Ophthalmology is a subject that highly depends on imaging examination.Artificial intelligence(AI)technology has great potential in medical imaging analysis,including image diagnosis,classification,grading,guiding trea...Ophthalmology is a subject that highly depends on imaging examination.Artificial intelligence(AI)technology has great potential in medical imaging analysis,including image diagnosis,classification,grading,guiding treatment and evaluating prognosis.The combination of the two can realize mass screening of grass-roots eye health,making it possible to seek medical treatment in the mode of“first treatment at the grass-roots level,two-way referral,emergency and slow treatment,and linkage between the upper and lower levels”.On the basis of summarizing the AI technology carried out by scholars and their teams all over the world in the field of ophthalmology,quite a lot of studies have confirmed that machine learning can assist in diagnosis,grading,providing optimal treatment plans and evaluating prognosis in corneal and conjunctival diseases,ametropia,lens diseases,glaucoma,iris diseases,etc.This paper systematically shows the application and progress of AI technology in common anterior segment ocular diseases,the current limitations,and prospects for the future.展开更多
AIM:To compare the postoperative efficacy,safety,predictability,and visual quality of implantable collamer lens(ICL)implantation versus small incision lenticule extraction(SMILE)in myopia eyes.METHODS:Pub Med,EMBASE,W...AIM:To compare the postoperative efficacy,safety,predictability,and visual quality of implantable collamer lens(ICL)implantation versus small incision lenticule extraction(SMILE)in myopia eyes.METHODS:Pub Med,EMBASE,Web of Science,Cochrane Library and several Chinese databases were searched at May 2021 to select relevant studies in comparison of clinical outcomes between ICL implantation and SMILE for myopia.The primary outcomes were efficacy,safety,and predictability.And the secondary outcomes were postoperative higher-order ocular aberrations(HOAs),modulation transfer function cutoff frequency(MTF),objective scatter index(OSI),contrast sensitivity and a quality of vision(Qo V)questionnaire.RESULTS:A total of 1036 eyes from 10 studies,of which 503 eyes underwent ICL implantation and 533 eyes underwent SMILE,were enrolled in this Meta-analysis.Pooled results revealed that ICL group had a better safety index and post-corrected distance visual acuity(CDVA)(P=0.007,<0.00001,respectively),and a lower percentage of eyes with a postoperative CDVA lost 1 line(P=0.007)than the SMILE group.No significant differences were found in comparison of the other primary outcomes.In the longterm follow-up(>6mo),ICL group had a lower total HOA,coma,and spherical aberration than SMILE group(P=0.003,<0.00001,0.04).Yet higher trefoil was found in ICL group at 6mo after surgery(P=0.003).Additionally,ICL group also had a higher MTF value(P=0.02),and a higher contrast sensitivity score for spatial frequencies of 1.5,6,and 12 cpds(P=0.02,0.005,0.02,respectively).And it also had a lower score of bothersome in Qo V questionnaire than SMILE group(P=0.003).CONCLUSION:ICL implantation and SMILE have similar and comparable outcomes in term of the efficacy and predictability for correcting high myopia.However,ICL group is relatively safer and also has better visual quality in comparison of SMILE group.展开更多
Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Curre...Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.展开更多
AIM:To explore the effect of silent information regulator factor 2-related enzyme 1(SIRT1)on modulating apoptosis of human lens epithelial cells(HLECs)and alleviating lens opacification of rats through suppressing end...AIM:To explore the effect of silent information regulator factor 2-related enzyme 1(SIRT1)on modulating apoptosis of human lens epithelial cells(HLECs)and alleviating lens opacification of rats through suppressing endoplasmic reticulum(ER)stress.METHODS:HLECs(SRA01/04)were treated with varying concentrations of tunicamycin(TM)for 24h,and the expression of SIRT1 and C/EBP homologous protein(CHOP)was assessed using real-time quantitative polymerase chain reaction(RT-PCR),Western blotting,and immunofluorescence.Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8(CCK-8)assay,respectively.In the SRA01/04 cell apoptosis model,which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation,the expression levels of SIRT1,CHOP,glucose regulated protein 78(GRP78),and activating transcription factor 4(ATF4)were examined.The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid(4-PBA;an ER stress inhibitor)was investigated.In vivo,age-related cataract(ARC)rat models were induced by sodium selenite injection,and the protective role of SIRT1,activated by SRT1720 intraperitoneal injections,was evaluated through morphology observation,hematoxylin and eosin(H&E)staining,Western blotting,and RT-PCR.RESULTS:SIRT1 expression was downregulated in TMinduced SRA01/04 cells.Besides,in SRA01/04 cells,both cell apoptosis and CHOP expression increased with the rising doses of TM.ER stress was stimulated by TM,as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model.Inhibition of SIRT1 by siRNA knockdown increased ER stress activation,whereas SRT1720 treatment had opposite results.4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis.In vivo,SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models.CONCLUSION:SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress.These findings suggest a novel strategy for cataract treatment focused on targeting ER stress,highlighting the therapeutic potential of SIRT1 modulation in ARC development.展开更多
Purpose: The surgical risk and complication rate after cataract surgery are extremely high in patients with nanophthalmos.This study is designed to compare the visual and refractive outcomes before and after coaxial m...Purpose: The surgical risk and complication rate after cataract surgery are extremely high in patients with nanophthalmos.This study is designed to compare the visual and refractive outcomes before and after coaxial micro-incision phacoemulsification and evaluate postoperative complications.Methods:.Fifty nine patients(89 eyes) with axial length(AL)< 21 mm diagnosed with nanophthalmos were enrolled in this retrospective study. All patients underwent coaxial micro-incision phacoemulsification and IOL implantation..The main outcome measures included anterior chamber depth(ACD),anterior chamber volume(ACV), anterior chamber angle(A CA), intraocular pressure(IOP) and best corrected visual acuity(BCVA). Wilcoxon signed rank test or Mann-Whitney test,and Chi-square test and logistic regression analysis were performed for statistical tests as appropriate.Results:.The median AL was 19.63 mm...Sixty-six eyes(74.16%) had a history of surgical intervention. Postoperative ACD, ACV and ACA were increased significantly(all P<0.001),whereas postoperative IOP was decreased significantly.