Circadian rhythm is ubiquitous in nature.Circadian clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network,and regulate a variety of physiological and pathological processes,i...Circadian rhythm is ubiquitous in nature.Circadian clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network,and regulate a variety of physiological and pathological processes,including bone and cartilage metabolism.Deletion of the core clock gene Bmal1 leads to pathological bone alterations,while the phenotypes are not consistent.Studies have shown that multiple signaling pathways are involved in the process of Bmal1 regulating bone and cartilage metabolism,but the exact regulatory mechanisms remain unclear.This paper reviews the signaling pathways by which Bmal1 regulates bone/cartilage metabolism,the upstream regulatory factors that control Bmal1,and the current Bmal1 knockout mouse models for research.We hope to provide new insights for the prevention and treatment of bone/cartilage diseases related to circadian rhythms.展开更多
AIM:To investigate the protective role of ghrelin against diabetic retinopathy(DR),focusing on its anti-ferroptotic mechanism in high glucose-induced retinal endothelial injury.METHODS:First,small interfering RNA(siRN...AIM:To investigate the protective role of ghrelin against diabetic retinopathy(DR),focusing on its anti-ferroptotic mechanism in high glucose-induced retinal endothelial injury.METHODS:First,small interfering RNA(siRNA)-mediated interference was conducted to knockdown nuclear factor erythroid 2-related factor 2(Nrf2).Using reverse transcription-polymerase chain reaction(RT-PCR),the expression level of Nrf2 was determined from human retinal microvascular endothelial cells(HRMECs)transfected with either si-NC or si-Nrf2.After that,cells were treated with 10 nmol/L ghrelin and then cultured in a high glucose(30 mmol/L)environment.EdU assay was utilized to assess cell proliferation,while transmission electron microscopy was employed to observe mitochondrial morphology.Flow cytometry was used to measure the level of intracellular reactive oxygen species(ROS),and biochemical assays were conducted to detect malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),and ferrous iron(Fe2+).Western blotting was used to identify the presence of ferroptosis-related proteins such as glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),Nrf2,and haem oxygenase-1(HO-1).RESULTS:Under a high glucose environment,ghrelin could significantly promote the proliferation of HRMECs and mitochondrial status,remarkably decrease the levels of intracellular ROS and MDA,and up-regulate the level of GSH and SOD.Besides,ghrelin greatly reduced Fe2+level in the cells while increased protein levels of GPX4 and SLC7A11.Subsequently,we found that high glucose induced inactivation of Nrf2/HO-1 axis and the protein expression profile were significantly promoted by ghrelin.Moreover,silencing of Nrf2 by siRNA delivery markedly diminished the changes induced by ghrelin in high glucose-induced HRMECs,shown as reduced cell proliferation and increased mitochondrial malformation,up-regulated ROS,MDA,Fe^(2+),GPX4 and SLC7A11,as well as down-regulated GSH,SOD,Nrf2 and HO-1.CONCLUSION:Ghrelin attenuates high glucose-induced injury of retinal endothelial cells via inhibiting ferroptosis,and activation of Nrf2/HO-1 pathway may be one of the mechanisms involved in this effect of ghrelin.展开更多
Reproductive hormones associated with the hypothalamic-pituitary-gonadal(HPG)axis are closely linked to bone homeostasis.In this study,we demonstrate that Gonadotropin inhibitory hormone(GnIH,one of the key reproducti...Reproductive hormones associated with the hypothalamic-pituitary-gonadal(HPG)axis are closely linked to bone homeostasis.In this study,we demonstrate that Gonadotropin inhibitory hormone(GnIH,one of the key reproductive hormones upstream of the HPG axis)plays an indispensable role in regulating bone homeostasis and maintaining bone mass.We find that deficiency of GnIH or its receptor Gpr147 leads to a significant reduction in bone mineral density(BMD)in mice primarily by enhancement of osteoclast activation in vivo and in vitro.Mechanistically,GnIH/Gpr147 inhibits osteoclastogenesis by the PI3K/AKT,MAPK,NF-κB and Nfatc1 signaling pathways.Furthermore,GnIH treatment was able to alleviate bone loss in aging,ovariectomy(OVX)or LPS-induced mice.Moreover,the therapy using green light promotes the release of GnIH and rescues OVX-induced bone loss.In humans,serum GnIH increases and bone resorption markers decrease after green light exposure.Therefore,our study elucidates that GnIH plays an important role in maintaining bone homeostasis via modulating osteoclast differentiation and demonstrates the potential of GnIH therapy or green light therapy in preventing osteoporosis.展开更多
Dear Editor,I diopathic macular telangiectasia(MacTel)type 1 is a retinal vascular disease characterized by abnormal dilation of macular capillaries,leading to metamorphopsia,progressive vision loss,and temporal scoto...Dear Editor,I diopathic macular telangiectasia(MacTel)type 1 is a retinal vascular disease characterized by abnormal dilation of macular capillaries,leading to metamorphopsia,progressive vision loss,and temporal scotoma enlargement.Currently,there is no standardized treatment protocol for MacTel type 1[1-2].Treatment outcomes can vary significantly among individuals,highlighting the ongoing need for further exploration of new and more effective treatment options.This paper presents a case of refractory macular edema associated with MacTel type 1,which showed a favorable response to pars plana vitrectomy(PPV)and internal limiting membrane(ILM)peeling.展开更多
Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human prim...Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human primates is limited.Therefore,our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis.In a previous study,we created an SCI model in M.fascicularis by controlling the contusion displacement.We used Eriochrome Cyanine staining,immunohistochemical analysis,and toluidine blue staining to evaluate demyelination and remyelination.The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally,the former mainly impacting sensory pathways,while the latter primarily affected motor pathways.Toluidine blue staining showed myelin loss and axonal distension at the injury site.Schwann cell-derived myelin sheaths were only found at the center,while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas.Our study showed that long-lasting demyelination occurs in the spinal cord of M.fascicularis after SCI,with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.展开更多
