RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progre...RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progression of numerous diseases,making RBPs potential therapeutic targets.However,the limited tissue penetration of 254 nm UV irradiation makes it difficult to efficiently crosslink weak and dynamic RNA-protein interactions in mammal tissues.Additionally,RNA degradation in metal catalyzed click reaction further hinders the enrichment of RNA-protein complexes(RPCs).Due to these inherent limitations,globally profiling the RNA binding proteome in mammal organs has long been a challenge.Herein,we proposed a novel method,which utilized a dual crosslinking with formaldehyde and 254 nm UV irradiation,metabolic labeling and metal-free thiol-yne click reaction to enable large-scale enrichment and identification of RBPs in mouse liver,called FTYc_UV.In this method,formaldehyde is first used to crosslink the crude RNA-protein complexes(cRPCs) in situ to address the problem of poor tissue penetration of 254 nm UV irradiation.Furthermore,this method integrates metabolic labeling with a metal-free thiol-yne click reaction to achieve non-destructive RNA tagging.After specifically RNA-RBPs crosslinking by 254 nm UV irradiation in tissue lysates,formaldehyde decrosslinking is employed to remove non-specific proteins,leading to effective enrichment of RPCs from mouse liver and thereby overcoming the poor specificity of formaldehyde crosslinking.Application of FTYc_UV in mouse liver successfully identified over 1600 RBPs covering approximately 75 % of previously reported RBPs.Furthermore,420 candidate RBPs,including 151metabolic enzymes,were also obtained,demonstrating the sensitivity of FTYc_UV and the potential of this method for in-depth exploration of RNA-protein interactions in biological and clinical research.展开更多
The rapid development of genome editing technology has brought major breakthroughs in the fields of life science and medicine. In recent years, the clustered regularly interspaced short palindromic repeats(CRISPR)-bas...The rapid development of genome editing technology has brought major breakthroughs in the fields of life science and medicine. In recent years, the clustered regularly interspaced short palindromic repeats(CRISPR)-based genome editing toolbox has been greatly expanded, not only with emerging CRISPR-associated protein(Cas) nucleases, but also novel applications through combination with diverse effectors. Recently, transposon-associated programmable RNA-guided genome editing systems have been uncovered, adding myriads of potential new tools to the genome editing toolbox. CRISPR-based genome editing technology has also revolutionized cardiovascular research. Here we first summarize the advances involving newly identified Cas orthologs, engineered variants and novel genome editing systems, and then discuss the applications of the CRISPR-Cas systems in precise genome editing, such as base editing and prime editing. We also highlight recent progress in cardiovascular research using CRISPR-based genome editing technologies, including the generation of genetically modified in vitro and animal models of cardiovascular diseases(CVD) as well as the applications in treating different types of CVD. Finally, the current limitations and future prospects of genome editing technologies are discussed.展开更多
AIM:To evaluate the effects of polarized and nonpolarized sunglasses on visual functions,including distance and near visual acuity,phoria,stereopsis and contrast sensitivity across five spatial frequencies(1.5,3,6,12,...AIM:To evaluate the effects of polarized and nonpolarized sunglasses on visual functions,including distance and near visual acuity,phoria,stereopsis and contrast sensitivity across five spatial frequencies(1.5,3,6,12,18 cycles/degree).METHODS:A before-after study was conducted on 45 emmetropic students from Shahid Beheshti University of Medical Sciences.Visual acuity,contrast sensitivity,stereopsis and phoria were measured under three conditions:without sunglasses,with non-polarized sunglasses and with polarized sunglasses.Tests were conducted under controlled glare conditions to simulate outdoor environments.RESULTS:A total of 45 participants were evaluated,comprising 17 males(37.8%)and 28 females(62.2%).The mean age was 21.67±2.31y(range 18-27y).The mean of distance and near visual acuity in all three conditions were equal to 0.00 logMAR.Contrast sensitivity generally decreased slightly with the use of non-polarized sunglasses compared to the no-sunglasses condition.The mean stereopsis with polarized sunglasses was 101.33±56.139 arc sec,which was worse than the no-sunglasses condition(94.33±46.632 arc sec)and better than the non-polarized sunglasses condition(105.67±58.965 arc sec),although these changes were not significant.In the phoria parameter,distance phoria appeared more affected than near phoria.CONCLUSION:Polarized and non-polarized sunglasses do not significantly affect visual acuity,stereopsis,or phoria under controlled glare conditions.Slight changes in contrast sensitivity are noted,but they are not statistically significant.展开更多
Radiological or nuclear accidents can lead to serious outcomes for individuals exposed to ionizing radiation,with health effects that are either acute or delayed,deterministic or stochastic,depending on the effective ...Radiological or nuclear accidents can lead to serious outcomes for individuals exposed to ionizing radiation,with health effects that are either acute or delayed,deterministic or stochastic,depending on the effective dose of exposure.Mechanistically,ionizing radiation can inflict damage either directly on DNA or through oxidative stress,which may trigger a cascade of damages to tissues and organs.The development of effective radiation medical countermeasures is an unmet need and should be a top priority in preparing for radiation emergencies.This paper aims to address the critical questions of whether current countermeasures are available,what additional measures are needed,and what actions can be taken to enhance the development of radiation medical countermeasures from a systematic perspective.展开更多
