Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological change...Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.展开更多
Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and ...Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.展开更多
The plasma membrane(PM)plays an essential role in maintaining cell homeostasis,therefore,timely and effective repair of damage caused by factors such as mechanical rupture,pore-forming toxins,or pore-forming proteins ...The plasma membrane(PM)plays an essential role in maintaining cell homeostasis,therefore,timely and effective repair of damage caused by factors such as mechanical rupture,pore-forming toxins,or pore-forming proteins is crucial for cell survival.PM damage induces membrane rupture and stimulates an immune response.However,damage resulting from regulated cell death processes,including pyroptosis,ferroptosis,and necroptosis,cannot be repaired by simple sealing mechanisms and thus,requires specialized repair machinery.Recent research has identified a PM repair mechanism of regulated cell death-related injury,mediated by the endosomal sorting complexes required for transport(ESCRT)machinery.Here,we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury,with particular focus on processes related to regulated cell death.This overview,along with continued research in this field,may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.展开更多
Adipocyte-secreted extracellular vesicles(EVs)and adipose-derived stem cells(ADSCs)regulate physiological and pathological processes by delivering nucleic acids,proteins,and lipids.Both adipocyte-and ADSC-derived EVs ...Adipocyte-secreted extracellular vesicles(EVs)and adipose-derived stem cells(ADSCs)regulate physiological and pathological processes by delivering nucleic acids,proteins,and lipids.Both adipocyte-and ADSC-derived EVs regulate local inflammatory levels,tumor progression,and insulin sensitivity.These two types of EVs also have significant therapeutic effects on damage repair,including wound healing,angiogenesis,myocardial damage,vessel re-endothelialization,bone and cartilage regeneration,muscle repair,and nerve repair.With regard to wound healing,microRNA-21,microRNA-126,microRNA-31,and long non-coding RNA-H19 accelerate the proliferation and migration of fibroblasts,human immortalized keratinocytes,and endothelial cells via the PI3K/Akt/ERK pathway or fibrillin 1.ADSC-derived EVs contain various growth factors that are beneficial for wound healing.Numerous miRNAs in ADSC-derived EVs and β3-adrenergic receptors on brown adipocytes exhibit protective effects against myocardial infarction.Proteins in adipocyte-and ADSC-derived EVs play a role in promoting vessel re-endothelialization and regulating vasodilation.Angiogenesis is beneficial for the regeneration and repair of injured bone,cartilage,muscle,and nerves.Compared with adipocyte EVs,ADSC-EVs contain a greater variety of miRNAs and proteins that promote tissue regeneration.EV therapy is a promising cell-free therapy,and EV-loaded materials have been used for wound healing and myocardial damage.Future research will focus on identifying the molecules in EVs and the repair mechanisms that contribute to damage repair and regeneration.In addition,we aim to discover materials designed for slow release and specificity to facilitate tissue repair and optimize EV transportation.展开更多
To address the issue of extreme thermal-induced arching in CRTS II slab tracks due to joint damage,an optimized joint repair model was proposed.First,the formula for calculating the safe temperature rise of the track ...To address the issue of extreme thermal-induced arching in CRTS II slab tracks due to joint damage,an optimized joint repair model was proposed.First,the formula for calculating the safe temperature rise of the track was derived based on the principle of stationary potential energy.Considering interlayer evolution and structural crack propagation,an optimized joint repair model for the track was established and validated.Subsequently,the impact of joint repair on track damage and arch stability under extreme temperatures was studied,and a comprehensive evaluation of the feasibility of joint repair and the evolution of damage after repair was conducted.The results show that after the joint repair,the temperature rise of the initial damage of the track structure can be increased by 11℃.Under the most unfavorable heating load with a superimposed temperature gradient,the maximum stiffness degradation index SDEG in the track structure is reduced by about 81.16%following joint repair.The joint repair process could effectively reduce the deformation of the slab arching under high temperatures,resulting in a reduction of 93.96%in upward arching deformation.After repair,with the damage to interfacing shear strength,the track arch increases by 2.616 mm.展开更多
In order to thoroughly understand the mechanism Of drought resistance in plants at DNA level, the DNA damage of two ecotypes of reeds (Phragmites communis T.) stressed by PEG 6000 was analyzed by means of fluorescence...In order to thoroughly understand the mechanism Of drought resistance in plants at DNA level, the DNA damage of two ecotypes of reeds (Phragmites communis T.) stressed by PEG 6000 was analyzed by means of fluorescence analysis of DNA unwinding (FADU). The results showed that the residual double strand DNA percentages (dsDNA%) in dune reed (DR) were significantly higher than those in swamp reed (SR) treated with either 20% or 30% PEG 6000. This meant that the DNA of DR was less damaged in comparison with SR. Similarly, DR resisted DNA damage more strongly than SR as reactive oxygen species (ROS) increased by adding ROS producers diethyldithio carbamate (DDC), H2O2 and Fe2+ of different concentrations. Meanwhile, treating PEG stressed SR with ROS scavengers such as dimethyl sulphoxide (DMSO) and ascorbic acid (Vc) resulted in the reduction of DNA damage, suggesting that ROS could cause DNA damage. In addition, the DNA repair for water-stressed reeds indicated that DR repaired DNA damage much faster and more completely. This might be the first indication that drought stress led to DNA damage in plants and that drought resistance of plants was closely related to DNA damage and repair.展开更多
