OBJECTIVE To investigate the expression of E-cadherin andCEA in serum in colorectal carcinoma and their relationship withliver metastasis.METHODS CEA level was measured post-operativelyby radioimmunoassay of 60 patien...OBJECTIVE To investigate the expression of E-cadherin andCEA in serum in colorectal carcinoma and their relationship withliver metastasis.METHODS CEA level was measured post-operativelyby radioimmunoassay of 60 patients with colorectal cancer.Immunohistochemical analysis was used to evaluate theexpression of E-cadherin.RESULTS In liver metastasis group,24 patients (24/26,92.3%)were high level of CEA,but only 9 patients in non-liver metastasisgroup.The difference is significant (P=0.004).Expression ofE-cadherin significantly correlated with differentiation,but wasnot associated with Tstage or N stage.Liver metastatic rate innegative expression was higher than that in positive expression.And the survival analysis showed that time of liver metastasis wassignificant different in two groups (P<0.05).CONCLUSION The expression of CEA in serum can be usedto predict liver mestatasis of colorectal cancer after operation.E-cadherin,associated with tumor differentiation,is also a hopefulindicator for the prediction of liver metastasis in patients withcolorectal cancer.展开更多
Objective:Postoperative recurrence of esophageal carcinoma was the main factor that affect the patients' survival and quality of life.This study mainly investigated the clinical features of thoracic stomach cancer...Objective:Postoperative recurrence of esophageal carcinoma was the main factor that affect the patients' survival and quality of life.This study mainly investigated the clinical features of thoracic stomach cancer (TSC) after surgical treatment for esophageal carcinoma.Methods:We retrospectively reviewed 51 cases of postoperative TSC in our hospital (Henan Province Tumor Hospital,Zhengzhou,China).Results:The 51 (10.97%) of all 465 cases that underwent endoscope after surgical treatment for esophageal carcinoma in our hospital were TSCs.There were 13 cases with complicating anastomotic recurrence.The locations of 46 cases (90.2%) were the same as the primary cancer.The 48 cases were squamous cell carcinomas and 3 cases were adenocarcinomas after esophagectomy for esophageal carcinoma.Endoscopic manifestations were puffiness-infiltrating type at 39.2% (20/51),massive type at 15.7% (8/51),ulcerative type at 7.8% (4/51) and ulcerative infiltrating type at 3.9% (2/51) and stenotic type etc.Conclusion:The incidence of TSC after surgical treatment for esophageal carcinoma is high.The main cause was that the local residual cancer invaded gastric wall.The gastroscopic features of TSC are different from those of gastric cancer.Regular review with endoscopy in postoperative esophageal carcinoma patients was a major way to diagnose TSC.展开更多
Objective:We analyzed the relationship between the expression of ERCC-1(excisition repair cross complement-1), survivin and sensitivity and prognosis of cisplatin contained regimens first-line chemotherapy in advanced...Objective:We analyzed the relationship between the expression of ERCC-1(excisition repair cross complement-1), survivin and sensitivity and prognosis of cisplatin contained regimens first-line chemotherapy in advanced lung adenocarcinoma.Methods:Immunohistochemical(IHC) method was used to evaluate the expression of ERCC-1 and survivin in 80 pathologically confirmed advanced lung adenocarcinoma patients given cisplatin-contained regimens first-line chemotherapy.The response rate and survival time were analyzed according to the expression of ERCC-1 and survivin.Results:Only 77 patients could be reviewed by IHC staining.The expression rates of ERCC-1 and survivin were 33.77% and 53.25 % respectively.The worse response rate and shorter TTP/ PFS could be identified in ERCC-1 positive group.Patients with positive expression of survivin had worse survival time.Conclusion:Expression of ERCC-1 may be a molecular marker of cisplatincontained regimens first-line chemotherapy resistance and poor prognosis in advanced lung adenocarcinoma patients.Positive expression of survivin predicates poor prognosis for patients with advanced lung adenocarcinoma.展开更多
Recently,we have shown that FOXP3,a critical transcription factor in regulatory T cells(Tregs),is expressed in pancreatic epithelial cells,and restrain the activity of CD8+T cells by upregulating PD-L1,which in turn r...Recently,we have shown that FOXP3,a critical transcription factor in regulatory T cells(Tregs),is expressed in pancreatic epithelial cells,and restrain the activity of CD8+T cells by upregulating PD-L1,which in turn regulates immune escape in pancreatic ductal adenocarcinoma(PDAC)^(1).On the basis of a series of studies of our laboratory,we hypothesize that a subset of pancreatic epithelial cells mimics the phenotype and function of Tregs(named quasi-Tregs or qTregs);this concept has been supported by a peer-reviewed commentary^(2).Moreover,evidence suggests that tumor epithelial cells can mimic other types of immune cells and participate in the formation of a tumor immunosuppressive microenvironment(TIM).展开更多
