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
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
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
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
Recent advances in drug development and bioactive molecules that covalently target lysine residues have shown substantial progress.Both reversible and irreversible covalent inhibitors are developed for targeting lysin...Recent advances in drug development and bioactive molecules that covalently target lysine residues have shown substantial progress.Both reversible and irreversible covalent inhibitors are developed for targeting lysine residues.The identification of protein targets and binding sites of these lysine-targeting molecules in the whole proteome is crucial to understand their proteome-wide selectivity.For covalent inhibitors,the pull down-based methods including activity-based protein profiling(ABPP)are commonly used to profile their target proteins.For covalent reversible inhibitors,it is not easy to pull down the potential protein targets as the captured proteins may get off beads because of the reversible manner.Here,we report a pair of isotope-labelled click-free probes to competitively identify the protein targets of lysine-targeting covalent reversible small molecules.This pair of isotopic probes consists of a lysinereactive warhead,a desthiobiotin moiety and isotopicable linker.This integrated probe could eliminate the background proteins induced by the click chemistry during the pull-down process.To demonstrate the feasibility of our newly-developed probes for the protein target identification,we selected the natural product Gossypol in that we proved for the first time that it could modify the lysine residue in a covalent reversible manner.Finally,we confirmed that this pair of integrated probes can be used in a competitive manner to precisely identify the protein target as well as binding sites of Gossypol.Interestingly,pretreatment of Gossypol could stop the antibody from recognizing Gossypol-binding proteins.Together,our isotope-labeled click-free probes could be used for whole-proteome profiling of lysine-targeting covalent reversible small molecules.展开更多
In this work,a flexible battery structure is fabricated using soft lithography and three-dimensional(3D) printing technology.Ga_(52.5)Sn_(39.5)Zn_(8) anode material,Bi_(67)In_(33) cathode material,and alkaline hydroge...In this work,a flexible battery structure is fabricated using soft lithography and three-dimensional(3D) printing technology.Ga_(52.5)Sn_(39.5)Zn_(8) anode material,Bi_(67)In_(33) cathode material,and alkaline hydrogel electrolyte are introduced to form the flexible battery.A variety of circuit structures are fabricated to realize the series-parallel integration of different numbers of single cells and achieve the fabrication of batteries with different voltages and powers,with a maximum open-circuit voltage(OCV) of 4.6 V and a maximum output power of 1.193 mW.A reconfigurable soft battery group is proposed,and the regulation of the battery voltage has been realized through the microfluidic perfusion process without the need for an external variable-voltage circuit.We have also fabricated an EGaIn-NaOH microfluidic switch to achieve the control of the light emitting diode(LED).In addition,a wristband with a flexible battery is demonstrated to realize power supply to a liquid crystal display(LCD) with a clock or a temperature sensor.展开更多
AIM:To explore the changes in early retinal development after the occurrence of ischemia.METHODS:Human retinal organoids(hROs)of day 18 or day 30 were treated with oxygen-glucose deprivation and reperfusion(OGD/R)to s...AIM:To explore the changes in early retinal development after the occurrence of ischemia.METHODS:Human retinal organoids(hROs)of day 18 or day 30 were treated with oxygen-glucose deprivation and reperfusion(OGD/R)to simulate the retinal ischemia.All hROs were maintained normally until day 60 to evaluate changes in ischemic injuries during retinal development.Paraffin section staining was used for detecting changes in organoid structure and cell number.Real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot(WB)analyses were used to observe the change in the expression of retinal cell markers.RESULTS:In hROs,OGD/R induced the decrease of proliferating cells,inhibited the expression of proliferated marker Ki67 and promoted early apoptosis of retinal cells(P<0.05).Under OGD/R condition,the progenitor cell layer and ganglion cell layer of hROs lost normal structure,and the number of neural stem cells(SOX2^(+)),retinal progenitor cells(CHX10^(+))and retinal ganglion cells(TUJ1^(+)/BRN3^(+)/ATOH7^(+))decreased(P<0.05).The expression of corresponding retinal cell markers also decreased(P<0.05).Organoids treated with OGD/R on day 30 had similar injuries in retinal structure and retinal cell markers to those on day 18.Long-term observations revealed that day 18-treated organoids remained disorganized progenitor and ganglion cell layers by day 60,with no recovery in proliferating cell nuclear antigen(PCNA)protein expression.RT-qPCR showed persistently low Ki67 transcription levels(P<0.001),while other retinal cell markers recovered or exceeded normal levels,indicating a limited self-repair happened in the development of hROs.In contrast,day 30-treated organoids exhibited normal structure and marker expression by day 60,with transcription levels of retinal cell markers returning to normal(P>0.05),demonstrating complete recovery from OGD/R damage.CONCLUSION:Retinal ischemia damage the retinal development in the short-term.After the restoration of retinal blood supply,the retinal ischemic damage can be recovered during subsequent development.However,retinal ischemic injuries at different developmental stages exhibit varying degrees of reversibility.The earlier ischemic injury occurs,the more difficult it is to repair retinal cell and structure damage.展开更多