NF-κB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin κ-chain enhancer and enhance transcriptional activity. NF-κB/Rel proteins, as a dimeric transcription factor, control th...NF-κB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin κ-chain enhancer and enhance transcriptional activity. NF-κB/Rel proteins, as a dimeric transcription factor, control the expression of genes that regulate a broad range of biological processes through canonical and non-canonical pathways. In the central nervous system, NF-κB controls inflammatory reactions and the apoptotic cell death following nerve injury. It also contributes to the infarction and cell death in stroke models and patients. However, NF-κB is essential for neurosurvival as well. NF-κB activation is a part of recovery process that may protect neurons against oxidative-stresses or brain ischemia-induced apoptosis and neurodegeneration. Inhibition of NF-κB may reduce its neuroprotection activity. Hence the dual opposite effects of NF-κB on cells. The ultimate survival or death of neurons depends on which, where and when the NF-κB factors are activated.展开更多
Modal parameters can accurately characterize the structural dynamic properties and assess the physical state of the structure.Therefore,it is particularly significant to identify the structural modal parameters accordi...Modal parameters can accurately characterize the structural dynamic properties and assess the physical state of the structure.Therefore,it is particularly significant to identify the structural modal parameters according to the monitoring data information in the structural health monitoring(SHM)system,so as to provide a scientific basis for structural damage identification and dynamic model modification.In view of this,this paper reviews methods for identifying structural modal parameters under environmental excitation and briefly describes how to identify structural damages based on the derived modal parameters.The paper primarily introduces data-driven modal parameter recognition methods(e.g.,time-domain,frequency-domain,and time-frequency-domain methods,etc.),briefly describes damage identification methods based on the variations of modal parameters(e.g.,natural frequency,modal shapes,and curvature modal shapes,etc.)and modal validation methods(e.g.,Stability Diagram and Modal Assurance Criterion,etc.).The current status of the application of artificial intelligence(AI)methods in the direction of modal parameter recognition and damage identification is further discussed.Based on the pre-vious analysis,the main development trends of structural modal parameter recognition and damage identification methods are given to provide scientific references for the optimized design and functional upgrading of SHM systems.展开更多
In this study, three rapid repair techniques are proposed to retrofit circular bridge piers that are severely damaged by the flexural failure mode in major earthquakes. The quasi-static tests on three 1：2.5 scaled ci...In this study, three rapid repair techniques are proposed to retrofit circular bridge piers that are severely damaged by the flexural failure mode in major earthquakes. The quasi-static tests on three 1：2.5 scaled circular pier specimens are conducted to evaluate the efficiency of the proposed repair techniques. For the purpose of rapid repair, the repair procedure for all the specimens is conducted within four days, and the behavior of the repaired specimens is evaluated and compared with the original ones. A finite element model is developed to predict the cyclic behavior of the repaired specimens and the numerical results are compared with the test data. It is found that all the repaired specimens exhibit similar or larger lateral strength and deformation capacity than the original ones. The initial lateral stiffness of all the repaired specimens is lower than that of the original ones, while they show a higher lateral stiffness at the later stage of the test. No noticeable difference is observed for the energy dissipation capacity between the original and repaired pier specimens. It is suggested that the repair technique using the early-strength concrete jacket confined by carbon fiber reinforced polymer （CFRP） sheets can be an optimal method for the rapid repair of severely earthquake-damaged circular bridge piers with flexural failure mode.展开更多
One of the main factors of laser induced damage is the modulation to incident laser which is caused by the defect in the subsurface of the fused silica. In this work, the repaired damage site irradiated by CO2 laser i...One of the main factors of laser induced damage is the modulation to incident laser which is caused by the defect in the subsurface of the fused silica. In this work, the repaired damage site irradiated by CO2 laser is simplified to a Gaussian rotation according to the corresponding experimental results. Then, the three-dimensional finite-difference time-domain method is employed to simulate the electric field intensity distribution in the vicinity of this kind of defect in fused silica front subsurface. The simulated results show that the modulation is notable, the Emax is about 2.6 times the irradiated electric field intensity in the fused silica with the damage site （the width is 1.5 μm and depth is 2.3 μm） though the damage site is repaired by CO2 laser. The phenomenon and the theoretical result of the annular laser enhancement existed on the rear surface are first verified effectively, which agrees well with the corresponding experimental results. The relations between the maximal electric field intensity in fused silica with defect depth and width are given respectively. Meanwhile, the corresponding physical mechanism is analysed theoretically in detail.展开更多
Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal c...Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal cancer(CRC)progression.The present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells,as well as the underlying mechanism.The relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues,as well as in radiosensitive and radioresistant samples.The correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square test.Functional assays such as cell proliferation,colony formation and apoptosis assays were conducted to determine the radiosensitivity in CRC cells with HOTAIR silencing after treatment with different doses of radiation.RNA pull-down assay andfluorescence in situ hybridization(FISH)were used to determine the interaction between HOTAIR and DNA damage response mediator ataxia-telangiectasia mutated-and Rad3-related(ATR).HOTAIR was significantly upregulated in CRC tumor tissues,especially in radioresistant tumor samples.The elevated expression of HOTAIR was correlated with more advanced histological grades,distance metastasis and the poor prognosis in patients with CRC.Silencing HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC cells.HOTAIR knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft model.Moreover,the data showed that HOTAIR could interact with ATR to regulate the DNA damage repair signaling pathway.Silencing HOTAIR impaired the ATR-ATR interacting protein(ATRIP)complex and signaling in cell cycle progression.Collectively,the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting ATR.展开更多
Objective To compare the asbestos-induced DNA damage and repair capacities of DNA damage between 104 asbestosexposed workers and 101 control workers in Qingdao City of China and to investigate the possible association...Objective To compare the asbestos-induced DNA damage and repair capacities of DNA damage between 104 asbestosexposed workers and 101 control workers in Qingdao City of China and to investigate the possible association between polymorphisms in codon 399 of XRCC1 and susceptibility to asbestosis. Methods DNA damage levels in peripheral blood lymphocytes were determined by comet assay, and XRCC1 genetic polymorphisms of DNA samples from 51 asbestosis cases and 53 non-asbestosis workers with a similar asbestos exposure history were analyzed by PCR/RFLP. Results The basal comet scores （3.95±2.95） were significantly higher in asbestos-exposed workers than in control workers （0.10±0.28）. After 1 h H2O2 stimulation, DNA damage of lymphocytes exhibited different increases. After a 4 h repair period, the comet scores were 50.98±19.53 in asbestos-exposed workers and 18.32±12.04 in controls. The residual DNA damage （RD） was significantly greater （P〈0.01） in asbestos-exposed workers （35.62%） than in controls （27.75%）. XRCC1 genetic polymorphism in 104 asbestos-exposed workers was not associated with increased risk of asbestosis. But compared with polymorphisms in the DNA repair gene XRCC1 （polymorphisms in codon 399） and the DNA damage induced by asbestos, the comet scores in asbestosis cases with Gin/Gin, Gln/Arg, and Arg/Arg were 40.26±18.94, 38.03±28.22, and 32.01±11.65, respectively, which were higher than those in non-asbestosis workers with the same genotypes （25.58±11.08, 37.08±14.74, and 29.38±10.15）. There were significant differences in the comet scores between asbestosis cases and non-asbestosis workers with Gin/Gin by Student＇s t-test （P〈0.05 or 0.01）. The comet scores were higher in asbestosis workers with Gin/Gin than in those with Arg/Arg and in non-asbestosis workers exposed to asbestos, but without statistically significant difference. Conclusions Exposure to asbestos may be related to DNA damage or the capacity of cells to repair H2O2-induced DNA damage. DNA repair gene XRCC 1 codon 399 may be responsible for the inter-individual susceptibility in DNA damage and repair capacities.展开更多
Genome stability can be threatened by both endogenous and exogenous agents.Organisms have evolved numerous mechanisms to repair DNA damage,including homologous recombination(HR)and non-homologous end joining(NHEJ).Amo...Genome stability can be threatened by both endogenous and exogenous agents.Organisms have evolved numerous mechanisms to repair DNA damage,including homologous recombination(HR)and non-homologous end joining(NHEJ).Among the factors associated with DNA repair,the MRE11-RAD50-NBS1(MRN)complex(MRE11-RAD50-XRS2 in Saccharomyces cerevisiae)plays important roles not only in DNA damage recognition and signaling but also in subsequent HR or NHEJ repair.Upon detecting DNA damage,the MRN complex activates signaling molecules,such as the protein kinase ataxia-telangiectasia mutated(ATM),to trigger a broad DNA damage response,including cell cycle arrest.The nuclease activity of the MRN complex is responsible for DNA end resection,which guides DNA repair to HR in the presence of sister chromatids.The MRN complex is also involved in NHEJ,and has a species-specific role in hairpin repair.This review focuses on the structure of the MRN complex and its function in DNA damage repair.展开更多
Local CO2 laser treatment has proved to be an effective method to prevent the 351-nm laser-induced damage sites in a fused silica surface from exponentially growing, which is responsible for limiting the lifetime of o...Local CO2 laser treatment has proved to be an effective method to prevent the 351-nm laser-induced damage sites in a fused silica surface from exponentially growing, which is responsible for limiting the lifetime of optics in high fluence laser systems. However, the CO2 laser induced ablation crater is often surrounded by a raised rim at the edge, which can also result in the intensification of transmitted ultraviolet light that may damage the downstream optics. In this work, the three-dimensional finite-difference time-domain method is developed to simulate the distribution of electrical field intensity in the vicinity of the CO2 laser mitigated damage site located in the exit subsurface of fused silica. The simulated results show that the repaired damage sites with raised rims cause more notable modulation to the incident laser than those without rims.Speeifically,we present a theoretical model of using dimpled patterning to control the rim structure around the edge of repaired damage sites to avoid damage to downstream optics. The calculated results accord well with previous experimental results and the underlying physical mechanism is analysed in detail展开更多