The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pa...The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pathogenicity,and autophagy of the rice blast fungus.In this study,we further revealed that PoElp3 functions via tRNA-mediated protein integrity.Phenotypic analyses revealed that overexpression of two of the tRNAs,tK(UUU)and tQ(UUG)could rescue the defects inΔPoelp3 strain.TMT-based proteomic and transcriptional analyses demonstrated that 386 proteins were down-regulated inΔPoelp3 strain compared with wild type strain Guy11,in a transcription-independent manner.Codon usage assays revealed an enrichment of Glutamine CAA-biased mRNA in the 386 proteins compared with the 70-15 genome.In addition to those reported previously,we also found that PoErp9,a sphingolipid C9-methyltransferase,was down-regulated in theΔPoelp3strain.Through an ILV2-specific integration of PoERP9-GFP into the wild type andΔPoelp3 strain,we were able to show that PoErp9 was positively regulated by PoElp3 translationally but not transcriptionally.Functional analyses revealed that PoErp9 was involved in the fungal growth,conidial development,pathogenicity,and TORrelated autophagy homeostasis in Pyricularia oryzae.Taken together,our results suggested that PoElp3 acts through the tRNA-mediated translational efficiency to regulate asexual development,pathogenicity,sphingolipid metabolism,and autophagy in the rice blast fungus.展开更多
Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are ...Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus.Genetic mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^(ERT2) developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient mice.Mechanistically, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore,inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA.展开更多
Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers fo...Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.展开更多
Background:Toll-like receptor 5(TLR5)-mediated pathways play critical roles in regulating the hepatic immune response and show hepatoprotective effects in mouse models of hepatic diseases.However,the role of TLR5 in e...Background:Toll-like receptor 5(TLR5)-mediated pathways play critical roles in regulating the hepatic immune response and show hepatoprotective effects in mouse models of hepatic diseases.However,the role of TLR5 in experimental models of liver regeneration has not been reported.This study aimed to investigate the role of TLR5 in partial hepatectomy(PHx)-induced liver regeneration.Methods:We performed 2/3 PHx in wild-type(WT)mice,TLR5 knockout mice,or TLR5 agonist CBLB502 treated mice,as a model of liver regeneration.Bacterial flagellin content was measured with ELISA,and hepatic TLR5 expression was determined with quantitative PCR analyses and flow cytometry.To study the effects of TLR5 on hepatocyte proliferation,we analyzed bromodeoxyuridine(BrdU)incorporation and proliferating cell nuclear antigen(PCNA)expression with immunohistochemistry(IHC)staining.The effects of TLR5 during the priming phase of liver regeneration were examined with quantitative PCR analyses of immediate early gene mRNA levels,and with Western blotting analysis of hepatic NF-κB and STAT3 activation.Cytokine and growth factor production after PHx were detected with real-time PCR and cytometric bead array(CBA)assays.Oil Red O staining and hepatic lipid concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after PHx.Results:The bacterial flagellin content in the serum and liver increased,and the hepatic TLR5 expression was significantly up-regulated in WT mice after PHx.TLR5-deficient mice exhibited diminished numbers of BrdU-and PCNA-positive cells,suppressed immediate early gene expression,and decreased cytokine and growth factor production.Moreover,PHx-induced hepatic NF-κB and STAT3 activation was inhibited in Tlr5–/–mice,as compared with WT mice.Consistently,the administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation,which was correlated with enhanced production of proinflammatory cytokines and the recruitment of macrophages and neutrophils in the liver.Furthermore,Tlr5–/–mice displayed significantly lower hepatic lipid concentrations and smaller Oil Red O positive areas than those in control mice after PHx.Conclusions:We reveal that TLR5 activation contributes to the initial events of liver regeneration after PHx.Our findings demonstrate that TLR5 signaling positively regulates liver regeneration and suggest the potential of TLR5 agonist to promote liver regeneration.展开更多
Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on ...Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on rat behaviors remain poorly understood. In this study, we used nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous sciatic nerve to bridge 30-ram-long rat sciatic nerve gaps. Within 4 months after surgery, rat sciatic nerve functional re- covery was evaluated per month by behavioral analyses, including toe out angle, toe spread anal- ysis, walking track analysis, extensor postural thrust, swimming test, open-field analysis and no- ciceptive function. Results showed that rat sciatic nerve functional recovery was similar after nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous nerve grafting. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit is suitable in use for repair of long-segment sciatic nerve defects.展开更多
Genome sequencing opened the flood gate of"-omics"studies,among which the research about correlations between genomic and phenomic variables is an important part.With the development of functional genomics a...Genome sequencing opened the flood gate of"-omics"studies,among which the research about correlations between genomic and phenomic variables is an important part.With the development of functional genomics and systems biology,genome-wide investigation of the correlations between many genomic and phenomic variables became possible.In this review,five genomic variables,such as evolution rate(or"age"of the gene),the length of intron and ORF(protein length)in one gene,the biases of amino acid composition and codon usage,along with the phenomic variables related to expression patterns(level and breadth)are focused on.In most cases,genes with higher mRNA/protein expression level tend to evolve slowly,have less intronic DNA,code for smaller proteins,and have higher biases of amino acid composition and codon usage.In addition,broadly expressed proteins evolve more slowly and are shorter than tissue-specific proteins.Studies in this field are helpful for deeper understanding the signatures of selection mediated by the features of gene expression and are of great significance to enrich the evolution theory.展开更多
O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine （GlcNAc） transferase （OGT） me...O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine （GlcNAc） transferase （OGT） mediated O-GlcNAcylation of histone H2B Ser 112 （H2B S 112 GlcNAcylation） plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress- inducing agents. OGT mediated H2B Sl12 GlcNAcylation increased locally upon the induction of double-strand breaks （DSBs）, and depletion of OGT or overexpression of H2B S 112A mutant impaired homologous recombination （HR） and nonhomologous end-joining （NHEJ）. Mechanistically, H2B Sl12 GlcNAcylation could bind Nijmegen breakage syndrome 1 （NBS1） and regulate NBS1 foci for- mation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response （DDR）.展开更多
Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and diffe...Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.展开更多
It has been confirmed that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve...It has been confirmed that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were macroscopi- cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson＇s trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3- hydroxyvalerate） nerve conduit is suitable for repair of long-segment sciatic nerve defects.展开更多
AIM To assess how serum gamma-glutamyltransferase(GGT) fractions vary in patients with alcoholic liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD). METHODS Serum samples were obtained from 14 patients wi...AIM To assess how serum gamma-glutamyltransferase(GGT) fractions vary in patients with alcoholic liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD). METHODS Serum samples were obtained from 14 patients with biopsy-proven alcoholic liver diseases and 9 patients with biopsy proven non-alcoholic fatty liver disease. In addition to these biopsy-proven cases, 16 obese(body mass index > 25) patients without any history of alcohol consumption but with a fatty liver on ultrasound examination and with elevated GGT were included for an additional analysis. Serum GGT fractionation was conducted by high-performance gel filtration liquid chromatography and was separated into the four fractions, big-GGT, medium-GGT, small-GGT(s-GGT), and free-GGT(f-GGT).RESULTS The results were expressed as a ratio of each fraction including the total GGT(t-GGT). The s-GGT/t-GGT ratioswere lowest for the control group and highest for the ALD group. The differences between the control and NAFLD groups and also between the NAFLD and ALD groups were statistically significant. In contrast, the f-GGT/t-GGT ratios were highest in the control group and lowest in the ALD group, with the differences being statistically significant. As a result, the s-GGT/f-GGT ratios were markedly increased in the NAFLD group as compared with the control group. The increase of the s-GGT/t-GGT ratios, the decrease of the f-GGT/t-GGT ratios, and the increase of s-GGT/F-GGT ratios as compared with the control group subjects were also found in obese patients with clinically diagnosed fatty change of the liver.CONCLUSION Serum GGT fractionation by high-performance gel filtration liquid chromatography is potentially useful for the differential diagnosis of ALD and NAFLD.展开更多
Background This prospective study integrated multiple clinical indexes and inflammatory markers associated with coronary atherosclerotic vulnerable plaque to establish a risk prediction model that can evaluate a patie...Background This prospective study integrated multiple clinical indexes and inflammatory markers associated with coronary atherosclerotic vulnerable plaque to establish a risk prediction model that can evaluate a patient with certain risk factors for the likelihood of the occurrence of a coronary heart disease event within one year. Methods This study enrolled in 2686 patients with mild to moderate coronary artery lesions. Eighty-five indexes were recorded, included baseline clinical data, laboratory studies, and procedural characteristics. During the 1-year follow-up, 233 events occurred, five patients died, four patients suffered a nonfatal myocardial infarction, four patients underwent revascularization, and 220 patients were readmitted for angina pectoris. The Risk Estimation Model and the Simplified Model were conducted using Bayesian networks and compared with the Single Factor Models. Results The area under the curve was 0.88 for the Bayesian Model and 0.85 for the Simplified Model, while the Single Factor Model had a maximum area under the curve of 0.65. Conclusion The new models can be used to assess the short-term risk of individual coronary heart disease events and may assist in guiding preventive care.展开更多
AIM:To investigate the effect of astigmatism and spherical equivalent(SE)correction on contrast sensitivity(CS).METHODS:In this cross-sectional study,103 visually normal subjects aged 18 to 36y with bilateral regular ...AIM:To investigate the effect of astigmatism and spherical equivalent(SE)correction on contrast sensitivity(CS).METHODS:In this cross-sectional study,103 visually normal subjects aged 18 to 36y with bilateral regular astigmatism in range of 1.00 diopter cylinder(DC)to 4.00 DC and normal best-corrected visual acuity(20/20)were recruited.Binocular CS was assessed by linear sine-wave gratings at 1.5,3,6,12,and 18 cycles per degree(cpd),before correction of astigmatism,after full correction of astigmatism by cylindrical spectacle lenses,and after SE of refractive error.The repeated measures ANOVA and Bonferroni test were used to compare the effects of astigmatism correction on logCS.RESULTS:Totally 39 patients were male and 64 patients were female with the mean age of 28.25±5.38y.The average degree of astigmatism in right and left eye was 2.03±0.83 and 2.10±0.78,respectively.Increases in uncorrected astigmatic power correlated with decreases in the logCS,especially at high spatial frequencies.A statistically significant difference in logCS was found between these three cases:before correction of astigmatism,after SE of refractive error,and after full correction of astigmatism by cylindrical spectacle lenses at all frequencies(P<0.001),except at 18 cpd.At 18 cpd,there was no statistically significant difference between logCS before and after SE of refractive error(P=1.0).Also,there was no statistically significant difference in mean CS between with-the-rule(WTR)and against-the-rule(ATR)astigmatism,before correction of astigmatism,after correction of astigmatism with cylindrical lenses,and after SE of refractive error.CONCLUSION:Binocular astigmatism defocus decreases CS depending on the degree of astigmatism power;correction of this will improve patent’s quality of vision.Although high astigmatism refractive error(more than 2.00 DC)that is fully corrected by cylindrical spectacle lenses doesn’t increase the CS to the maximum value,especially at higher spatial frequencies(12 and 18).Also SE refractive error effects on improving CS in low astigmatism power(less than 2.00 DC),especially at lower spatial frequencies.展开更多