Background:Allergic eosinophilic asthma(EA)and eosinophilic granulomatosis with polyangiitis(EGPA)share significant overlaps in both epidemiology and pathogenesis,suggesting a potential link between the two con-dition...Background:Allergic eosinophilic asthma(EA)and eosinophilic granulomatosis with polyangiitis(EGPA)share significant overlaps in both epidemiology and pathogenesis,suggesting a potential link between the two con-ditions.Despite these associations,the underlying molecular and cellular mechanisms driving their connection remain poorly understood.Methods:We retrieved GSE143303 of EA and GSE144302 of EGPA from the GEO database and conducted dif-ferential expression analysis as well as functional enrichment analysis to identify differentially expressed genes(DEGs)and potential pathogenic pathways.A protein-protein interaction(PPI)network was generated using the STRING database.Key hub genes were determined through cytoHubba.We added two publicly reported EA and EGPA-related transcriptome datasets,GSE117038 and GSE119136,for mutual verification.Subsequent valida-tion was performed via immune infiltration assessment utilizing CIBERSORT.Results:In total,267 DEGs were identified,in which HSP90AA1,HSPA8,CCND1,RPS20,CD74,RPL5,RPS6,RHOA,RPS3A and FLT3LG are the top 10 hub genes,while the antigen processing and presentation pathway and leukocyte cell-cell adhesion pathway were the potential influential pathways.Increased naïve B cells and M1 type of Macrophages were detected in EA patients through immune infiltration analysis.Conclusions:Utilizing bioinformatics techniques,this study is the initial investigation to uncover the shared mechanisms involving the antigen processing and presentation pathway and leukocyte adhesion pathways in the progression of both EA and EGPA.It may offer potential biomarkers for future studies on the underlying path-ogenesis and treatment of EA and EGPA as well as eosinophilia related co-morbidities.展开更多
Developing an efficient photocatalyst is the key to realize the practical application of photocatalysis.The S-scheme heterojunction has great potential in photocatalysis due to its unique charge-carrier migration path...Developing an efficient photocatalyst is the key to realize the practical application of photocatalysis.The S-scheme heterojunction has great potential in photocatalysis due to its unique charge-carrier migration pathway,effective light absorption and high redox capacity.However,further enhancing the built-in electric field of the S-scheme,accelerating carrier separation,and achieving higher photocatalytic performance remain unresolved challenges.Herein,based on the continuously adjustable band structure of continuous solid-solution,a novel 0D/2D all solid-solution S-scheme heterojunction with adjustable internal electric field was designed and fabricated by employing a solid-solution of ZnxCd_(1–x)S and Bi_(2)MoyW_(1–y)O_(6)respectively as reduction and oxidation semiconductors.The synergistic optimization of effective light absorption,fast photogenerated carrier separation,and high redox potential leads can be tuned to promote photocatalytic activity.Under visible light,the S-scheme system constructed by Zn_(0.4)Cd_(0.6)S quantum dot(QDs)and Bi_(2)Mo_(0.2)W_(0.8)O_(6)monolayer exhibits a high rate for photocatalytic degradation C_(2)H_(4)(150.6×10^(–3)min^(–1)),which is 16.5 times higher than that of pure Zn_(0.4)Cd_(0.6)S(9.1×10^(–3)min^(–1))and 53.8 times higher than pure Bi_(2)Mo_(0.2)W_(0.8)O_(6)(2.8×10^(–3)min^(–1)).Due to the unique charge-carrier migration pathway,photo-corrosion of Zn_(x)Cd_(1–x)S is further inhibited simultaneously.In-situ irradiation X-ray photoelectron spectroscopy,photoluminescence spectroscopy,time-resolved photoluminescence,transient absorption spectroscopy and electron paramagnetic resonance provide compelling evidence for interfacial charge transfer via S-scheme pathways,while in-situ diffuse reflectance infrared Fourier transform spectroscopy identifies the reaction pathway for C_(2)H_(4)degradation.This novel S-scheme photocatalysts demonstrates excellent performance and potential for the practical application of the fruits and vegetables preservation at room temperatures.展开更多
Low thermal conductivity and excellent mechanical strength are essential to pyrochlore A2B2O7 ceramic for environmental/thermal barrier coating applications.To collaboratively tailor the mechanical and thermal propert...Low thermal conductivity and excellent mechanical strength are essential to pyrochlore A2B2O7 ceramic for environmental/thermal barrier coating applications.To collaboratively tailor the mechanical and thermal properties of A2B2O7 ceramic,a novel high entropy pyrochlore ceramic(La_(0.3)Gd_(0.3)Ca_(0.4))_(2)(Ti_(0.2)Zr_(0.2)Hf_(0.2)Nb_(0.2)Ta_(0.2))_(2)O_(7) with significant atomic radius and mass fluctuation is proposed by simultaneously introducing various elements with different valence states at A and B cation sites.The as-synthesized(La_(0.3)Gd_(0.3)Ca_(0.4))_(2)(Ti_(0.2)Zr_(0.2)Hf_(0.2)Nb_(0.2)Ta_(0.2))_(2)O_(7) exhibits enhanced fracture toughness(1.68 MPa m^(1/2)),amorphous-like low thermal conductivity(1.45 W m^(-1) K^(-1) at 900℃)and matched thermal expansion coefficient(9.0×10^(-6) K^(-1) at 1200℃)with Al_(2)O_(3)/Al_(2)O_(3) CMCs.The extensive misfits in atomic weight,ionic radius among the substitutional cations in combination with the intrinsic oxygen vacancies in the anion sublattice play significant roles in the thermal conductivity reduction of(La_(0.3)Gd_(0.3)Ca_(0.4))_(2)(Ti_(0.2)Zr_(0.2)Hf_(0.2)Nb_(0.2)Ta_(0.2))_(2)O_(7) ceramic.The combination of outstanding mechanical and thermal properties indicates that this type of material has a good application prospect for environmental/thermal barrier coatings.展开更多
Anti-Mullerian hormone(AMH)is a functional marker of fetal Sertoli cells.The germ cell number in adults depends on the number of Sertoli cells produced duri ng peri natal development.Rece ntly,AMH has received increas...Anti-Mullerian hormone(AMH)is a functional marker of fetal Sertoli cells.The germ cell number in adults depends on the number of Sertoli cells produced duri ng peri natal development.Rece ntly,AMH has received increasi ng attenti on in research of disorders related to male fertility.This paper reviews and summarizes the articles on the regulation of AMH in males and the serum levels of AMH in male fertility-related disorders.We have determined that follicle-stimulating hormone(FSH)promotes AMH transcription in the absenee of androgen signaling.Testosterone inhibits the transcriptional activation of AMH.The undetectable levels of serum AMH and testosterone levels indicate a lack of functional testicular tissue,for example,that in patients with anorchia or severe Klinefelter syndrome suffering from impaired spermatogenesis.The normal serum testosterone level and undetectable AMH are highly suggestive of persistent Mullerian duct syndrome(PMDS),combined with clinical manifestations.The levels of both AMH and testosterone are always subnormal in patients with mixed disorders of sex development(DSD).Mixed DSD is an early-onset complete type of disorder with fetal hypogonadism resulting from the dysfunction of both Leydig and Sertoli cells.Serum AMH levels are varying in patients with male fertility-related disorders,in cludi ng pubertal delay,severe con genital hypog on adotropic hypogonadism,nonobstructive azoospermia,Klinefelter syndrome,varicocele,McCune-Albright syndrome,and male senescence.展开更多
In vitro maturation(IvM)of human oocytes offers cost efficiency and minimal invasiveness,serving as a valuable supplementary tool in assisted reproduction for fertility preservation,ovarian hyperstimulation syndrome p...In vitro maturation(IvM)of human oocytes offers cost efficiency and minimal invasiveness,serving as a valuable supplementary tool in assisted reproduction for fertility preservation,ovarian hyperstimulation syndrome prevention,and other reproductive strategies.Despite its availability for three decades,the clinical use of IVM remains limited due to efficacy and safety concerns.This study examines the DNA methylation profile of IVM oocytes collected during laparoscopic/hysteroscopic surgeries compared to in vivo matured oocytes via reduced representation bisulfite sequencing.Results indicate IVM oocytes exhibit a higher global methylation level.Differentially methylated regions(DMRs)analysis reveals that the in vitro group displays more hypermethylated and fewer hypomethylated DMRs compared to the in vivo group.Additionally,the in vitro group exhibits a higher level of non-CpG methylation than the in vivo group.However,no significant correlation between methylation levels and transcriptional activity in these oocytes is found,especially for those specific imprinted genes or genes related to embryonic development.These findings shed light on the epigenetic landscape of IvM oocytes,contributing to the ongoing assessment of their clinical feasibility and safety in assisted reproduction.展开更多