A real case of a steel lattice shell suffering a fire was studied. Based on the theory of field modeling, fire dynamic simulator (FDS) was used to identify the temperature field. The damage mechanism of the structure ...A real case of a steel lattice shell suffering a fire was studied. Based on the theory of field modeling, fire dynamic simulator (FDS) was used to identify the temperature field. The damage mechanism of the structure was determined by FEM analysis. After damage assessment, the shell was repaired with the pipe-encasement method. Finally, field test was employed to check the capacity of the structure after repair. The numerical study results indicate that the damage assessment agrees well with field inspection, verifying the accuracy of fire numerical simulation and FEM analysis. The field test results prove that the pipe-encasement method is secure and reasonable, and the repaired shell is safe.展开更多
An experimental study was conducted to investigate the feasibility of a proposed rapid repair technique for severely earthquake-damaged bridge piers with flexural-shear failure mode. Six circular pier specimens were f...An experimental study was conducted to investigate the feasibility of a proposed rapid repair technique for severely earthquake-damaged bridge piers with flexural-shear failure mode. Six circular pier specimens were first tested to severe damage in flexural-shear mode and repaired using early-strength concrete with high-fluidity and carbon fiber reinforced polymers （CFRP）. After about four days, the repaired specimens were tested to failure again. The seismic behavior of the repaired specimens was evaluated and compared to the original specimens. Test results indicate that the proposed repair technique is highly effective. Both shear strength and lateral displacement of the repaired piers increased when compared to the original specimens, and the failure mechanism of the piers shifted from flexural-shear failure to ductile flexural failure. Finally, a simple design model based on the Seible formulation for post-earthquake repair design was compared to the experimental results. It is concluded that the design equation for bridge pier strengthening before an earthquake could be applicable to seismic repairs after an earthquake if the shear strength contribution of the spiral bars in the repaired piers is disregarded and 1.5 times more FRP sheets is provided.展开更多
Objective To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells （NSCs） in the adult mice subjected to glutamate-induced excitotoxic injury. Methods M...Objective To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells （NSCs） in the adult mice subjected to glutamate-induced excitotoxic injury. Methods Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum （dpc）. The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry. Immunofluorescence staining was carried out to observe the survival and location of transplanted NSCs. The animals in the MSG＋NSCs group received intracerebroventricular transplantation of NSCs （approximately 1.0×10^5 cells） separately on day 1 and day 10 after 10-d MSG exposure （4.0 g/kg per day）. The mice in control and MSG groups received intracerebroventricular injection of Dulbecco＇s minimum essential medium （DMEM） instead of NSCs. On day 11 after the last NSC transplantation, the test of Y-maze discrimination learning was performed, and then the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes of brain and the effects of intracerebroventricular transplantation of NSCs on the brain repair. Results The isolated cells were Nestin-positive. The grafted NSCs in the host brain were region-specifically survived at 10-d post-transplantation. Intracerebroventricular transplantation of NSCs obviously facilitated the brain recovery from glutamate-induced behavioral disturbances and histopathological impairs in adult mice. Conclusion Intracerebroventricular transplantation of NSCs may be feasible in repairing diseased or damaged brain tissue.展开更多
Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multip...Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.展开更多
Investigating the combined effects of mining damage and creep damage on slope stability is crucial,as it can comprehensively reveal the non-linear deformation characteristics of rock under their joint influence.This s...Investigating the combined effects of mining damage and creep damage on slope stability is crucial,as it can comprehensively reveal the non-linear deformation characteristics of rock under their joint influence.This study develops a fractional-order nonlinear creep constitutive model that incorporates the double damage effect and implements a non-linear creep subroutine for soft rock using the threedimensional finite difference method on the FLAC3D platform.Comparative analysis of the theoretical,numerical,and experimental results reveals that the fractional-order constitutive model,which incorporates the double damage effect,accurately reflects the distinct deformation stages of green mudstone during creep failure and effectively captures the non-linear deformation in the accelerated creep phase.The numerical results show a fitting accuracy exceeding 97%with the creep test curves,significantly outperforming the 61%accuracy of traditional creep models.展开更多
Homologous recombination （HR） comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks （DSBs） and interstrand crosslinks （ICLs）. In addition, recombination provides c...Homologous recombination （HR） comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks （DSBs） and interstrand crosslinks （ICLs）. In addition, recombination provides critical support for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR： homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modalities of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support.展开更多
基金supported by the National Key Research and Development Program of China,No.2019YFA0111200the National Natural Science Foundation of China,Nos.U23A20436,82371047+3 种基金Key Research Project in Shanxi Province,No.202302130501008Shanxi Provincial Science Fund for Distinguished Young Scholars,No.202103021221008Key Research and Development Program in Shanxi Province,No.202204051001023Shanxi Medical University Doctor’s Startup Fund Project,No.SD22028(all to YG)。
文摘Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.
基金supported by the Shaanxi Qinchuang Yuan“scientist+engineer”team construction(No.2023KXJ-080)Shaanxi Chiral Drug Engineering Technology Research Center(Department of Science and Technology of Shaanxi Province.No.[2011]-251).