AIM:To evaluate the effect of axial length(AL)and anterior chamber depth(ACD)on peripheral refractive profile in myopic patients compared to emmetropic participants.METHODS:This cross-sectional study was conducted in ...AIM:To evaluate the effect of axial length(AL)and anterior chamber depth(ACD)on peripheral refractive profile in myopic patients compared to emmetropic participants.METHODS:This cross-sectional study was conducted in right eyes of 58 participants of whom 38 were emmetropic and 20 were myopic.Central and peripheral refraction were measured at 10°,20°,and 30°eccentricities in nasal and temporal fields using an open-field autorefractor.The Lenstar LS900 was used to measure ACD and AL.The participants were divided into three groups of short(<22.5 mm),normal(22.5-24.5 mm),and long eye(>24.5 mm)according to AL and three groups of low ACD(<3.00 mm),normal ACD(3.00-3.60 mm),and high ACD(>3.60 mm)according to ACD.RESULTS:The mean age of the participants was 22.26±3.09 y(range 18-30 y).The peripheral mean spherical refractive error showed a hypermetropic shift in myopic and emmetropic groups although this shift was more pronounced in the myopic group.The results showed significant changes in the spherical equivalent,J0,and J45 astigmatism in all gazes with an increase in eccentricity(P<0.001).The pattern of refractive error changes was more noticeable in long and short eyes versus normal AL eyes.Moreover,the pattern of peripheral refractive changes was much more prominent in the high ACD group versus the normal ACD group and in the normal ACD group versus the low ACD group.CONCLUSION:Peripheral refraction changes are greater in participants with AL values outside the normal range and deeper ACD values compared to participants with normal AL and ACD.展开更多
AIM: To investigate a novel therapeutic strategy to target and suppress c-myc in human cancers using far up stream element (FUSE)-binding protein-interacting repressor (FIR).
Recombinant batroxobin(S3101)is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system.A literature survey showed no adequate method that could determine sufficient c...Recombinant batroxobin(S3101)is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system.A literature survey showed no adequate method that could determine sufficient concentrations to evaluate pharmacokinetic parameters for phase I clinical studies.Therefore,a sensitive method is urgently needed to support the clinical pharmacokinetic evaluation of S3101.In this study,a sensitive bioanalytical method was developed and validated,using a Quanterix single molecular array(Simoa)assay.Moreover,to thoroughly assess the platform,enzyme-linked immunosorbent assay and electrochemiluminescence assay were also developed,and their performance was compared with that of this novel technology platform.The assay was validated in compliance with the current guidelines.Measurements with the Simoa assay were precise and accurate,presenting a valid assay range from 6.55 to 4000 pg/mL.The intra-and inter-run accuracy and precision were within-19.3%to 15.3%and 5.5%to 17.0%,respectively.S3101 was stable in human serum for 280 days at-20℃and-70℃,for 2 h prior to pre-treatment and 24 h post pre-treatment at room temperature(22℃-28℃),respectively,and after five and two freeze-thaw cycles at-70℃and-20oC,respectively.The Simoa assay also demonstrated sufficient dilution linearity,assay sensitivity,and parallelism for quantifying S3101 in human serum.The Simoa assay is a sensitive and adequate method for evaluating the pharmacokinetic parameters of S3101 in human serum.展开更多
Background and objective: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation that is associated with an abnormal inflammatory response of the lung to noxious particles or g...Background and objective: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation that is associated with an abnormal inflammatory response of the lung to noxious particles or gases. Cigarette smoking is the major risk factor for the development of COPD. This study evaluated the levels of cyclophilin B in sputa from patients with COPD and COPD with acute exacerbation (AECOPD). Materials and Methods: Two-dimensional electrophoresis was used for differential display proteomics. Western blotting was used to identify and quantify cyclophilin B in sputum from subjects with AECOPD and COPD. Results: Forty-nine protein spots differed in relative intensity between the AECOPD (n = 6) and COPD (n = 6) subjects. Twenty proteins showed increased expression in the sputum of AECOPD subjects, and 29 proteins were present at lower levels in AECOPD sputum compared with COPD sputum. One of these proteins was associated with cyclophilin B. Cyclophilin B concentrations were lower in sputum from subjects with COPD (n = 4) versus AECOPD (n = 4). Conclusion: The sputum proteomic analysis suggests that changes in various proteins are associated with the development of AECOPD.展开更多
基金financial support from the National Key R&D Program of China (No.2021YFA1302604)Scientific and technological innovation project of China Academy of Chinese Medical Sciences (No.CI2021B017)China Postdoctoral Science Foundation (No.2023T160727)。
文摘RNA binding proteins(RBPs) are a crucial class of proteins that interact with RNA and play a key role in various biological process.Deficiencies or abnormalities of RBPs are closely linked to the occurrence and progression of numerous diseases,making RBPs potential therapeutic targets.However,the limited tissue penetration of 254 nm UV irradiation makes it difficult to efficiently crosslink weak and dynamic RNA-protein interactions in mammal tissues.Additionally,RNA degradation in metal catalyzed click reaction further hinders the enrichment of RNA-protein complexes(RPCs).Due to these inherent limitations,globally profiling the RNA binding proteome in mammal organs has long been a challenge.Herein,we proposed a novel method,which utilized a dual crosslinking with formaldehyde and 254 nm UV irradiation,metabolic labeling and metal-free thiol-yne click reaction to enable large-scale enrichment and identification of RBPs in mouse liver,called FTYc_UV.In this method,formaldehyde is first used to crosslink the crude RNA-protein complexes(cRPCs) in situ to address the problem of poor tissue penetration of 254 nm UV irradiation.Furthermore,this method integrates metabolic labeling with a metal-free thiol-yne click reaction to achieve non-destructive RNA tagging.After specifically RNA-RBPs crosslinking by 254 nm UV irradiation in tissue lysates,formaldehyde decrosslinking is employed to remove non-specific proteins,leading to effective enrichment of RPCs from mouse liver and thereby overcoming the poor specificity of formaldehyde crosslinking.Application of FTYc_UV in mouse liver successfully identified over 1600 RBPs covering approximately 75 % of previously reported RBPs.Furthermore,420 candidate RBPs,including 151metabolic enzymes,were also obtained,demonstrating the sensitivity of FTYc_UV and the potential of this method for in-depth exploration of RNA-protein interactions in biological and clinical research.