Micro-sized anatase TiO_(2) displays inferior capacity as cathode material for magnesium ion batteries because of the higher diffusion energy barrier of Mg^(2+)in anatase TiO_(2) lattice.Herein,we report that nanosize...Micro-sized anatase TiO_(2) displays inferior capacity as cathode material for magnesium ion batteries because of the higher diffusion energy barrier of Mg^(2+)in anatase TiO_(2) lattice.Herein,we report that nanosized anatase TiO_(2) exposed(001)facet doubles the capacity compared to the micro-sized sample ascribed to the interfacial Mg^(2+)ion storage.First-principles calculations reveal that the diffusion energy barrier of Mg^(2+)on the(001)facet is significantly lower than those in the bulk phase and on(100)facet,and the adsorption energy of Mg^(2+)on the(001)facet is also considerably lower than that on(100)facet,which guarantees superior interfacial Mg^(2+)storage of(001)facet.Moreover,anatase TiO_(2) exposed(001)facet displays a significantly higher capacity of 312.9 mAh g^(−1) in Mg-Li dual-salt electrolyte compared to 234.3 mAh g^(−1) in Li salt electrolyte.The adsorption energies of Mg^(2+)on(001)facet are much lower than the adsorption energies of Li+on(001)facet,implying that the Mg^(2+)ion interfacial storage is more favorable.These results highlight that controlling the crystal facet of the nanocrystals effectively enhances the interfacial storage of multivalent ions.This work offers valuable guidance for the rational design of high-capacity storage systems.展开更多
Large-eddy simulation(LES)is conducted to study the statistical properties of mixed-phase turbulence induced by the breaking of bow waves in flow past a partially submerged plate.The simulation is performed using a fi...Large-eddy simulation(LES)is conducted to study the statistical properties of mixed-phase turbulence induced by the breaking of bow waves in flow past a partially submerged plate.The simulation is performed using a finite difference method,with the air-water interface captured by a coupled level-set and volume-of-fluid method.Four cases are conducted to investigate the effects of Froude number on turbulent statistics,including the mean velocity,turbulence kinetic energy,and turbulence mass flux(TMF),which is an additional unclosed term in the Reynolds-averaged momentum equation.The TMF,especially its vertical component,shows a complex behaviour with respect to the Froude number.This property of the TMF imposes high demands on the robustness of the closure model of TMF.The present LES data is further used to examine a closure model of the TMF production term,which shows a high correlation with the data obtained from LES.展开更多
OBJECTIVE： To assess the effects of using Chinese herbs in assisted reproductive technology. METHODS： Four hundred and thirty-three subjects aged less than 42 years with infertility due to Fallo- pian tube or male-r...OBJECTIVE： To assess the effects of using Chinese herbs in assisted reproductive technology. METHODS： Four hundred and thirty-three subjects aged less than 42 years with infertility due to Fallo- pian tube or male-related factors who were willing to undertake in vitro fertilization and embryo trans- plantation were randomly allocated to a Chinese herb intervention group （n=216） or a conventional treatment control group （n=217）. All subjects re- ceived one of four routine ultra-ovulation-promot- ing therapies at the Reproductive Center in the Third Hospital Affiliated to Beijing University ac- cording to their physician＇s assessments. The sub- jects in the intervention group received various Chi- nese herbs depending on their conventional treat- ment. Endometrial thickness, number of acquired eggs, and rates of normal fertility, high-quality em- bryos, biochemical and clinical pregnancy of sub- jects were assessed in both groups.RESULTS： The high-quality embryo rate of 51.9%, biochemical pregnancy rate of 51.0%, clinical preg- nancy rate of 44.2% and endometrial thickness of （10.84± 1.75） mm in the intervention group were all significantly higher than those in the control group [48.7%, 38.9%, 34.8%, and （10.52±1.50） mm, respec- tively; P〈O.05]. The normal fertility rate of 58.5% in the Chinese herb group was also significantly supe- rior to the 54.7% achieved in the control group （P〈 0.01）. There were no statistically significant differ- ences （P〉0.05） in the average number of acquired eggs within a single cycle, incidence of excessive stimulation of ovary, rates of embryo transplanta- tion or early abortion and birth of living babies be- tween the two groups. CONCLUSION： Our findings indicate that Chinese herbs increase endometrial thickness, improve the quality of fertility and embryo, and promote embry- onic nidation, thus enhancing the success rate of in vitro fertilization/intracytoplasmic sperm injec- tion-embryo transplantation cycle. Using Chinese herbs improves the outcomes and safety of assist- ed reproductive technologies.展开更多
Conventional PCR methods combined with linkage analysis based on short tandem repeats （STRs） or Karyomapping with single nucleotide polymorphism （SNP） arrays, have been applied to preimplantation genetic diagnosis...Conventional PCR methods combined with linkage analysis based on short tandem repeats （STRs） or Karyomapping with single nucleotide polymorphism （SNP） arrays, have been applied to preimplantation genetic diagnosis （PGD） for spinal muscular atrophy （SMA）, an autosome recessive disorder. However, it has limitations in SMA diagnosis by Karyomapping, and these methods are unable to distinguish wild- type embryos with carriers effectively. Mutated allele revealed by sequencing with aneuploidy and linkage analyses （MARSALA） is a new method allowing embryo selection by a one-step next-generation sequencing （NGS） procedure, which has been applied in PGD for both autosome dominant and X-linked diseases in our group previously. In this study, we carried out PGD based on MARSALA for two carrier families with SMA affected children. As a result, one of the couples has given birth to a healthy baby free of mutations in SMA-causing gene. It is the first time that MARSALA was applied to PGD for SMA, and we can distinguish the embryos with heterozygous deletion （carriers） from the wild-type （normal） ones accurately through this NGS-based method. In addition, direct mutation detection allows us to identify the affected embryos （homozygous deletion）, which can be regarded as probands for linkage analysis, in case that the affected family member is absent, In the future, the NGS-based MARSALA method is expected to be used in PGD for all monogenetic disorders with known pathogenic gene mutation.展开更多
