is a life-threatening complication for patients with hepatocellular carcinoma(HCC)undergoing liver transplantation(LT).In addition to the common mechanisms underlying tumor metastasis,another inevitable factor is that the application of immunosuppressive agents,including calcineurin inhibitors(CNIs)and rapamycin inhibitors(mTORis),after transplantation could influence tumor recurrence and metastasis.In recent years,several studies have reported that mTORis,unlike CNIs,have the capacity to modulate the tumorigenic landscape post-liver transplantation by targeting metastasis-initiating cells and reshaping the pulmonary microenvironment.Therefore,we focused on the effects of immunosuppressive agents on the lung metastatic microenvironment and how mTORis impact tumor growth in distant organs.This revelation has provided profound insights into transplant oncology,leading to a renewed understanding of the use of immunosuppressants after LT for HCC.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
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
Introduction With the continuous advancement of surgical technique,combined vascular resection has become increasingly common during complex surgical procedures.In such cases,ensuring the safe and effective reconstruc...Introduction With the continuous advancement of surgical technique,combined vascular resection has become increasingly common during complex surgical procedures.In such cases,ensuring the safe and effective reconstruction of blood vessels after resection is of paramount importance.When direct vascular reconstruction is not feasible,the application of vascular grafts becomes necessary to restore vascular continuity and function.Commonly employed vascular grafts in clinical practice include allogeneic graft vessels(AGVs),autologous vessels,and artificial vessels.Among these,AGVs offer distinct advantages particularly in its complex structures and satisfying histocompatibility,making it a valuable option for vascular reconstruction.展开更多
基金supported by grants from the Major Re-search Plan of the National Natural Science Foundation of China(92159202)the National Key Research and Development Pro-gram of China(2021YFA1100500)+5 种基金the Key Research&Develop-ment Plan of Zhejiang Province(2024C03051)the Innovation Team of Hangzhou Medical College(CXLJ202401)Joint TCM Science&Technology Projects of National Demonstration Zones for Compre-hensive TCM Reform(GZY-KJS-ZJ-2025-002)the National Natural Science Foundation of China(82303387)the Natural Science Foun-dation of Zhejiang Province(LQ23H160048)the Construction Fund of Key Medical Disciplines of Hangzhou(2025HZGF05).
文摘Hepatocellular carcinoma(HCC)is a highly heterogenous dis-ease in histology,genetic aberrations,and protein expression.Over the past decade,the development of new omics techniques has fa-cilitated significant advances in the field of molecular typing stud-ies of HCC.In the era of precision medicine,it is of great signif-icance to improve the efficacy of HCC treatment based on tumor molecular subtyping.Cytokeratin(CK)19-positive HCC has gained increasing atten-tion.Although CK19 is a marker of biliary epithelial cells,10%−30%of HCCs are observed to be CK19 positive[1].Differing from com-bined hepatocellular and cholangiocarcinoma,CK19-positive HCC displays typical HCC morphological features,exhibiting strong co-express of both hepatocyte and cholangiocyte markers within the same tumor cells.Consequently,CK19-positive HCC is also referred to as dual-phenotype HCC,with displaying cholangiolar differenti-ation.
基金supported by the National Natural Science Foun-dation of China(92159202)the National Science and Technology Major Project of China(2017ZX10203205)+4 种基金the Fundamental Research Funds for the Central Universities(2022ZFJH003)the Major Research Plan of Key Research and Development Project of Zhejiang Province(2024C03149 and 2023C03046)the National Key Research and Development Program of China(2021YFF1200404 and 2021YFA1201200)the Zhejiang Provincial Natural Science Foundation of China(LQ24C050005 and LQ22H160052)the Medical and Health Technology Program Project of Zhejiang Province(2021434810).
文摘Alcohol consumption poses an escalating public health challenge.However,the impact of alcoholic liver disease(ALD)on post-transplant hepatitis B virus(HBV)reactivation and surgical outcomes remains inadequately characterized.Herein,we retrospectively analyzed our cohort(NCT06114251)comprising 453 patients with an HBV background.Propensity score matching(PSM)and sensitivity analyses were employed to assess the influence of ALD on surgical outcomes.Benchmark analysis compared the predictive performance of 21 models for post-transplant HBV reactivation.The Shapley additive explanation(SHAP)algorithm facilitated feature ranking and model interpretation.Patients were stratified into three subgroups based on the alcohol-modified HBV reactivation index(AMBRI).Among the cohort,113 patients(24.9%)had concurrent pre-transplant diagnoses of ALD and HBV infection,while 340(75.1%)had HBV infection alone.The presence of ALD was associated with an elevated risk of HBV reactivation and liver metastasis.PSM and sensitivity analyses revealed significantly lower five-year HBV reactivation-free survival(74.9%vs 85.4%),overall survival(OS,56.2%vs 70.5%),and tumor recurrence-free survival(RFS,47.8%vs 63.3%)in the ALD cohort.In recipients without HBV reactivation,hepatocellular carcinomas(HCCs)arising from both ALD and HBV exhibited inferior RFS(log-rank P=0.026)and OS beyond one year(landmark P=0.032)compared to HBV-related HCC alone.Benchmark analysis identified the surv.cforest model as the optimal predictor,achieving an area under the receiver operating characteristic(AUC)curve of 0.914 in internal validation and 0.884 in external validation,outperforming the published Cox model(AUC=0.78).AMBRI-based stratification delineated three distinct risk subgroups,with the intermediate-and high-risk groups exhibiting significantly worse OS and RFS than the low-risk group.In this study,stratification by AMBRI identified intermediate-and high-risk groups with poorer post-transplant outcomes,underscoring the necessity for intensified surveillance and enhanced HBV treatment regimens,particularly in recipients with pre-transplant ALD.