(P <0.001) after surgery. Previous surgical intervention was related to a reduction in the postoperative ACD and ACA(P<0.01),and both preoperative and postoperative IOP.(P <0.001).Postoperative BCVA was improved in 94.38% of the cases.Intraoperative complications mainly included iridoschisis(6eyes, 6.74%). Early postoperative complications included temporary corneal edema(TCE)(23 eyes, 25.84%), anterior inflammatory response(AIR)(19 eyes, 21.35%), cystoid macular edema(CME)(14 eyes, 15.73%), and uveal effusion(4 eyes, 4.49%). Late postoperative complications included CME(8 eyes, 8.99%), uveal effusion(8 eyes, 8.99%),malignant glaucoma(2 eyes, 2.25%) and posterior capsular opacification(PCO)(10 eyes, 11.24%). The majority of complications(80%) were successfully resolved by pharmacotherapy or operation. The risk of surgical complications was greater in patients with lower AL,ACD,ACV or ACA andhigher nuclear hardness or mean keratometry(Km).Conclusion: With reasonable preoperative management, prudent selection of the lens,.rigorous surgical technique and unerring cognition of potential complications, coaxial microincision phacoemulsification lens surgery can be performed in patients with nanophthalmos and yield favorable outcomes and a low incidence of complications.展开更多
Implementing autonomous bus services in several cities has garnered substantial research attention worldwide.However,the benefits and challenges of this emerging mode remain insufficiently understood.Consequently,VOSv...Implementing autonomous bus services in several cities has garnered substantial research attention worldwide.However,the benefits and challenges of this emerging mode remain insufficiently understood.Consequently,VOSviewer was employed for a bibliometric analysis involving 300 publications,investigating the associations among authors,journals,and keywords.Subsequently,we comprehensively reviewed the current state of research on two topics and proposed future recommendations.Results indicate that the first document related to autonomous bus services was published in 2009.Most user attitude-related research data are obtained via questionnaires and analyzed using statistical techniques.Autonomous bus services are expected to benefit passengers regarding travel time,cost,safety,etc.,while passenger preferences are inconsistent.However,integrating the service into existing bus systems requires careful consideration of the schedule sequences.Notably,modular autonomous bus services present a new opportunity for the further optimization of bus services.In future studies,standardized data acquisition procedures should be developed to achieve comparable results.Regarding traveler choice behavior,the effect of specific autonomous bus service policies over time and the heterogeneity due to cultural or social contexts across regions should be assessed.To further promote autonomous bus services,based on fluctuating travel demands,the effects of vehicle capacity,speed,and cost of fleet composition should be evaluated comprehensively to optimize the bus network and schedule sequence.Owing to the protracted nature of the transition from conventional to fully autonomous buses,one should prioritize semi-autonomous bus services.Another essential future research direction is to integrate modular autonomous bus assembly or disassembly strategies with different fine-grained operation optimization techniques in various scenarios.展开更多
Two novel compounds including a cyclohelminthol type polyketide(namely oxaleimide K,1)and a maleimide deriva-tive(namely peniroquefortine A,2),and a new natural product(namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-...Two novel compounds including a cyclohelminthol type polyketide(namely oxaleimide K,1)and a maleimide deriva-tive(namely peniroquefortine A,2),and a new natural product(namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-acetamide,3),together with four known compounds(4-7),were isolated and identified from fungus Penicillium roqueforti,which was separated from the root soil of Hypericum beanii N.Robson collected from the Shennongjia For-estry District,Hubei Province.Their structures including absolute configurations were mainly established by the NMR spectroscopy analyses and single-crystal X-ray diffraction experiment.Compound 1 represents the second example of a cyclohelminthol type polyketide,which features a rare 6/6/5/5 tetracyclic system and a branched aliphatic chain containing a terminal olefin(oct-1-en-3-yl)moiety,and compound 2 possesses an unprecedented carbon skeleton that is uniquely defined by a maleimide moiety linked to the respective 4-methylene-2-(3-methylbut-2-en-1-yl)-phenol and para-substituted aromatic moieties via the carbon-carbon bonds.Remarkably,the absolute configuration of a cyclohelminthol type polyketide as exemplified by compound 1 is determined by the single-crystal diffraction analysis for the first time,highlighting an E-configuration for the linkage of a succinimide moiety and a tetrahydro-furan moiety for 1 rather than a Z-configuration as previously reported in the biosynthesis study,which gives a new insight into the structural elucidation of this category of polyketides.Additionally,compound 1 exhibited significant cytotoxic activity against multiple tumor cells,especially against the Farage and SU-DHL-2 cells(IC_(50)<20μM,48 h).Further mechanism study revealed that compound 1 significantly induced cell cycle arrest in Farage and SU-DHL-2 cells by causing abnormal ROS level and triggering oxidative stress.展开更多
AIM:To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell(hiPSC)-derived retinal organoids(ROs).METHODS:The hiPSC and a three-dimensional culture method were use...AIM:To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell(hiPSC)-derived retinal organoids(ROs).METHODS:The hiPSC and a three-dimensional culture method were used for the experiments.Generated embryoid bodies(EBs)were randomly and equally divided into hypoxic and normoxic groups.Photographs of the EBs were taken on days 38,45,and 52,and the corresponding volume of EBs was calculated.Simultaneously,samples were collected at these three timepoints,followed by fixation,sectioning,and immunofluorescence.RESULTS:The proportion of Ki67-positive proliferating cells increased steadily on day 38;this proliferationpromoting effect tended to increase tissue density rather than tissue volume.On days 45 and 52,the two groups had relatively similar ratios of Ki67-positive cells.Further immunofluorescence analysis showed that the ratio of SOX2-positive cells significantly increased within the neural retina on day 52(P<0.05).In contrast,the percentage of PAX6-and CHX10-positive cells significantly decreased following hypoxia treatment at all three timepoints(P<0.01),except for CHX10 at day 45(P>0.05).Moreover,the proportion of PAX6-/TUJ1+cells within the neural retinas increased considerably(P<0.01,<0.05,<0.05 respectively).CONCLUSION:Low oxygen promotes stemness and proliferation of neural retinas,suggesting that hypoxic conditions can enlarge the retinal progenitor cell pool in hiPSC-derived ROs.展开更多
