Objective： Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 （HER2）-positive breast cancer, the resistance to anti-HER2 therapy is a growing cl...Objective： Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 （HER2）-positive breast cancer, the resistance to anti-HER2 therapy is a growing clinical dilemma. We aim to determine whether HER2-specific T cells generated from dendritic cells （DCs） modified with HER2 gene could effectively kill the HER2-positive breast cancer cells, especially the trastuzumab-resistant cells. Methods： The peripheral blood mononuclear cells （PBMCs） from healthy donors, whose HLA haplotypes were compatible with the tumor cell lines, were transfected with reconstructive human adeno-association virus （rhAAV/HER2） to obtain the specific killing activities of T cells, and were evaluated by lactate dehydrogenase （LDH） releasing assay. Results： Trastuzumab produced a significant inhibiting effect on SK-BR-3, the IC50 was 100ng/ml. MDA-MB-453 was resistant to trastuzumab even at a concentration of 10,000 ng/ml in vitro. HER2-specific T lymphocytes killed effectively SK-BR-3 [（69.86±13.41）%] and MDA-MB-453 [（78.36±10.68）%] at 40：1 （effector：target ratio, E：T）, but had no significant cytotoxicity against HER2-negative breast cancer cell lines MDA-MB-231 or MCF-7 （less than 10%）. Conclusion： The study showed that HER2-specific T lymphocytes generated from DCs modified by rhAAV/HER2 could kill HER2-positive breast cancer cell lines in a HER2-dependent manner, and result in significantly high inhibition rates on the intrinsic trastuzumab-resistant cell line MDA-MB-453 and the tastuzumab-sensitive cell line SK-BR-3. These results imply that this immunotherapy might be a potential treatment to HER2-positive breast cancer.展开更多
AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment...AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.展开更多
FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways ...FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.展开更多
The design of efficient and cost‐effective bifunctional catalysts, which are capable of driving both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), is of paramount importance for advancing...The design of efficient and cost‐effective bifunctional catalysts, which are capable of driving both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), is of paramount importance for advancing overall water splitting. Here, we developed an innovative heterogeneous interface engineering strategy to boost the electrocatalytic performance of overall water splitting. This approach involves the synergistic integration of ultra‐fine CoMoP nanocrystals coupled with three‐ dimensional (3D) porous C3N4/N‐doped carbon (NC) architectures, constructing a distinctive CoMoP/C3N4/NC heterogeneous interface. The CoMoP/C3N4/NC exhibits distinguished overall water splitting performance. To drive the overall water splitting current of 10 mA cm−2, the CoMoP/C3N4/NC||CoMoP/C3N4/NC electrolysis cell only needs an ultralow cell voltage of 1.496 V. The electronic properties and localized coordination environments characterizations, and density functional theory (DFT) calculations elucidate that the improved catalytic activities of CoMoP/C3N4/NC are primarily attributed to the synergistic interfacial coupling between CoMoP/C3N4/NC heterogeneous interface. A novel multi‐site synergistic catalytic mechanism was revealed by the DFT calculations, in which the optimum H* adsorption site on CoMoP/C3N4/NC for HER is on the cobalt atoms in CoMoP with the ultralow Gibbs free energy of hydrogen bonding (ΔGH*) of 0.018 eV, while for the OER, the optimum intermediates adsorption site of the CoMoP/C3N4/NC is on the carbon atoms in C3N4/NC. Besides, the intricately engineered 3D hierarchical porous framework of the CoMoP/C3N4/NC can facilitate the ion and electron transport and improve mass transfer, which gives rise to enhanced water splitting performance.展开更多
A series of single-phase high-entropy perovskite ceramics(HEPCs)(La_(0.25)Nd_(0.25)Sm_(0.25)Gd_(0.25))_(1-x)Yb_(x)MnO_(3)(x=0.25,0.3,0.35 and 0.4)was synthesized using solid-state reactions.The effect of Yb on the str...A series of single-phase high-entropy perovskite ceramics(HEPCs)(La_(0.25)Nd_(0.25)Sm_(0.25)Gd_(0.25))_(1-x)Yb_(x)MnO_(3)(x=0.25,0.3,0.35 and 0.4)was synthesized using solid-state reactions.The effect of Yb on the structure and magnetic properties was systematically investigated.The results show that all samples are in orthorhombic perovskite structures with a space group of Pbnm and exhibit a strong crystallization trend sintered at 1300℃for 16 h.All HEPCs have a smooth surface morphology with distinct grain boundaries and exhibit significant hysteresis effects at T=5 K.With the increase of Yb,high lattice distortion and weak double exchange lead to the decrease of T_(C).The presence of Jahn-Teller(JT)distortion and the enhancement of MnO_(6)octahedral distortion result in different magnetic interactions.Moreover,the sample has the best magnetic properties at x=0.35 among the four HEPCs,which is attributed to the large content of Mn^(3+),remnant ratio(Mr/Ms)and lattice distortion(σ^(2)).This work provides a valuable reference for regulating the magnetism of high-entropy ceramics based on rare-earth perovskite manganese oxides.展开更多