Grouping different oxide materials with coupled charge, spin, and orbital degrees of freedom together to form heterostructures provides a rich playground to explore the emergent interfacial phenomena. The perovskite/b...Grouping different oxide materials with coupled charge, spin, and orbital degrees of freedom together to form heterostructures provides a rich playground to explore the emergent interfacial phenomena. The perovskite/brownmillerite heterostructure is particularly interesting since symmetry mismatch may produce considerable interface reconstruction and unexpected physical effects. Here, we systemically study the magnetic anisotropy of tensely strained La2/3Sr1/3Co1-xMnxO2.5+δ/La2/3Sr1/3MnO3/La2/3Sr1/3Co1-xMnxO2.5+δ trilayers with interface structures changing from perovskite/brownmillerite type to perovskite/perovskite type. Without Mn doping, the initial La2/3Sr1/3CoO2.5+δ/La2/3Sr1/3MnO3/La2/3Sr1/3CoO2.5+δ trilayer with perovskite/brownmillerite interface type exhibits perpendicular magnetic anisotropy and the maximal anisotropy constant is 3.385×106 erg/cm3, which is more than one orders of magnitude larger than that of same strained LSMO film. By increasing the Mn doping concentration, the anisotropy constant displays monotonic reduction and even changes from perpendicular magnetic anisotropy to in-plane magnetic anisotropy, which is possible because of the reduced CoO4 tetrahedra concentration in the La2/3Sr1/3Co1-xMnxO2.5+δ layers near the interface. Based on the analysis of the x-ray linear dichroism, the orbital reconstruction of Mn ions occurs at the interface of the trilayers and thus results in the controllable magnetic anisotropy.展开更多
The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA...The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA)/RVA nano-vectors can sequentially respond to pH&redox stimuli,and guarantee efficient therapeutic gene delivery and control release of all-trans retinoic acid.The design provides a facile but promising strategy to treat refractory cancers.展开更多
To the Editor:Liposarcoma is a common subtype of retroperitoneal sarcoma.Due to the complicated anatomical heterogeneity of retroperitoneal liposarcoma(RPLS),it compresses and invades adjacent important organs,and mas...To the Editor:Liposarcoma is a common subtype of retroperitoneal sarcoma.Due to the complicated anatomical heterogeneity of retroperitoneal liposarcoma(RPLS),it compresses and invades adjacent important organs,and massive bleeding frequently occurs during surgery.Therefore,a combined visceral resection is required,which means that RPLS surgery has greater difficulty and a lower complete resection rate compared to surgeries for other solid tumors.Although in our previous studies we found that intraperitoneal thermoperfusion chemotherapy including cisplatin may improve the prognosis of patients with RPLS,[1]surgery is the most effective treatment for RPLS,and adjuvant therapies have shown almost ineffective.There is a paucity of research focusing specifically on molecular mechanisms underlying RPLS pathogenesis.Consequently,no diagnostic biomarkers,druggable targets,or prognostic factors are available for RPLS.展开更多
Pancreatic neuroendocrine neoplasms(pNENs)are rare and highly heterogeneous tumors originating from pluripotent stem cells with neuroendocrine differentiation in the pancreas,constituting approximately 3%of all pancre...Pancreatic neuroendocrine neoplasms(pNENs)are rare and highly heterogeneous tumors originating from pluripotent stem cells with neuroendocrine differentiation in the pancreas,constituting approximately 3%of all pancreatic tumors.^([1])The global incidence of pNENs has been increasing recently,and most cases are sporadic and more common in women.^([1,2])pNENs are clinically divided into functioning and nonfunctioning tumors depending on whether the tumors are accompanied by a clinical syndrome related to specific hormone overproduction.展开更多
Neuronal synapses are functional nodes in neural circuits.Their organization and activity define an individual's level of intelligence,emotional state and mental health.Changes in the structure and efficacy of syn...Neuronal synapses are functional nodes in neural circuits.Their organization and activity define an individual's level of intelligence,emotional state and mental health.Changes in the structure and efficacy of synapses are the biological basis of learning and memory.However,investigation of the molecular architecture of synapses has been impeded by the lack of efficient techniques with sufficient resolution.Recent developments in state-of-the-art nano-imaging techniques have opened up a new window for dissecting the molecular organization of neuronal synapses with unprecedented resolution.Here,we review recent technological advances in nano-imaging techniques as well as their applications to the study of synapses,emphasizing super-resolution light microscopy and 3-dimensional electron tomography.展开更多