AIM: To identify the effect and regulatory mechanism of amyloid β (Aβ) protein on retinal pigment epithelial (RPE) cells in cell proliferation and apoptosis, and clarify Aβ role in the pathogenesis of age-rela...AIM: To identify the effect and regulatory mechanism of amyloid β (Aβ) protein on retinal pigment epithelial (RPE) cells in cell proliferation and apoptosis, and clarify Aβ role in the pathogenesis of age-related macular degeneration (AMD). METHODS: The model of Aβ25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of Aβ protein on RPE cells in vitro. Based on Aβ protein, the specific inhibitors (HY-50682 or BAY11-7082) or activating agent (lipopolysaccharide) was used to analyze the regulatory mechanism of Aβ protein to RPE cells on cell proliferation and apoptosis by flow cytometry, real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and dual-luciferase reporter gene assay. RESULTS: The number of RPE cells, treated with Aβ25-35 from 0.3 to 60 μmol/L, significantly reduce (P〈0.01), and had the dose-dependent effect. Aβ protein 60 μmol/L inhibits the G1/S phase transition (P〈0.01) and down-regulated cyclin E mRNA level (P〈0.01). Similarly, Aβ25-35 induced a significant increase of cell apoptosis, accompanied by the significantly higher level of activated caspase 3 protein. Furthermore, nuclear factor-kappaB (NF-κB) activity and hosphorylated Iκ-Ba level would significantly lower in treated RPE cells. Using specific inhibitors or activating agent based on the Aβ, the cell numbers, NF-κB activity, phosphorylated Iκ-Ba level, receptor for advanced glycation endproducts (RAGE) gene expression levels, cyclin E mRNA level and activated caspase 3 level had accordingly changed by different methods, confirming that RAGE/NF-κB signaling pathway involved in the regulation of Aβ protein on RPE cell apoptosis and proliferation. CONCLUSION: Aβ protein inhibits cell proliferation and activates apoptosis via inactivation of the RAGE/NF-κB signaling pathway in RPE cell.展开更多
Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development.The advantageous effects of covalent compounds compared with non...Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development.The advantageous effects of covalent compounds compared with non-covalent ones are highly dependent on electrophilic warheads.Hence,electrophilic warheads with tunable reactivity and selectivity are highly demanded in fields of medicinal chemistry and chemical biology.Herein,we report a novel electrophilic warhead,chloromethyl group activated by thiol-substituted 1,2,4-triazole.Interestingly,a pair of regioisomers could be simultaneously occurred in the step of alkylation during the synthesis of this unique motif.This is a rare example that the alkylation could simultaneously generate these two separable regioisomers of 1,2,4-triazole at the nitrogen or sulfur atom.The covalent-working mechanism of this new warhead is confirmed by various chemoproteomics experiments including target identification and binding site mapping.Importantly,the reactivity and selectivity of this new electrophilic warhead could be efficiently tuned by virtue of stereo effect.Interestingly,one pair of regioisomers(19S and 19X)induced distinct modes of cell death.Isomer 19S could induce apoptosis of colon cancer cells while 19X could induce both apoptosis and ferroptosis.Together,this study provides pairs of novel electrophilic warheads that could be useful not only in supporting the design of covalent compounds for drug discovery but also in providing chemical probes for the fundamental biological study.展开更多
The short-term impacts of urban air pollution on the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) remain obscure.In this study,we included 3487 urban adults from the Wuhan-Zhuhai cohort.Indivi...The short-term impacts of urban air pollution on the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) remain obscure.In this study,we included 3487 urban adults from the Wuhan-Zhuhai cohort.Individual inhalation exposure to air pollutants was estimated by combining participants’daily breath volume and ambient concentrations of six air pollutants (includingfine particulate matter (PM_(2.5)),inhalable particulate matter(PM_(10)),nitrogen dioxide (NO_(2)),sulfur dioxide (SO_(2)),carbon monoxide (CO) and ozone (O_(3))).The cumulative impacts were assessed by applying lag structures of up to 7 days before the survey date.Associations of air pollutants with PLR and NLR were assessed using a linear mixed model and Bayesian kernel machine regression (BKMR) model.We found that PLR was negatively related to PM_(2.5)(lag02-lag06),PM_(10)(lag02-lag07),NO_(2)(lag02-lag07),and SO_(2)(lag03-lag05) and NLR was negatively related to PM_(10)(lag05 and lag07).In the BKMR model,a negative joint association between the six-air-pollutant mixture and PLR and NLR was observed,whereas PM_(10)and NO_(2)appeared to be more important than the other pollutants in the mixture.The negative impact of air pollutants was stronger in males,participants with lower body mass index (<24 kg/m^(2)),those cooking meals at home,drinkers,and nonexercisers.In conclusion,short-term exposure to air pollutants is significantly related to PLR and NLR in peripheral blood.PLR and NLR may provide new insight into the molecular mechanism underlying the adverse health impact of air pollutants.展开更多
To the Editor:High-frequency resistance(typically≥15-25%viral quasispecies)detected by conventional resistance assays has long been associated with failure of antiretroviral therapy(ART)to suppress viral replication,...To the Editor:High-frequency resistance(typically≥15-25%viral quasispecies)detected by conventional resistance assays has long been associated with failure of antiretroviral therapy(ART)to suppress viral replication,[1]but the impact of pre-existing lowfrequency resistance on virological response is controversial.Previous studies have shown an increased likelihood of virological response failure in patients with preexisting low-frequency resistance mutations after initiation of antiviral therapy,especially primary ART regimens containing non-nucleoside reverse transcriptase inhibitors(NNRTIs).[2]However,some studies have concluded differently,suggesting that pre-existing lowfrequency resistance mutations do not correlate with viral response failure.[3]This may be related to the method of detection of pre-existing low-frequency resistance mutations.展开更多
