Combining photocatalytic organic reactions with CO_(2)reduction is an efficient solar energy utilization mode,but it is still limited by the organic species that can be matched and the low conversion.Herein,ultrathin ...Combining photocatalytic organic reactions with CO_(2)reduction is an efficient solar energy utilization mode,but it is still limited by the organic species that can be matched and the low conversion.Herein,ultrathin organic polymer with p-πconjugated structure(TPP)was rationally designed and prepared,and showed a high yield of CO(15.2 mmol g^(-1))and conversion of SAS coupled products(100%),far exceeding the organic polymer with P=O structure.The enhanced photoredox activity of TPP is ascribed to the orbital interaction between the p-orbital on phosphorus and theπ-orbitals of aromatic,which can accelerate the photoinduced charge carrier separation and improve the CO_(2)adsorption capacity.TPP can also be used for the dehydrocoupling of various benzyl mercaptans to the corresponding SAS bond products.This work provides a new concept for the efficient synthesis of disulfide bonds combined with CO_(2)reduction in a photoreaction system.展开更多
The development of insertion-type anodes is the key to designing“rocking chair”zinc-ion batteries.However,there is rare report on high mass loading anode with high performances.Here,{001}-oriented Bi OCl nanosheets ...The development of insertion-type anodes is the key to designing“rocking chair”zinc-ion batteries.However,there is rare report on high mass loading anode with high performances.Here,{001}-oriented Bi OCl nanosheets with Sn doping are proposed as a promising insertion-type anode.The designs of cross-linked CNTs conductive network,{001}-oriented nanosheet,and Sn doping significantly enhance ion/electron transport,proved via experimental tests and theoretical calculations(density of states and diffusion barrier).The H^(+)/Zn^(2+)synergistic co-insertion mechanism is proved via ex situ XRD,Raman,XPS,and SEM tests.Accordingly,this optimized electrode delivers a high reversible capacity of 194 m A h g^(-1)at 0.1 A g^(-1)with a voltage of≈0.37 V and an impressive cyclability with 128 m A h g^(-1)over 2500 cycles at 1 A g^(-1).It also shows satisfactory performances at an ultrahigh mass loading of 10 mg cm^(-2).Moreover,the Sn-Bi OCl//MnO_(2)full cell displays a reversible capacity of 85 m A h g^(-1)at 0.2 A g^(-1)during cyclic test.展开更多
AIM: To explore whether acute cellular DNA damage response is induced upon hepatitis B virus (HBV) infection and the effects of the HBV infection. METHODS: We incubated HL7702 hepatocytes with HBV-positive serum, ...AIM: To explore whether acute cellular DNA damage response is induced upon hepatitis B virus (HBV) infection and the effects of the HBV infection. METHODS: We incubated HL7702 hepatocytes with HBV-positive serum, mimicking a natural HBV infection process. We used immunoblotting to evaluate protein expression levels in HBV-infected cells or in non-infected cells; immunofluorescence to show ATR foci ands Chkl phosphorylation foci formation; flow cytometry to analyze the cell cycle and apoptosis; ultraviolet (UV) radiation and ionizing radiation (IR)-treated cells to mimic DNA damage; and Trypan blue staining to count the viable cells. RESULTS: We found that HBV infection induced an increased steady state of ATR protein and increased phosphorylation of multiple downstream targets including Chkl, p53 and H2AX. In contrast to ATR and its target, the phosphorylated form of ATM at Ser-1981 and its downstream substrate Chk2 phosphorylation at Thr-68 did not visibly increase upon infection. However, the level of Mre11 and p21 were reduced beginning at 0.5 h aEer HBV-positive serum addition. Also, HBV infection led to transient cell cycle arrest in the S and the G2 phases without accompanying increasedapoptosis. Research on cell survival changes upon radiation following HBV infection showed that survival of UV-treated host cells was greatly increased by HBV infection, owing to the reduced apoptosis. Meanwhile, survival of IR-treated host cells was reduced by HBV infection. CONCLUSION: HBV infection activates ATR DNA damage response to replication stress and abrogates the checkpoint signaling controlled by DNA damage response.展开更多
As a transparent avascular tissue located at the front of the eyeball, the cornea is an important barrier to external damage. Both epithelial and endothelial cells of the cornea harbor primary cilia, which sense chang...As a transparent avascular tissue located at the front of the eyeball, the cornea is an important barrier to external damage. Both epithelial and endothelial cells of the cornea harbor primary cilia, which sense changes in the external environment and regulate intracellular signaling pathways. Accumulating evidence suggests that the primary cilium regulates corneal development in several ways, including participation in corneal epithelial stratification and maintenance of corneal endothelial cell morphology.In addition, the primary cilium has been implicated in the pathogenesis of several corneal diseases. In this review, we discuss recent findings that demonstrate the critical role of the primary cilium in corneal development. We also discuss the link between ciliary dysfunction and corneal diseases, which suggests that the primary cilium could be targeted to treat these diseases.展开更多