The membrane protein claudin-3(CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the pos...The membrane protein claudin-3(CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both in vitro and in vivo. Of interest, CLDN3 undergoes S-palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3. Moreover, the deprivation of S-palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins.Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis. Thus, our work reveals S-palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 S-palmitoylation might be a potential strategy for ovarian cancer therapy.展开更多
Background and Aims:Recent accumulating evidence indicates the biological actions of autotaxin(ATX)in liver disease.However,the relationship between ATX and liver failure has not been reported.The present study aimed ...Background and Aims:Recent accumulating evidence indicates the biological actions of autotaxin(ATX)in liver disease.However,the relationship between ATX and liver failure has not been reported.The present study aimed to examine alterations of serum ATX in acute-on-chronic liver failure(ACLF)and evaluate whether serum ATX could be useful as an early warning biomarker of ACLF.Methods:Serum ATX was measured in 50 patients with hepatitis B-related ACLF,14 patients with alcohol-related ACLF,11 patients with hepatitis B-related pre-ACLF,11 patients with alcohol-related Child-Pugh A cirrhosis,39 patients with hepatitis B-related Child-Pugh A cirrhosis,26 patients with chronic hepatitis B,and 38 healthy volunteers by enzyme-linked immunosorbent assay.Results:Serum ATX level was significantly higher in the pre-ACLF group than in the Child-Pugh A cirrhosis and chronic hepatitis B groups but lower than in the ACLF group;furthermore,patients with pre-ACLF deteriorated to ACLF had significantly higher serum ATX levels than pre-ACLF patients that did not progress to ACLF.Serum ATX levels were significantly higher among male ACLF patients with preclinical infection,spontaneous bacterial peritonitis or pneumonia,as compared to patients with ACLF but no spontaneous bacterial peritonitis or pneumonia.Serum ATX levels were well correlated with serum biochemical parameters of liver function and model for end-stage liver disease score.Serum ATX≥584.1 ng/mL was a poor prognostic factor for ACLF(hazard ratio of 4.750,95%confidence interval of 1.106-20.392,p=0.036).Conclusions:Serum ATX level may be a useful early warning biomarker for ACLF.展开更多
β-Mannanase catalyzes endo-wise hydrolysis of the backbone of mannan and heteromannan,which are abun-dant in the cell wall structure of ungerminated leguminous seeds.The mature β-mannanase originated from Bacillus s...β-Mannanase catalyzes endo-wise hydrolysis of the backbone of mannan and heteromannan,which are abun-dant in the cell wall structure of ungerminated leguminous seeds.The mature β-mannanase originated from Bacillus subtilis was expressed in Pichia pastoris,a methylotrophic yeast,using the leader peptide sequence of Saccharomyces cerevisiae α-factor.The cultivation of β-mannanase express-ing Pichia pastoris yields up to 1.8 g/L protein.In the super-natant the activity of the 40 kDa—total mannanase attained a level of 1102.0 IU/mL.The properties of the β-mannanase were characterized.Optimum pH and temperature for the recombinant enzyme were 5.5 and 50℃ respectively.The enzyme was stable at pH 5.0-10.0 and maintained over 30%original activity after incubating at 70℃ for 30 min.展开更多
cis-dichlorodiammineplatinum(II)(CDDP)-loaded polymeric micelles for cancer therapy have been developed to reduce the serious side effects of cisplatin CDDP.Herein,polymeric micelles incorporated with cisplatin are pr...cis-dichlorodiammineplatinum(II)(CDDP)-loaded polymeric micelles for cancer therapy have been developed to reduce the serious side effects of cisplatin CDDP.Herein,polymeric micelles incorporated with cisplatin are prepared based on the complexation between CDDP and hydrophilic poly(L-glutamic acid)-b-poly(2-methacryloyloxyethyl phosphorylcholine)(PLG-b-PMPC)diblock copolymers.These CDDP-loaded micelles possess an average size of 91nm with narrow distribution,providing remarkable stability in media containing proteins.The release of CDDP from the micelles is faster at pH 5.0 and pH 6.0 than that at pH 7.4 and in a sustained manner without initial burst release.In addition,there is almost no difference in cellular uptake between these CDDP-loaded micelles and free CDDP.Moreover,in vitro cytotoxicity test shows they possess high efficacy to kill 4T1 cells as compared with free drug.Thus,PLG-b-PMPC copolymer might be a promising carrier for CDDP incorporating in cancer therapy.展开更多