Background:Due to media opacity,it is usually difficult to accurately evaluate the postoperative visual acuity in cataracts patients.As a small and portable tool,the critical flicker fusion frequency(CFF)device reflec...Background:Due to media opacity,it is usually difficult to accurately evaluate the postoperative visual acuity in cataracts patients.As a small and portable tool,the critical flicker fusion frequency(CFF)device reflects the temporal resolution of visual function and has been widely used in clinical research.However,poor understanding of the technique and equipment limitations have restricted its clinical application in China.Main text:There was a decrease in the CFF value in various ophthalmic diseases,indicating that the CFF is sensitive to detect visual functional changes.A number of studies have shown that the CFF test can accurately distinguish patients with simple cataracts from those with cataracts combined with fundus disease,and,as a visual test,it can more accurately predict postoperative visual acuity without being affected by media opacity.This study comprehensive reviews the basic principles of CFF and its application in ophthalmology,especially in cataracts.Conclusions:As one of the tools for dynamic visual function detection,the CFF test could help doctors to assess the possible presence of fundus disease in cataracts patients,especially in eyes with dense cataracts,and more precisely provide a reasonable visual prognosis than other available visual tests.展开更多
AIM:To observe the changes in corneal subepithelial nerve fibers(CNFs)and Langerhans cells(LCs)in patients with type 2 diabetes using corneal laser confocal microscopy(CLCM).METHODS:A total of 60 patients(64 eyes),inc...AIM:To observe the changes in corneal subepithelial nerve fibers(CNFs)and Langerhans cells(LCs)in patients with type 2 diabetes using corneal laser confocal microscopy(CLCM).METHODS:A total of 60 patients(64 eyes),including 40 patients with type 2 diabetes(DM group)and 20 subjects without diabetes(control group)were included with CLCM.Neuron J plugin of Image J software were used for quantitative analysis of CNF length(CNFL),CNF density(CNFD),corneal nerve branch fiber density(CNBD),main branch length density,branch length density,corneal nerve fiber tortuosity(NT)score,and LCs density.An independent samples t-test to analyze the variability between the two groups was performed,and Pearson correlation analysis was used to analyze the relationships between CNF and multiple biochemical indicators in the DM group.The predictive power of CNF for type 2 diabetes was assessed using the receiver operating characteristic(ROC)curve.RESULTS:There were significant differences in the CNFL,CNFD,and main branch length density between two groups.The results of Pearson correlation analysis showed a significant negative correlation between CNFD and the duration of diabetes as well as triglyceride levels and total cholesterol,and a significant positive correlation between CNFD and serum albumin.In addition,the NT score showed a positive correlation and urea nitrogen,similar to the positive correlation observed between LC density and glycosylated hemoglobin(HbA1c)levels.CNFD showed the highest area under the curve(AUC of ROC)value,followed by main branch length density and CNFL.The AUC of the ROC curve under the logistic regression model also demonstrated good predictive values.The cut-off values of CNFD,CNFL,and main branch length density for diabetes showed 31.25,18.85,and 12.56,respectively.CONCLUSION:In patients with type 2 diabetes,there is a notable reduction in both CNFL and CNFD.These measurements can be influenced by various blood biochemical factors.However,the compromised nerve fibers can serve as valuable indicators for predicting the onset of type 2 diabetes and also as biomarkers for detecting diabetic neuropathy and its related complications.展开更多
Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes,yet the mechanisms are not completely understood.Here,we demonstrated that serum LPS levels were significantly higher in newly diagno...Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes,yet the mechanisms are not completely understood.Here,we demonstrated that serum LPS levels were significantly higher in newly diagnosed diabetic patients than in normal control.miR-145 level in peripheral blood mononuclear cells decreased in type 2 diabetics.LPS repressed the transcription of miR-143/145 cluster and decreased miR-145 levels.Attenuation of miR-145 activity by anti-miR-145 triggered liver inflammation and increased serum chemokines in C57BL/6 J mice.Conversely,lentivirus-mediated miR-145 overexpression inhibited macrophage infiltration,reduced body weight,and improved glucose metabolism in db/db mice.And miR-145 overexpression markedly reduced plaque size in the aorta in ApoE−/−mice.Both OPG and KLF5 were targets of miR-145.miR-145 repressed cell proliferation and induced apoptosis partially by targeting OPG and KLF5.miR-145 also suppressed NF-κB activation by targeting OPG and KLF5.Our findings provide an association of the environment with the progress of metabolic disorders.Increasing miR-145 may be a new potential therapeutic strategy in preventing and treating metabolic diseases such as type 2 diabetes and atherosclerosis.展开更多
Single-particle tracking photoactivated local- ization microscopy (sptPALM) has recently emerged as a powerful tool for high-density imaging and tracking of individual molecules in living cells. In this work, we hav...Single-particle tracking photoactivated local- ization microscopy (sptPALM) has recently emerged as a powerful tool for high-density imaging and tracking of individual molecules in living cells. In this work, we have monitored and compared the diffusion dynamics of TGF-β type II receptor (TβRII) at high expression level using both traditional single-particle tracking (SPT) and sptPALM. The ligand-induced aggregation of TβRII oligomers was further indicated by sptPALM. Due to the capacity of distinguishing and tracking single molecules within diffraction limit, sptPALM outperforms traditional SPT by providing more accurate biophysical information,展开更多
基金Supported by National Natural Science Foundation of China(No.82101097,No.82070937).