The authors wish to amend the following information“The Western blotting of the CHOP protein in Figure 2D,the internal reference used is GAPDH,which has a molecular weight of 36 kDa”and“the SRT1720 group immunofluo...The authors wish to amend the following information“The Western blotting of the CHOP protein in Figure 2D,the internal reference used is GAPDH,which has a molecular weight of 36 kDa”and“the SRT1720 group immunofluorescence image in Figure 4G”.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
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
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
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
Background:Lung cancer is one of the most common cancers globally with high incidence and mortality rate.Acupuncture and moxibustion have been used as adjuvant therapies to relieve the symptoms and complications of lu...Background:Lung cancer is one of the most common cancers globally with high incidence and mortality rate.Acupuncture and moxibustion have been used as adjuvant therapies to relieve the symptoms and complications of lung cancer.At present,acupuncture and moxibustion can partially improve the quality of life(QOL)of cancer patients.However,the evidence that acupuncture and moxibustion can improve patient-reported outcomes(PROs)in patients with lung cancer is still insufficient.We aimed to conduct a systematic review and meta-analysis of published randomized controlled trials(RCTs)to determine whether acupuncture and moxibustion can improve PROs among patients with lung cancer,providing a support basis for acupuncture and moxibustion inclusion in relevant guidelines.Methods:We will search the following electronic databases:PubMed,Embase,Cochrane Library,Web of Science,CNKI,CQVIP,Wanfang Data,Sinomed,and gray literature including the ClinicalTrials.gov Database(clinicaltrials.gov)and Chinese Clinical Trial Register(chictr.org.cn).All English and Chinese articles will be searched until July 1,2021.Two researchers independently extracted data.Any disagreement was resolved by discussion until consensus was reached or by consulting a third researcher.The primary outcomes mainly included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30),functional assessment of cancer therapy-lung(FACT-L),and Karnofsky Performance Status(KPS).The secondary outcomes included improvement of individual lung cancerrelated symptoms and the safety of acupuncture intervention.Discussion:Our study is the first to focus on the PROs of acupuncture and moxibustion for lung cancer treatment.The results will contribute to a deeper understanding of the evidence distribution of acupuncture and moxibustion in PROs,which may support the use of acupuncture and moxibustion in lung cancer patients.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
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
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
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 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.
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.
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 funding from The National Natural Science Foundation of China(No.22177136)the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2022-I2M-2-002).
文摘Recent advances in drug development and bioactive molecules that covalently target lysine residues have shown substantial progress.Both reversible and irreversible covalent inhibitors are developed for targeting lysine residues.The identification of protein targets and binding sites of these lysine-targeting molecules in the whole proteome is crucial to understand their proteome-wide selectivity.For covalent inhibitors,the pull down-based methods including activity-based protein profiling(ABPP)are commonly used to profile their target proteins.For covalent reversible inhibitors,it is not easy to pull down the potential protein targets as the captured proteins may get off beads because of the reversible manner.Here,we report a pair of isotope-labelled click-free probes to competitively identify the protein targets of lysine-targeting covalent reversible small molecules.This pair of isotopic probes consists of a lysinereactive warhead,a desthiobiotin moiety and isotopicable linker.This integrated probe could eliminate the background proteins induced by the click chemistry during the pull-down process.To demonstrate the feasibility of our newly-developed probes for the protein target identification,we selected the natural product Gossypol in that we proved for the first time that it could modify the lysine residue in a covalent reversible manner.Finally,we confirmed that this pair of integrated probes can be used in a competitive manner to precisely identify the protein target as well as binding sites of Gossypol.Interestingly,pretreatment of Gossypol could stop the antibody from recognizing Gossypol-binding proteins.Together,our isotope-labeled click-free probes could be used for whole-proteome profiling of lysine-targeting covalent reversible small molecules.
基金supported by the Science and Technology Program from State Grid Corporation of China through the Development of Flexible Liquid Metal Based Micro-Sensor with Anti-Electromagnetic Interference Ability for Power Engineering Applications under Grant 5700-202155453A-00-00。
文摘In this work,a flexible battery structure is fabricated using soft lithography and three-dimensional(3D) printing technology.Ga_(52.5)Sn_(39.5)Zn_(8) anode material,Bi_(67)In_(33) cathode material,and alkaline hydrogel electrolyte are introduced to form the flexible battery.A variety of circuit structures are fabricated to realize the series-parallel integration of different numbers of single cells and achieve the fabrication of batteries with different voltages and powers,with a maximum open-circuit voltage(OCV) of 4.6 V and a maximum output power of 1.193 mW.A reconfigurable soft battery group is proposed,and the regulation of the battery voltage has been realized through the microfluidic perfusion process without the need for an external variable-voltage circuit.We have also fabricated an EGaIn-NaOH microfluidic switch to achieve the control of the light emitting diode(LED).In addition,a wristband with a flexible battery is demonstrated to realize power supply to a liquid crystal display(LCD) with a clock or a temperature sensor.
