BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown...BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.展开更多
Loss of plasma membrane integrity can compromise cell functioning and viability.To countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the em...Loss of plasma membrane integrity can compromise cell functioning and viability.To countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the emergence of vital membrane processes(Cooper and McNeil,2015).This relationship between basic cellular functioning and membrane repair highlights the fundamental significance of preserving membrane integrity for cellular life.展开更多
A new scour countermeasure using solidified slurry for offshore foundation has been proposed recently.Fluidized solidified slurry is pumped to seabed area around foundation for scour protection or pumped into the deve...A new scour countermeasure using solidified slurry for offshore foundation has been proposed recently.Fluidized solidified slurry is pumped to seabed area around foundation for scour protection or pumped into the developed scour holes for scour repair as the fluidized material solidifies gradually.In the pumping operation and solidification,the engineering behaviors of solidified slurry require to be considered synthetically for the reliable application in scour repair and protection of ocean engineering such as the pumpability related flow value,flow diffusion behavior related rheological property,anti-scour performance related retention rate in solidification and bearing capacity related strength property after solidification.In this study,a series of laboratory tests are conducted to investigate the effects of mix proportion(initial water content and binder content)on the flow value,rheological properties,density,retention rate of solidified slurry and unconfined compressive strength(UCS).The results reveal that the flow value increases with the water content and decreases with the binder amount.All the solidified slurry exhibits Bingham plastic behavior when the shear rate is larger than 5 s^(-1).The Bingham model has been employed to fit the rheology test results,and empirical formulas for obtaining the density,yield stress and viscosity are established,providing scientific support for the numerical assessment of flow and diffusion of solidified slurry.Retention rate of solidified slurry decreases with the water flow velocity and flow value,which means the pumpability of solidified slurry is contrary to anti-scour performance.The unconfined compressive strength after solidification reduces as the water content increases and binder content decreases.A design and application procedure of solidified soil for scour repair and protection is also proposed for engineering reference.展开更多
The conserved DNA damage repair complex,MMS21-SMC5/6(Methyl methane sulfonate 21-Structural maintenance of chromosomes 5/6),has been extensively studied in yeast,animals,and plants.However,its role in phytopathogenic ...The conserved DNA damage repair complex,MMS21-SMC5/6(Methyl methane sulfonate 21-Structural maintenance of chromosomes 5/6),has been extensively studied in yeast,animals,and plants.However,its role in phytopathogenic fungi,particularly in the highly destructive rice blast fungus Magnaporthe oryzae,remains unknown.In this study,we functionally characterized the homologues of this complex,MoMMS21 and MoSMC5,in M.oryzae.We first demonstrated the importance of DNA damage repair in M.oryzae by showing that the DNA damage inducer phleomycin inhibited vegetative growth,infection-related development and pathogenicity in this fungus.Additionally,we discovered that MoMMS21 and MoSMC5 interacted in the nuclei,suggesting that they also function as a complex in M.oryzae.Gene deletion experiments revealed that both MoMMS21 and MoSMC5 are required for infection-related development and pathogenicity in M.oryzae,while only MoMMS21 deletion affected growth and sensitivity to phleomycin,indicating its specific involvement in DNA damage repair.Overall,our results provide insights into the roles of MoMMS21 and MoSMC5 in M.oryzae,highlighting their functions beyond DNA damage repair.展开更多
Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to ev...Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.展开更多
Probiotics participate in various physiological activities and contribute to body health.However,their viability and bioefficacy are adversely affected by gastrointestinal harsh conditions,such as gastric acid,bile sa...Probiotics participate in various physiological activities and contribute to body health.However,their viability and bioefficacy are adversely affected by gastrointestinal harsh conditions,such as gastric acid,bile salts and various enzymes.Fortunately,encapsulation based on various nanomaterials shows tremendous potential to protect probiotics.In this review,we introduced some novel encapsulation technologies involving nanomaterials in view of predesigned stability and viability,selective adhesion,smart release and colonization,and efficacy exertion of encapsulated probiotics.Furthermore,the interactions between encapsulated probiotics and the gastrointestinal tract were summarized and analyzed,with highlighting the regulatory mechanisms of encapsulated probiotics on intestinal mechanical barrier,chemical barrier,biological barrier and immune barrier.This review would benefit the food and pharmaceutical industries in preparation and utilization of multifunctional encapsulated probiotics.展开更多