基金supported by the National Natural Science Foundation of China (82270355, 82270354, 81970134, 82030011, 31630093)the National Key Research and Development Program of China (2019YFA0801601, 2021YFA1101801)。
文摘The rapid development of genome editing technology has brought major breakthroughs in the fields of life science and medicine. In recent years, the clustered regularly interspaced short palindromic repeats(CRISPR)-based genome editing toolbox has been greatly expanded, not only with emerging CRISPR-associated protein(Cas) nucleases, but also novel applications through combination with diverse effectors. Recently, transposon-associated programmable RNA-guided genome editing systems have been uncovered, adding myriads of potential new tools to the genome editing toolbox. CRISPR-based genome editing technology has also revolutionized cardiovascular research. Here we first summarize the advances involving newly identified Cas orthologs, engineered variants and novel genome editing systems, and then discuss the applications of the CRISPR-Cas systems in precise genome editing, such as base editing and prime editing. We also highlight recent progress in cardiovascular research using CRISPR-based genome editing technologies, including the generation of genetically modified in vitro and animal models of cardiovascular diseases(CVD) as well as the applications in treating different types of CVD. Finally, the current limitations and future prospects of genome editing technologies are discussed.
文摘AIM:To evaluate the effects of polarized and nonpolarized sunglasses on visual functions,including distance and near visual acuity,phoria,stereopsis and contrast sensitivity across five spatial frequencies(1.5,3,6,12,18 cycles/degree).METHODS:A before-after study was conducted on 45 emmetropic students from Shahid Beheshti University of Medical Sciences.Visual acuity,contrast sensitivity,stereopsis and phoria were measured under three conditions:without sunglasses,with non-polarized sunglasses and with polarized sunglasses.Tests were conducted under controlled glare conditions to simulate outdoor environments.RESULTS:A total of 45 participants were evaluated,comprising 17 males(37.8%)and 28 females(62.2%).The mean age was 21.67±2.31y(range 18-27y).The mean of distance and near visual acuity in all three conditions were equal to 0.00 logMAR.Contrast sensitivity generally decreased slightly with the use of non-polarized sunglasses compared to the no-sunglasses condition.The mean stereopsis with polarized sunglasses was 101.33±56.139 arc sec,which was worse than the no-sunglasses condition(94.33±46.632 arc sec)and better than the non-polarized sunglasses condition(105.67±58.965 arc sec),although these changes were not significant.In the phoria parameter,distance phoria appeared more affected than near phoria.CONCLUSION:Polarized and non-polarized sunglasses do not significantly affect visual acuity,stereopsis,or phoria under controlled glare conditions.Slight changes in contrast sensitivity are noted,but they are not statistically significant.
基金Beijing Nova Program,Grant/Award Number:20220484086。
文摘Radiological or nuclear accidents can lead to serious outcomes for individuals exposed to ionizing radiation,with health effects that are either acute or delayed,deterministic or stochastic,depending on the effective dose of exposure.Mechanistically,ionizing radiation can inflict damage either directly on DNA or through oxidative stress,which may trigger a cascade of damages to tissues and organs.The development of effective radiation medical countermeasures is an unmet need and should be a top priority in preparing for radiation emergencies.This paper aims to address the critical questions of whether current countermeasures are available,what additional measures are needed,and what actions can be taken to enhance the development of radiation medical countermeasures from a systematic perspective.
基金supported by National Natural Science Foundation of China(32172365 and 32272513)the Central Guidance on Local Science and Technology Development Fund of Fujian Province,China(2022L3088)the Innovative Research Funding of Fujian Agriculture and Forestry University,China(CXZX2020153D)。
文摘The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pathogenicity,and autophagy of the rice blast fungus.In this study,we further revealed that PoElp3 functions via tRNA-mediated protein integrity.Phenotypic analyses revealed that overexpression of two of the tRNAs,tK(UUU)and tQ(UUG)could rescue the defects inΔPoelp3 strain.TMT-based proteomic and transcriptional analyses demonstrated that 386 proteins were down-regulated inΔPoelp3 strain compared with wild type strain Guy11,in a transcription-independent manner.Codon usage assays revealed an enrichment of Glutamine CAA-biased mRNA in the 386 proteins compared with the 70-15 genome.In addition to those reported previously,we also found that PoErp9,a sphingolipid C9-methyltransferase,was down-regulated in theΔPoelp3strain.Through an ILV2-specific integration of PoERP9-GFP into the wild type andΔPoelp3 strain,we were able to show that PoErp9 was positively regulated by PoElp3 translationally but not transcriptionally.Functional analyses revealed that PoErp9 was involved in the fungal growth,conidial development,pathogenicity,and TORrelated autophagy homeostasis in Pyricularia oryzae.Taken together,our results suggested that PoElp3 acts through the tRNA-mediated translational efficiency to regulate asexual development,pathogenicity,sphingolipid metabolism,and autophagy in the rice blast fungus.