The glymphatic system plays a pivotal role in maintaining cerebral homeostasis.Chronic cerebral hypoperfusion,arising from small vessel disease or carotid stenosis,results in cerebrometabolic disturbances ultimately m...The glymphatic system plays a pivotal role in maintaining cerebral homeostasis.Chronic cerebral hypoperfusion,arising from small vessel disease or carotid stenosis,results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction.However,whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown.Here,we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis.We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glym・phatic system function.The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization.Treatment of digoxin rescued changes in glymphatic transport,white matter structure,and cognitive function.Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury.Our research yields new insight into the relationship between hemodynamics,glymphatic transport,white matter injury,and cognitive changes after chronic cerebral hypoperfusion.展开更多
AIM: To compare apelin-13, a ligand of G-proteincoupled receptor which has been shown to be involved in retinal angiogenesis, and vascular endothelial growth factor(VEGF) serum levels in type 2 diabetes mellitus(T2DM)...AIM: To compare apelin-13, a ligand of G-proteincoupled receptor which has been shown to be involved in retinal angiogenesis, and vascular endothelial growth factor(VEGF) serum levels in type 2 diabetes mellitus(T2DM) with or without retinopathy, and to investigate the relationship between the serum concentration of apelin-13 and diabetes retinopathy.METHODS: Sixty-nine patients with T2 DM were enrolled.Of the 69 patients, 16 had proliferative diabetic retinopathy(PDR group), 23 had non-PDR(NPDR group)and 30 had no retinopathy(T2DM group). Subjects’ information, including demographics, medical history,and use of medications were recorded. Their serum samples were collected for measuring the levels of C-reactive protein(CRP), serum lipid and glycosylated hemoglobin. Apelin-13 and VEGF serum levels were measured by enzyme-linked immunosorbent assay.Kruskal-Wallis test and one-way ANOVA were used to compare the differences among these groups. Chi-square test was used to assess categorical variables.Correlations between variables were investigated by Spearman rho correlation test and stepwise regression analysis. All statistical analyses were performed through SPSS 17.0 software.RESULTS: Sex, age, body mass index(BMI), blood pressure, CRP, hemoglobin A1c(Hb A1c) have no significantly difference in the three groups. Serum level of apelin-13 was significantly elevated in PDR group as compared with T2 DM group(P =0.041). Differences of VEGF serum concentration in the three groups were statistically significant(P =0.007, P =0.007 and P 【0.001,respectively). Spearman rho correlation test showed that serum apelin-13 was positively correlated with BMI,serum triglycerides, VEGF, but not with age, duration of diabetes, blood pressure, CRP, Hb A1 c and total-cholesterol. Stepwise regression analysis showed that BMI also significantly associated with serum apelin-13(P =0.002), while VEGF and serum triglycerides were irrelevant. CONCLUSION: This study elucidated a positive association of apelin-13 serum level with PDR, but not with VEGF. Apelin-13 may influence the promotion of PDR but unrelated with VEGF.展开更多
AIM: To investigate the regulation of vascular endothelial growth factors(VEGF) and pigment epithelium-derived factor(PEDF) expression by autophagy in retinal pigment epithelium(RPE) cells on exposure to hypoxia. METH...AIM: To investigate the regulation of vascular endothelial growth factors(VEGF) and pigment epithelium-derived factor(PEDF) expression by autophagy in retinal pigment epithelium(RPE) cells on exposure to hypoxia. METHODS: ARPE-19, an RPE cell line, was treated as following: the control group was kept in a normoxic incubator; the hypoxia group was incubated in a hypoxic incubator with 1% O_2/5% CO_2/94% N_2 for 24 h; the hypoxia + 3-methyladenine(3-MA) group was pretreated with 10 mmol/L 3-MA for 1 h and then in the hypoxic incubator for 24 h; and the hypoxia + chloroquine(CQ) group was pretreated with 50 μmol/L CQ for 1 h and then in the hypoxic incubator for 24 h. The morphology and ultrastructure of the cells was observed by an inverted microscope or a transmission electronic microscope(TEM). Western blot was performed to assay the expression of autophagy-associated markers, including microtubule associated protein 1 light chain 3 B(LC3 B), Beclin-1, Atg5 and p62. The concentration of VEGF and PEDF in the culture supernatant was determined by ELISA, and the ratio of VEGF/PEDF was calculated. RESULTS: There were no obvious differences in cell morphology among different groups and autolysosomes could be observed in the cytoplasm in all groups. Compared to the control cells, the LC3 B-II/I ratio and levels of Beclin-1 and Atg5 were significantly increased and p62 level was significantly decreased in the hypoxia group. With the increase of VEGF and decrease of PEDF concentration, the VEGF/PEDF ratio was significantly increased in the hypoxia group compared to the control cells. The LC3 B-II/I ratio was significantly reduced by 3-MA treatment and increased by CQ treatment. The expressions of Beclin-1 and Atg5 were significantly reduced by 3-MA or CQ treatment, while expression of p62 was increased in the 3-MA or CQ treated cells. The concentration of VEGF was significantly decreased and PEDF increased, thereby the VEGF/PEDF ratio was decreased in the hypoxia + 3-MA group and hypoxia + CQ group compared with that in the hypoxia group. CONCLUSION: Hypoxia leads to elevated autophagy in RPE cells, and expression of VEGF and PEDF might be regulated by autophagy on exposure to hypoxia to further participate in regulating the formation of retinal neovascularization.展开更多
In this paper, a neural network based adaptive prescribed performance control scheme is proposed for the altitude and attitude tracking system of the unmanned helicopter in the presence of state and output constraints...In this paper, a neural network based adaptive prescribed performance control scheme is proposed for the altitude and attitude tracking system of the unmanned helicopter in the presence of state and output constraints. For handling the state constraints, the barrier Lyapunov function and the saturation function are employed. And, the prescribed performance method is used to deal with the flapping angle constraints for the unmanned helicopter. It is proved that the proposed control approach can ensure that all the signals of the resulting closed-loop system are bounded, and the tracking errors are within the prescribed performance bounds for all time. The numerical simulation is given to illustrate the performance of the proposed scheme.展开更多
基金National Natural Science Foundation of China(82171003 and 82171002)Research and Develop Program of West China Hospital of Stomatology Sichuan University(NO.LCYJ-2022-YY-1)。
文摘Circadian rhythm is ubiquitous in nature.Circadian clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network,and regulate a variety of physiological and pathological processes,including bone and cartilage metabolism.Deletion of the core clock gene Bmal1 leads to pathological bone alterations,while the phenotypes are not consistent.Studies have shown that multiple signaling pathways are involved in the process of Bmal1 regulating bone and cartilage metabolism,but the exact regulatory mechanisms remain unclear.This paper reviews the signaling pathways by which Bmal1 regulates bone/cartilage metabolism,the upstream regulatory factors that control Bmal1,and the current Bmal1 knockout mouse models for research.We hope to provide new insights for the prevention and treatment of bone/cartilage diseases related to circadian rhythms.