The digital twin-driven performance model provides an attractive option for the warn gas-path faults of the gas turbines.However,three technical difficulties need to be solved:(1)low modeling precision caused by indiv...The digital twin-driven performance model provides an attractive option for the warn gas-path faults of the gas turbines.However,three technical difficulties need to be solved:(1)low modeling precision caused by individual differences between gas turbines,(2)poor solution efficiency due to excessive iterations,and(3)the false alarm and missing alarm brought by the traditional fixed threshold method.This paper proposes a digital twin model-based early warning method for gas-path faults that breaks through the above obstacles from three aspects.Firstly,a novel performance modeling strategy is proposed to make the simulation effect close to the actual gas turbine by fusing the mechanism model and measurement data.Secondly,the idea of controlling the relative accuracy of model parameters is developed.The introduction of an error module to the existing model can greatly shorten the modeling cycle.The third solution focuses on the early warning based on the digital twin model,which self-learns the alarm threshold of the warning feature of gas-path parameters using the kernel density estimation.The proposed method is utilized to analyze actual measured data of LM2500+,and the results verify that the new-built digital model has higher accuracy and better efficiency.The comparisons show that the proposed method shows evident superiority in early warning of performance faults for gas turbines over other methods.展开更多
AIM:To Investigate the effects of transforming growth factorβ2(TGF-β2)and connective tissue growth factor(CTGF)on transdifferentiation of human lens epithelial cells(HLECs)cultured in vitro and synthesis of extracel...AIM:To Investigate the effects of transforming growth factorβ2(TGF-β2)and connective tissue growth factor(CTGF)on transdifferentiation of human lens epithelial cells(HLECs)cultured in vitro and synthesis of extracellular matrix(ECM).METHODS:HLECs were treated with TGF-β2(0,0.5,1.0,5,10μg/L)and CTGF(0,15,30,60,100μg/L)for different times(0,24,48,72h)in vitro and the expression ofα-smooth muscle actin(α-SMA),the main component of the extracellular matrix typeⅠcollagen(Col-1)and fibronectin(Fn)were measured by using real-time polymerase chain reaction(PCR)and western-blot.RESULTS:TGF-β2 and CTGF significantly increased expression ofα-SMA mRNA and protein(P【0.05,P【0.001),Fn mRNA and protein(P【0.001),Col-1 mRNA and protein(P【0.001).TGF-β2 could induce HLECs expression of CTGF mRNA and protein in dosedependent manner(P【0.05,P【0.001).TGF-β2 and CTGF could induce HLECs to expressα-SMA,Fn and Col-1 in time-dependent manner.Each time of TGF-β2and CTGF induced HELCs expression ofα-SMA,Fn,Col-1 mRNA and protein was significant increase compared with control(P【0.05,P【0.001).CONCLUSION:TGF-β2 and CTGF could induce HLECs epithelial mesenchymal transition and ECM synthesis.展开更多
Liquid phase epitaxy （LPE） is a mature technology. Early experiments on single magnetic crystal films fabricated by LPE were focused mainly on thick films for microwave and magneto-optical devices. The LPE is an exc...Liquid phase epitaxy （LPE） is a mature technology. Early experiments on single magnetic crystal films fabricated by LPE were focused mainly on thick films for microwave and magneto-optical devices. The LPE is an excellent way to make a thick film, low damping magnetic garnet film and high-quality magneto-optical material. Today, the principal challenge in the applied material is to create sub-micrometer devices by using modern photolithography technique. Until now the magnetic garnet films fabricated by LPE still show the best quality even on a nanoscale （about 100 nm）, which was considered to be impossible for LPE method.展开更多
AIM:To investigate the role of reactive oxygen species(ROS)in epithelial–mesenchymal transition(EMT)and apoptosis of human lens epithelial cells(HLECs).METHODS:Flow cytometry was used to assess ROS production after t...AIM:To investigate the role of reactive oxygen species(ROS)in epithelial–mesenchymal transition(EMT)and apoptosis of human lens epithelial cells(HLECs).METHODS:Flow cytometry was used to assess ROS production after transforming growth factorβ2(TGF-β2)induction.Apoptosis of HLECs after H_(2)O_(2) and TGF-β2 interference with or without ROS scavenger N-acetylcysteine(NAC)were assessed by flow cytometry.The corresponding protein expression levels of the EMT markerα-smooth muscle actin(α-SMA),the extracellular matrix(ECM),marker fibronectin(Fn),and apoptosis-associated proteins were detected by using Western blotting in the presence of an ROS scavenger(NAC).Wound-healing and Transwell assays were used to assess the migration capability of HLECs.RESULTS:TGF-β2 stimulates ROS production within 8h in HLECs.Additionally,TGF-β2 induced HLECs cell apoptosis,EMT/ECM synthesis protein markers expression,and pro-apoptotic proteins production;nonetheless,NAC treatment prevented these responses.Similarly,TGF-β2 promoted HLECs cell migration,whereas NAC inhibited cell migration.We further determined that although ROS initiated apoptosis,it only induced the accumulation of the EMT markerα-SMA protein,but not COL-1 or Fn.CONCLUSION:ROS contribute to TGF-β2-induced EMT/ECM synthesis and cell apoptosis of HLECs;however,ROS alone are not sufficient for EMT/ECM synthesis.展开更多
