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
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
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
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
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
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
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
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
Objective: To explore the effect of salinomycin on the metastasis and invasion of bladder cancer cell line T24 by regulating the related protein expression in the process of epithelialmesenchymal transition(EMT), and ...Objective: To explore the effect of salinomycin on the metastasis and invasion of bladder cancer cell line T24 by regulating the related protein expression in the process of epithelialmesenchymal transition(EMT), and to provide experimental basis for the treatment of urological tumors. Methods: The bladder cancer cell line T24 was cultured in vitro. The rat bladder tumor model was established in vivo. The rats were randomized into two groups, among which the rats in the experiment group were given intraperitoneal injection of salinomycin, while the rats in the control group were given intraperitoneal injection of normal saline. The change of tumor cells in the two groups was observed. Transwell was used to detect the cell migration and invasion abilities, Real-time PCR was used to detect the expression of m RNA, while Western-blot was utilized for the determination of the expressions of E-cadherin and vimentin proteins. Results: The metastasis and invasion abilities of serum bladder cancer cell line T24 after salinomycin treatment in the experiment group were significantly reduced when compared with those in the control group, and the tumor metastasis lesions were decreased from an average of 1.59 to 0.6(P<0.05). T24 cell proliferation in the experiment group was gradually decreasing. T24 cell proliferation at 48 h was significantly lower than that at 12 h and 24 h(P<0.05). T24 cell proliferation at 24 h was significantly lower than that at 12 h(P<0.05). T24 cell proliferation at each timing point in the experiment group was significantly lower than that in the control group(P<0.05). The serum m RNA level and E-cadherin expression in the tumor tissues in the experiment group were significantly higher than those in the control group, while vimentin expression level was significantly lower than that in the control group(P<0.05). Conclusions: Salinomycin can suppress the metastasis and invasion of bladder cancer cells, of which the mechanism is probably associated with the inhibition of EMT of tumor cells.展开更多
AIM: To investigate the early outcomes of vision, objective visual quality and their correlation after cataract surgery with trifocal intraocular lens implantation.METHODS: The visual examination and objective visual ...AIM: To investigate the early outcomes of vision, objective visual quality and their correlation after cataract surgery with trifocal intraocular lens implantation.METHODS: The visual examination and objective visual quality analysis using Optical Quality Analysis System(OQAS) at 1 mo and 3 mo, and defocus curve examination at 3 mo were performed in 20 patients(27 eyes) after phacoemulsification combined with trifocal intraocular lens implantation surgery.RESULTS: The uncorrected distant(UD), intermediate and near visual acuity(VA) were significantly improved after surgery(P<0.001). UDVA at 1 mo after the surgery was slightly better than that after 3 mo(P=0.026). The defocus curve after 3 mo indicated that the peak of distant vision was close to 0 logMAR, and UDVA was lower than 0.3 logMAR in the range of-1.5 D to-3.0 D. The modulation transfer function(MTF) cutoff frequency, strehl ratio(SR), Optical Quality Analysis System values(OVs), includes OV100, OV20 and OV9 after the surgery were significantly better than before surgery(P<0.001), but the objective scattering index(OSI) was significantly decreased(P<0.001). UDVA at 3 mo after the surgery had correlations with MTF cutoff, OSI, OV100 and OV20(r=-0.400, 0.431,-0.437,-0.411, P=0.039, 0.025, 0.023, 0.033). The uncorrected intermediate VA after 3 mo of the surgery had correlations with OSI and OV100(r=0.478,-0.411, P=0.012, 0.033). CONCLUSION: Trifocal intraocular lens implantation can provide good distant, intermediate and near VA, and the vision shows a well correlation with objective visual quality during early surgery.展开更多
AIM： To investigate the expression differences of transforming growth factor-β2（TGF-β2）, basic fibroblast growth factor（b FGF） and intercellular cell-adhesion molecule-1（ICAM-1） in lens epithelial cells（LECs...AIM： To investigate the expression differences of transforming growth factor-β2（TGF-β2）, basic fibroblast growth factor（b FGF） and intercellular cell-adhesion molecule-1（ICAM-1） in lens epithelial cells（LECs） of complicated cataract with silicone oil tamponade and agerelated cataract. METHODS： Totally 150 eyes of 150 patients（aged 35 to 77y） were investigated, including 75 patients with complicated cataract after silicone oil tamponade and 75 patients with age-related cataract. The central piece of anterior capsules was collected during cataract surgery. TGF-β2, b FGF and ICAM-1 were detected in