A model-free adaptive control method is proposed for the spacecrafts whose dynamical parameters change over time and cannot be acquired accurately. The algorithm is based on full form dynamic linearization.A dimension...A model-free adaptive control method is proposed for the spacecrafts whose dynamical parameters change over time and cannot be acquired accurately. The algorithm is based on full form dynamic linearization.A dimension reduction matrix is introduced to construct an augmented system with the same dimension input and output. The design of the controller depends on the system input and output data rather than the knowledge of the controlled plant. The numerical simulation results show that the improved controller can deal with different models with the same set of controller parameters,and the controller performance is better than that of PD controller for the time-varying system with disturbance.展开更多
Given the booming of internet usage in its domain, Chinese on-line shopping business is not growing proportionately. The absence of a market mechanism based on trust among suppliers and customers is to blame, although...Given the booming of internet usage in its domain, Chinese on-line shopping business is not growing proportionately. The absence of a market mechanism based on trust among suppliers and customers is to blame, although other factors as well holding the responsibility. Beginning with an introduction to the theory of "lemons", this paper reviews the status quo of trust in the Chinese cyber market, from the perspective of legislation, regulation and institution. It also prescribes several possible micro-solutions.展开更多
Adipose-derived stem cells(ADSCs)have considerable potential for bone regeneration.However,their performance is limited by a lack of scaffolds that adequately mimic the hierarchical structure of bone to promote prolif...Adipose-derived stem cells(ADSCs)have considerable potential for bone regeneration.However,their performance is limited by a lack of scaffolds that adequately mimic the hierarchical structure of bone to promote proliferation and osteogenic differentiation of ADSCs.In this study,nanofiber membranes composed of polycaprolactone,poly(lactide-co-glycolide),and hydroxyapatite(HAp)were prepared via electrospinning,and the membranes curled after responding to temperature stimuli in an aqueous solution.Transmission electron microscopy and scanning electron microscopy observations indicated that needle-like HAp nanoparticles with an average diameter of 57±39 nm and a length–diameter ratio of 7.4±1.56 were entrapped in the nanofiber matrix and did not affect the surface morphology of fibers.After cutting and deformation,the nanofibers changed from straight to bent,and the diameters increased;they were 1105±200 nm for BPLG85-H and 1120±199 nm for BPLG80-H.Additionally,tubular units with a single layer(BPLG-H(1.5))or multiple layers(BPLG-H(3.5))were obtained by controlling the initial shape and size of the membranes.rADSCs on the concave surface of BPLG-H(3.5)proliferated faster and exhibited better osteogenic activity than those on the convex side of BPLG-H(3.5)and both surfaces of BPLG-H(1.5),which was correlated with the higher expressions of vascular endothelial growth factor and bone morphogenetic protein 2.Additionally,rADSCs on both units maintained osteogenic activity after storage at-80◦C for 20 d.In rat skull defect(diameter of 8 mm)models,rADSC-loaded BPLG-H(3.5)units fixed using gelatin hydrogel(ADSC@BHM)exhibited 84.1±6.6%BV/TV after implantation for 12 weeks,which was 155.6%higher than that of the Blank group.H&E and Masson’s staining results demonstrated that there was more bone regeneration at the defect center of ADSC@BHM than in the BHM and Blank groups.In conclusion,rADSC-loaded BPLG-H(3.5)with an osteon-mimic structure provides a potential strategy to repair bone defects.展开更多
Natural killer (NK) cells are a major component of the host innate immune defense against various pathogens. Several viruses, including hepatitis C virus (HCV), have developed strategies to evade the NK-cell respo...Natural killer (NK) cells are a major component of the host innate immune defense against various pathogens. Several viruses, including hepatitis C virus (HCV), have developed strategies to evade the NK-cell response. In our study, we found HCV infection could trigger DNA damage response by both ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) pathways. Recent reports had revealed that NKG2D ligands (NK cell- activating ligands) were upregulated when a major DNA damage checkpoint pathway was activated. However, here we found that DNA damage response was activated but NKG2D ligands were downregulated upon HCV infection. Further studies showed that the protease NS3/4A of HCV which had been shown relation with immune invasion contributed to the reduced expression of NKG2D ligands. These findings provide a novel insight into the mechanisms evolved by HCV to escape from the NK cell response. Cellular & Molecular Immunology. 2008;5(6): 475-478.展开更多
Epithelial morphogenesis and homeostasis are essential for animal development and tissue regeneration, and epithelial disorganization is associated with developmental disorders and tumorigenesis. However, the molecula...Epithelial morphogenesis and homeostasis are essential for animal development and tissue regeneration, and epithelial disorganization is associated with developmental disorders and tumorigenesis. However, the molecular mechanisms that contribute to the morphogenesis and homeostasis of the epithelium remain elusive. Herein, we report a novel role for the cylindromatosis (CYLD) tumor suppressor in these events. Our results show that CYLD depletion disrupts epithelial organization in both Drosophila egg chambers and mouse skin and intestinal epithelia. Microscopic analysis of proliferating cells in mouse epithelial tissues and cultured organoids reveals that loss of CYLD synergizes with tumor-promoting agents to cause the misorientation of the mitotic spindle. Mechanistic studies show that CYLD accu- mulates at the cell cortex in epithelial tissues and cultured ceils, where it promotes the formation of epithelial adherens junctions through the modulation of microtuhule dynamics. These data suggest that CYLD controls epithelial morphogenesis and homeostasis by modulating the assembly of adherens junctions and ensuring proper orientation of the mitotic spindle. Our findings thus provide novel insight into the role of CYLD in development, tissue homeostasis, and tumorigenesis.展开更多