Bi_(5)FeTi_(2.5)Co_(0.5)O_(15)(BFTC)ceramics was successfully synthesized using the sol-gel method.It exhibits simultaneously visible-light response,ferroelectric and weak ferromagnetic orders at room temperature.The ...Bi_(5)FeTi_(2.5)Co_(0.5)O_(15)(BFTC)ceramics was successfully synthesized using the sol-gel method.It exhibits simultaneously visible-light response,ferroelectric and weak ferromagnetic orders at room temperature.The narrow band gap of 2.06 eV was determined via the UVevis diffuse absorption spectrum.The x-ray photoelectron spectroscopy results show that the Fe ions in the samples is 3 t and 2 t valence states while the doped Co ions is 2 t valence state.The BFTC sample undergoes a ferromagnetic-like transition at~552 K.Weak ferromagnetism is mainly due to spin-canting of Fe-based and Co-based sublattices via Dzyaloshinskii-Moriya(DM)interaction.Dielectric loss and dielectric modulus exhibit the characteristics of dielectric relaxation,which can be ascribed to oxygen/vacancy hopping.These results reveal many potentially useful physical phenomena and open a new avenue to design of novel solar-energy conversion devices and multiferroic applications.展开更多
Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for surgery.The proteomic and metabolic profiles of RLPS have remaine...Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for surgery.The proteomic and metabolic profiles of RLPS have remained unclear.The aim of our study was to reveal the metabolic profile of RLPS.Here,we performed proteomic analysis(n=10),metabolomic analysis(n=51),and lipidomic analysis(n=50)of retroperitoneal dedifferentiated liposarcoma(RDDLPS)and retroperitoneal well-differentiated liposarcoma(RWDLPS)tissue and paired adjacent adipose tissue obtained during surgery.Data analysis mainly revealed that glycolysis,purine metabolism,pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue,whereas the tricarboxylic acid(TCA)cycle,lipid absorption and synthesis,fatty acid degradation and biosynthesis,as well as glycine,serine,and threonine metabolism were downregulated.Of particular importance,the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway(PPP)inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib.Our study not only describes the metabolic profiles of RDDLPS and RWDLPS,but also offers potential therapeutic targets and strategies for RLPS.展开更多
Patients with advanced gastric cancer typically face a grim prognosis.This phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemo...Patients with advanced gastric cancer typically face a grim prognosis.This phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction adenocarcinoma.The primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and 1b.Phase 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and S-1.Dose regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days 1-14.Dose regimen 2:same as dose regimen 1,but oxaliplatin 130mg/m.Dose regimen3:same as dose regimen 2,but apatinib 250 mg daily.Thirty-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was identified.Dose 3 was set for the recommended phase 2 doses and administered in phase 1b.The confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(OS)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team evaluation.Among 24 patients without surgery,the median OS was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse events.Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).展开更多
文摘OBJECTIVE To investigate the expression of E-cadherin andCEA in serum in colorectal carcinoma and their relationship withliver metastasis.METHODS CEA level was measured post-operativelyby radioimmunoassay of 60 patients with colorectal cancer.Immunohistochemical analysis was used to evaluate theexpression of E-cadherin.RESULTS In liver metastasis group,24 patients (24/26,92.3%)were high level of CEA,but only 9 patients in non-liver metastasisgroup.The difference is significant (P=0.004).Expression ofE-cadherin significantly correlated with differentiation,but wasnot associated with Tstage or N stage.Liver metastatic rate innegative expression was higher than that in positive expression.And the survival analysis showed that time of liver metastasis wassignificant different in two groups (P<0.05).CONCLUSION The expression of CEA in serum can be usedto predict liver mestatasis of colorectal cancer after operation.E-cadherin,associated with tumor differentiation,is also a hopefulindicator for the prediction of liver metastasis in patients withcolorectal cancer.