基金supported by the National Key Research and Development Programs-Intergovernmental International Cooperation in Science and Technology Innovation Project(Grant No.2022YFE0118400)the Natural Science Foundation of Hunan Province(2023JJ50132)+1 种基金Shenzhen Science and Technology Innovation Committee(Grants Nos.JCYJ20220818100211025,and KCXST20221021111616039)Shenzhen Science and Technology Program(No.20231128110928003)。
文摘The introduction of two-dimensional(2D)perovskite layers on top of three-dimensional(3D)perovskite films enhances the performance and stability of perovskite solar cells(PSCs).However,the electronic effect of the spacer cation and the quality of the 2D capping layer are critical factors in achieving the required results.In this study,we compared two fluorinated salts:4-(trifluoromethyl)benzamidine hydrochloride(4TF-BA·HCl)and 4-fluorobenzamidine hydrochloride(4F-BA·HCl)to engineer the 3D/2D perovskite films.Surprisingly,4F-BA formed a high-performance 3D/2D heterojunction,while4TF-BA produced an amorphous layer on the perovskite films.Our findings indicate that the balanced intramolecular charge polarization,which leads to effective hydrogen bonding,is more favorable in 4F-BA than in 4TF-BA,promoting the formation of a crystalline 2D perovskite.Nevertheless,4TF-BA managed to improve efficiency to 24%,surpassing the control device,primarily due to the natural passivation capabilities of benzamidine.Interestingly,the devices based on 4F-BA demonstrated an efficiency exceeding 25%with greater longevity under various storage conditions compared to 4TF-BA-based and the control devices.
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National Natural Science Foundation of China(Grant Nos.92268204,32160209,82160175)Yunling Scholar Project of Yunnan Revitalization Talent Support Program,the Foundation of Expert Workstation of Bai Xiaochun(YSZJGZZ-2020040)Applied Basic Research Foundation of Yunnan Province(Grant Nos.202001AY070001-014,202201AY070001-032)。
文摘Intervertebral disc degeneration(IDD),osteoarthritis(OA),and osteoporosis(OP)are common musculoskeletal disorders(MSDs)with similar age-related risk factors,representing the leading causes of disability.However,successful therapeutic development and translation have been hampered by the lack of clinically-relevant animal models.In this study,we investigated the potential suitability of the tree shrew,a small mammal with a close genetic relationship to primates,as a new animal model for MSDs.Age-related spontaneous IDD in parallel with a gradual disappearance of notochordal cells were commonly observed in tree shrews upon skeletal maturity with no sex differences,while age-related osteoporotic changes including bone loss in the metaphyses were primarily presented in aged females,similar to observations in humans.Moreover,in the osteochondral defect model,tree shrew cartilage exhibited behavior similar to that of humans,characterized by a more restricted self-healing capacity compared to the rapid spontaneous healing of joint surfaces observed in rats.The induced OA model in tree shrews was highly efficient and reproducible,characterized by gradual deterioration of articular cartilage,recapitulating the human OA phenotype to some degree.Surgery-induced IDD models were successfully established in tree shrews,in which the lumbar spine instability model developed slow progressive disc degeneration with more similarity to the clinical state,whereas the needle puncture model led to the rapid development of IDD with more severe symptoms.Taken together,our findings pave the way for the development of the tree shrew as a new animal model for the study of MSDs and aging.