基金Supported by the National Natural Science Foundation of China(No.82070937).
文摘AIM:To explore the changes in early retinal development after the occurrence of ischemia.METHODS:Human retinal organoids(hROs)of day 18 or day 30 were treated with oxygen-glucose deprivation and reperfusion(OGD/R)to simulate the retinal ischemia.All hROs were maintained normally until day 60 to evaluate changes in ischemic injuries during retinal development.Paraffin section staining was used for detecting changes in organoid structure and cell number.Real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot(WB)analyses were used to observe the change in the expression of retinal cell markers.RESULTS:In hROs,OGD/R induced the decrease of proliferating cells,inhibited the expression of proliferated marker Ki67 and promoted early apoptosis of retinal cells(P<0.05).Under OGD/R condition,the progenitor cell layer and ganglion cell layer of hROs lost normal structure,and the number of neural stem cells(SOX2^(+)),retinal progenitor cells(CHX10^(+))and retinal ganglion cells(TUJ1^(+)/BRN3^(+)/ATOH7^(+))decreased(P<0.05).The expression of corresponding retinal cell markers also decreased(P<0.05).Organoids treated with OGD/R on day 30 had similar injuries in retinal structure and retinal cell markers to those on day 18.Long-term observations revealed that day 18-treated organoids remained disorganized progenitor and ganglion cell layers by day 60,with no recovery in proliferating cell nuclear antigen(PCNA)protein expression.RT-qPCR showed persistently low Ki67 transcription levels(P<0.001),while other retinal cell markers recovered or exceeded normal levels,indicating a limited self-repair happened in the development of hROs.In contrast,day 30-treated organoids exhibited normal structure and marker expression by day 60,with transcription levels of retinal cell markers returning to normal(P>0.05),demonstrating complete recovery from OGD/R damage.CONCLUSION:Retinal ischemia damage the retinal development in the short-term.After the restoration of retinal blood supply,the retinal ischemic damage can be recovered during subsequent development.However,retinal ischemic injuries at different developmental stages exhibit varying degrees of reversibility.The earlier ischemic injury occurs,the more difficult it is to repair retinal cell and structure damage.
文摘The authors wish to amend the following information“The Western blotting of the CHOP protein in Figure 2D,the internal reference used is GAPDH,which has a molecular weight of 36 kDa”and“the SRT1720 group immunofluorescence image in Figure 4G”.
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 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Supported by the Project BEBPC-TCM2019XZZX-ZJ0011Shanghai Clinical Research Center for Acupuncture and Moxibustion Accelerating20MC1920500Clinical Key Specialty Construction Foundation of Shanghaishslczdzk04701。
文摘Background:Lung cancer is one of the most common cancers globally with high incidence and mortality rate.Acupuncture and moxibustion have been used as adjuvant therapies to relieve the symptoms and complications of lung cancer.At present,acupuncture and moxibustion can partially improve the quality of life(QOL)of cancer patients.However,the evidence that acupuncture and moxibustion can improve patient-reported outcomes(PROs)in patients with lung cancer is still insufficient.We aimed to conduct a systematic review and meta-analysis of published randomized controlled trials(RCTs)to determine whether acupuncture and moxibustion can improve PROs among patients with lung cancer,providing a support basis for acupuncture and moxibustion inclusion in relevant guidelines.Methods:We will search the following electronic databases:PubMed,Embase,Cochrane Library,Web of Science,CNKI,CQVIP,Wanfang Data,Sinomed,and gray literature including the ClinicalTrials.gov Database(clinicaltrials.gov)and Chinese Clinical Trial Register(chictr.org.cn).All English and Chinese articles will be searched until July 1,2021.Two researchers independently extracted data.Any disagreement was resolved by discussion until consensus was reached or by consulting a third researcher.The primary outcomes mainly included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30),functional assessment of cancer therapy-lung(FACT-L),and Karnofsky Performance Status(KPS).The secondary outcomes included improvement of individual lung cancerrelated symptoms and the safety of acupuncture intervention.Discussion:Our study is the first to focus on the PROs of acupuncture and moxibustion for lung cancer treatment.The results will contribute to a deeper understanding of the evidence distribution of acupuncture and moxibustion in PROs,which may support the use of acupuncture and moxibustion in lung cancer patients.
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 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.