Method development has always been and will continue to be a core driving force of microbiome science, In this perspective, we argue that in the next decade, method development in microbiome analysis will be driven by...Method development has always been and will continue to be a core driving force of microbiome science, In this perspective, we argue that in the next decade, method development in microbiome analysis will be driven by three key changes in both ways of thinking and technological platforms： ① a shift from dissecting microbiota structure by sequencing to tracking microbiota state, function, and intercellular interaction via imaging; ② a shift from interrogating a consortium or population of cells to probing individual cells; and ③a shift from microbiome data analysis to microbiome data science. Some of the recent methoddevelopment efforts by Chinese microbiome scientists and their international collaborators that underlie these technological trends are highlighted here. It is our belief that the China Microbiome Initiative has the opportunity to deliver outstanding ＂Made-in-China＂ tools to the international research community, by building an ambitious, competitive, and collaborative program at the forefront of method development for microbiome science.展开更多
The nearby bright M-dwarf star L 98–59 has three terrestrial-sized planets.One challenge remaining in characterizing atmospheres around such planets is that it is not known a priori whether they possess any atmospher...The nearby bright M-dwarf star L 98–59 has three terrestrial-sized planets.One challenge remaining in characterizing atmospheres around such planets is that it is not known a priori whether they possess any atmospheres.Here we report on study of the atmospheres of L 98–59 c and L 98–59 d using near-infrared spectral data from the G141 grism of Hubble Space Telescope(HST)/Wide Field Camera 3.We can reject the hypothesis of a clear atmosphere dominated by hydrogen and helium at a confidence level of ~3σ for both planets.Thus they could have a primary hydrogen-dominated atmosphere with an opaque cloud layer,or could have lost their primary hydrogen-dominated atmosphere and re-established a secondary thin atmosphere,or have no atmosphere at all.We cannot distinguish between these scenarios for the two planets using the current HST data.Future observations with the James Webb Space Telescope would be capable of confirming the existence of atmospheres around L 98–59 c and d and determining their compositions.展开更多
Objective:To study the different effects of mechanical embolus removal and intra-arterial thrombolysis on neural functional recovery in patients with acute middle cerebral artery occlusion.Methods: Patients with acute...Objective:To study the different effects of mechanical embolus removal and intra-arterial thrombolysis on neural functional recovery in patients with acute middle cerebral artery occlusion.Methods: Patients with acute middle cerebral artery occlusion who were treated in the First Hospital of Yulin between September 2013 and October 2017 were selected and retrospectively studied, and the differences in reperfusion therapies in history data were referred to divide them into study group A and study group B who underwent mechanical embolus removal and intra-arterial thrombolysis respectively. The levels of neurocyte damage markers, apoptosis markers and stress markers in serum as well as the expression of Wnt pathway molecules in peripheral blood were determined before treatment and 24 h after treatment.Results: Compared with those of same group before treatment, serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of both groups were decreasing whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were increasing, and serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of study group A after treatment were lower than those of study group B whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were higher than those of study group B.Conclusion: Mechanical embolus removal for acute middle cerebral artery occlusion can be more effective than intra-arterial thrombolysis to reduce the nerve function damage as well as the corresponding oxidative stress and apoptosis.展开更多
The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and contin...The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.展开更多