文摘Objective:Postoperative recurrence of esophageal carcinoma was the main factor that affect the patients' survival and quality of life.This study mainly investigated the clinical features of thoracic stomach cancer (TSC) after surgical treatment for esophageal carcinoma.Methods:We retrospectively reviewed 51 cases of postoperative TSC in our hospital (Henan Province Tumor Hospital,Zhengzhou,China).Results:The 51 (10.97%) of all 465 cases that underwent endoscope after surgical treatment for esophageal carcinoma in our hospital were TSCs.There were 13 cases with complicating anastomotic recurrence.The locations of 46 cases (90.2%) were the same as the primary cancer.The 48 cases were squamous cell carcinomas and 3 cases were adenocarcinomas after esophagectomy for esophageal carcinoma.Endoscopic manifestations were puffiness-infiltrating type at 39.2% (20/51),massive type at 15.7% (8/51),ulcerative type at 7.8% (4/51) and ulcerative infiltrating type at 3.9% (2/51) and stenotic type etc.Conclusion:The incidence of TSC after surgical treatment for esophageal carcinoma is high.The main cause was that the local residual cancer invaded gastric wall.The gastroscopic features of TSC are different from those of gastric cancer.Regular review with endoscopy in postoperative esophageal carcinoma patients was a major way to diagnose TSC.
基金Supported by a grant from the Science and Technology Key Project of Henan Province (No. 200538).
文摘Objective:We analyzed the relationship between the expression of ERCC-1(excisition repair cross complement-1), survivin and sensitivity and prognosis of cisplatin contained regimens first-line chemotherapy in advanced lung adenocarcinoma.Methods:Immunohistochemical(IHC) method was used to evaluate the expression of ERCC-1 and survivin in 80 pathologically confirmed advanced lung adenocarcinoma patients given cisplatin-contained regimens first-line chemotherapy.The response rate and survival time were analyzed according to the expression of ERCC-1 and survivin.Results:Only 77 patients could be reviewed by IHC staining.The expression rates of ERCC-1 and survivin were 33.77% and 53.25 % respectively.The worse response rate and shorter TTP/ PFS could be identified in ERCC-1 positive group.Patients with positive expression of survivin had worse survival time.Conclusion:Expression of ERCC-1 may be a molecular marker of cisplatincontained regimens first-line chemotherapy resistance and poor prognosis in advanced lung adenocarcinoma patients.Positive expression of survivin predicates poor prognosis for patients with advanced lung adenocarcinoma.
基金This work was funded by the National Natural Science Foundation of China(Grant No.81772633)the Taishan Researchers Program of Shandong Province,and the Major State Basic Research Development Program of Natural Science Foundation of Shandong Province in China(Grant No.ZR2020ZD11).
文摘Recently,we have shown that FOXP3,a critical transcription factor in regulatory T cells(Tregs),is expressed in pancreatic epithelial cells,and restrain the activity of CD8+T cells by upregulating PD-L1,which in turn regulates immune escape in pancreatic ductal adenocarcinoma(PDAC)^(1).On the basis of a series of studies of our laboratory,we hypothesize that a subset of pancreatic epithelial cells mimics the phenotype and function of Tregs(named quasi-Tregs or qTregs);this concept has been supported by a peer-reviewed commentary^(2).Moreover,evidence suggests that tumor epithelial cells can mimic other types of immune cells and participate in the formation of a tumor immunosuppressive microenvironment(TIM).
基金Project supported by the National Basic Research Program of China(Grant Nos.2016YFA0300701,2017YFA0206300,2017YFA0303601,and 2018YFA0305704)the National Natural Science Foundation of China(Grant Nos.11520101002,51590880,11674378,11934016,and 51972335)the Key Program of the Chinese Academy of Sciences.