基金Supported by the Scientific Research Development Project of North Sichuan Medical College(No.CBY24-QDA01)Science and Technology Program of Shaanxi Province(No.2024SF-YBXM-324,No.2024SFYBXM-341).
文摘AIM:To investigate the protective role of ghrelin against diabetic retinopathy(DR),focusing on its anti-ferroptotic mechanism in high glucose-induced retinal endothelial injury.METHODS:First,small interfering RNA(siRNA)-mediated interference was conducted to knockdown nuclear factor erythroid 2-related factor 2(Nrf2).Using reverse transcription-polymerase chain reaction(RT-PCR),the expression level of Nrf2 was determined from human retinal microvascular endothelial cells(HRMECs)transfected with either si-NC or si-Nrf2.After that,cells were treated with 10 nmol/L ghrelin and then cultured in a high glucose(30 mmol/L)environment.EdU assay was utilized to assess cell proliferation,while transmission electron microscopy was employed to observe mitochondrial morphology.Flow cytometry was used to measure the level of intracellular reactive oxygen species(ROS),and biochemical assays were conducted to detect malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),and ferrous iron(Fe2+).Western blotting was used to identify the presence of ferroptosis-related proteins such as glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),Nrf2,and haem oxygenase-1(HO-1).RESULTS:Under a high glucose environment,ghrelin could significantly promote the proliferation of HRMECs and mitochondrial status,remarkably decrease the levels of intracellular ROS and MDA,and up-regulate the level of GSH and SOD.Besides,ghrelin greatly reduced Fe2+level in the cells while increased protein levels of GPX4 and SLC7A11.Subsequently,we found that high glucose induced inactivation of Nrf2/HO-1 axis and the protein expression profile were significantly promoted by ghrelin.Moreover,silencing of Nrf2 by siRNA delivery markedly diminished the changes induced by ghrelin in high glucose-induced HRMECs,shown as reduced cell proliferation and increased mitochondrial malformation,up-regulated ROS,MDA,Fe^(2+),GPX4 and SLC7A11,as well as down-regulated GSH,SOD,Nrf2 and HO-1.CONCLUSION:Ghrelin attenuates high glucose-induced injury of retinal endothelial cells via inhibiting ferroptosis,and activation of Nrf2/HO-1 pathway may be one of the mechanisms involved in this effect of ghrelin.
基金National Key Research and Development Program of China(2023YFB3810200 to J.L.)National Natural Science Foundation of China(92168204,82225030 to J.L.)Fundamental Research Funds for the Central Universities(22120210586 to J.L.)。
文摘Reproductive hormones associated with the hypothalamic-pituitary-gonadal(HPG)axis are closely linked to bone homeostasis.In this study,we demonstrate that Gonadotropin inhibitory hormone(GnIH,one of the key reproductive hormones upstream of the HPG axis)plays an indispensable role in regulating bone homeostasis and maintaining bone mass.We find that deficiency of GnIH or its receptor Gpr147 leads to a significant reduction in bone mineral density(BMD)in mice primarily by enhancement of osteoclast activation in vivo and in vitro.Mechanistically,GnIH/Gpr147 inhibits osteoclastogenesis by the PI3K/AKT,MAPK,NF-κB and Nfatc1 signaling pathways.Furthermore,GnIH treatment was able to alleviate bone loss in aging,ovariectomy(OVX)or LPS-induced mice.Moreover,the therapy using green light promotes the release of GnIH and rescues OVX-induced bone loss.In humans,serum GnIH increases and bone resorption markers decrease after green light exposure.Therefore,our study elucidates that GnIH plays an important role in maintaining bone homeostasis via modulating osteoclast differentiation and demonstrates the potential of GnIH therapy or green light therapy in preventing osteoporosis.
基金Supported by Science and Technology Project of Sichuan Provincial Health Commission(No.24WXXT13)North Sichuan Medical College Doctor Start-up Fund Project(No.CBY24-QDA01).
文摘Dear Editor,I diopathic macular telangiectasia(MacTel)type 1 is a retinal vascular disease characterized by abnormal dilation of macular capillaries,leading to metamorphopsia,progressive vision loss,and temporal scotoma enlargement.Currently,there is no standardized treatment protocol for MacTel type 1[1-2].Treatment outcomes can vary significantly among individuals,highlighting the ongoing need for further exploration of new and more effective treatment options.This paper presents a case of refractory macular edema associated with MacTel type 1,which showed a favorable response to pars plana vitrectomy(PPV)and internal limiting membrane(ILM)peeling.
基金supported by the National Natural Science Foundation of China(81972064)the Guangdong Basic and Applied Basic Research Foundation(2021A1515111117,2020A1515011415).
文摘Demyelination and remyelination play key roles in spinal cord injury(SCI),affecting the recovery of motor and sensory functions.Research in rodent models is extensive,but the study of these processes in non-human primates is limited.Therefore,our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis.In a previous study,we created an SCI model in M.fascicularis by controlling the contusion displacement.We used Eriochrome Cyanine staining,immunohistochemical analysis,and toluidine blue staining to evaluate demyelination and remyelination.The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally,the former mainly impacting sensory pathways,while the latter primarily affected motor pathways.Toluidine blue staining showed myelin loss and axonal distension at the injury site.Schwann cell-derived myelin sheaths were only found at the center,while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas.Our study showed that long-lasting demyelination occurs in the spinal cord of M.fascicularis after SCI,with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
基金funded by National Natural Science Foundation of China(NO.82370083).