Accurate crown control is paramount for ensuring the quality of hot-rolled strip products.Given the multitude of influencing parameters and the intricate coupling and genetic relationships among them,the conventional ...Accurate crown control is paramount for ensuring the quality of hot-rolled strip products.Given the multitude of influencing parameters and the intricate coupling and genetic relationships among them,the conventional crown control method is no longer sufficient to meet the precision requirements of schedule-free rolling.To address this limitation,an optimization framework for hot-rolled strip crown control was developed based on model-driven digital twin(MDDT).This framework enhances the strip crown control precision by facilitating collaborative operations among physical entities,virtual models,and functional application layers.In virtual modeling,a data-driven approach that integrates the extreme gradient boosting and the improved Harris hawk optimization algorithm was firstly proposed to fit the relationship between key process parameters and strip crown,and a global-local collaborative training strategy was proposed to enhance the model adaptability to diverse working conditions.Subsequently,the influence of crucial process factors on the virtual model was examined through model responses.Furthermore,a novel optimization mode for crown control based on MDDT was established by aligning and reconstructing both the physical and virtual models,thereby enhancing the crown control precision.Finally,data trials were conducted to validate the effectiveness of the proposed framework.The results indicated that the proposed method exhibited satisfactory performance and could be effectively utilized to improve the crown control precision.展开更多
The prediction of the rolling force and thickness ratio plays an important role in the development and application of bimetallic composite plates.To analyze the rolling force of the bimetallic composite plate more acc...The prediction of the rolling force and thickness ratio plays an important role in the development and application of bimetallic composite plates.To analyze the rolling force of the bimetallic composite plate more accurately,a novel hypothesis based on Orowan's theory was proposed.The variation in the thickness of each differential element at different positions was considered to establish the analytical model.According to the characteristics of bimetallic composite plate rolling,the rolling deformation can be divided into forward and backward slip zones.The initial thickness ratio after rolling was predetermined by the thickness ratio before rolling;the rolling force balance of the upper and lower rollers was considered the convergence condition;and the final thickness ratio of the bimetallic composite plate was obtained by iterative calculation.The calculation results of the analytical model were compared with the measured and simulated data.The results showed that the errors in the calculation of the rolling force and thickness ratio were both less than 10%.The analytical model has high precision,meets engineering requirements,and has important reference significance for rolling process optimization and thickness ratio prediction.展开更多
Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive...Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive circulating progenitor cells （CPCs： CD34^＋） and endothelial progenitor cells （EPCs： CD34^＋KDR^＋） were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes （n=7）, non-prolif- erative DR （NPDR, n=7）, proliferative DR （PDR, n=8）, and PDR complicated with diabetic nephropathy （PDR-DN, n=7）. Results The numbers of EPOR^＋ CPCs and EPOR^＋ EPCs were reduced remarkably in NPDR corn pared with the control group （both P（0.01）, whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^＋ CPCs in CPCs （NPDR vs. control, P（0.01） and that of EPOR^＋ EPCs in EPCs （NPDR vs. control, P〈0.05）. Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^＋ EPCs associated with ischemia.展开更多
基金supported by the grant from the National"973"Basic Research Program of China(No.2009CB521703)Medical Oncology Leadership of Beijing Municipal Government Health Burean(No.2009-2-16)
文摘Objective： Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 （HER2）-positive breast cancer, the resistance to anti-HER2 therapy is a growing clinical dilemma. We aim to determine whether HER2-specific T cells generated from dendritic cells （DCs） modified with HER2 gene could effectively kill the HER2-positive breast cancer cells, especially the trastuzumab-resistant cells. Methods： The peripheral blood mononuclear cells （PBMCs） from healthy donors, whose HLA haplotypes were compatible with the tumor cell lines, were transfected with reconstructive human adeno-association virus （rhAAV/HER2） to obtain the specific killing activities of T cells, and were evaluated by lactate dehydrogenase （LDH） releasing assay. Results： Trastuzumab produced a significant inhibiting effect on SK-BR-3, the IC50 was 100ng/ml. MDA-MB-453 was resistant to trastuzumab even at a concentration of 10,000 ng/ml in vitro. HER2-specific T lymphocytes killed effectively SK-BR-3 [（69.86±13.41）%] and MDA-MB-453 [（78.36±10.68）%] at 40：1 （effector：target ratio, E：T）, but had no significant cytotoxicity against HER2-negative breast cancer cell lines MDA-MB-231 or MCF-7 （less than 10%）. Conclusion： The study showed that HER2-specific T lymphocytes generated from DCs modified by rhAAV/HER2 could kill HER2-positive breast cancer cell lines in a HER2-dependent manner, and result in significantly high inhibition rates on the intrinsic trastuzumab-resistant cell line MDA-MB-453 and the tastuzumab-sensitive cell line SK-BR-3. These results imply that this immunotherapy might be a potential treatment to HER2-positive breast cancer.