The authors regret that the published version of the above article contained two errors which were not identified during the proofing stage.Also,Figure 2A and 6C have been replaced.The authors apologize for these erro...The authors regret that the published version of the above article contained two errors which were not identified during the proofing stage.Also,Figure 2A and 6C have been replaced.The authors apologize for these errors and state that these corrections do not change the scientific conclusions of the article in any way.展开更多
The Triassic rocks are widespread in China, and both marine and terrestrial strata are well developed. The Triassic stratigraphic architecture of China is very complex in both spatial variation of the so-called "...The Triassic rocks are widespread in China, and both marine and terrestrial strata are well developed. The Triassic stratigraphic architecture of China is very complex in both spatial variation of the so-called "South Marine and North Continental", i.e. the southern areas of China occupied mostly by marine facies while the northern China by terrestrial facies during the Triassic Period, and temporal transition of the "Lower Marine and Upper Continental", i.e. the lower part of the Triassic System composed mainly of marine facies and the upper part of terrestrial strata especially in South China. Although the Global Stratotype Section and Point(GSSP) of the Permian-Triassic boundary is located in South China, the Triassic of China except for some marine Lower-Middle Triassic depositions shows significantly local characteristics and is hardly correlated with the global chronostratigraphic chart. Consequently, the Triassic of China contains not only the international research hotspots but also difficult points in stratigraphic study. This paper aims to present a brief review of the Triassic in China, including chronostratigraphy, biostratigraphy, magnetostratigraphy and chemostratigraphy, and summarize an integrated Triassic stratigraphic framework of China. Accordingly, a stratigraphic correlation is proposed for the lithostratigraphic sequences among the three tectono-paleogeographic stratigraphic regions. The comprehensive study indicates that ammonoids are the classic index fossils in Triassic biostratigraphy but conodonts are more advantageous in the study and definition of the Triassic chronostratigraphic boundaries. China still has the potential to optimize the GSSPs of the Induan-Olenekian boundary and Olenekian-Anisian boundary. The correlation of the Permian-Triassic boundary between marine and terrestrial facies might be achieved with the help of the Permian-Triassic "transitional bed" and its related biotic and environmental events in association with the biostratigraphic study of conchostracan, vertebrate and plant fossils. In addition, the carbon isotopes have been proved to be one of the powerful methods in marine Triassic stratigraphic study, whereas the oxygen and strontium isotopes may be additional important bridges to establish the correlation between the marine and terrestrial strata, but as yet lacking of relevant studies in terrestrial strata. Considering the most stratigraphic intervals of the Triassic and the terrestrial Triassic in China are difficult to be correlated to the global chart, the proposed Chinese(regional) Triassic chronostratigraphic chart of marine and terrestrial stages would be of importance to the study of Chinese Triassic stratigraphy and related aspects, but the stages must be conceptually in line with international standards and studied as soon as possible in order to finalize the definition.展开更多
We investigate the influence of the source’s energy fluctuation on both computational ghost imaging and computational ghost imaging via sparsity constraint,and if the reconstruction quality will decrease with the inc...We investigate the influence of the source’s energy fluctuation on both computational ghost imaging and computational ghost imaging via sparsity constraint,and if the reconstruction quality will decrease with the increase of the source’s energy fluctuation.In order to overcome the problem of image degradation,a correction approach against the source’s energy fluctuation is proposed by recording the source’s fluctuation with a monitor before modulation and correcting the echo signal or the intensity of computed reference light field with the data recorded by the monitor.Both the numerical simulation and experimental results demonstrate that computational ghost imaging via sparsity constraint can be enhanced by correcting the echo signal or the intensity of computed reference light field,while only correcting the echo signal is valid for computational ghost imaging.展开更多