文摘Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.
文摘The plasma membrane(PM)plays an essential role in maintaining cell homeostasis,therefore,timely and effective repair of damage caused by factors such as mechanical rupture,pore-forming toxins,or pore-forming proteins is crucial for cell survival.PM damage induces membrane rupture and stimulates an immune response.However,damage resulting from regulated cell death processes,including pyroptosis,ferroptosis,and necroptosis,cannot be repaired by simple sealing mechanisms and thus,requires specialized repair machinery.Recent research has identified a PM repair mechanism of regulated cell death-related injury,mediated by the endosomal sorting complexes required for transport(ESCRT)machinery.Here,we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury,with particular focus on processes related to regulated cell death.This overview,along with continued research in this field,may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.
基金supported by the National Natural Science Foundation of China(grant no.82272287).
文摘Adipocyte-secreted extracellular vesicles(EVs)and adipose-derived stem cells(ADSCs)regulate physiological and pathological processes by delivering nucleic acids,proteins,and lipids.Both adipocyte-and ADSC-derived EVs regulate local inflammatory levels,tumor progression,and insulin sensitivity.These two types of EVs also have significant therapeutic effects on damage repair,including wound healing,angiogenesis,myocardial damage,vessel re-endothelialization,bone and cartilage regeneration,muscle repair,and nerve repair.With regard to wound healing,microRNA-21,microRNA-126,microRNA-31,and long non-coding RNA-H19 accelerate the proliferation and migration of fibroblasts,human immortalized keratinocytes,and endothelial cells via the PI3K/Akt/ERK pathway or fibrillin 1.ADSC-derived EVs contain various growth factors that are beneficial for wound healing.Numerous miRNAs in ADSC-derived EVs and β3-adrenergic receptors on brown adipocytes exhibit protective effects against myocardial infarction.Proteins in adipocyte-and ADSC-derived EVs play a role in promoting vessel re-endothelialization and regulating vasodilation.Angiogenesis is beneficial for the regeneration and repair of injured bone,cartilage,muscle,and nerves.Compared with adipocyte EVs,ADSC-EVs contain a greater variety of miRNAs and proteins that promote tissue regeneration.EV therapy is a promising cell-free therapy,and EV-loaded materials have been used for wound healing and myocardial damage.Future research will focus on identifying the molecules in EVs and the repair mechanisms that contribute to damage repair and regeneration.In addition,we aim to discover materials designed for slow release and specificity to facilitate tissue repair and optimize EV transportation.
基金Project(K2022G038)supported by the Science Technology Research and Development Program of China State Railway Group Co.,LtdProject(52178405)supported by the National Natural Science Foundation of China。
文摘To address the issue of extreme thermal-induced arching in CRTS II slab tracks due to joint damage,an optimized joint repair model was proposed.First,the formula for calculating the safe temperature rise of the track was derived based on the principle of stationary potential energy.Considering interlayer evolution and structural crack propagation,an optimized joint repair model for the track was established and validated.Subsequently,the impact of joint repair on track damage and arch stability under extreme temperatures was studied,and a comprehensive evaluation of the feasibility of joint repair and the evolution of damage after repair was conducted.The results show that after the joint repair,the temperature rise of the initial damage of the track structure can be increased by 11℃.Under the most unfavorable heating load with a superimposed temperature gradient,the maximum stiffness degradation index SDEG in the track structure is reduced by about 81.16%following joint repair.The joint repair process could effectively reduce the deformation of the slab arching under high temperatures,resulting in a reduction of 93.96%in upward arching deformation.After repair,with the damage to interfacing shear strength,the track arch increases by 2.616 mm.
文摘In order to thoroughly understand the mechanism Of drought resistance in plants at DNA level, the DNA damage of two ecotypes of reeds (Phragmites communis T.) stressed by PEG 6000 was analyzed by means of fluorescence analysis of DNA unwinding (FADU). The results showed that the residual double strand DNA percentages (dsDNA%) in dune reed (DR) were significantly higher than those in swamp reed (SR) treated with either 20% or 30% PEG 6000. This meant that the DNA of DR was less damaged in comparison with SR. Similarly, DR resisted DNA damage more strongly than SR as reactive oxygen species (ROS) increased by adding ROS producers diethyldithio carbamate (DDC), H2O2 and Fe2+ of different concentrations. Meanwhile, treating PEG stressed SR with ROS scavengers such as dimethyl sulphoxide (DMSO) and ascorbic acid (Vc) resulted in the reduction of DNA damage, suggesting that ROS could cause DNA damage. In addition, the DNA repair for water-stressed reeds indicated that DR repaired DNA damage much faster and more completely. This might be the first indication that drought stress led to DNA damage in plants and that drought resistance of plants was closely related to DNA damage and repair.
基金National Natural Science Foundation of China （No. 30571909） the Youth Teacher＇s Research Foundation of Jiangsu Province, China （No. BU 134701 ） the Medical Development Foundation of Soochow University （No. EE134615）.