基金Supported by the Key Research&Development Program of Shaanxi Province(No.2022SF-311,No.2024SFYBXM-328,No.2024SF-YBXM-325)the Natural Science Basic Research Program of Shaanxi Province,China(No.2021JQ-385).
文摘AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.
基金supported by the National Natural Science Foundation of China,No.81971177(to YK)the Natural Science Foundation of Beijing,No.7222198(to NH)the Peking University People's Hospital Research and Development Fund,No.RDX2021-01(to YK)。
文摘FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.
基金supported by the National Natural Science Foundation of China(Grant No.12375303)the Natural Science Foundation of Guangdong Province(Grants No.2024A1515030034 and 2023A1515140156).
文摘The design of efficient and cost‐effective bifunctional catalysts, which are capable of driving both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), is of paramount importance for advancing overall water splitting. Here, we developed an innovative heterogeneous interface engineering strategy to boost the electrocatalytic performance of overall water splitting. This approach involves the synergistic integration of ultra‐fine CoMoP nanocrystals coupled with three‐ dimensional (3D) porous C3N4/N‐doped carbon (NC) architectures, constructing a distinctive CoMoP/C3N4/NC heterogeneous interface. The CoMoP/C3N4/NC exhibits distinguished overall water splitting performance. To drive the overall water splitting current of 10 mA cm−2, the CoMoP/C3N4/NC||CoMoP/C3N4/NC electrolysis cell only needs an ultralow cell voltage of 1.496 V. The electronic properties and localized coordination environments characterizations, and density functional theory (DFT) calculations elucidate that the improved catalytic activities of CoMoP/C3N4/NC are primarily attributed to the synergistic interfacial coupling between CoMoP/C3N4/NC heterogeneous interface. A novel multi‐site synergistic catalytic mechanism was revealed by the DFT calculations, in which the optimum H* adsorption site on CoMoP/C3N4/NC for HER is on the cobalt atoms in CoMoP with the ultralow Gibbs free energy of hydrogen bonding (ΔGH*) of 0.018 eV, while for the OER, the optimum intermediates adsorption site of the CoMoP/C3N4/NC is on the carbon atoms in C3N4/NC. Besides, the intricately engineered 3D hierarchical porous framework of the CoMoP/C3N4/NC can facilitate the ion and electron transport and improve mass transfer, which gives rise to enhanced water splitting performance.
基金Project supported by the Guangxi Natural Science Foundation,China(2024GXNSFAA010415)the Opening Fund of the Key Laboratory of New Processing Technology for Nonferrous Metals&Materials of the Ministry of Education(22AA-9)。
文摘A series of single-phase high-entropy perovskite ceramics(HEPCs)(La_(0.25)Nd_(0.25)Sm_(0.25)Gd_(0.25))_(1-x)Yb_(x)MnO_(3)(x=0.25,0.3,0.35 and 0.4)was synthesized using solid-state reactions.The effect of Yb on the structure and magnetic properties was systematically investigated.The results show that all samples are in orthorhombic perovskite structures with a space group of Pbnm and exhibit a strong crystallization trend sintered at 1300℃for 16 h.All HEPCs have a smooth surface morphology with distinct grain boundaries and exhibit significant hysteresis effects at T=5 K.With the increase of Yb,high lattice distortion and weak double exchange lead to the decrease of T_(C).The presence of Jahn-Teller(JT)distortion and the enhancement of MnO_(6)octahedral distortion result in different magnetic interactions.Moreover,the sample has the best magnetic properties at x=0.35 among the four HEPCs,which is attributed to the large content of Mn^(3+),remnant ratio(Mr/Ms)and lattice distortion(σ^(2)).This work provides a valuable reference for regulating the magnetism of high-entropy ceramics based on rare-earth perovskite manganese oxides.