文摘Grouping different oxide materials with coupled charge, spin, and orbital degrees of freedom together to form heterostructures provides a rich playground to explore the emergent interfacial phenomena. The perovskite/brownmillerite heterostructure is particularly interesting since symmetry mismatch may produce considerable interface reconstruction and unexpected physical effects. Here, we systemically study the magnetic anisotropy of tensely strained La2/3Sr1/3Co1-xMnxO2.5+δ/La2/3Sr1/3MnO3/La2/3Sr1/3Co1-xMnxO2.5+δ trilayers with interface structures changing from perovskite/brownmillerite type to perovskite/perovskite type. Without Mn doping, the initial La2/3Sr1/3CoO2.5+δ/La2/3Sr1/3MnO3/La2/3Sr1/3CoO2.5+δ trilayer with perovskite/brownmillerite interface type exhibits perpendicular magnetic anisotropy and the maximal anisotropy constant is 3.385×106 erg/cm3, which is more than one orders of magnitude larger than that of same strained LSMO film. By increasing the Mn doping concentration, the anisotropy constant displays monotonic reduction and even changes from perpendicular magnetic anisotropy to in-plane magnetic anisotropy, which is possible because of the reduced CoO4 tetrahedra concentration in the La2/3Sr1/3Co1-xMnxO2.5+δ layers near the interface. Based on the analysis of the x-ray linear dichroism, the orbital reconstruction of Mn ions occurs at the interface of the trilayers and thus results in the controllable magnetic anisotropy.
基金financially supported by National Natural Science Foundation of China(NSFC,Nos.81873921 and 51903174)Sino-German Cooperation Group Project(No.GZ1512)+2 种基金China Postdoctoral Science Foundation(No.2021M702772)Chengdu Science and Technology Program(No.2020-GH02-00007-HZ)Sichuan University Postdoctoral Interdisciplinary Innovation Startup Foundation and the Fundamental Research Funds for Central Universities(No.2021SCU12070)。
文摘The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA)/RVA nano-vectors can sequentially respond to pH&redox stimuli,and guarantee efficient therapeutic gene delivery and control release of all-trans retinoic acid.The design provides a facile but promising strategy to treat refractory cancers.
基金Peking University International Hospital Research Grant(No.YN2019QN11)Beijing Science and Technology Commission"Applied research on clinical characteristics of the capital city"(No.Z171100001017095)
文摘To the Editor:Liposarcoma is a common subtype of retroperitoneal sarcoma.Due to the complicated anatomical heterogeneity of retroperitoneal liposarcoma(RPLS),it compresses and invades adjacent important organs,and massive bleeding frequently occurs during surgery.Therefore,a combined visceral resection is required,which means that RPLS surgery has greater difficulty and a lower complete resection rate compared to surgeries for other solid tumors.Although in our previous studies we found that intraperitoneal thermoperfusion chemotherapy including cisplatin may improve the prognosis of patients with RPLS,[1]surgery is the most effective treatment for RPLS,and adjuvant therapies have shown almost ineffective.There is a paucity of research focusing specifically on molecular mechanisms underlying RPLS pathogenesis.Consequently,no diagnostic biomarkers,druggable targets,or prognostic factors are available for RPLS.
基金supported by grants from the Shanghai Hospital Development Center(SHDC)for the promotion and management optimization of diagnosis and treatment technologies in Shanghai municipal hospitals(No.SHDC12022611)Shanghai Key Clinical Specialty(Oncology),and Shanghai Leading Talents Project and Clinical Research Plan of SHDC(No.SHDC2020CR1035B).
文摘Pancreatic neuroendocrine neoplasms(pNENs)are rare and highly heterogeneous tumors originating from pluripotent stem cells with neuroendocrine differentiation in the pancreas,constituting approximately 3%of all pancreatic tumors.^([1])The global incidence of pNENs has been increasing recently,and most cases are sporadic and more common in women.^([1,2])pNENs are clinically divided into functioning and nonfunctioning tumors depending on whether the tumors are accompanied by a clinical syndrome related to specific hormone overproduction.
基金supported by grants from the National Natural Science Foundation of China (30725017 and 30928003)MOST (2009CB941300)
文摘Neuronal synapses are functional nodes in neural circuits.Their organization and activity define an individual's level of intelligence,emotional state and mental health.Changes in the structure and efficacy of synapses are the biological basis of learning and memory.However,investigation of the molecular architecture of synapses has been impeded by the lack of efficient techniques with sufficient resolution.Recent developments in state-of-the-art nano-imaging techniques have opened up a new window for dissecting the molecular organization of neuronal synapses with unprecedented resolution.Here,we review recent technological advances in nano-imaging techniques as well as their applications to the study of synapses,emphasizing super-resolution light microscopy and 3-dimensional electron tomography.