文摘NF-κB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin κ-chain enhancer and enhance transcriptional activity. NF-κB/Rel proteins, as a dimeric transcription factor, control the expression of genes that regulate a broad range of biological processes through canonical and non-canonical pathways. In the central nervous system, NF-κB controls inflammatory reactions and the apoptotic cell death following nerve injury. It also contributes to the infarction and cell death in stroke models and patients. However, NF-κB is essential for neurosurvival as well. NF-κB activation is a part of recovery process that may protect neurons against oxidative-stresses or brain ischemia-induced apoptosis and neurodegeneration. Inhibition of NF-κB may reduce its neuroprotection activity. Hence the dual opposite effects of NF-κB on cells. The ultimate survival or death of neurons depends on which, where and when the NF-κB factors are activated.
基金supported by the Innovation Foundation of Provincial Education Department of Gansu(2024B-005)the Gansu Province National Science Foundation(22YF7GA182)the Fundamental Research Funds for the Central Universities(No.lzujbky2022-kb01)。
文摘Modal parameters can accurately characterize the structural dynamic properties and assess the physical state of the structure.Therefore,it is particularly significant to identify the structural modal parameters according to the monitoring data information in the structural health monitoring(SHM)system,so as to provide a scientific basis for structural damage identification and dynamic model modification.In view of this,this paper reviews methods for identifying structural modal parameters under environmental excitation and briefly describes how to identify structural damages based on the derived modal parameters.The paper primarily introduces data-driven modal parameter recognition methods(e.g.,time-domain,frequency-domain,and time-frequency-domain methods,etc.),briefly describes damage identification methods based on the variations of modal parameters(e.g.,natural frequency,modal shapes,and curvature modal shapes,etc.)and modal validation methods(e.g.,Stability Diagram and Modal Assurance Criterion,etc.).The current status of the application of artificial intelligence(AI)methods in the direction of modal parameter recognition and damage identification is further discussed.Based on the pre-vious analysis,the main development trends of structural modal parameter recognition and damage identification methods are given to provide scientific references for the optimized design and functional upgrading of SHM systems.
基金National Natural Science Foundation of China under Grant No.51678150Science for Earthquake Resilience under Grant No.XH17064Australian Research Council Discovery Early Career Researcher Award(DECRA)
文摘In this study, three rapid repair techniques are proposed to retrofit circular bridge piers that are severely damaged by the flexural failure mode in major earthquakes. The quasi-static tests on three 1：2.5 scaled circular pier specimens are conducted to evaluate the efficiency of the proposed repair techniques. For the purpose of rapid repair, the repair procedure for all the specimens is conducted within four days, and the behavior of the repaired specimens is evaluated and compared with the original ones. A finite element model is developed to predict the cyclic behavior of the repaired specimens and the numerical results are compared with the test data. It is found that all the repaired specimens exhibit similar or larger lateral strength and deformation capacity than the original ones. The initial lateral stiffness of all the repaired specimens is lower than that of the original ones, while they show a higher lateral stiffness at the later stage of the test. No noticeable difference is observed for the energy dissipation capacity between the original and repaired pier specimens. It is suggested that the repair technique using the early-strength concrete jacket confined by carbon fiber reinforced polymer （CFRP） sheets can be an optimal method for the rapid repair of severely earthquake-damaged circular bridge piers with flexural failure mode.
基金Project supported by the National High Technology Research and Development Program of China (Grant No.2008AA8040508)the Youth Foundation of University of Science and Technology of China (Grant Nos.L08010401JX0834 and L08010401JX0806)the Fundamental Research Funds for the Central Universities of China
文摘One of the main factors of laser induced damage is the modulation to incident laser which is caused by the defect in the subsurface of the fused silica. In this work, the repaired damage site irradiated by CO2 laser is simplified to a Gaussian rotation according to the corresponding experimental results. Then, the three-dimensional finite-difference time-domain method is employed to simulate the electric field intensity distribution in the vicinity of this kind of defect in fused silica front subsurface. The simulated results show that the modulation is notable, the Emax is about 2.6 times the irradiated electric field intensity in the fused silica with the damage site （the width is 1.5 μm and depth is 2.3 μm） though the damage site is repaired by CO2 laser. The phenomenon and the theoretical result of the annular laser enhancement existed on the rear surface are first verified effectively, which agrees well with the corresponding experimental results. The relations between the maximal electric field intensity in fused silica with defect depth and width are given respectively. Meanwhile, the corresponding physical mechanism is analysed theoretically in detail.
基金This study was supported by the Inner Mongolia Science and Technology Department Science and Technology Research Project(No.2021GG0270)National Natural Science Foundation of China(81860534)+5 种基金Natural Science Foundation of Inner Mongolia(2021MS08152)Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region(NJYT22004)Scientific and Technological Innovative Research Team for Inner Mongolia Medical University of Transformation Application of Organoid in Medical and Industrial Interdiscipline(YKD2022TD002)Major Project of Inner Mongolia Medical University(YKD2022 ZD002)Radiobiology System and Team Construction of Radiotherapy for Inner Mongolia Medical University(YKD2022XK014)Key Laboratoy of Radiation Physics and Biology of Inner Mongolia Medical University(PIKY2023030).