基金co-supported by the National Postdoctoral Program for Innovative Talent(No.BX20180031)。
文摘The digital twin-driven performance model provides an attractive option for the warn gas-path faults of the gas turbines.However,three technical difficulties need to be solved:(1)low modeling precision caused by individual differences between gas turbines,(2)poor solution efficiency due to excessive iterations,and(3)the false alarm and missing alarm brought by the traditional fixed threshold method.This paper proposes a digital twin model-based early warning method for gas-path faults that breaks through the above obstacles from three aspects.Firstly,a novel performance modeling strategy is proposed to make the simulation effect close to the actual gas turbine by fusing the mechanism model and measurement data.Secondly,the idea of controlling the relative accuracy of model parameters is developed.The introduction of an error module to the existing model can greatly shorten the modeling cycle.The third solution focuses on the early warning based on the digital twin model,which self-learns the alarm threshold of the warning feature of gas-path parameters using the kernel density estimation.The proposed method is utilized to analyze actual measured data of LM2500+,and the results verify that the new-built digital model has higher accuracy and better efficiency.The comparisons show that the proposed method shows evident superiority in early warning of performance faults for gas turbines over other methods.
基金National Natural Science Foundation of China(No.81070721)Inernational Exchange Program of Shaanxi Province,China(No.2012kw-31)
文摘AIM:To Investigate the effects of transforming growth factorβ2(TGF-β2)and connective tissue growth factor(CTGF)on transdifferentiation of human lens epithelial cells(HLECs)cultured in vitro and synthesis of extracellular matrix(ECM).METHODS:HLECs were treated with TGF-β2(0,0.5,1.0,5,10μg/L)and CTGF(0,15,30,60,100μg/L)for different times(0,24,48,72h)in vitro and the expression ofα-smooth muscle actin(α-SMA),the main component of the extracellular matrix typeⅠcollagen(Col-1)and fibronectin(Fn)were measured by using real-time polymerase chain reaction(PCR)and western-blot.RESULTS:TGF-β2 and CTGF significantly increased expression ofα-SMA mRNA and protein(P【0.05,P【0.001),Fn mRNA and protein(P【0.001),Col-1 mRNA and protein(P【0.001).TGF-β2 could induce HLECs expression of CTGF mRNA and protein in dosedependent manner(P【0.05,P【0.001).TGF-β2 and CTGF could induce HLECs to expressα-SMA,Fn and Col-1 in time-dependent manner.Each time of TGF-β2and CTGF induced HELCs expression ofα-SMA,Fn,Col-1 mRNA and protein was significant increase compared with control(P【0.05,P【0.001).CONCLUSION:TGF-β2 and CTGF could induce HLECs epithelial mesenchymal transition and ECM synthesis.
基金Project supported by the National Key Research and Development Program of China(Grant No.2016YFA0300801)the National Natural Science Foundation of China(Grant Nos.51702042,61734002,61571079,51572042,and 61471096)+1 种基金the International Science&Technology Cooperation Program of China(Grant No.2015DFR50870)the Sichuan Science and Technology Support Project,China(Grant Nos.2016GZ0250 and 2017JY0002)
文摘Liquid phase epitaxy （LPE） is a mature technology. Early experiments on single magnetic crystal films fabricated by LPE were focused mainly on thick films for microwave and magneto-optical devices. The LPE is an excellent way to make a thick film, low damping magnetic garnet film and high-quality magneto-optical material. Today, the principal challenge in the applied material is to create sub-micrometer devices by using modern photolithography technique. Until now the magnetic garnet films fabricated by LPE still show the best quality even on a nanoscale （about 100 nm）, which was considered to be impossible for LPE method.
基金Supported by the National Natural Science Foundation of China(No.82201163,No.81800812)Natural Science Foundation Youth Foundation of Shaanxi Province(No.2023-JC-QN-0861)Shaanxi Province Key Research and Development Program(No.2023-YBSF-483).