The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment(TME).Here,we ...The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment(TME).Here,we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes(TILs)using hybrid micelles(HM),which encapsulated colony stimulating factor 1 receptor(CSF1-R)inhibitor BLZ-945 and indoleamine 2,3-dioxygenase(IDO)inhibitor NLG-919 in its core and displayed a model antigen ovalbumin(OVA)on its surface(denoted as BN@HM-OVA).The bioactive nanovaccine is coated with a polyethylene glycol(PEG)shell for extending nanoparticle circulation.The shell can be shed in response to the weakly acidic tumor microenvironment.The decrease in size and the increase in positive charge may cause the deep tumor penetration of drugs.We demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells(DCs)and drugs transportation into M1-like tumor-associated macrophages(TAMs)and tumor cells via size reduction and increasing positive charge caused by the weakly acidic TME.Such bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment,leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor models.Furthermore,combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition,based on the optimal timing and sequence of PD-1 blockade against T cell receptor.This research provides a new strategy for the development of efficient cancer immunotherapy.展开更多
Objectives:To investigate whether a precise circular resection of the uterine tissue at the placental attachment part is effective in cases with placenta previa complicated with placenta percreta (PPWPP).Methods:Patie...Objectives:To investigate whether a precise circular resection of the uterine tissue at the placental attachment part is effective in cases with placenta previa complicated with placenta percreta (PPWPP).Methods:Patients diagnosed with PPWPP were assessed for pregnancy termination at 34-36 weeks of gestation.During the operation,we performed circular resection of the uterine tissue at the placental attachment part.Then the characteristics of the operation and the follow-ups were recorded.Results:During the operation,the vital signs were stable.The mean intraoperative blood loss,packed red blood cells units transfusion,fresh frozen plasma transfusion,and operation time were 2140 mL,6 U,440 mL,and 179.8 minutes,respectively.There was no bowel,ureter,or bladder injury.And there was no patient transferred to the ICU after operation.The mean postoperative blood loss was 458.6mL.There was no fever,infection,intestinal obstruction,or other complications after operation during the hospitalization.The shape and the blood flow of the uterus were normal.After the patients were discharged,one had developed cesarean scar diverticulum.The mean lochia duration was 30 days.The menstrual cycle and volume were as before.The shape and the blood flow of the uterus and the ovarian were normal.Conclusions:The circular resection following end-to-end anastomosis is an effective precision surgical approach for PPWPP.It can achieve the purpose of hemostasis while maximizing the protection of organ function and reducing surgical trauma.展开更多
Background:Inhibitors of B-cell CLL/Iymphoma 2(Bcl-2)family proteins have shown hope as antitumor drugs.While the notion that it is efficient to coordinate,balance,and neutralize both arms of the anti-apoptotic Bcl-2 ...Background:Inhibitors of B-cell CLL/Iymphoma 2(Bcl-2)family proteins have shown hope as antitumor drugs.While the notion that it is efficient to coordinate,balance,and neutralize both arms of the anti-apoptotic Bcl-2 family has been validated in many cancer cells,the weights of the two arms contributing to apoptosis inhibition have not been explored.This study analyzed the best combination ratio for different Bcl-2 selective inhibitors.Methods:We used a previously established mathematical model to study the weights of Bcl-2(representing both Bcl-2 and BcI-xL in this study)and myeloid cell leukemia-1(Mcl-1).Correlation and single-parameter sensitivity analysis were used to find the major molecular determinants for Bcl-2 and Mcl-1 dependency,as well as their weights.Biological experiments were used to verify the mathematical model.Results:Bcl-2 protein level and Mcl-1 protein level,production,and degradation rates were the major molecular determinants for Bcl-2 and Mcl-1 dependency.The model gained agreement with the experimental assays for ABT-737/A-1210477 and ABT-737/compound 5 combination effect in MCF-7 and MDA-MB-231.Two sets of equations composed of Bcl-2 and Mcl-1 levels were obtained to predict the best combination ratio for Bcl-2 inhibitors with Mcl-1 inhibitors that stabilize and downregulate Mcl-1,respectively.Conclusions:The two sets of equations can be used as tools to bypass time-consuming and laborious experimental screening to predict the best drug combination ratio for treatment.展开更多
基金the financial support of the research fund of the Science and Technology Innovation Program of Hunan Province(2020RC2076)the General Project of Education Department of Hunan Province(21C008)+2 种基金the Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University(2022C02)the Youth Science and Technology Talent Project of Hunan Province(2022RC1197)the Hunan Provincial Natural Science Foundation of China(2021JJ40529)。
文摘Combining photocatalytic organic reactions with CO_(2)reduction is an efficient solar energy utilization mode,but it is still limited by the organic species that can be matched and the low conversion.Herein,ultrathin organic polymer with p-πconjugated structure(TPP)was rationally designed and prepared,and showed a high yield of CO(15.2 mmol g^(-1))and conversion of SAS coupled products(100%),far exceeding the organic polymer with P=O structure.The enhanced photoredox activity of TPP is ascribed to the orbital interaction between the p-orbital on phosphorus and theπ-orbitals of aromatic,which can accelerate the photoinduced charge carrier separation and improve the CO_(2)adsorption capacity.TPP can also be used for the dehydrocoupling of various benzyl mercaptans to the corresponding SAS bond products.This work provides a new concept for the efficient synthesis of disulfide bonds combined with CO_(2)reduction in a photoreaction system.