文摘Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal cancer(CRC)progression.The present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells,as well as the underlying mechanism.The relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues,as well as in radiosensitive and radioresistant samples.The correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square test.Functional assays such as cell proliferation,colony formation and apoptosis assays were conducted to determine the radiosensitivity in CRC cells with HOTAIR silencing after treatment with different doses of radiation.RNA pull-down assay andfluorescence in situ hybridization(FISH)were used to determine the interaction between HOTAIR and DNA damage response mediator ataxia-telangiectasia mutated-and Rad3-related(ATR).HOTAIR was significantly upregulated in CRC tumor tissues,especially in radioresistant tumor samples.The elevated expression of HOTAIR was correlated with more advanced histological grades,distance metastasis and the poor prognosis in patients with CRC.Silencing HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC cells.HOTAIR knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft model.Moreover,the data showed that HOTAIR could interact with ATR to regulate the DNA damage repair signaling pathway.Silencing HOTAIR impaired the ATR-ATR interacting protein(ATRIP)complex and signaling in cell cycle progression.Collectively,the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting ATR.
基金This study was supported by a grant from National Natural Science Foundation of China (No. 30100147).
文摘Objective To compare the asbestos-induced DNA damage and repair capacities of DNA damage between 104 asbestosexposed workers and 101 control workers in Qingdao City of China and to investigate the possible association between polymorphisms in codon 399 of XRCC1 and susceptibility to asbestosis. Methods DNA damage levels in peripheral blood lymphocytes were determined by comet assay, and XRCC1 genetic polymorphisms of DNA samples from 51 asbestosis cases and 53 non-asbestosis workers with a similar asbestos exposure history were analyzed by PCR/RFLP. Results The basal comet scores （3.95±2.95） were significantly higher in asbestos-exposed workers than in control workers （0.10±0.28）. After 1 h H2O2 stimulation, DNA damage of lymphocytes exhibited different increases. After a 4 h repair period, the comet scores were 50.98±19.53 in asbestos-exposed workers and 18.32±12.04 in controls. The residual DNA damage （RD） was significantly greater （P〈0.01） in asbestos-exposed workers （35.62%） than in controls （27.75%）. XRCC1 genetic polymorphism in 104 asbestos-exposed workers was not associated with increased risk of asbestosis. But compared with polymorphisms in the DNA repair gene XRCC1 （polymorphisms in codon 399） and the DNA damage induced by asbestos, the comet scores in asbestosis cases with Gin/Gin, Gln/Arg, and Arg/Arg were 40.26±18.94, 38.03±28.22, and 32.01±11.65, respectively, which were higher than those in non-asbestosis workers with the same genotypes （25.58±11.08, 37.08±14.74, and 29.38±10.15）. There were significant differences in the comet scores between asbestosis cases and non-asbestosis workers with Gin/Gin by Student＇s t-test （P〈0.05 or 0.01）. The comet scores were higher in asbestosis workers with Gin/Gin than in those with Arg/Arg and in non-asbestosis workers exposed to asbestos, but without statistically significant difference. Conclusions Exposure to asbestos may be related to DNA damage or the capacity of cells to repair H2O2-induced DNA damage. DNA repair gene XRCC 1 codon 399 may be responsible for the inter-individual susceptibility in DNA damage and repair capacities.
基金supported by the National Key Research and Development Program of China(No.2018YFC2000100)the National Natural Science Foundation of China(Nos.31730021,31971220,and 31961160725)+1 种基金the Fok Ying Tung Education Foundationthe China’s Fundamental Research Funds for the Central Universities。
文摘Genome stability can be threatened by both endogenous and exogenous agents.Organisms have evolved numerous mechanisms to repair DNA damage,including homologous recombination(HR)and non-homologous end joining(NHEJ).Among the factors associated with DNA repair,the MRE11-RAD50-NBS1(MRN)complex(MRE11-RAD50-XRS2 in Saccharomyces cerevisiae)plays important roles not only in DNA damage recognition and signaling but also in subsequent HR or NHEJ repair.Upon detecting DNA damage,the MRN complex activates signaling molecules,such as the protein kinase ataxia-telangiectasia mutated(ATM),to trigger a broad DNA damage response,including cell cycle arrest.The nuclease activity of the MRN complex is responsible for DNA end resection,which guides DNA repair to HR in the presence of sister chromatids.The MRN complex is also involved in NHEJ,and has a species-specific role in hairpin repair.This review focuses on the structure of the MRN complex and its function in DNA damage repair.