文摘Ophthalmology is a subject that highly depends on imaging examination.Artificial intelligence(AI)technology has great potential in medical imaging analysis,including image diagnosis,classification,grading,guiding treatment and evaluating prognosis.The combination of the two can realize mass screening of grass-roots eye health,making it possible to seek medical treatment in the mode of“first treatment at the grass-roots level,two-way referral,emergency and slow treatment,and linkage between the upper and lower levels”.On the basis of summarizing the AI technology carried out by scholars and their teams all over the world in the field of ophthalmology,quite a lot of studies have confirmed that machine learning can assist in diagnosis,grading,providing optimal treatment plans and evaluating prognosis in corneal and conjunctival diseases,ametropia,lens diseases,glaucoma,iris diseases,etc.This paper systematically shows the application and progress of AI technology in common anterior segment ocular diseases,the current limitations,and prospects for the future.
基金Supported by National Natural Science Foundation of China(No.82070937,No.81870640)National Science Foundation for Young Scientists of China(No.82101097)。
文摘AIM:To compare the postoperative efficacy,safety,predictability,and visual quality of implantable collamer lens(ICL)implantation versus small incision lenticule extraction(SMILE)in myopia eyes.METHODS:Pub Med,EMBASE,Web of Science,Cochrane Library and several Chinese databases were searched at May 2021 to select relevant studies in comparison of clinical outcomes between ICL implantation and SMILE for myopia.The primary outcomes were efficacy,safety,and predictability.And the secondary outcomes were postoperative higher-order ocular aberrations(HOAs),modulation transfer function cutoff frequency(MTF),objective scatter index(OSI),contrast sensitivity and a quality of vision(Qo V)questionnaire.RESULTS:A total of 1036 eyes from 10 studies,of which 503 eyes underwent ICL implantation and 533 eyes underwent SMILE,were enrolled in this Meta-analysis.Pooled results revealed that ICL group had a better safety index and post-corrected distance visual acuity(CDVA)(P=0.007,<0.00001,respectively),and a lower percentage of eyes with a postoperative CDVA lost 1 line(P=0.007)than the SMILE group.No significant differences were found in comparison of the other primary outcomes.In the longterm follow-up(>6mo),ICL group had a lower total HOA,coma,and spherical aberration than SMILE group(P=0.003,<0.00001,0.04).Yet higher trefoil was found in ICL group at 6mo after surgery(P=0.003).Additionally,ICL group also had a higher MTF value(P=0.02),and a higher contrast sensitivity score for spatial frequencies of 1.5,6,and 12 cpds(P=0.02,0.005,0.02,respectively).And it also had a lower score of bothersome in Qo V questionnaire than SMILE group(P=0.003).CONCLUSION:ICL implantation and SMILE have similar and comparable outcomes in term of the efficacy and predictability for correcting high myopia.However,ICL group is relatively safer and also has better visual quality in comparison of SMILE group.
文摘Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion injury.Current studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion injury.However,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional exploration.In this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and autophagy.The therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box O.This review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins expression.This review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk factors.While Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug therapies.Overall,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.
基金Supported by National Natural Science Foundation for Young Scientists of China(No.82101097)National Natural Science Foundation of China(No.82070937).
文摘AIM:To explore the effect of silent information regulator factor 2-related enzyme 1(SIRT1)on modulating apoptosis of human lens epithelial cells(HLECs)and alleviating lens opacification of rats through suppressing endoplasmic reticulum(ER)stress.METHODS:HLECs(SRA01/04)were treated with varying concentrations of tunicamycin(TM)for 24h,and the expression of SIRT1 and C/EBP homologous protein(CHOP)was assessed using real-time quantitative polymerase chain reaction(RT-PCR),Western blotting,and immunofluorescence.Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8(CCK-8)assay,respectively.In the SRA01/04 cell apoptosis model,which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation,the expression levels of SIRT1,CHOP,glucose regulated protein 78(GRP78),and activating transcription factor 4(ATF4)were examined.The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid(4-PBA;an ER stress inhibitor)was investigated.In vivo,age-related cataract(ARC)rat models were induced by sodium selenite injection,and the protective role of SIRT1,activated by SRT1720 intraperitoneal injections,was evaluated through morphology observation,hematoxylin and eosin(H&E)staining,Western blotting,and RT-PCR.RESULTS:SIRT1 expression was downregulated in TMinduced SRA01/04 cells.Besides,in SRA01/04 cells,both cell apoptosis and CHOP expression increased with the rising doses of TM.ER stress was stimulated by TM,as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model.Inhibition of SIRT1 by siRNA knockdown increased ER stress activation,whereas SRT1720 treatment had opposite results.4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis.In vivo,SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models.CONCLUSION:SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress.These findings suggest a novel strategy for cataract treatment focused on targeting ER stress,highlighting the therapeutic potential of SIRT1 modulation in ARC development.