文摘Background:Allergic eosinophilic asthma(EA)and eosinophilic granulomatosis with polyangiitis(EGPA)share significant overlaps in both epidemiology and pathogenesis,suggesting a potential link between the two con-ditions.Despite these associations,the underlying molecular and cellular mechanisms driving their connection remain poorly understood.Methods:We retrieved GSE143303 of EA and GSE144302 of EGPA from the GEO database and conducted dif-ferential expression analysis as well as functional enrichment analysis to identify differentially expressed genes(DEGs)and potential pathogenic pathways.A protein-protein interaction(PPI)network was generated using the STRING database.Key hub genes were determined through cytoHubba.We added two publicly reported EA and EGPA-related transcriptome datasets,GSE117038 and GSE119136,for mutual verification.Subsequent valida-tion was performed via immune infiltration assessment utilizing CIBERSORT.Results:In total,267 DEGs were identified,in which HSP90AA1,HSPA8,CCND1,RPS20,CD74,RPL5,RPS6,RHOA,RPS3A and FLT3LG are the top 10 hub genes,while the antigen processing and presentation pathway and leukocyte cell-cell adhesion pathway were the potential influential pathways.Increased naïve B cells and M1 type of Macrophages were detected in EA patients through immune infiltration analysis.Conclusions:Utilizing bioinformatics techniques,this study is the initial investigation to uncover the shared mechanisms involving the antigen processing and presentation pathway and leukocyte adhesion pathways in the progression of both EA and EGPA.It may offer potential biomarkers for future studies on the underlying path-ogenesis and treatment of EA and EGPA as well as eosinophilia related co-morbidities.
文摘Developing an efficient photocatalyst is the key to realize the practical application of photocatalysis.The S-scheme heterojunction has great potential in photocatalysis due to its unique charge-carrier migration pathway,effective light absorption and high redox capacity.However,further enhancing the built-in electric field of the S-scheme,accelerating carrier separation,and achieving higher photocatalytic performance remain unresolved challenges.Herein,based on the continuously adjustable band structure of continuous solid-solution,a novel 0D/2D all solid-solution S-scheme heterojunction with adjustable internal electric field was designed and fabricated by employing a solid-solution of ZnxCd_(1–x)S and Bi_(2)MoyW_(1–y)O_(6)respectively as reduction and oxidation semiconductors.The synergistic optimization of effective light absorption,fast photogenerated carrier separation,and high redox potential leads can be tuned to promote photocatalytic activity.Under visible light,the S-scheme system constructed by Zn_(0.4)Cd_(0.6)S quantum dot(QDs)and Bi_(2)Mo_(0.2)W_(0.8)O_(6)monolayer exhibits a high rate for photocatalytic degradation C_(2)H_(4)(150.6×10^(–3)min^(–1)),which is 16.5 times higher than that of pure Zn_(0.4)Cd_(0.6)S(9.1×10^(–3)min^(–1))and 53.8 times higher than pure Bi_(2)Mo_(0.2)W_(0.8)O_(6)(2.8×10^(–3)min^(–1)).Due to the unique charge-carrier migration pathway,photo-corrosion of Zn_(x)Cd_(1–x)S is further inhibited simultaneously.In-situ irradiation X-ray photoelectron spectroscopy,photoluminescence spectroscopy,time-resolved photoluminescence,transient absorption spectroscopy and electron paramagnetic resonance provide compelling evidence for interfacial charge transfer via S-scheme pathways,while in-situ diffuse reflectance infrared Fourier transform spectroscopy identifies the reaction pathway for C_(2)H_(4)degradation.This novel S-scheme photocatalysts demonstrates excellent performance and potential for the practical application of the fruits and vegetables preservation at room temperatures.
基金support from the National Natural Science Foundation of China under grant No.52302065the Yunnan Fundamental Research Projects under grant Nos.202201BE070001-008 and 202201AU070142the National Key Research and Development Program of China under grant No.2023YFB3711200.
文摘Low thermal conductivity and excellent mechanical strength are essential to pyrochlore A2B2O7 ceramic for environmental/thermal barrier coating applications.To collaboratively tailor the mechanical and thermal properties of A2B2O7 ceramic,a novel high entropy pyrochlore ceramic(La_(0.3)Gd_(0.3)Ca_(0.4))_(2)(Ti_(0.2)Zr_(0.2)Hf_(0.2)Nb_(0.2)Ta_(0.2))_(2)O_(7) with significant atomic radius and mass fluctuation is proposed by simultaneously introducing various elements with different valence states at A and B cation sites.The as-synthesized(La_(0.3)Gd_(0.3)Ca_(0.4))_(2)(Ti_(0.2)Zr_(0.2)Hf_(0.2)Nb_(0.2)Ta_(0.2))_(2)O_(7) exhibits enhanced fracture toughness(1.68 MPa m^(1/2)),amorphous-like low thermal conductivity(1.45 W m^(-1) K^(-1) at 900℃)and matched thermal expansion coefficient(9.0×10^(-6) K^(-1) at 1200℃)with Al_(2)O_(3)/Al_(2)O_(3) CMCs.The extensive misfits in atomic weight,ionic radius among the substitutional cations in combination with the intrinsic oxygen vacancies in the anion sublattice play significant roles in the thermal conductivity reduction of(La_(0.3)Gd_(0.3)Ca_(0.4))_(2)(Ti_(0.2)Zr_(0.2)Hf_(0.2)Nb_(0.2)Ta_(0.2))_(2)O_(7) ceramic.The combination of outstanding mechanical and thermal properties indicates that this type of material has a good application prospect for environmental/thermal barrier coatings.
文摘Anti-Mullerian hormone(AMH)is a functional marker of fetal Sertoli cells.The germ cell number in adults depends on the number of Sertoli cells produced duri ng peri natal development.Rece ntly,AMH has received increasi ng attenti on in research of disorders related to male fertility.This paper reviews and summarizes the articles on the regulation of AMH in males and the serum levels of AMH in male fertility-related disorders.We have determined that follicle-stimulating hormone(FSH)promotes AMH transcription in the absenee of androgen signaling.Testosterone inhibits the transcriptional activation of AMH.The undetectable levels of serum AMH and testosterone levels indicate a lack of functional testicular tissue,for example,that in patients with anorchia or severe Klinefelter syndrome suffering from impaired spermatogenesis.The normal serum testosterone level and undetectable AMH are highly suggestive of persistent Mullerian duct syndrome(PMDS),combined with clinical manifestations.The levels of both AMH and testosterone are always subnormal in patients with mixed disorders of sex development(DSD).Mixed DSD is an early-onset complete type of disorder with fetal hypogonadism resulting from the dysfunction of both Leydig and Sertoli cells.Serum AMH levels are varying in patients with male fertility-related disorders,in cludi ng pubertal delay,severe con genital hypog on adotropic hypogonadism,nonobstructive azoospermia,Klinefelter syndrome,varicocele,McCune-Albright syndrome,and male senescence.
基金supported by funding from the National Natural Science Foundation of China(81971349 and 81300456).