基金supported by the Fundamental Research Funds for the Central Universities (Grant No. ZYGX2010J045)the National Natural Science Fundation of China and the China Academy of Engineering Physics United Foundation (NSAF) (Grant No. 11076008)the Foundation for Young Scholars of University of Electronic Science and Technology of China (Grant No. L08010401JX0806)
文摘Local CO2 laser treatment has proved to be an effective method to prevent the 351-nm laser-induced damage sites in a fused silica surface from exponentially growing, which is responsible for limiting the lifetime of optics in high fluence laser systems. However, the CO2 laser induced ablation crater is often surrounded by a raised rim at the edge, which can also result in the intensification of transmitted ultraviolet light that may damage the downstream optics. In this work, the three-dimensional finite-difference time-domain method is developed to simulate the distribution of electrical field intensity in the vicinity of the CO2 laser mitigated damage site located in the exit subsurface of fused silica. The simulated results show that the repaired damage sites with raised rims cause more notable modulation to the incident laser than those without rims.Speeifically,we present a theoretical model of using dimpled patterning to control the rim structure around the edge of repaired damage sites to avoid damage to downstream optics. The calculated results accord well with previous experimental results and the underlying physical mechanism is analysed in detail
基金Supported by National Natural Science Foundation of China (No. 50778122)
文摘A real case of a steel lattice shell suffering a fire was studied. Based on the theory of field modeling, fire dynamic simulator (FDS) was used to identify the temperature field. The damage mechanism of the structure was determined by FEM analysis. After damage assessment, the shell was repaired with the pipe-encasement method. Finally, field test was employed to check the capacity of the structure after repair. The numerical study results indicate that the damage assessment agrees well with field inspection, verifying the accuracy of fire numerical simulation and FEM analysis. The field test results prove that the pipe-encasement method is secure and reasonable, and the repaired shell is safe.
基金National Natural Science Foundation of China Under Grant No.51008041 and 50978042the National Special Foundation of Earthquake Science of China Under Grant No.200808021the Fundamental Research Funds for the Central Universities Under Grant No.2011JC011
文摘An experimental study was conducted to investigate the feasibility of a proposed rapid repair technique for severely earthquake-damaged bridge piers with flexural-shear failure mode. Six circular pier specimens were first tested to severe damage in flexural-shear mode and repaired using early-strength concrete with high-fluidity and carbon fiber reinforced polymers （CFRP）. After about four days, the repaired specimens were tested to failure again. The seismic behavior of the repaired specimens was evaluated and compared to the original specimens. Test results indicate that the proposed repair technique is highly effective. Both shear strength and lateral displacement of the repaired piers increased when compared to the original specimens, and the failure mechanism of the piers shifted from flexural-shear failure to ductile flexural failure. Finally, a simple design model based on the Seible formulation for post-earthquake repair design was compared to the experimental results. It is concluded that the design equation for bridge pier strengthening before an earthquake could be applicable to seismic repairs after an earthquake if the shear strength contribution of the spiral bars in the repaired piers is disregarded and 1.5 times more FRP sheets is provided.
文摘Objective To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells （NSCs） in the adult mice subjected to glutamate-induced excitotoxic injury. Methods Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum （dpc）. The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry. Immunofluorescence staining was carried out to observe the survival and location of transplanted NSCs. The animals in the MSG＋NSCs group received intracerebroventricular transplantation of NSCs （approximately 1.0×10^5 cells） separately on day 1 and day 10 after 10-d MSG exposure （4.0 g/kg per day）. The mice in control and MSG groups received intracerebroventricular injection of Dulbecco＇s minimum essential medium （DMEM） instead of NSCs. On day 11 after the last NSC transplantation, the test of Y-maze discrimination learning was performed, and then the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes of brain and the effects of intracerebroventricular transplantation of NSCs on the brain repair. Results The isolated cells were Nestin-positive. The grafted NSCs in the host brain were region-specifically survived at 10-d post-transplantation. Intracerebroventricular transplantation of NSCs obviously facilitated the brain recovery from glutamate-induced behavioral disturbances and histopathological impairs in adult mice. Conclusion Intracerebroventricular transplantation of NSCs may be feasible in repairing diseased or damaged brain tissue.
基金This work was supported by the National Key R&D Program of China(Grant No.2018YFC1313300)the National Natural Science Foundation of China(Grant No.81572331).
文摘Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.
基金support from the National Natural Science Foundation of China(No.52308316)the Scientific Research Foundation of Weifang University(Grant No.2024BS42)+2 种基金China Postdoctoral Science Foundation(No.2022M721885)the Key Laboratory of Rock Mechanics and Geohazards of Zhejiang Province(No.ZJRMG-2022-01)supported by Open Research Fund of State Key Laboratory of Geomechanics and Geotechnical Engineering,Institute of Rock and Soil Mechanics,Chinese Academy of Sciences(NO.SKLGME023017).
文摘Investigating the combined effects of mining damage and creep damage on slope stability is crucial,as it can comprehensively reveal the non-linear deformation characteristics of rock under their joint influence.This study develops a fractional-order nonlinear creep constitutive model that incorporates the double damage effect and implements a non-linear creep subroutine for soft rock using the threedimensional finite difference method on the FLAC3D platform.Comparative analysis of the theoretical,numerical,and experimental results reveals that the fractional-order constitutive model,which incorporates the double damage effect,accurately reflects the distinct deformation stages of green mudstone during creep failure and effectively captures the non-linear deformation in the accelerated creep phase.The numerical results show a fitting accuracy exceeding 97%with the creep test curves,significantly outperforming the 61%accuracy of traditional creep models.
文摘Homologous recombination （HR） comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks （DSBs） and interstrand crosslinks （ICLs）. In addition, recombination provides critical support for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR： homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modalities of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support.