文摘AIM:To investigate the role of reactive oxygen species(ROS)in epithelial–mesenchymal transition(EMT)and apoptosis of human lens epithelial cells(HLECs).METHODS:Flow cytometry was used to assess ROS production after transforming growth factorβ2(TGF-β2)induction.Apoptosis of HLECs after H_(2)O_(2) and TGF-β2 interference with or without ROS scavenger N-acetylcysteine(NAC)were assessed by flow cytometry.The corresponding protein expression levels of the EMT markerα-smooth muscle actin(α-SMA),the extracellular matrix(ECM),marker fibronectin(Fn),and apoptosis-associated proteins were detected by using Western blotting in the presence of an ROS scavenger(NAC).Wound-healing and Transwell assays were used to assess the migration capability of HLECs.RESULTS:TGF-β2 stimulates ROS production within 8h in HLECs.Additionally,TGF-β2 induced HLECs cell apoptosis,EMT/ECM synthesis protein markers expression,and pro-apoptotic proteins production;nonetheless,NAC treatment prevented these responses.Similarly,TGF-β2 promoted HLECs cell migration,whereas NAC inhibited cell migration.We further determined that although ROS initiated apoptosis,it only induced the accumulation of the EMT markerα-SMA protein,but not COL-1 or Fn.CONCLUSION:ROS contribute to TGF-β2-induced EMT/ECM synthesis and cell apoptosis of HLECs;however,ROS alone are not sufficient for EMT/ECM synthesis.
基金We are grateful to the support from the National Natural Science Foundation of China （NSFC） （31425002, 91231205, 81430011, 61303161, 31470220, and 31327001）, and the Frontier Science Research Program, the Soil-Microbe System Function and Regulation Program, and the Science and Technology Service Network Initiative （STS） from the Chinese Academy of Sciences （CAS）.
文摘Method development has always been and will continue to be a core driving force of microbiome science, In this perspective, we argue that in the next decade, method development in microbiome analysis will be driven by three key changes in both ways of thinking and technological platforms： ① a shift from dissecting microbiota structure by sequencing to tracking microbiota state, function, and intercellular interaction via imaging; ② a shift from interrogating a consortium or population of cells to probing individual cells; and ③a shift from microbiome data analysis to microbiome data science. Some of the recent methoddevelopment efforts by Chinese microbiome scientists and their international collaborators that underlie these technological trends are highlighted here. It is our belief that the China Microbiome Initiative has the opportunity to deliver outstanding ＂Made-in-China＂ tools to the international research community, by building an ambitious, competitive, and collaborative program at the forefront of method development for microbiome science.
基金the financial support from the National Key R&D Program of China(2020YFC2201400)National Natural Science Foundation of China(NSFC,Grant Nos.12073092,12103097,and 12103098)+5 种基金the science research grants from the China Manned Space Project(No.CMS-CSST-2021-B09,B12)Guangzhou Basic and Applied Basic Research Program(202102080371)the Strategic Priority Program on Space Science,the Chinese Academy of Sciences(Grant No.XDA15020601)China Postdoctoral Science Foundation(No.2020M672936)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University,Hainan Provincial Natural Science Foundation of China under Grant No.122RC546the National Natural Science Foundation of China under grant Nos.12063001。
文摘The nearby bright M-dwarf star L 98–59 has three terrestrial-sized planets.One challenge remaining in characterizing atmospheres around such planets is that it is not known a priori whether they possess any atmospheres.Here we report on study of the atmospheres of L 98–59 c and L 98–59 d using near-infrared spectral data from the G141 grism of Hubble Space Telescope(HST)/Wide Field Camera 3.We can reject the hypothesis of a clear atmosphere dominated by hydrogen and helium at a confidence level of ~3σ for both planets.Thus they could have a primary hydrogen-dominated atmosphere with an opaque cloud layer,or could have lost their primary hydrogen-dominated atmosphere and re-established a secondary thin atmosphere,or have no atmosphere at all.We cannot distinguish between these scenarios for the two planets using the current HST data.Future observations with the James Webb Space Telescope would be capable of confirming the existence of atmospheres around L 98–59 c and d and determining their compositions.
文摘Objective:To study the different effects of mechanical embolus removal and intra-arterial thrombolysis on neural functional recovery in patients with acute middle cerebral artery occlusion.Methods: Patients with acute middle cerebral artery occlusion who were treated in the First Hospital of Yulin between September 2013 and October 2017 were selected and retrospectively studied, and the differences in reperfusion therapies in history data were referred to divide them into study group A and study group B who underwent mechanical embolus removal and intra-arterial thrombolysis respectively. The levels of neurocyte damage markers, apoptosis markers and stress markers in serum as well as the expression of Wnt pathway molecules in peripheral blood were determined before treatment and 24 h after treatment.Results: Compared with those of same group before treatment, serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of both groups were decreasing whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were increasing, and serum NSE, S100B, VILIP1, sFas, sFasL, ET-1 and MDA levels as well as peripheral blood GSK3β, LC3-II and Beclin1 expression intensity of study group A after treatment were lower than those of study group B whereas serum BDNF, NTF, sLivin and SOD levels as well as peripheral bloodβ-catenin and mTOR expression intensity were higher than those of study group B.Conclusion: Mechanical embolus removal for acute middle cerebral artery occlusion can be more effective than intra-arterial thrombolysis to reduce the nerve function damage as well as the corresponding oxidative stress and apoptosis.