文摘Purpose: The surgical risk and complication rate after cataract surgery are extremely high in patients with nanophthalmos.This study is designed to compare the visual and refractive outcomes before and after coaxial micro-incision phacoemulsification and evaluate postoperative complications.Methods:.Fifty nine patients(89 eyes) with axial length(AL)< 21 mm diagnosed with nanophthalmos were enrolled in this retrospective study. All patients underwent coaxial micro-incision phacoemulsification and IOL implantation..The main outcome measures included anterior chamber depth(ACD),anterior chamber volume(ACV), anterior chamber angle(A CA), intraocular pressure(IOP) and best corrected visual acuity(BCVA). Wilcoxon signed rank test or Mann-Whitney test,and Chi-square test and logistic regression analysis were performed for statistical tests as appropriate.Results:.The median AL was 19.63 mm...Sixty-six eyes(74.16%) had a history of surgical intervention. Postoperative ACD, ACV and ACA were increased significantly(all P<0.001),whereas postoperative IOP was decreased significantly.(P <0.001) after surgery. Previous surgical intervention was related to a reduction in the postoperative ACD and ACA(P<0.01),and both preoperative and postoperative IOP.(P <0.001).Postoperative BCVA was improved in 94.38% of the cases.Intraoperative complications mainly included iridoschisis(6eyes, 6.74%). Early postoperative complications included temporary corneal edema(TCE)(23 eyes, 25.84%), anterior inflammatory response(AIR)(19 eyes, 21.35%), cystoid macular edema(CME)(14 eyes, 15.73%), and uveal effusion(4 eyes, 4.49%). Late postoperative complications included CME(8 eyes, 8.99%), uveal effusion(8 eyes, 8.99%),malignant glaucoma(2 eyes, 2.25%) and posterior capsular opacification(PCO)(10 eyes, 11.24%). The majority of complications(80%) were successfully resolved by pharmacotherapy or operation. The risk of surgical complications was greater in patients with lower AL,ACD,ACV or ACA andhigher nuclear hardness or mean keratometry(Km).Conclusion: With reasonable preoperative management, prudent selection of the lens,.rigorous surgical technique and unerring cognition of potential complications, coaxial microincision phacoemulsification lens surgery can be performed in patients with nanophthalmos and yield favorable outcomes and a low incidence of complications.
基金supported by the Natural Science Foundation of China(No.51808187,No.52062027)the Key Research and Development Project of Gansu Province(No.22YF7GA142)+2 种基金Soft Science Special Project of Gansu Basic Research PIan(No.22JR4ZA035)Gansu Provincial Science and Technology Major Special Project-Enterprise Innovation Consortium Project(No.21ZD3GA002,No.22ZD6GA010)Lanzhou Jiaotong University Basic Research Top Talents Training Program(No.2022JC02).
文摘Implementing autonomous bus services in several cities has garnered substantial research attention worldwide.However,the benefits and challenges of this emerging mode remain insufficiently understood.Consequently,VOSviewer was employed for a bibliometric analysis involving 300 publications,investigating the associations among authors,journals,and keywords.Subsequently,we comprehensively reviewed the current state of research on two topics and proposed future recommendations.Results indicate that the first document related to autonomous bus services was published in 2009.Most user attitude-related research data are obtained via questionnaires and analyzed using statistical techniques.Autonomous bus services are expected to benefit passengers regarding travel time,cost,safety,etc.,while passenger preferences are inconsistent.However,integrating the service into existing bus systems requires careful consideration of the schedule sequences.Notably,modular autonomous bus services present a new opportunity for the further optimization of bus services.In future studies,standardized data acquisition procedures should be developed to achieve comparable results.Regarding traveler choice behavior,the effect of specific autonomous bus service policies over time and the heterogeneity due to cultural or social contexts across regions should be assessed.To further promote autonomous bus services,based on fluctuating travel demands,the effects of vehicle capacity,speed,and cost of fleet composition should be evaluated comprehensively to optimize the bus network and schedule sequence.Owing to the protracted nature of the transition from conventional to fully autonomous buses,one should prioritize semi-autonomous bus services.Another essential future research direction is to integrate modular autonomous bus assembly or disassembly strategies with different fine-grained operation optimization techniques in various scenarios.
基金the National Program for Support of Top-notch Young Professionals(No.0106514050)the National Natural Science Foundation of China(Nos.82273811 and 31870326)+4 种基金the National Key R&D Program of China(No.2021YFA0910500)the National Natural Science Foundation for Distinguished Young Scholars(No.81725021)the Innovative Research Groups of the National Natural Science Foundation of China(No.81721005)the Research and Development Program of Hubei Province(No.2020BCA058)the Chinese Medicine Research Foundation of Health Commission of Hubei Province(No.ZY2021Z019).
文摘Two novel compounds including a cyclohelminthol type polyketide(namely oxaleimide K,1)and a maleimide deriva-tive(namely peniroquefortine A,2),and a new natural product(namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-acetamide,3),together with four known compounds(4-7),were isolated and identified from fungus Penicillium roqueforti,which was separated from the root soil of Hypericum beanii N.Robson collected from the Shennongjia For-estry District,Hubei Province.Their structures including absolute configurations were mainly established by the NMR spectroscopy analyses and single-crystal X-ray diffraction experiment.Compound 1 represents the second example of a cyclohelminthol type polyketide,which features a rare 6/6/5/5 tetracyclic system and a branched aliphatic chain containing a terminal olefin(oct-1-en-3-yl)moiety,and compound 2 possesses an unprecedented carbon skeleton that is uniquely defined by a maleimide moiety linked to the respective 4-methylene-2-(3-methylbut-2-en-1-yl)-phenol and para-substituted aromatic moieties via the carbon-carbon bonds.Remarkably,the absolute configuration of a cyclohelminthol type polyketide as exemplified by compound 1 is determined by the single-crystal diffraction analysis for the first time,highlighting an E-configuration for the linkage of a succinimide moiety and a tetrahydro-furan moiety for 1 rather than a Z-configuration as previously reported in the biosynthesis study,which gives a new insight into the structural elucidation of this category of polyketides.Additionally,compound 1 exhibited significant cytotoxic activity against multiple tumor cells,especially against the Farage and SU-DHL-2 cells(IC_(50)<20μM,48 h).Further mechanism study revealed that compound 1 significantly induced cell cycle arrest in Farage and SU-DHL-2 cells by causing abnormal ROS level and triggering oxidative stress.
基金Supported by the National Nature Science Foundation of China(No.82070937,No.81870640,No.82000923).