基金supported by the Natural Science Foundation of China (52102312,51672234,and 52072325)the Natural Science Foundation of Hunan Province of China (2021JJ40528)+2 种基金the China Postdoctoral Science Foundation (2020M682581)the Macao Young Scholars Program (AM2021011)the College Student Innovation and Entrepreneurship Training Program (S202210530051)。
文摘The development of insertion-type anodes is the key to designing“rocking chair”zinc-ion batteries.However,there is rare report on high mass loading anode with high performances.Here,{001}-oriented Bi OCl nanosheets with Sn doping are proposed as a promising insertion-type anode.The designs of cross-linked CNTs conductive network,{001}-oriented nanosheet,and Sn doping significantly enhance ion/electron transport,proved via experimental tests and theoretical calculations(density of states and diffusion barrier).The H^(+)/Zn^(2+)synergistic co-insertion mechanism is proved via ex situ XRD,Raman,XPS,and SEM tests.Accordingly,this optimized electrode delivers a high reversible capacity of 194 m A h g^(-1)at 0.1 A g^(-1)with a voltage of≈0.37 V and an impressive cyclability with 128 m A h g^(-1)over 2500 cycles at 1 A g^(-1).It also shows satisfactory performances at an ultrahigh mass loading of 10 mg cm^(-2).Moreover,the Sn-Bi OCl//MnO_(2)full cell displays a reversible capacity of 85 m A h g^(-1)at 0.2 A g^(-1)during cyclic test.
基金National Natural Science Foundation of China,No.30700413
文摘AIM: To explore whether acute cellular DNA damage response is induced upon hepatitis B virus (HBV) infection and the effects of the HBV infection. METHODS: We incubated HL7702 hepatocytes with HBV-positive serum, mimicking a natural HBV infection process. We used immunoblotting to evaluate protein expression levels in HBV-infected cells or in non-infected cells; immunofluorescence to show ATR foci ands Chkl phosphorylation foci formation; flow cytometry to analyze the cell cycle and apoptosis; ultraviolet (UV) radiation and ionizing radiation (IR)-treated cells to mimic DNA damage; and Trypan blue staining to count the viable cells. RESULTS: We found that HBV infection induced an increased steady state of ATR protein and increased phosphorylation of multiple downstream targets including Chkl, p53 and H2AX. In contrast to ATR and its target, the phosphorylated form of ATM at Ser-1981 and its downstream substrate Chk2 phosphorylation at Thr-68 did not visibly increase upon infection. However, the level of Mre11 and p21 were reduced beginning at 0.5 h aEer HBV-positive serum addition. Also, HBV infection led to transient cell cycle arrest in the S and the G2 phases without accompanying increasedapoptosis. Research on cell survival changes upon radiation following HBV infection showed that survival of UV-treated host cells was greatly increased by HBV infection, owing to the reduced apoptosis. Meanwhile, survival of IR-treated host cells was reduced by HBV infection. CONCLUSION: HBV infection activates ATR DNA damage response to replication stress and abrogates the checkpoint signaling controlled by DNA damage response.