基金supported by the Major Research Plan of the National Natural Science Foundation of China(No.92159202)the National Key Research and Development Program of China(No.2021YFA1100500)+2 种基金the Key Research&Development Plan of Zhejiang Province(No.2019C03050)National S&T Major Project(No.2017ZX10203205)the Health Science&Technology Plan of Zhejiang Province(No.2022RC060)。
文摘Objective:The role of non-alcoholic steatohepatitis(NASH)in hepatitis B virus(HBV)reactivation following liver transplantation for hepatocellular carcinoma(HCC)remains unclear,and the metabolic differences between patients with NASH and those with HBV reactivation are also yet to be elucidated.This study is to investigate the impact of NASH on HBV reactivation risk and prognosis following liver transplantation for HCC,and to develop a predictive model and identify therapeutic targets.Methods:This study included 274 patients who underwent liver transplantation for HCC.The HBV reactivation status of patients with NASH was analyzed,and the metabolic characteristics of peripheral blood were examined to compare NASH and non-NASH patients with or without HBV reactivation.Results:The HBV reactivation free survival was better in non-NASH patients(P<0.0001).Furthermore,NASH patients with HBV reactivation had worse recurrence-free survival(RFS)than non-NASH patients with HBV reactivation(P=0.016).In contrast,the RFS of NASH patients without HBV reactivation was comparable to that of non-NASH patients without HBV reactivation(P=0.810).Subsequently,we constructed a model to predict HBV reactivation by incorporating 7 clinical indicators using the Least Absolute Shrinkage and Selection Operator-Cox(LASSO-Cox)approach.The area under the receiver operating characteristic curve(AUROC)values for predictions at 500,1,000,and 1,500 d were 0.759,0.809,and 0.814,respectively.Finally,metabolic pathway analysis identified key pathways involved in HBV reactivation,and glutamine was found to be an independent protective factor against HBV reactivation following liver transplantation for HCC.Conclusions:NASH patients are more prone to HBV reactivation following liver transplantation for HCC and exhibit worse recurrence-free survival.Glutamine may serve as a potential therapeutic target or predictive biomarker for HBV reactivation.
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 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 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.
基金This work was financially supported by the Nuclear Power Technology Innovation Center(HDLCXZX-2018-HD-027-03)Science and Technology on Reactor System Design Technology Laboratory(HT-KFKT-02-2017006).
文摘Electrical additive manufacturing can improve manufacturing efficiency and reduce the cost of 16MND5 reactor pres-sure vessel steel. Impact tests were conducted to compare the impact toughness of 16MND5 steels manufactured by the electrical additive manufacturing and conventional forging, respectively. It is found that the impact toughness of electrical additive manufacturing specimen was slightly higher than that of conventional forging specimen. The characterizations of microstructure show that there were large ferrites and carbides in electrical additive manufacturing specimen. The fracture mechanisms of electrical additive manufacturing specimen were that microvoids or microcracks were prone to nucleate at the large ferrite/bainite interface and large carbide/bainitic ferrite interface, where the stress concentration was high. In addi-tion, the block size and high-angle grain boundaries played a vital role in hindering crack propagation of electrical additive manufacturing specimen, helping to improve the impact energy and leading to a low ductile–brittle transition temperature. The results suggest that the electrical additive manufacturing technology was an effective method to enhance the impact toughness of 16MND5 steel.
基金This work was supported by the National Natural Science Foundation of China (Grant 11872334).
文摘Toward understanding the macroscopic mechanical behaviors of responsive deoxyribonucleic acid(DNA)hydrogels integrated with DNA motors,here we construct the state map for the translocation process of a single C-terminal translocase domain(FtsKC)on a single DNA chain at the molecular level and then investigate the movement of single or multiple FtsKC motors on DNA chains with varied branch topology.Our studies indicate that multiple FtsKC motors can have coordinated motion,which is mainly due to the force responsive behavior of individual FtsKC motor.We further suggest the potential application of motors of FtsKC,together with DNA chains of specific branch topology,to serve as strain sensors in hydrogels.
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supported by the Major Research Plan of the National Natural Science Foundation of China(Grant No.92159202)the Key Research&Development Plan of Zhejiang Province(Grant No.2024C03051)+2 种基金the National Key Research and Development Program of China(Grant No.2021YFA1100500)the National Natural Science Foundation of China(Grant No.82303387)Natural Science Foundation of Zhejiang Province(Grant No.LQ23H160048)。
文摘Pulmonary metastasis is a life-threatening complication for patients with hepatocellular carcinoma(HCC)undergoing liver transplantation(LT).In addition to the common mechanisms underlying tumor metastasis,another inevitable factor is that the application of immunosuppressive agents,including calcineurin inhibitors(CNIs)and rapamycin inhibitors(mTORis),after transplantation could influence tumor recurrence and metastasis.In recent years,several studies have reported that mTORis,unlike CNIs,have the capacity to modulate the tumorigenic landscape post-liver transplantation by targeting metastasis-initiating cells and reshaping the pulmonary microenvironment.Therefore,we focused on the effects of immunosuppressive agents on the lung metastatic microenvironment and how mTORis impact tumor growth in distant organs.This revelation has provided profound insights into transplant oncology,leading to a renewed understanding of the use of immunosuppressants after LT for HCC.
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 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supported by grants from the Research and Demonstration Application of Clinical Diagnostic and Treatment Techniques in the Capital(Z211100002921025)Capital’s Funds for Health Improvement and Research(CFH2020-2-2036)。
文摘Introduction With the continuous advancement of surgical technique,combined vascular resection has become increasingly common during complex surgical procedures.In such cases,ensuring the safe and effective reconstruction of blood vessels after resection is of paramount importance.When direct vascular reconstruction is not feasible,the application of vascular grafts becomes necessary to restore vascular continuity and function.Commonly employed vascular grafts in clinical practice include allogeneic graft vessels(AGVs),autologous vessels,and artificial vessels.Among these,AGVs offer distinct advantages particularly in its complex structures and satisfying histocompatibility,making it a valuable option for vascular reconstruction.