文摘AIM:To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell(hiPSC)-derived retinal organoids(ROs).METHODS:The hiPSC and a three-dimensional culture method were used for the experiments.Generated embryoid bodies(EBs)were randomly and equally divided into hypoxic and normoxic groups.Photographs of the EBs were taken on days 38,45,and 52,and the corresponding volume of EBs was calculated.Simultaneously,samples were collected at these three timepoints,followed by fixation,sectioning,and immunofluorescence.RESULTS:The proportion of Ki67-positive proliferating cells increased steadily on day 38;this proliferationpromoting effect tended to increase tissue density rather than tissue volume.On days 45 and 52,the two groups had relatively similar ratios of Ki67-positive cells.Further immunofluorescence analysis showed that the ratio of SOX2-positive cells significantly increased within the neural retina on day 52(P<0.05).In contrast,the percentage of PAX6-and CHX10-positive cells significantly decreased following hypoxia treatment at all three timepoints(P<0.01),except for CHX10 at day 45(P>0.05).Moreover,the proportion of PAX6-/TUJ1+cells within the neural retinas increased considerably(P<0.01,<0.05,<0.05 respectively).CONCLUSION:Low oxygen promotes stemness and proliferation of neural retinas,suggesting that hypoxic conditions can enlarge the retinal progenitor cell pool in hiPSC-derived ROs.
文摘AIM: To identify the effect and regulatory mechanism of amyloid β (Aβ) protein on retinal pigment epithelial (RPE) cells in cell proliferation and apoptosis, and clarify Aβ role in the pathogenesis of age-related macular degeneration (AMD). METHODS: The model of Aβ25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of Aβ protein on RPE cells in vitro. Based on Aβ protein, the specific inhibitors (HY-50682 or BAY11-7082) or activating agent (lipopolysaccharide) was used to analyze the regulatory mechanism of Aβ protein to RPE cells on cell proliferation and apoptosis by flow cytometry, real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and dual-luciferase reporter gene assay. RESULTS: The number of RPE cells, treated with Aβ25-35 from 0.3 to 60 μmol/L, significantly reduce (P〈0.01), and had the dose-dependent effect. Aβ protein 60 μmol/L inhibits the G1/S phase transition (P〈0.01) and down-regulated cyclin E mRNA level (P〈0.01). Similarly, Aβ25-35 induced a significant increase of cell apoptosis, accompanied by the significantly higher level of activated caspase 3 protein. Furthermore, nuclear factor-kappaB (NF-κB) activity and hosphorylated Iκ-Ba level would significantly lower in treated RPE cells. Using specific inhibitors or activating agent based on the Aβ, the cell numbers, NF-κB activity, phosphorylated Iκ-Ba level, receptor for advanced glycation endproducts (RAGE) gene expression levels, cyclin E mRNA level and activated caspase 3 level had accordingly changed by different methods, confirming that RAGE/NF-κB signaling pathway involved in the regulation of Aβ protein on RPE cell apoptosis and proliferation. CONCLUSION: Aβ protein inhibits cell proliferation and activates apoptosis via inactivation of the RAGE/NF-κB signaling pathway in RPE cell.
基金The National Natural Science Foundation of China(No.22177136)CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.CIFMS-2021-I2M-1-007,2022-I2M-2-002)。
文摘Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development.The advantageous effects of covalent compounds compared with non-covalent ones are highly dependent on electrophilic warheads.Hence,electrophilic warheads with tunable reactivity and selectivity are highly demanded in fields of medicinal chemistry and chemical biology.Herein,we report a novel electrophilic warhead,chloromethyl group activated by thiol-substituted 1,2,4-triazole.Interestingly,a pair of regioisomers could be simultaneously occurred in the step of alkylation during the synthesis of this unique motif.This is a rare example that the alkylation could simultaneously generate these two separable regioisomers of 1,2,4-triazole at the nitrogen or sulfur atom.The covalent-working mechanism of this new warhead is confirmed by various chemoproteomics experiments including target identification and binding site mapping.Importantly,the reactivity and selectivity of this new electrophilic warhead could be efficiently tuned by virtue of stereo effect.Interestingly,one pair of regioisomers(19S and 19X)induced distinct modes of cell death.Isomer 19S could induce apoptosis of colon cancer cells while 19X could induce both apoptosis and ferroptosis.Together,this study provides pairs of novel electrophilic warheads that could be useful not only in supporting the design of covalent compounds for drug discovery but also in providing chemical probes for the fundamental biological study.
基金supported by the Key Program of the National Natural Science Foundation of China (No. 91543207)the Major Research Program of the National Natural Science Foundation of China (No. 91843302)。
文摘The short-term impacts of urban air pollution on the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) remain obscure.In this study,we included 3487 urban adults from the Wuhan-Zhuhai cohort.Individual inhalation exposure to air pollutants was estimated by combining participants’daily breath volume and ambient concentrations of six air pollutants (includingfine particulate matter (PM_(2.5)),inhalable particulate matter(PM_(10)),nitrogen dioxide (NO_(2)),sulfur dioxide (SO_(2)),carbon monoxide (CO) and ozone (O_(3))).The cumulative impacts were assessed by applying lag structures of up to 7 days before the survey date.Associations of air pollutants with PLR and NLR were assessed using a linear mixed model and Bayesian kernel machine regression (BKMR) model.We found that PLR was negatively related to PM_(2.5)(lag02-lag06),PM_(10)(lag02-lag07),NO_(2)(lag02-lag07),and SO_(2)(lag03-lag05) and NLR was negatively related to PM_(10)(lag05 and lag07).In the BKMR model,a negative joint association between the six-air-pollutant mixture and PLR and NLR was observed,whereas PM_(10)and NO_(2)appeared to be more important than the other pollutants in the mixture.The negative impact of air pollutants was stronger in males,participants with lower body mass index (<24 kg/m^(2)),those cooking meals at home,drinkers,and nonexercisers.In conclusion,short-term exposure to air pollutants is significantly related to PLR and NLR in peripheral blood.PLR and NLR may provide new insight into the molecular mechanism underlying the adverse health impact of air pollutants.