the 60 specimens of the two groups by immunohistochemistry. The expression levels of the three kinds of messenger ribonucleic acid（m RNA） were determined by real-time quantitative reverse transcriptionpolymerase chain reaction in the 90 specimens of the two groups.RESULTS： TGF-β2 was detected in the cytomembrane and cytoplasm of the LECs and b FGF was detected in the nucleus. ICAM-1 was positive in the cytomembrane of the LECs and the distribution of positive cells was uneven. The m RNA genes expression of the TGF-β2, b FGF and ICAM-1 was significant differences between the two groups and markedly increased in complicated cataract group（P〈0.05）.CONCLUSION： The up-regulated TGF-β2, b FGF and ICAM-1 maybe associate with the occurrence and development of complicated cataract with silicone oil tamponade.展开更多
Dear Editor,We are writing this letter to report two unusual cases of femtosecond laser-assisted cataract surgery(FLACS)in two ICL-implanted patients with significant different vault.FLACS has been confirmed by accumu...Dear Editor,We are writing this letter to report two unusual cases of femtosecond laser-assisted cataract surgery(FLACS)in two ICL-implanted patients with significant different vault.FLACS has been confirmed by accumulating evidence to improve the safety and precision of surgery from common cases to complicated cases in treating cataracts[1-3].Implantable collamer lens(ICL)implantation possesses a good performance in its predictability,reversibility,and the rapid visual recovery.展开更多
Objective:The objective of this study is to investigate the effect of scraping therapy in the treatment of knee osteoarthritis.Materials and Methods:A total of eighty patients with knee osteoarthritis were assigned to...Objective:The objective of this study is to investigate the effect of scraping therapy in the treatment of knee osteoarthritis.Materials and Methods:A total of eighty patients with knee osteoarthritis were assigned to the moxibustion group and the scraping therapy group according to the random numerical table method,with forty cases in each group.Patients in both two groups received functional exercise and moxibustion therapy,and those in the scraping therapy group were supplemented with scraping therapy.The serum indexes of interleukin‑1(IL‑1),IL‑6,tumor necrosis factor‑alpha(TNF‑α),and superoxide dismutase(SOD)were detected before and after the treatment.The clinical syndrome integral and Visual Analog Scale(VAS)on pain of patients were assessed.The clinical therapeutic efficacy was evaluated and compared between the two groups.Results:Patients in the scraping therapy group received better outcomes of serum IL‑1,IL‑6,TNF‑α,and SOD compared with those in the moxibustion group at 2 months after treatment(P<0.05).The scores of clinical syndrome integral and VAS on pain were decreased in two groups at 2 months after the treatment and were lower in the scraping therapy group than those in the moxibustion group(P<0.05).The overall effective rate in the scraping therapy group was higher than that in the control group(87.50%vs.67.50%,P<0.05).Conclusion:The scraping therapy is potentially effective to ameliorate the clinical symptom and pain degree of patients with knee osteoarthritis.展开更多
·AIM:To compare visual quality after unilateral cataract surgery with implantation of trifocal intraocular lens(IOL)and asymmetric refractive multifocal IOL.·METHODS:The prospective nonrandom,comparative stu...·AIM:To compare visual quality after unilateral cataract surgery with implantation of trifocal intraocular lens(IOL)and asymmetric refractive multifocal IOL.·METHODS:The prospective nonrandom,comparative study consisted of 60 eyes of 60 patients suffering unilateral cataract surgery with implantation of two different IOLs:AT LISA tri 839 MP(30 eyes;Carl Zeiss Meditec,Germany)and LS-313 MF30(30 eyes;Oculentis GmbH,Germany).Visual acuity,refractive outcome,contrast sensitivity,defocus curves,quality of vision,and optical phenomena were evaluated at3 mo postoperatively.·RESULTS:There were no statistical differences between groups in uncorrected distance visual acuity(P=0.13)and uncorrected near visual acuity(P=0.54).In contrast,uncorrected intermediate visual acuity was better in trifocal group compared to the refractive multifocal group(P=0.02).No significant statistical between-group difference was detected in cylinder(P=0.43).Compared to trifocal group,spherical refraction and spherical equivalent in refractive multi focal group were more myopic(P<0.01).Under photopic conditions,no significant statistical differences were found between groups in contrast sensitivity at 3 and 6 cycles per degree(cpd).The refractive multifocal group performed better at 12 and 18 cpd than the trifocal group(P=0.01,P=0.034,respectively).The questionnaires of quality of vision and optical phenomena showed no differences between groups.·CONCLUSION:Trifocal IOL is superior to refractive multifocal IOL in intermediate visual acuity.Rotationally asymmetric refractive multifocal IOL is more myopic in automated refraction and significantly better for the photopic contrast sensitivity at high frequency.展开更多
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 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 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.