文摘In vitro maturation(IvM)of human oocytes offers cost efficiency and minimal invasiveness,serving as a valuable supplementary tool in assisted reproduction for fertility preservation,ovarian hyperstimulation syndrome prevention,and other reproductive strategies.Despite its availability for three decades,the clinical use of IVM remains limited due to efficacy and safety concerns.This study examines the DNA methylation profile of IVM oocytes collected during laparoscopic/hysteroscopic surgeries compared to in vivo matured oocytes via reduced representation bisulfite sequencing.Results indicate IVM oocytes exhibit a higher global methylation level.Differentially methylated regions(DMRs)analysis reveals that the in vitro group displays more hypermethylated and fewer hypomethylated DMRs compared to the in vivo group.Additionally,the in vitro group exhibits a higher level of non-CpG methylation than the in vivo group.However,no significant correlation between methylation levels and transcriptional activity in these oocytes is found,especially for those specific imprinted genes or genes related to embryonic development.These findings shed light on the epigenetic landscape of IvM oocytes,contributing to the ongoing assessment of their clinical feasibility and safety in assisted reproduction.
基金supported by the National Key R&D Program of China(No.2023YFB3809500)the Fundamental Research Funds for the Central Universities(No.2024CDJXY003)+1 种基金the Venture&Innovation Support Program for Chongqing Overseas Returnees(cx2023087)The Chongqing Technology Innovation and Application Development Project(No.2024TIAD-KPX0003).
文摘Micro-sized anatase TiO_(2) displays inferior capacity as cathode material for magnesium ion batteries because of the higher diffusion energy barrier of Mg^(2+)in anatase TiO_(2) lattice.Herein,we report that nanosized anatase TiO_(2) exposed(001)facet doubles the capacity compared to the micro-sized sample ascribed to the interfacial Mg^(2+)ion storage.First-principles calculations reveal that the diffusion energy barrier of Mg^(2+)on the(001)facet is significantly lower than those in the bulk phase and on(100)facet,and the adsorption energy of Mg^(2+)on the(001)facet is also considerably lower than that on(100)facet,which guarantees superior interfacial Mg^(2+)storage of(001)facet.Moreover,anatase TiO_(2) exposed(001)facet displays a significantly higher capacity of 312.9 mAh g^(−1) in Mg-Li dual-salt electrolyte compared to 234.3 mAh g^(−1) in Li salt electrolyte.The adsorption energies of Mg^(2+)on(001)facet are much lower than the adsorption energies of Li+on(001)facet,implying that the Mg^(2+)ion interfacial storage is more favorable.These results highlight that controlling the crystal facet of the nanocrystals effectively enhances the interfacial storage of multivalent ions.This work offers valuable guidance for the rational design of high-capacity storage systems.
基金supported by the National Natural Science Foundation of China(NSFC)Basic Science Center Program for‘Multiscale Problems in Nonlinear Mechanics’(Grant No.11988102)NSFC project(Grant No.11972038)Chinese Academy of Sciences Project for Young Scientists in Basic Research(Grant No.YSBR-087).
文摘Large-eddy simulation(LES)is conducted to study the statistical properties of mixed-phase turbulence induced by the breaking of bow waves in flow past a partially submerged plate.The simulation is performed using a finite difference method,with the air-water interface captured by a coupled level-set and volume-of-fluid method.Four cases are conducted to investigate the effects of Froude number on turbulent statistics,including the mean velocity,turbulence kinetic energy,and turbulence mass flux(TMF),which is an additional unclosed term in the Reynolds-averaged momentum equation.The TMF,especially its vertical component,shows a complex behaviour with respect to the Froude number.This property of the TMF imposes high demands on the robustness of the closure model of TMF.The present LES data is further used to examine a closure model of the TMF production term,which shows a high correlation with the data obtained from LES.
基金Supported by the Capital Fund for Development of Medical Scienceand Technology(No.SF-2009-III-33)
文摘OBJECTIVE： To assess the effects of using Chinese herbs in assisted reproductive technology. METHODS： Four hundred and thirty-three subjects aged less than 42 years with infertility due to Fallo- pian tube or male-related factors who were willing to undertake in vitro fertilization and embryo trans- plantation were randomly allocated to a Chinese herb intervention group （n=216） or a conventional treatment control group （n=217）. All subjects re- ceived one of four routine ultra-ovulation-promot- ing therapies at the Reproductive Center in the Third Hospital Affiliated to Beijing University ac- cording to their physician＇s assessments. The sub- jects in the intervention group received various Chi- nese herbs depending on their conventional treat- ment. Endometrial thickness, number of acquired eggs, and rates of normal fertility, high-quality em- bryos, biochemical and clinical pregnancy of sub- jects were assessed in both groups.RESULTS： The high-quality embryo rate of 51.9%, biochemical pregnancy rate of 51.0%, clinical preg- nancy rate of 44.2% and endometrial thickness of （10.84± 1.75） mm in the intervention group were all significantly higher than those in the control group [48.7%, 38.9%, 34.8%, and （10.52±1.50） mm, respec- tively; P〈O.05]. The normal fertility rate of 58.5% in the Chinese herb group was also significantly supe- rior to the 54.7% achieved in the control group （P〈 0.01）. There were no statistically significant differ- ences （P〉0.05） in the average number of acquired eggs within a single cycle, incidence of excessive stimulation of ovary, rates of embryo transplanta- tion or early abortion and birth of living babies be- tween the two groups. CONCLUSION： Our findings indicate that Chinese herbs increase endometrial thickness, improve the quality of fertility and embryo, and promote embry- onic nidation, thus enhancing the success rate of in vitro fertilization/intracytoplasmic sperm injec- tion-embryo transplantation cycle. Using Chinese herbs improves the outcomes and safety of assist- ed reproductive technologies.
基金supported by the National Natural Science Foundation of China (Nos. 31522034, 31571544 and 31230047)the National High Technology Research and Development Program (No. 2015AA020407)+1 种基金Beijing Municipal Science and Technology Commission (No. D151100002415004)Research Fund of National Health and Family Planning Commission of China (No. 201402004)
文摘Conventional PCR methods combined with linkage analysis based on short tandem repeats （STRs） or Karyomapping with single nucleotide polymorphism （SNP） arrays, have been applied to preimplantation genetic diagnosis （PGD） for spinal muscular atrophy （SMA）, an autosome recessive disorder. However, it has limitations in SMA diagnosis by Karyomapping, and these methods are unable to distinguish wild- type embryos with carriers effectively. Mutated allele revealed by sequencing with aneuploidy and linkage analyses （MARSALA） is a new method allowing embryo selection by a one-step next-generation sequencing （NGS） procedure, which has been applied in PGD for both autosome dominant and X-linked diseases in our group previously. In this study, we carried out PGD based on MARSALA for two carrier families with SMA affected children. As a result, one of the couples has given birth to a healthy baby free of mutations in SMA-causing gene. It is the first time that MARSALA was applied to PGD for SMA, and we can distinguish the embryos with heterozygous deletion （carriers） from the wild-type （normal） ones accurately through this NGS-based method. In addition, direct mutation detection allows us to identify the affected embryos （homozygous deletion）, which can be regarded as probands for linkage analysis, in case that the affected family member is absent, In the future, the NGS-based MARSALA method is expected to be used in PGD for all monogenetic disorders with known pathogenic gene mutation.