基金supported by grants from the National Natural Science Foundation of China(No.91753114 to Hong JiangNo.81872885 to Ji Cao)+1 种基金Zhejiang Provincial Natural Science Foundation(No.Y18H310005 to Ji Cao,China)the Talent Project of Zhejiang Association for Science and Technology(No.2018YCGC002 to Ji Cao,China)
文摘The membrane protein claudin-3(CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both in vitro and in vivo. Of interest, CLDN3 undergoes S-palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3. Moreover, the deprivation of S-palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins.Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis. Thus, our work reveals S-palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 S-palmitoylation might be a potential strategy for ovarian cancer therapy.
基金supported by the National 13th 5-Year Plan for Hepatitis Research(No.2017ZX10203201)the National Natural Science Foundation of China(No.81870429).
文摘Background and Aims:Recent accumulating evidence indicates the biological actions of autotaxin(ATX)in liver disease.However,the relationship between ATX and liver failure has not been reported.The present study aimed to examine alterations of serum ATX in acute-on-chronic liver failure(ACLF)and evaluate whether serum ATX could be useful as an early warning biomarker of ACLF.Methods:Serum ATX was measured in 50 patients with hepatitis B-related ACLF,14 patients with alcohol-related ACLF,11 patients with hepatitis B-related pre-ACLF,11 patients with alcohol-related Child-Pugh A cirrhosis,39 patients with hepatitis B-related Child-Pugh A cirrhosis,26 patients with chronic hepatitis B,and 38 healthy volunteers by enzyme-linked immunosorbent assay.Results:Serum ATX level was significantly higher in the pre-ACLF group than in the Child-Pugh A cirrhosis and chronic hepatitis B groups but lower than in the ACLF group;furthermore,patients with pre-ACLF deteriorated to ACLF had significantly higher serum ATX levels than pre-ACLF patients that did not progress to ACLF.Serum ATX levels were significantly higher among male ACLF patients with preclinical infection,spontaneous bacterial peritonitis or pneumonia,as compared to patients with ACLF but no spontaneous bacterial peritonitis or pneumonia.Serum ATX levels were well correlated with serum biochemical parameters of liver function and model for end-stage liver disease score.Serum ATX≥584.1 ng/mL was a poor prognostic factor for ACLF(hazard ratio of 4.750,95%confidence interval of 1.106-20.392,p=0.036).Conclusions:Serum ATX level may be a useful early warning biomarker for ACLF.
基金This research was supported by International Foundation for Science(Grant No.B/3873-1)the National High Technology Research and Development Program of China(Grant Nos.2003AA241160 and 2005AA246010)International S&T Cooperation Program of China(Grant No.20050048).
文摘β-Mannanase catalyzes endo-wise hydrolysis of the backbone of mannan and heteromannan,which are abun-dant in the cell wall structure of ungerminated leguminous seeds.The mature β-mannanase originated from Bacillus subtilis was expressed in Pichia pastoris,a methylotrophic yeast,using the leader peptide sequence of Saccharomyces cerevisiae α-factor.The cultivation of β-mannanase express-ing Pichia pastoris yields up to 1.8 g/L protein.In the super-natant the activity of the 40 kDa—total mannanase attained a level of 1102.0 IU/mL.The properties of the β-mannanase were characterized.Optimum pH and temperature for the recombinant enzyme were 5.5 and 50℃ respectively.The enzyme was stable at pH 5.0-10.0 and maintained over 30%original activity after incubating at 70℃ for 30 min.
基金This research was supported by National Natural Science Foundation of China(Projects 51403131)Sichuan province Science-Technology Support Plan Project(2016SZ0004)+1 种基金the Programme of Introducing Talents of Discipline to Universities(B16033)China Postdoctoral Science Foundation Funded Project(2015M570783).
文摘cis-dichlorodiammineplatinum(II)(CDDP)-loaded polymeric micelles for cancer therapy have been developed to reduce the serious side effects of cisplatin CDDP.Herein,polymeric micelles incorporated with cisplatin are prepared based on the complexation between CDDP and hydrophilic poly(L-glutamic acid)-b-poly(2-methacryloyloxyethyl phosphorylcholine)(PLG-b-PMPC)diblock copolymers.These CDDP-loaded micelles possess an average size of 91nm with narrow distribution,providing remarkable stability in media containing proteins.The release of CDDP from the micelles is faster at pH 5.0 and pH 6.0 than that at pH 7.4 and in a sustained manner without initial burst release.In addition,there is almost no difference in cellular uptake between these CDDP-loaded micelles and free CDDP.Moreover,in vitro cytotoxicity test shows they possess high efficacy to kill 4T1 cells as compared with free drug.Thus,PLG-b-PMPC copolymer might be a promising carrier for CDDP incorporating in cancer therapy.