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.
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 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.
文摘Objective: To explore the effect of salinomycin on the metastasis and invasion of bladder cancer cell line T24 by regulating the related protein expression in the process of epithelialmesenchymal transition(EMT), and to provide experimental basis for the treatment of urological tumors. Methods: The bladder cancer cell line T24 was cultured in vitro. The rat bladder tumor model was established in vivo. The rats were randomized into two groups, among which the rats in the experiment group were given intraperitoneal injection of salinomycin, while the rats in the control group were given intraperitoneal injection of normal saline. The change of tumor cells in the two groups was observed. Transwell was used to detect the cell migration and invasion abilities, Real-time PCR was used to detect the expression of m RNA, while Western-blot was utilized for the determination of the expressions of E-cadherin and vimentin proteins. Results: The metastasis and invasion abilities of serum bladder cancer cell line T24 after salinomycin treatment in the experiment group were significantly reduced when compared with those in the control group, and the tumor metastasis lesions were decreased from an average of 1.59 to 0.6(P<0.05). T24 cell proliferation in the experiment group was gradually decreasing. T24 cell proliferation at 48 h was significantly lower than that at 12 h and 24 h(P<0.05). T24 cell proliferation at 24 h was significantly lower than that at 12 h(P<0.05). T24 cell proliferation at each timing point in the experiment group was significantly lower than that in the control group(P<0.05). The serum m RNA level and E-cadherin expression in the tumor tissues in the experiment group were significantly higher than those in the control group, while vimentin expression level was significantly lower than that in the control group(P<0.05). Conclusions: Salinomycin can suppress the metastasis and invasion of bladder cancer cells, of which the mechanism is probably associated with the inhibition of EMT of tumor cells.
基金Supported by Key Research and Development Project of Shaanxi Province (No.2017SF-246)Science and Technology Planning Project of Xi’an City (No.2017116SF/ YX010)
文摘AIM: To investigate the early outcomes of vision, objective visual quality and their correlation after cataract surgery with trifocal intraocular lens implantation.METHODS: The visual examination and objective visual quality analysis using Optical Quality Analysis System(OQAS) at 1 mo and 3 mo, and defocus curve examination at 3 mo were performed in 20 patients(27 eyes) after phacoemulsification combined with trifocal intraocular lens implantation surgery.RESULTS: The uncorrected distant(UD), intermediate and near visual acuity(VA) were significantly improved after surgery(P<0.001). UDVA at 1 mo after the surgery was slightly better than that after 3 mo(P=0.026). The defocus curve after 3 mo indicated that the peak of distant vision was close to 0 logMAR, and UDVA was lower than 0.3 logMAR in the range of-1.5 D to-3.0 D. The modulation transfer function(MTF) cutoff frequency, strehl ratio(SR), Optical Quality Analysis System values(OVs), includes OV100, OV20 and OV9 after the surgery were significantly better than before surgery(P<0.001), but the objective scattering index(OSI) was significantly decreased(P<0.001). UDVA at 3 mo after the surgery had correlations with MTF cutoff, OSI, OV100 and OV20(r=-0.400, 0.431,-0.437,-0.411, P=0.039, 0.025, 0.023, 0.033). The uncorrected intermediate VA after 3 mo of the surgery had correlations with OSI and OV100(r=0.478,-0.411, P=0.012, 0.033). CONCLUSION: Trifocal intraocular lens implantation can provide good distant, intermediate and near VA, and the vision shows a well correlation with objective visual quality during early surgery.