基金supported by grants from the State Key Program of National Natural Science of China (31630093)the National Natural Science Foundation of China (31571512, 31871476, and 81241062)+1 种基金the Beijing Nova Program (Z161100004916146)the National Basic Research Program of China (2012CB966904)
文摘Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus.Genetic mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^(ERT2) developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient mice.Mechanistically, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore,inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA.
基金supported by grants from the Ministry of Science and Technology of China(2011CB504304 and 2012CB967003)the National Natural Science Foundation of China(81271902 and 81230045)
文摘Background:Elevated levels of serum C-reactive protein(CRP) have been reported to have prognostic significance in lung cancer patients.This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.Methods:CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis.CRP-bound serum amyloid A(CRP-SAA) was evaluated by coimmunoprecipitation(IP).Serum samples from two independent cohorts with lung cancer(retrospective cohort,242patients;prospective cohort,222 patients) and healthy controls(159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.Results:CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis.CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media.The level of CRP-SAA was significantly higher in patients than in healthy controls(0.37 ± 0.58 vs.0.03 ± 0.04,P < 0.001).Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer.The elevation of CRPSAA was associated with lower survival rates for both the retrospective(hazard ration[HR]= 2.181,95%confidence interval[CI]= 1.641-2.897,P < 0.001) and the prospective cohorts(HR = 2.744,95%CI = 1.810-4.161,P < 0.001).Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer.Remarkably,in stages l-ll patients,only CRP-SAA,not total SAA or CRP,showed significant association with overall survival in two cohorts.Moreover,univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.Conclusion:CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP,especially in earlystage patients.
基金the National Natural Science Foundation of China(81800561)the State Key Laboratory of Proteomics(SKLP-K201404).
文摘Background:Toll-like receptor 5(TLR5)-mediated pathways play critical roles in regulating the hepatic immune response and show hepatoprotective effects in mouse models of hepatic diseases.However,the role of TLR5 in experimental models of liver regeneration has not been reported.This study aimed to investigate the role of TLR5 in partial hepatectomy(PHx)-induced liver regeneration.Methods:We performed 2/3 PHx in wild-type(WT)mice,TLR5 knockout mice,or TLR5 agonist CBLB502 treated mice,as a model of liver regeneration.Bacterial flagellin content was measured with ELISA,and hepatic TLR5 expression was determined with quantitative PCR analyses and flow cytometry.To study the effects of TLR5 on hepatocyte proliferation,we analyzed bromodeoxyuridine(BrdU)incorporation and proliferating cell nuclear antigen(PCNA)expression with immunohistochemistry(IHC)staining.The effects of TLR5 during the priming phase of liver regeneration were examined with quantitative PCR analyses of immediate early gene mRNA levels,and with Western blotting analysis of hepatic NF-κB and STAT3 activation.Cytokine and growth factor production after PHx were detected with real-time PCR and cytometric bead array(CBA)assays.Oil Red O staining and hepatic lipid concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after PHx.Results:The bacterial flagellin content in the serum and liver increased,and the hepatic TLR5 expression was significantly up-regulated in WT mice after PHx.TLR5-deficient mice exhibited diminished numbers of BrdU-and PCNA-positive cells,suppressed immediate early gene expression,and decreased cytokine and growth factor production.Moreover,PHx-induced hepatic NF-κB and STAT3 activation was inhibited in Tlr5–/–mice,as compared with WT mice.Consistently,the administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation,which was correlated with enhanced production of proinflammatory cytokines and the recruitment of macrophages and neutrophils in the liver.Furthermore,Tlr5–/–mice displayed significantly lower hepatic lipid concentrations and smaller Oil Red O positive areas than those in control mice after PHx.Conclusions:We reveal that TLR5 activation contributes to the initial events of liver regeneration after PHx.Our findings demonstrate that TLR5 signaling positively regulates liver regeneration and suggest the potential of TLR5 agonist to promote liver regeneration.
基金supported by Tonekabon Branch,Islamic Azad University,Tonekabon,Iran,No.73/442453
文摘Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on rat behaviors remain poorly understood. In this study, we used nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous sciatic nerve to bridge 30-ram-long rat sciatic nerve gaps. Within 4 months after surgery, rat sciatic nerve functional re- covery was evaluated per month by behavioral analyses, including toe out angle, toe spread anal- ysis, walking track analysis, extensor postural thrust, swimming test, open-field analysis and no- ciceptive function. Results showed that rat sciatic nerve functional recovery was similar after nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous nerve grafting. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit is suitable in use for repair of long-segment sciatic nerve defects.