基金supported by the 2020 Annual Medical Research Project of Jiangsu Commission of Health(No.ZDA 2020014)the Key Project supported by Medical Science and Technology Development Foundation,Nanjing Department of Health(Nos.ZKX 22040 and ZKX 19048)
文摘To the Editor:High-frequency resistance(typically≥15-25%viral quasispecies)detected by conventional resistance assays has long been associated with failure of antiretroviral therapy(ART)to suppress viral replication,[1]but the impact of pre-existing lowfrequency resistance on virological response is controversial.Previous studies have shown an increased likelihood of virological response failure in patients with preexisting low-frequency resistance mutations after initiation of antiviral therapy,especially primary ART regimens containing non-nucleoside reverse transcriptase inhibitors(NNRTIs).[2]However,some studies have concluded differently,suggesting that pre-existing lowfrequency resistance mutations do not correlate with viral response failure.[3]This may be related to the method of detection of pre-existing low-frequency resistance mutations.
基金the Program of National Natural Science Foundation of China(No.82070937)(No.81870640)National Natural Science Foundation for Young Scientists of China(No.82000923)(No.82101097).
文摘Background:Due to media opacity,it is usually difficult to accurately evaluate the postoperative visual acuity in cataracts patients.As a small and portable tool,the critical flicker fusion frequency(CFF)device reflects the temporal resolution of visual function and has been widely used in clinical research.However,poor understanding of the technique and equipment limitations have restricted its clinical application in China.Main text:There was a decrease in the CFF value in various ophthalmic diseases,indicating that the CFF is sensitive to detect visual functional changes.A number of studies have shown that the CFF test can accurately distinguish patients with simple cataracts from those with cataracts combined with fundus disease,and,as a visual test,it can more accurately predict postoperative visual acuity without being affected by media opacity.This study comprehensive reviews the basic principles of CFF and its application in ophthalmology,especially in cataracts.Conclusions:As one of the tools for dynamic visual function detection,the CFF test could help doctors to assess the possible presence of fundus disease in cataracts patients,especially in eyes with dense cataracts,and more precisely provide a reasonable visual prognosis than other available visual tests.
文摘AIM:To observe the changes in corneal subepithelial nerve fibers(CNFs)and Langerhans cells(LCs)in patients with type 2 diabetes using corneal laser confocal microscopy(CLCM).METHODS:A total of 60 patients(64 eyes),including 40 patients with type 2 diabetes(DM group)and 20 subjects without diabetes(control group)were included with CLCM.Neuron J plugin of Image J software were used for quantitative analysis of CNF length(CNFL),CNF density(CNFD),corneal nerve branch fiber density(CNBD),main branch length density,branch length density,corneal nerve fiber tortuosity(NT)score,and LCs density.An independent samples t-test to analyze the variability between the two groups was performed,and Pearson correlation analysis was used to analyze the relationships between CNF and multiple biochemical indicators in the DM group.The predictive power of CNF for type 2 diabetes was assessed using the receiver operating characteristic(ROC)curve.RESULTS:There were significant differences in the CNFL,CNFD,and main branch length density between two groups.The results of Pearson correlation analysis showed a significant negative correlation between CNFD and the duration of diabetes as well as triglyceride levels and total cholesterol,and a significant positive correlation between CNFD and serum albumin.In addition,the NT score showed a positive correlation and urea nitrogen,similar to the positive correlation observed between LC density and glycosylated hemoglobin(HbA1c)levels.CNFD showed the highest area under the curve(AUC of ROC)value,followed by main branch length density and CNFL.The AUC of the ROC curve under the logistic regression model also demonstrated good predictive values.The cut-off values of CNFD,CNFL,and main branch length density for diabetes showed 31.25,18.85,and 12.56,respectively.CONCLUSION:In patients with type 2 diabetes,there is a notable reduction in both CNFL and CNFD.These measurements can be influenced by various blood biochemical factors.However,the compromised nerve fibers can serve as valuable indicators for predicting the onset of type 2 diabetes and also as biomarkers for detecting diabetic neuropathy and its related complications.
基金This work was supported by grants from the National Natural Science Foundation of China(81270902,81381220308,and 30230380).
文摘Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes,yet the mechanisms are not completely understood.Here,we demonstrated that serum LPS levels were significantly higher in newly diagnosed diabetic patients than in normal control.miR-145 level in peripheral blood mononuclear cells decreased in type 2 diabetics.LPS repressed the transcription of miR-143/145 cluster and decreased miR-145 levels.Attenuation of miR-145 activity by anti-miR-145 triggered liver inflammation and increased serum chemokines in C57BL/6 J mice.Conversely,lentivirus-mediated miR-145 overexpression inhibited macrophage infiltration,reduced body weight,and improved glucose metabolism in db/db mice.And miR-145 overexpression markedly reduced plaque size in the aorta in ApoE−/−mice.Both OPG and KLF5 were targets of miR-145.miR-145 repressed cell proliferation and induced apoptosis partially by targeting OPG and KLF5.miR-145 also suppressed NF-κB activation by targeting OPG and KLF5.Our findings provide an association of the environment with the progress of metabolic disorders.Increasing miR-145 may be a new potential therapeutic strategy in preventing and treating metabolic diseases such as type 2 diabetes and atherosclerosis.
基金supported by the National Basic Research Program of China(2013CB933701)the National Natural Science Foundation of China(21127901+2 种基金9141311991213305)the Chinese Academy of Science
文摘Single-particle tracking photoactivated local- ization microscopy (sptPALM) has recently emerged as a powerful tool for high-density imaging and tracking of individual molecules in living cells. In this work, we have monitored and compared the diffusion dynamics of TGF-β type II receptor (TβRII) at high expression level using both traditional single-particle tracking (SPT) and sptPALM. The ligand-induced aggregation of TβRII oligomers was further indicated by sptPALM. Due to the capacity of distinguishing and tracking single molecules within diffraction limit, sptPALM outperforms traditional SPT by providing more accurate biophysical information,