基金supported by Grants from the National Natural Science Foundation of China(81873749 and 81801072)。
文摘The glymphatic system plays a pivotal role in maintaining cerebral homeostasis.Chronic cerebral hypoperfusion,arising from small vessel disease or carotid stenosis,results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction.However,whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown.Here,we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis.We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glym・phatic system function.The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization.Treatment of digoxin rescued changes in glymphatic transport,white matter structure,and cognitive function.Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury.Our research yields new insight into the relationship between hemodynamics,glymphatic transport,white matter injury,and cognitive changes after chronic cerebral hypoperfusion.
基金Supported by National Natural Science Foundation of China (No.30971392 No.81170741)Science Foundation of Xi'an Bureau of Public Health (No.2013020)
文摘AIM: To compare apelin-13, a ligand of G-proteincoupled receptor which has been shown to be involved in retinal angiogenesis, and vascular endothelial growth factor(VEGF) serum levels in type 2 diabetes mellitus(T2DM) with or without retinopathy, and to investigate the relationship between the serum concentration of apelin-13 and diabetes retinopathy.METHODS: Sixty-nine patients with T2 DM were enrolled.Of the 69 patients, 16 had proliferative diabetic retinopathy(PDR group), 23 had non-PDR(NPDR group)and 30 had no retinopathy(T2DM group). Subjects’ information, including demographics, medical history,and use of medications were recorded. Their serum samples were collected for measuring the levels of C-reactive protein(CRP), serum lipid and glycosylated hemoglobin. Apelin-13 and VEGF serum levels were measured by enzyme-linked immunosorbent assay.Kruskal-Wallis test and one-way ANOVA were used to compare the differences among these groups. Chi-square test was used to assess categorical variables.Correlations between variables were investigated by Spearman rho correlation test and stepwise regression analysis. All statistical analyses were performed through SPSS 17.0 software.RESULTS: Sex, age, body mass index(BMI), blood pressure, CRP, hemoglobin A1c(Hb A1c) have no significantly difference in the three groups. Serum level of apelin-13 was significantly elevated in PDR group as compared with T2 DM group(P =0.041). Differences of VEGF serum concentration in the three groups were statistically significant(P =0.007, P =0.007 and P 【0.001,respectively). Spearman rho correlation test showed that serum apelin-13 was positively correlated with BMI,serum triglycerides, VEGF, but not with age, duration of diabetes, blood pressure, CRP, Hb A1 c and total-cholesterol. Stepwise regression analysis showed that BMI also significantly associated with serum apelin-13(P =0.002), while VEGF and serum triglycerides were irrelevant. CONCLUSION: This study elucidated a positive association of apelin-13 serum level with PDR, but not with VEGF. Apelin-13 may influence the promotion of PDR but unrelated with VEGF.
基金Supported by the National Natural Science Foundation of China(No.81500726)the Medical Research Project of Xi’an Science Technology Bureau [No.201805097YX5SF31(4)]+1 种基金the Health Research Foundation of Shaanxi Province(No.2018D074)the Outstanding Youth Talent Support Plan of Shaanxi Ordinary University
文摘AIM: To investigate the regulation of vascular endothelial growth factors(VEGF) and pigment epithelium-derived factor(PEDF) expression by autophagy in retinal pigment epithelium(RPE) cells on exposure to hypoxia. METHODS: ARPE-19, an RPE cell line, was treated as following: the control group was kept in a normoxic incubator; the hypoxia group was incubated in a hypoxic incubator with 1% O_2/5% CO_2/94% N_2 for 24 h; the hypoxia + 3-methyladenine(3-MA) group was pretreated with 10 mmol/L 3-MA for 1 h and then in the hypoxic incubator for 24 h; and the hypoxia + chloroquine(CQ) group was pretreated with 50 μmol/L CQ for 1 h and then in the hypoxic incubator for 24 h. The morphology and ultrastructure of the cells was observed by an inverted microscope or a transmission electronic microscope(TEM). Western blot was performed to assay the expression of autophagy-associated markers, including microtubule associated protein 1 light chain 3 B(LC3 B), Beclin-1, Atg5 and p62. The concentration of VEGF and PEDF in the culture supernatant was determined by ELISA, and the ratio of VEGF/PEDF was calculated. RESULTS: There were no obvious differences in cell morphology among different groups and autolysosomes could be observed in the cytoplasm in all groups. Compared to the control cells, the LC3 B-II/I ratio and levels of Beclin-1 and Atg5 were significantly increased and p62 level was significantly decreased in the hypoxia group. With the increase of VEGF and decrease of PEDF concentration, the VEGF/PEDF ratio was significantly increased in the hypoxia group compared to the control cells. The LC3 B-II/I ratio was significantly reduced by 3-MA treatment and increased by CQ treatment. The expressions of Beclin-1 and Atg5 were significantly reduced by 3-MA or CQ treatment, while expression of p62 was increased in the 3-MA or CQ treated cells. The concentration of VEGF was significantly decreased and PEDF increased, thereby the VEGF/PEDF ratio was decreased in the hypoxia + 3-MA group and hypoxia + CQ group compared with that in the hypoxia group. CONCLUSION: Hypoxia leads to elevated autophagy in RPE cells, and expression of VEGF and PEDF might be regulated by autophagy on exposure to hypoxia to further participate in regulating the formation of retinal neovascularization.
基金supported by the National Natural Science Foundation of China (Nos. 61573184, 61751210)Aeronautical Science Foundation of China (No. 20165752049)the Fundamental Research Funds for the Central Universities of China (No. NE2016101)
文摘In this paper, a neural network based adaptive prescribed performance control scheme is proposed for the altitude and attitude tracking system of the unmanned helicopter in the presence of state and output constraints. For handling the state constraints, the barrier Lyapunov function and the saturation function are employed. And, the prescribed performance method is used to deal with the flapping angle constraints for the unmanned helicopter. It is proved that the proposed control approach can ensure that all the signals of the resulting closed-loop system are bounded, and the tracking errors are within the prescribed performance bounds for all time. The numerical simulation is given to illustrate the performance of the proposed scheme.