基金This work was supported by the Taishan Scholars Program of Shandong Province(20161201)。
文摘As a transparent avascular tissue located at the front of the eyeball, the cornea is an important barrier to external damage. Both epithelial and endothelial cells of the cornea harbor primary cilia, which sense changes in the external environment and regulate intracellular signaling pathways. Accumulating evidence suggests that the primary cilium regulates corneal development in several ways, including participation in corneal epithelial stratification and maintenance of corneal endothelial cell morphology.In addition, the primary cilium has been implicated in the pathogenesis of several corneal diseases. In this review, we discuss recent findings that demonstrate the critical role of the primary cilium in corneal development. We also discuss the link between ciliary dysfunction and corneal diseases, which suggests that the primary cilium could be targeted to treat these diseases.
基金Sponsored by the National Natural Science Foundation of China(Grant No.11102007)the Fundamental Research Fund for the Central Universities(Grant No.YWF-14-YHXY-012)
文摘A model-free adaptive control method is proposed for the spacecrafts whose dynamical parameters change over time and cannot be acquired accurately. The algorithm is based on full form dynamic linearization.A dimension reduction matrix is introduced to construct an augmented system with the same dimension input and output. The design of the controller depends on the system input and output data rather than the knowledge of the controlled plant. The numerical simulation results show that the improved controller can deal with different models with the same set of controller parameters,and the controller performance is better than that of PD controller for the time-varying system with disturbance.
文摘Given the booming of internet usage in its domain, Chinese on-line shopping business is not growing proportionately. The absence of a market mechanism based on trust among suppliers and customers is to blame, although other factors as well holding the responsibility. Beginning with an introduction to the theory of "lemons", this paper reviews the status quo of trust in the Chinese cyber market, from the perspective of legislation, regulation and institution. It also prescribes several possible micro-solutions.
基金supported by the Shenzhen Fundamental Research Program(No.:JCYJ20190807155805818).
文摘Adipose-derived stem cells(ADSCs)have considerable potential for bone regeneration.However,their performance is limited by a lack of scaffolds that adequately mimic the hierarchical structure of bone to promote proliferation and osteogenic differentiation of ADSCs.In this study,nanofiber membranes composed of polycaprolactone,poly(lactide-co-glycolide),and hydroxyapatite(HAp)were prepared via electrospinning,and the membranes curled after responding to temperature stimuli in an aqueous solution.Transmission electron microscopy and scanning electron microscopy observations indicated that needle-like HAp nanoparticles with an average diameter of 57±39 nm and a length–diameter ratio of 7.4±1.56 were entrapped in the nanofiber matrix and did not affect the surface morphology of fibers.After cutting and deformation,the nanofibers changed from straight to bent,and the diameters increased;they were 1105±200 nm for BPLG85-H and 1120±199 nm for BPLG80-H.Additionally,tubular units with a single layer(BPLG-H(1.5))or multiple layers(BPLG-H(3.5))were obtained by controlling the initial shape and size of the membranes.rADSCs on the concave surface of BPLG-H(3.5)proliferated faster and exhibited better osteogenic activity than those on the convex side of BPLG-H(3.5)and both surfaces of BPLG-H(1.5),which was correlated with the higher expressions of vascular endothelial growth factor and bone morphogenetic protein 2.Additionally,rADSCs on both units maintained osteogenic activity after storage at-80◦C for 20 d.In rat skull defect(diameter of 8 mm)models,rADSC-loaded BPLG-H(3.5)units fixed using gelatin hydrogel(ADSC@BHM)exhibited 84.1±6.6%BV/TV after implantation for 12 weeks,which was 155.6%higher than that of the Blank group.H&E and Masson’s staining results demonstrated that there was more bone regeneration at the defect center of ADSC@BHM than in the BHM and Blank groups.In conclusion,rADSC-loaded BPLG-H(3.5)with an osteon-mimic structure provides a potential strategy to repair bone defects.
文摘Natural killer (NK) cells are a major component of the host innate immune defense against various pathogens. Several viruses, including hepatitis C virus (HCV), have developed strategies to evade the NK-cell response. In our study, we found HCV infection could trigger DNA damage response by both ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) pathways. Recent reports had revealed that NKG2D ligands (NK cell- activating ligands) were upregulated when a major DNA damage checkpoint pathway was activated. However, here we found that DNA damage response was activated but NKG2D ligands were downregulated upon HCV infection. Further studies showed that the protease NS3/4A of HCV which had been shown relation with immune invasion contributed to the reduced expression of NKG2D ligands. These findings provide a novel insight into the mechanisms evolved by HCV to escape from the NK cell response. Cellular & Molecular Immunology. 2008;5(6): 475-478.