基金supported by the National Hightech R&D Program(863 Program)(No.2006AA02A308)the National Basic Research Program of China(973 Program)(No.2006CB910401,2006CB910801 and 2006CB910600)+3 种基金the National Natural Science Foundation of China(No.30700988 and 30700356)the National Natural Science Foundation of China for Creative Research Groups(No.30621063)the Chinese State Key Project Specialized for Infectious Diseases(No.2008ZX10002-016,2009ZX10004-103 and 2009ZX09301002)supported by the State Key Laboratory of Proteomics(No.SKLP-Y200801)
文摘Genome sequencing opened the flood gate of"-omics"studies,among which the research about correlations between genomic and phenomic variables is an important part.With the development of functional genomics and systems biology,genome-wide investigation of the correlations between many genomic and phenomic variables became possible.In this review,five genomic variables,such as evolution rate(or"age"of the gene),the length of intron and ORF(protein length)in one gene,the biases of amino acid composition and codon usage,along with the phenomic variables related to expression patterns(level and breadth)are focused on.In most cases,genes with higher mRNA/protein expression level tend to evolve slowly,have less intronic DNA,code for smaller proteins,and have higher biases of amino acid composition and codon usage.In addition,broadly expressed proteins evolve more slowly and are shorter than tissue-specific proteins.Studies in this field are helpful for deeper understanding the signatures of selection mediated by the features of gene expression and are of great significance to enrich the evolution theory.
基金supported by the grants from the National Program on Key Basic Research Project (Nos. 2013CB910300 and 2012CB910300 to H.P.)the International Science and Technology Cooperation Program of China (No. 2015DFA31680)+2 种基金the One Thousand Young Talent Program (to H.P.)the State Key Laboratory of Proteomics (No. SKLP-O201303 to C.Y.)the National Natural Science Foundation of China (No. 31371433 to H.P.)
文摘O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine （GlcNAc） transferase （OGT） mediated O-GlcNAcylation of histone H2B Ser 112 （H2B S 112 GlcNAcylation） plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress- inducing agents. OGT mediated H2B Sl12 GlcNAcylation increased locally upon the induction of double-strand breaks （DSBs）, and depletion of OGT or overexpression of H2B S 112A mutant impaired homologous recombination （HR） and nonhomologous end-joining （NHEJ）. Mechanistically, H2B Sl12 GlcNAcylation could bind Nijmegen breakage syndrome 1 （NBS1） and regulate NBS1 foci for- mation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response （DDR）.
基金the financial support from the National Key Program for Basic Research of China(Grant Nos.:2018YFC0910302 and 2017YFF0205400)the National Natural Science Foundation of China(Grant No.:81530021)Innovation Foundation of Medicine(Grant Nos.:BWS14J052 and 16CXZ027)
文摘Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.
基金supported by Tonekabon Branch, Islamic Azad University, Tonekabon, Iran,No. 73/442453
文摘It has been confirmed that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were macroscopi- cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson＇s trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3- hydroxyvalerate） nerve conduit is suitable for repair of long-segment sciatic nerve defects.
文摘AIM To assess how serum gamma-glutamyltransferase(GGT) fractions vary in patients with alcoholic liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD). METHODS Serum samples were obtained from 14 patients with biopsy-proven alcoholic liver diseases and 9 patients with biopsy proven non-alcoholic fatty liver disease. In addition to these biopsy-proven cases, 16 obese(body mass index > 25) patients without any history of alcohol consumption but with a fatty liver on ultrasound examination and with elevated GGT were included for an additional analysis. Serum GGT fractionation was conducted by high-performance gel filtration liquid chromatography and was separated into the four fractions, big-GGT, medium-GGT, small-GGT(s-GGT), and free-GGT(f-GGT).RESULTS The results were expressed as a ratio of each fraction including the total GGT(t-GGT). The s-GGT/t-GGT ratioswere lowest for the control group and highest for the ALD group. The differences between the control and NAFLD groups and also between the NAFLD and ALD groups were statistically significant. In contrast, the f-GGT/t-GGT ratios were highest in the control group and lowest in the ALD group, with the differences being statistically significant. As a result, the s-GGT/f-GGT ratios were markedly increased in the NAFLD group as compared with the control group. The increase of the s-GGT/t-GGT ratios, the decrease of the f-GGT/t-GGT ratios, and the increase of s-GGT/F-GGT ratios as compared with the control group subjects were also found in obese patients with clinically diagnosed fatty change of the liver.CONCLUSION Serum GGT fractionation by high-performance gel filtration liquid chromatography is potentially useful for the differential diagnosis of ALD and NAFLD.
文摘Background This prospective study integrated multiple clinical indexes and inflammatory markers associated with coronary atherosclerotic vulnerable plaque to establish a risk prediction model that can evaluate a patient with certain risk factors for the likelihood of the occurrence of a coronary heart disease event within one year. Methods This study enrolled in 2686 patients with mild to moderate coronary artery lesions. Eighty-five indexes were recorded, included baseline clinical data, laboratory studies, and procedural characteristics. During the 1-year follow-up, 233 events occurred, five patients died, four patients suffered a nonfatal myocardial infarction, four patients underwent revascularization, and 220 patients were readmitted for angina pectoris. The Risk Estimation Model and the Simplified Model were conducted using Bayesian networks and compared with the Single Factor Models. Results The area under the curve was 0.88 for the Bayesian Model and 0.85 for the Simplified Model, while the Single Factor Model had a maximum area under the curve of 0.65. Conclusion The new models can be used to assess the short-term risk of individual coronary heart disease events and may assist in guiding preventive care.