基金supported by the National Natural Science Foundation of China,Nos.81901156(to ZZ),82271200(to ZZ),82171308(to XC)the Fundamental Research Funds for the Central Universities,No.xzy012022035(to ZZ)+1 种基金the Natural Science Foundation of Shaanxi Province,Nos.2021JM-261(to QK),2023-YBSF-303(to ZZ)Traditional Chinese Medicine Project of Shaanxi Province,No.2019-ZZ-JC047(to QK)。
文摘The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.
基金financially supported by the National Key Research and Development Program of China(Grant No.2023YFB3710204)Guangxi Science and Technology Major Program(Grant No.AA23023028-1)+1 种基金Natural Science Foundation of Heilongjiang Province of China for Distinguished Young Scientists(Grant No.JQ2022E007)Xinjiang Production and Construction Corps Science and Technology Plan(Grant No.2023AA003).
文摘Accurate crown control is paramount for ensuring the quality of hot-rolled strip products.Given the multitude of influencing parameters and the intricate coupling and genetic relationships among them,the conventional crown control method is no longer sufficient to meet the precision requirements of schedule-free rolling.To address this limitation,an optimization framework for hot-rolled strip crown control was developed based on model-driven digital twin(MDDT).This framework enhances the strip crown control precision by facilitating collaborative operations among physical entities,virtual models,and functional application layers.In virtual modeling,a data-driven approach that integrates the extreme gradient boosting and the improved Harris hawk optimization algorithm was firstly proposed to fit the relationship between key process parameters and strip crown,and a global-local collaborative training strategy was proposed to enhance the model adaptability to diverse working conditions.Subsequently,the influence of crucial process factors on the virtual model was examined through model responses.Furthermore,a novel optimization mode for crown control based on MDDT was established by aligning and reconstructing both the physical and virtual models,thereby enhancing the crown control precision.Finally,data trials were conducted to validate the effectiveness of the proposed framework.The results indicated that the proposed method exhibited satisfactory performance and could be effectively utilized to improve the crown control precision.
基金Supported by National Key Research and Development Program of China(Grant No.2018YFA0707300)Major Program of National Natural Science Foundation of China(Grant No.U22A20188)+1 种基金General Program of National Natural Science Foundation of China(Grant No.51974196)Postdoctoral Science Foundation of China(Grant No.201903D421047)。
文摘The prediction of the rolling force and thickness ratio plays an important role in the development and application of bimetallic composite plates.To analyze the rolling force of the bimetallic composite plate more accurately,a novel hypothesis based on Orowan's theory was proposed.The variation in the thickness of each differential element at different positions was considered to establish the analytical model.According to the characteristics of bimetallic composite plate rolling,the rolling deformation can be divided into forward and backward slip zones.The initial thickness ratio after rolling was predetermined by the thickness ratio before rolling;the rolling force balance of the upper and lower rollers was considered the convergence condition;and the final thickness ratio of the bimetallic composite plate was obtained by iterative calculation.The calculation results of the analytical model were compared with the measured and simulated data.The results showed that the errors in the calculation of the rolling force and thickness ratio were both less than 10%.The analytical model has high precision,meets engineering requirements,and has important reference significance for rolling process optimization and thickness ratio prediction.
基金Supported by Sciences and Technology Commission of Shanghai Municipality (08ZR1422100 and 08410701200)
文摘Objective To investigate the possible involvement of erythropoietin （EPO）/erythropoietin receptor （EPOR） system in neovascularization and vascular regeneration in diabetic retinopathy （DR）. Methods EPOR positive circulating progenitor cells （CPCs： CD34^＋） and endothelial progenitor cells （EPCs： CD34^＋KDR^＋） were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes （n=7）, non-prolif- erative DR （NPDR, n=7）, proliferative DR （PDR, n=8）, and PDR complicated with diabetic nephropathy （PDR-DN, n=7）. Results The numbers of EPOR^＋ CPCs and EPOR^＋ EPCs were reduced remarkably in NPDR corn pared with the control group （both P（0.01）, whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR^＋ CPCs in CPCs （NPDR vs. control, P（0.01） and that of EPOR^＋ EPCs in EPCs （NPDR vs. control, P〈0.05）. Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR^＋ EPCs associated with ischemia.