基金supported by the grants from the National Natural Science Foundation of China(Nos.31271437,31371382,31471262 and 31671403)
文摘Epithelial morphogenesis and homeostasis are essential for animal development and tissue regeneration, and epithelial disorganization is associated with developmental disorders and tumorigenesis. However, the molecular mechanisms that contribute to the morphogenesis and homeostasis of the epithelium remain elusive. Herein, we report a novel role for the cylindromatosis (CYLD) tumor suppressor in these events. Our results show that CYLD depletion disrupts epithelial organization in both Drosophila egg chambers and mouse skin and intestinal epithelia. Microscopic analysis of proliferating cells in mouse epithelial tissues and cultured organoids reveals that loss of CYLD synergizes with tumor-promoting agents to cause the misorientation of the mitotic spindle. Mechanistic studies show that CYLD accu- mulates at the cell cortex in epithelial tissues and cultured ceils, where it promotes the formation of epithelial adherens junctions through the modulation of microtuhule dynamics. These data suggest that CYLD controls epithelial morphogenesis and homeostasis by modulating the assembly of adherens junctions and ensuring proper orientation of the mitotic spindle. Our findings thus provide novel insight into the role of CYLD in development, tissue homeostasis, and tumorigenesis.
文摘The authors regret that the published version of the above article contained two errors which were not identified during the proofing stage.Also,Figure 2A and 6C have been replaced.The authors apologize for these errors and state that these corrections do not change the scientific conclusions of the article in any way.
基金supported by the National Natural Science Foundation of China (Grant Nos. 41530104 & 41661134047)
文摘The Triassic rocks are widespread in China, and both marine and terrestrial strata are well developed. The Triassic stratigraphic architecture of China is very complex in both spatial variation of the so-called "South Marine and North Continental", i.e. the southern areas of China occupied mostly by marine facies while the northern China by terrestrial facies during the Triassic Period, and temporal transition of the "Lower Marine and Upper Continental", i.e. the lower part of the Triassic System composed mainly of marine facies and the upper part of terrestrial strata especially in South China. Although the Global Stratotype Section and Point(GSSP) of the Permian-Triassic boundary is located in South China, the Triassic of China except for some marine Lower-Middle Triassic depositions shows significantly local characteristics and is hardly correlated with the global chronostratigraphic chart. Consequently, the Triassic of China contains not only the international research hotspots but also difficult points in stratigraphic study. This paper aims to present a brief review of the Triassic in China, including chronostratigraphy, biostratigraphy, magnetostratigraphy and chemostratigraphy, and summarize an integrated Triassic stratigraphic framework of China. Accordingly, a stratigraphic correlation is proposed for the lithostratigraphic sequences among the three tectono-paleogeographic stratigraphic regions. The comprehensive study indicates that ammonoids are the classic index fossils in Triassic biostratigraphy but conodonts are more advantageous in the study and definition of the Triassic chronostratigraphic boundaries. China still has the potential to optimize the GSSPs of the Induan-Olenekian boundary and Olenekian-Anisian boundary. The correlation of the Permian-Triassic boundary between marine and terrestrial facies might be achieved with the help of the Permian-Triassic "transitional bed" and its related biotic and environmental events in association with the biostratigraphic study of conchostracan, vertebrate and plant fossils. In addition, the carbon isotopes have been proved to be one of the powerful methods in marine Triassic stratigraphic study, whereas the oxygen and strontium isotopes may be additional important bridges to establish the correlation between the marine and terrestrial strata, but as yet lacking of relevant studies in terrestrial strata. Considering the most stratigraphic intervals of the Triassic and the terrestrial Triassic in China are difficult to be correlated to the global chart, the proposed Chinese(regional) Triassic chronostratigraphic chart of marine and terrestrial stages would be of importance to the study of Chinese Triassic stratigraphy and related aspects, but the stages must be conceptually in line with international standards and studied as soon as possible in order to finalize the definition.
基金supported by the Youth Innovation Promotion Association of the Chinese Academy of Sciences,the Defense Industrial Technology Development Program of China(No.D040301)the National Natural Science Foundation of China(No.61571427)the Civil Aerospace Pre-research Project(No.D020214)。
文摘We investigate the influence of the source’s energy fluctuation on both computational ghost imaging and computational ghost imaging via sparsity constraint,and if the reconstruction quality will decrease with the increase of the source’s energy fluctuation.In order to overcome the problem of image degradation,a correction approach against the source’s energy fluctuation is proposed by recording the source’s fluctuation with a monitor before modulation and correcting the echo signal or the intensity of computed reference light field with the data recorded by the monitor.Both the numerical simulation and experimental results demonstrate that computational ghost imaging via sparsity constraint can be enhanced by correcting the echo signal or the intensity of computed reference light field,while only correcting the echo signal is valid for computational ghost imaging.