基金Supported by the Natural Science Foundation of Shaanxi Province(No.2012JM4023)
文摘AIM： To investigate the expression differences of transforming growth factor-β2（TGF-β2）, basic fibroblast growth factor（b FGF） and intercellular cell-adhesion molecule-1（ICAM-1） in lens epithelial cells（LECs） of complicated cataract with silicone oil tamponade and agerelated cataract. METHODS： Totally 150 eyes of 150 patients（aged 35 to 77y） were investigated, including 75 patients with complicated cataract after silicone oil tamponade and 75 patients with age-related cataract. The central piece of anterior capsules was collected during cataract surgery. TGF-β2, b FGF and ICAM-1 were detected in the 60 specimens of the two groups by immunohistochemistry. The expression levels of the three kinds of messenger ribonucleic acid（m RNA） were determined by real-time quantitative reverse transcriptionpolymerase chain reaction in the 90 specimens of the two groups.RESULTS： TGF-β2 was detected in the cytomembrane and cytoplasm of the LECs and b FGF was detected in the nucleus. ICAM-1 was positive in the cytomembrane of the LECs and the distribution of positive cells was uneven. The m RNA genes expression of the TGF-β2, b FGF and ICAM-1 was significant differences between the two groups and markedly increased in complicated cataract group（P〈0.05）.CONCLUSION： The up-regulated TGF-β2, b FGF and ICAM-1 maybe associate with the occurrence and development of complicated cataract with silicone oil tamponade.
基金Supported by Key Research and Development Program of Shaanxi Province(No.2020SF-271,No.2017SF-273)。
文摘Dear Editor,We are writing this letter to report two unusual cases of femtosecond laser-assisted cataract surgery(FLACS)in two ICL-implanted patients with significant different vault.FLACS has been confirmed by accumulating evidence to improve the safety and precision of surgery from common cases to complicated cases in treating cataracts[1-3].Implantable collamer lens(ICL)implantation possesses a good performance in its predictability,reversibility,and the rapid visual recovery.
文摘Objective:The objective of this study is to investigate the effect of scraping therapy in the treatment of knee osteoarthritis.Materials and Methods:A total of eighty patients with knee osteoarthritis were assigned to the moxibustion group and the scraping therapy group according to the random numerical table method,with forty cases in each group.Patients in both two groups received functional exercise and moxibustion therapy,and those in the scraping therapy group were supplemented with scraping therapy.The serum indexes of interleukin‑1(IL‑1),IL‑6,tumor necrosis factor‑alpha(TNF‑α),and superoxide dismutase(SOD)were detected before and after the treatment.The clinical syndrome integral and Visual Analog Scale(VAS)on pain of patients were assessed.The clinical therapeutic efficacy was evaluated and compared between the two groups.Results:Patients in the scraping therapy group received better outcomes of serum IL‑1,IL‑6,TNF‑α,and SOD compared with those in the moxibustion group at 2 months after treatment(P<0.05).The scores of clinical syndrome integral and VAS on pain were decreased in two groups at 2 months after the treatment and were lower in the scraping therapy group than those in the moxibustion group(P<0.05).The overall effective rate in the scraping therapy group was higher than that in the control group(87.50%vs.67.50%,P<0.05).Conclusion:The scraping therapy is potentially effective to ameliorate the clinical symptom and pain degree of patients with knee osteoarthritis.
基金Supported by Key Research and Development Projects of Shaanxi Province(No.2017SF-246)Science and Technology Planning Project of Xi’an(No.2017116SF/YX010No.201805097YX5SF31)。
文摘·AIM:To compare visual quality after unilateral cataract surgery with implantation of trifocal intraocular lens(IOL)and asymmetric refractive multifocal IOL.·METHODS:The prospective nonrandom,comparative study consisted of 60 eyes of 60 patients suffering unilateral cataract surgery with implantation of two different IOLs:AT LISA tri 839 MP(30 eyes;Carl Zeiss Meditec,Germany)and LS-313 MF30(30 eyes;Oculentis GmbH,Germany).Visual acuity,refractive outcome,contrast sensitivity,defocus curves,quality of vision,and optical phenomena were evaluated at3 mo postoperatively.·RESULTS:There were no statistical differences between groups in uncorrected distance visual acuity(P=0.13)and uncorrected near visual acuity(P=0.54).In contrast,uncorrected intermediate visual acuity was better in trifocal group compared to the refractive multifocal group(P=0.02).No significant statistical between-group difference was detected in cylinder(P=0.43).Compared to trifocal group,spherical refraction and spherical equivalent in refractive multi focal group were more myopic(P<0.01).Under photopic conditions,no significant statistical differences were found between groups in contrast sensitivity at 3 and 6 cycles per degree(cpd).The refractive multifocal group performed better at 12 and 18 cpd than the trifocal group(P=0.01,P=0.034,respectively).The questionnaires of quality of vision and optical phenomena showed no differences between groups.·CONCLUSION:Trifocal IOL is superior to refractive multifocal IOL in intermediate visual acuity.Rotationally asymmetric refractive multifocal IOL is more myopic in automated refraction and significantly better for the photopic contrast sensitivity at high frequency.