文摘AIM:To investigate the effect of astigmatism and spherical equivalent(SE)correction on contrast sensitivity(CS).METHODS:In this cross-sectional study,103 visually normal subjects aged 18 to 36y with bilateral regular astigmatism in range of 1.00 diopter cylinder(DC)to 4.00 DC and normal best-corrected visual acuity(20/20)were recruited.Binocular CS was assessed by linear sine-wave gratings at 1.5,3,6,12,and 18 cycles per degree(cpd),before correction of astigmatism,after full correction of astigmatism by cylindrical spectacle lenses,and after SE of refractive error.The repeated measures ANOVA and Bonferroni test were used to compare the effects of astigmatism correction on logCS.RESULTS:Totally 39 patients were male and 64 patients were female with the mean age of 28.25±5.38y.The average degree of astigmatism in right and left eye was 2.03±0.83 and 2.10±0.78,respectively.Increases in uncorrected astigmatic power correlated with decreases in the logCS,especially at high spatial frequencies.A statistically significant difference in logCS was found between these three cases:before correction of astigmatism,after SE of refractive error,and after full correction of astigmatism by cylindrical spectacle lenses at all frequencies(P<0.001),except at 18 cpd.At 18 cpd,there was no statistically significant difference between logCS before and after SE of refractive error(P=1.0).Also,there was no statistically significant difference in mean CS between with-the-rule(WTR)and against-the-rule(ATR)astigmatism,before correction of astigmatism,after correction of astigmatism with cylindrical lenses,and after SE of refractive error.CONCLUSION:Binocular astigmatism defocus decreases CS depending on the degree of astigmatism power;correction of this will improve patent’s quality of vision.Although high astigmatism refractive error(more than 2.00 DC)that is fully corrected by cylindrical spectacle lenses doesn’t increase the CS to the maximum value,especially at higher spatial frequencies(12 and 18).Also SE refractive error effects on improving CS in low astigmatism power(less than 2.00 DC),especially at lower spatial frequencies.
文摘AIM:To evaluate the effect of axial length(AL)and anterior chamber depth(ACD)on peripheral refractive profile in myopic patients compared to emmetropic participants.METHODS:This cross-sectional study was conducted in right eyes of 58 participants of whom 38 were emmetropic and 20 were myopic.Central and peripheral refraction were measured at 10°,20°,and 30°eccentricities in nasal and temporal fields using an open-field autorefractor.The Lenstar LS900 was used to measure ACD and AL.The participants were divided into three groups of short(<22.5 mm),normal(22.5-24.5 mm),and long eye(>24.5 mm)according to AL and three groups of low ACD(<3.00 mm),normal ACD(3.00-3.60 mm),and high ACD(>3.60 mm)according to ACD.RESULTS:The mean age of the participants was 22.26±3.09 y(range 18-30 y).The peripheral mean spherical refractive error showed a hypermetropic shift in myopic and emmetropic groups although this shift was more pronounced in the myopic group.The results showed significant changes in the spherical equivalent,J0,and J45 astigmatism in all gazes with an increase in eccentricity(P<0.001).The pattern of refractive error changes was more noticeable in long and short eyes versus normal AL eyes.Moreover,the pattern of peripheral refractive changes was much more prominent in the high ACD group versus the normal ACD group and in the normal ACD group versus the low ACD group.CONCLUSION:Peripheral refraction changes are greater in participants with AL values outside the normal range and deeper ACD values compared to participants with normal AL and ACD.
基金Supported by In part by the 21st Century COE(Center Of Ex-cellence)Programs to Dr.Takenori Ochiaiby a Grant-in-Aid 18591453 to K.M from the Ministry of Education,Science,Sports and Culture of Japan
文摘AIM: To investigate a novel therapeutic strategy to target and suppress c-myc in human cancers using far up stream element (FUSE)-binding protein-interacting repressor (FIR).
文摘Recombinant batroxobin(S3101)is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system.A literature survey showed no adequate method that could determine sufficient concentrations to evaluate pharmacokinetic parameters for phase I clinical studies.Therefore,a sensitive method is urgently needed to support the clinical pharmacokinetic evaluation of S3101.In this study,a sensitive bioanalytical method was developed and validated,using a Quanterix single molecular array(Simoa)assay.Moreover,to thoroughly assess the platform,enzyme-linked immunosorbent assay and electrochemiluminescence assay were also developed,and their performance was compared with that of this novel technology platform.The assay was validated in compliance with the current guidelines.Measurements with the Simoa assay were precise and accurate,presenting a valid assay range from 6.55 to 4000 pg/mL.The intra-and inter-run accuracy and precision were within-19.3%to 15.3%and 5.5%to 17.0%,respectively.S3101 was stable in human serum for 280 days at-20℃and-70℃,for 2 h prior to pre-treatment and 24 h post pre-treatment at room temperature(22℃-28℃),respectively,and after five and two freeze-thaw cycles at-70℃and-20oC,respectively.The Simoa assay also demonstrated sufficient dilution linearity,assay sensitivity,and parallelism for quantifying S3101 in human serum.The Simoa assay is a sensitive and adequate method for evaluating the pharmacokinetic parameters of S3101 in human serum.
文摘Background and objective: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation that is associated with an abnormal inflammatory response of the lung to noxious particles or gases. Cigarette smoking is the major risk factor for the development of COPD. This study evaluated the levels of cyclophilin B in sputa from patients with COPD and COPD with acute exacerbation (AECOPD). Materials and Methods: Two-dimensional electrophoresis was used for differential display proteomics. Western blotting was used to identify and quantify cyclophilin B in sputum from subjects with AECOPD and COPD. Results: Forty-nine protein spots differed in relative intensity between the AECOPD (n = 6) and COPD (n = 6) subjects. Twenty proteins showed increased expression in the sputum of AECOPD subjects, and 29 proteins were present at lower levels in AECOPD sputum compared with COPD sputum. One of these proteins was associated with cyclophilin B. Cyclophilin B concentrations were lower in sputum from subjects with COPD (n = 4) versus AECOPD (n = 4). Conclusion: The sputum proteomic analysis suggests that changes in various proteins are associated with the development of AECOPD.