基金by the National Natural Science Foundation of China(U19A2006,12132004,12032007,11972111,31900940,32071304,32171309,32171395)the Sichuan Science and Technology Program(21YJ0130)+1 种基金the Joint Funds of Center for Engineering Medicine(ZYGX2021YGLH010,ZYGX2021YGLH017,ZYGX2021YGLH023)the technical support from the Public Experiment Centre of State Bioindustrial Base(Chongqing).
文摘The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment(TME).Here,we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes(TILs)using hybrid micelles(HM),which encapsulated colony stimulating factor 1 receptor(CSF1-R)inhibitor BLZ-945 and indoleamine 2,3-dioxygenase(IDO)inhibitor NLG-919 in its core and displayed a model antigen ovalbumin(OVA)on its surface(denoted as BN@HM-OVA).The bioactive nanovaccine is coated with a polyethylene glycol(PEG)shell for extending nanoparticle circulation.The shell can be shed in response to the weakly acidic tumor microenvironment.The decrease in size and the increase in positive charge may cause the deep tumor penetration of drugs.We demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells(DCs)and drugs transportation into M1-like tumor-associated macrophages(TAMs)and tumor cells via size reduction and increasing positive charge caused by the weakly acidic TME.Such bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment,leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor models.Furthermore,combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition,based on the optimal timing and sequence of PD-1 blockade against T cell receptor.This research provides a new strategy for the development of efficient cancer immunotherapy.
基金This study was supported by the National Key R&D Program of China(2016YFC1000405)Guangdong Natural Science Foundation(2015A030310115)
文摘Objectives:To investigate whether a precise circular resection of the uterine tissue at the placental attachment part is effective in cases with placenta previa complicated with placenta percreta (PPWPP).Methods:Patients diagnosed with PPWPP were assessed for pregnancy termination at 34-36 weeks of gestation.During the operation,we performed circular resection of the uterine tissue at the placental attachment part.Then the characteristics of the operation and the follow-ups were recorded.Results:During the operation,the vital signs were stable.The mean intraoperative blood loss,packed red blood cells units transfusion,fresh frozen plasma transfusion,and operation time were 2140 mL,6 U,440 mL,and 179.8 minutes,respectively.There was no bowel,ureter,or bladder injury.And there was no patient transferred to the ICU after operation.The mean postoperative blood loss was 458.6mL.There was no fever,infection,intestinal obstruction,or other complications after operation during the hospitalization.The shape and the blood flow of the uterus were normal.After the patients were discharged,one had developed cesarean scar diverticulum.The mean lochia duration was 30 days.The menstrual cycle and volume were as before.The shape and the blood flow of the uterus and the ovarian were normal.Conclusions:The circular resection following end-to-end anastomosis is an effective precision surgical approach for PPWPP.It can achieve the purpose of hemostasis while maximizing the protection of organ function and reducing surgical trauma.
基金This research was supported by the National Natural Science Foundation of China(81430083,81903462 and 82073703)the China Postdoctoral Science Foundation(2018M641694)the Fundamental Research Funds for the Central Universities(DUT20LK28 and DUT20YG133).
文摘Background:Inhibitors of B-cell CLL/Iymphoma 2(Bcl-2)family proteins have shown hope as antitumor drugs.While the notion that it is efficient to coordinate,balance,and neutralize both arms of the anti-apoptotic Bcl-2 family has been validated in many cancer cells,the weights of the two arms contributing to apoptosis inhibition have not been explored.This study analyzed the best combination ratio for different Bcl-2 selective inhibitors.Methods:We used a previously established mathematical model to study the weights of Bcl-2(representing both Bcl-2 and BcI-xL in this study)and myeloid cell leukemia-1(Mcl-1).Correlation and single-parameter sensitivity analysis were used to find the major molecular determinants for Bcl-2 and Mcl-1 dependency,as well as their weights.Biological experiments were used to verify the mathematical model.Results:Bcl-2 protein level and Mcl-1 protein level,production,and degradation rates were the major molecular determinants for Bcl-2 and Mcl-1 dependency.The model gained agreement with the experimental assays for ABT-737/A-1210477 and ABT-737/compound 5 combination effect in MCF-7 and MDA-MB-231.Two sets of equations composed of Bcl-2 and Mcl-1 levels were obtained to predict the best combination ratio for Bcl-2 inhibitors with Mcl-1 inhibitors that stabilize and downregulate Mcl-1,respectively.Conclusions:The two sets of equations can be used as tools to bypass time-consuming and laborious experimental screening to predict the best drug combination ratio for treatment.