基金the National Science Foundation of China(Grant No.51402256 and Grant No.11374227)Natural Science Foundation of Jiangsu Province,China(No.BK 20161409)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province,China(Grant No.12KJB140013).
文摘Bi_(5)FeTi_(2.5)Co_(0.5)O_(15)(BFTC)ceramics was successfully synthesized using the sol-gel method.It exhibits simultaneously visible-light response,ferroelectric and weak ferromagnetic orders at room temperature.The narrow band gap of 2.06 eV was determined via the UVevis diffuse absorption spectrum.The x-ray photoelectron spectroscopy results show that the Fe ions in the samples is 3 t and 2 t valence states while the doped Co ions is 2 t valence state.The BFTC sample undergoes a ferromagnetic-like transition at~552 K.Weak ferromagnetism is mainly due to spin-canting of Fe-based and Co-based sublattices via Dzyaloshinskii-Moriya(DM)interaction.Dielectric loss and dielectric modulus exhibit the characteristics of dielectric relaxation,which can be ascribed to oxygen/vacancy hopping.These results reveal many potentially useful physical phenomena and open a new avenue to design of novel solar-energy conversion devices and multiferroic applications.
基金funded by grants from the National Natural Science Foundation of China(No.82272935 to Wengang Li.,Nos.91957120 and 21974114 to Shuhai Lin.)the Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University(No.PM20180917008 to Wengang Li.)+3 种基金Joint laboratory of School of Medicine,Xiamen University-Shanghai Jiangxia Blood Technology Co.Ltd.(No.XDHT2020010C to Wengang Lin and Ye Shen.)the Fundamental Research Funds for the Central Universities(No.20720210001 to Shuhai Lin.)Major Science and Technology Special Project of Fujian Province(No.2022YZ036012 to Shuhai Lin)Natural Science Foundation of Fujian Province(No.2021J01123522 to Zhigang Zheng).
文摘Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for surgery.The proteomic and metabolic profiles of RLPS have remained unclear.The aim of our study was to reveal the metabolic profile of RLPS.Here,we performed proteomic analysis(n=10),metabolomic analysis(n=51),and lipidomic analysis(n=50)of retroperitoneal dedifferentiated liposarcoma(RDDLPS)and retroperitoneal well-differentiated liposarcoma(RWDLPS)tissue and paired adjacent adipose tissue obtained during surgery.Data analysis mainly revealed that glycolysis,purine metabolism,pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue,whereas the tricarboxylic acid(TCA)cycle,lipid absorption and synthesis,fatty acid degradation and biosynthesis,as well as glycine,serine,and threonine metabolism were downregulated.Of particular importance,the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway(PPP)inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib.Our study not only describes the metabolic profiles of RDDLPS and RWDLPS,but also offers potential therapeutic targets and strategies for RLPS.
基金funded by the Jiangsu Province 333 High Level Talents Project,the Beijing Xisike Clinical Oncology Research Foundation (Y-HR2019-0367)the National Natural Science Foundation of China (82102981)+3 种基金the Pukou District Social Cause Science and Technology Development Project in 2020 (S2020-21)the Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital)General Project of Science and Technology Development Fund in 2021 (KJ2021-22)the Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital)Major Project of Science and Technology Development Fund in 2021 (KJ2021-1)Jiangsu Hengrui Pharmaceuticals.
文摘Patients with advanced gastric cancer typically face a grim prognosis.This phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction adenocarcinoma.The primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and 1b.Phase 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and S-1.Dose regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days 1-14.Dose regimen 2:same as dose regimen 1,but oxaliplatin 130mg/m.Dose regimen3:same as dose regimen 2,but apatinib 250 mg daily.Thirty-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was identified.Dose 3 was set for the recommended phase 2 doses and administered in phase 1b.The confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(OS)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team evaluation.Among 24 patients without surgery,the median OS was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse events.Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).