Spent battery recycling has received considerable attention because of its economic and environmental potential.A large amount of retired graphite has been produced as the main electrode material,accompanied by a deta...Spent battery recycling has received considerable attention because of its economic and environmental potential.A large amount of retired graphite has been produced as the main electrode material,accompanied by a detailed exploration of the repair mechanism.However,they still suffer from unclear repair mechanisms and physicochemical evolution.In this study,spent graphite was repaired employing three methodologies:pickling-sintering,pyrogenic-recovery,and high-temperature sintering.Owing to the catalytic effect of the metal-based impurities and temperature control,the as-obtained samples displayed an ordered transformation,including the interlayer distance,crystalline degree,and grain size.As anodes of lithium ions batteries,the capacity of repaired samples reached up to 310 mA h g^(-1)above after 300loops at 1.0 C,similar to that of commercial graphite.Meanwhile,benefitting from the effective assembly of carbon atoms in internal structure of graphite at>1400℃,their initial coulombic efficiency were>87%.Even at 2.0 C,the capacity of samples remained approximately 244 mA h g^(-1)after 500 cycles.Detailed electrochemical and kinetic analyses revealed that a low temperature enhanced the isotropy,thereby enhancing the rate properties.Further,economic and environmental analyses revealed that the revenue obtained through suitable pyrogenic-recovering manners was approximately the largest value(5500$t^(-1)).Thus,this study is expected to clarify the in-depth effect of different repair methods on the traits of graphite,while offering all-round evaluations of repaired graphite.展开更多
Repairs of corroded high-pressure pipelines are essential for fluids transportation under high pressure.One of the methods used in their repairs is the use of layered composites.The composite used must have the necess...Repairs of corroded high-pressure pipelines are essential for fluids transportation under high pressure.One of the methods used in their repairs is the use of layered composites.The composite used must have the necessary strength.Therefore,the experiments and analytical solutions presented in this paper are performed according to the relevant standards and codes,including ASME PCC-2,ASME B31.8S,ASME B31.4,ISO 24817 and ASME B31.G.In addition,the experimental tests are replicated numerically using the finite element method.Setting the strain gauges at different distances from the defect location,can reduce the nonlinear effects,deformation,and fluctuations due to the high pressure.The direct relationship between the depth of an axial defect and the stress concentration is observed at the inner side edges of the defect.Composite reparation reduces the non-linearities related to the sharp variation of the geometry and a more reliable numerical simulation could be performed.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
Additive friction stir deposition(AFSD)is a novel structural repair and manufacturing technology has become a research hotspot at home and abroad in the past five years.In this work,the microstructural evolution and m...Additive friction stir deposition(AFSD)is a novel structural repair and manufacturing technology has become a research hotspot at home and abroad in the past five years.In this work,the microstructural evolution and mechanical performance of the Al-Mg-Si alloy plate repaired by the preheating-assisted AFSD process were investigated.To evaluate the tool rotation speed and substrate preheating for repair quality,the AFSD technique was used to additively repair 5 mm depth blind holes on 6061 aluminum alloy substrates.The results showed that preheat-assisted AFSD repair significantly improved joint bonding and joint strength compared to the control non-preheat substrate condition.Moreover,increasing rotation speed was also beneficial to improve the metallurgical bonding of the interface and avoid volume defects.Under preheating conditions,the UTS and elongation were positively correlated with rotation speed.Under the process parameters of preheated substrate and tool rotation speed of 1000 r/min,defect-free specimens could be obtained accompanied by tensile fracture occurring in the substrate rather than the repaired zone.The UTS and elongation reached the maximum values of 164.2MPa and 13.4%,which are equivalent to 99.4%and 140%of the heated substrate,respectively.展开更多
Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation,the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures.In the present...Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation,the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures.In the present work,degradable magnesium(Mg)alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4±0 absorbable suture as control.The shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4,8,and 12 weeks after operation.The Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to failure.Gross observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture groups.In the histological analysis,for Mg alloy suture groups,chondrocytes appear to proliferate at 4 weeks postoperatively,and the tendon-bone interface showed an orderly structural transition zone at 8 weeks postoperatively.The collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed,where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous enthesis.In vivo degradation of the magnesium alloy wire was completed within 12 weeks.The results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.展开更多
Cesarean scar pregnancy(CSP)is a rare form of ectopic pregnancy that is defined as a pregnancy sac located within the scar of a previous cesarean section.Recurrent cesarean scar pregnancy(RCSP)is even more uncommon,1 ...Cesarean scar pregnancy(CSP)is a rare form of ectopic pregnancy that is defined as a pregnancy sac located within the scar of a previous cesarean section.Recurrent cesarean scar pregnancy(RCSP)is even more uncommon,1 with Hasegawa et al reporting the first RCSP in 2005.2 RCSP is a high-risk pregnancy condition with potential complications that include heavy bleeding,uterine rupture,and maternal shock.The exact incidence rates for CSP and RCSP are unknown,although the incidence of CSP is 1/2656–1/1800 of the total number of cesarean sections,and the incidence of RCSP can reach 6.9%–34.3%.3,4,5 With the promulgation of the second and third child policies in China,an increasing number of patients now manifest fertility needs after cesarean section.With improvements in examination methods and awareness of CSP,we also suspect that the rates of CSP and RCSP may be even higher.Unfortunately,there is no standard treatment for CSP.We herein report a case in which the patient was treated by combined hysteroscopic and laparoscopic uterine repair without scar resection during the third RCSP,and the fourth RCSP occurred 6 months later;the patient then selected expectant management.The outcome was a successful cesarean section delivery of a live baby at 34 weeks of gestation,and the uterus was successfully preserved.Placental pathology was examined after delivery and revealed that the chorionic villi penetrated deeply into the myometrium.展开更多
BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-imm...BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.展开更多
Filling methods in the mining industry can maximize the recovery of mineral resources and protect the underground and surface environments.In recent years,such methods have been widely used in metal mines where pipeli...Filling methods in the mining industry can maximize the recovery of mineral resources and protect the underground and surface environments.In recent years,such methods have been widely used in metal mines where pipeline transportation typically plays a decisive role in the safety and stability of the entirefilling system.Because thefilling slurry contains a large percentage of solid coarse particles,the involved pipeline is typically eroded and often damaged during such a process.A possible solution is the so-called nesting repair technology.In the present study,nesting a 127 mm outer diameter pipeline in 151 mm inner diameter borehole is considered to meet the repair objective.First,by using the rheological theory,the pipeline transmission resistance and self-flow conveying range are calculated under different working conditions.It is shown that the pipeline transmission resistance is larger when the inner diameter of casing is 80 mm,and the limitflow rate of vertical pipeline self-flow is 120 m^(3)/h;moreover,when the pipeline diameter is 100 mm and theflow rate is 140 m^(3)/h,the self-flow conveying can be satisfied in most of the underground−455 m stage.Accordingly,a plan is presented for the nesting repair strategy,based on the installation of a drill bit under the casing and lowering the casing into the borehole as if it were a drill pipe.Finally,the outcomes of such a strategy are verified.Thefillingflow rate range using the new pipelines is found to be in the range from 188.60 to 224.39 m^(3)/h,and its averagefillingflow rate reaches 209.83 m^(3)/h when conveying 2319.6 m long-distance quarry.展开更多
Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-de...Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.展开更多
BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing f...BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.展开更多
Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Walle...Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.展开更多
The reuse of waste recycled concrete from harsh environments has become a research hotspot in the field of construction.This study investigated the repair effect of carbonation treatment on second-generation recycled ...The reuse of waste recycled concrete from harsh environments has become a research hotspot in the field of construction.This study investigated the repair effect of carbonation treatment on second-generation recycled fine aggregate(SRFA)obtained from recycled fine aggregate concrete(RFAC)subjected to freeze-thaw(FT)cycles.Before and after carbonation,the properties of SRFA were evaluated.Carbonated second-generation recycled fine aggregate(CSRFA)at five substitution rates(0%,25%,50%,75%,100%)to replace SRFA was used to prepare carbonated second-generation recycled fine aggregate concrete(CSRFAC).The water absorption,porosity and mechanical properties of CSRFAC were tested,and its frost-resisting durability was evaluated.The results showed after carbonation treatment,the physical properties of SRFA was improved and met the requirements of II aggregate.The micro-hardness of the interfacial transition zone and attached mortar in CSRFA was 50.5%and 31.2%higher than that in SRFA,respectively.With the increase of CSRFA replacement rate,the water absorption and porosity of CSRFAC gradually decreased,and the mechanical properties and frost resistance of CSRFAC were gradually improved.Carbonation treatment effectively repairs the damage of SRFA caused by FT cycles and improves its application potential.展开更多
Damage caused due to low-velocity impacts in composites leads to substantial deterioration in their residual strength and eventually provokes structural failure.This work presents an experimental investigation on the ...Damage caused due to low-velocity impacts in composites leads to substantial deterioration in their residual strength and eventually provokes structural failure.This work presents an experimental investigation on the effects of different patch and parent laminate stacking sequences on the enhancement of impact strength of Carbon Fiber Reinforced Polymers(CFRP)composites by utilising the adhesively bonded external patch repair technique.Damage evolution study is also performed with the aid of Acoustic Emission(AE).Two different quasi-isotropic configurations were selected for the parent laminate,viz.,[45°/45°/0°/0°]s and[45°/0°/45°/0°]s.Quasi Static Indentation(QSI)test was performed on both the pristine laminates,and damage areas were detected by using the C-scan inspection technique.Damaged laminates were repaired by using a single-sided patch of two different configurations,viz.,[45°/45°/45°/45°]and[45°/0°/0°/45°],and employing a circular plug to fill the damaged hole.Four different combinations of repaired laminates with two configurations of each parent and patch laminate were produced,which were further subjected to the QSI test.The results reveal the effectiveness of the repair method,as all the repaired laminates show higher impact resistance compared to the respective pristine laminates.Patches of[45°/0°/0°/45°]configuration when repaired by taking[45°/45°/0°/0°]s and[45°/0°/45°/0°]s as parents exhibited 68%and 73%higher peak loads,respectively,than the respective pristine laminates.Furthermore,parent and patch of configuration[45°/0°/45°/0°]s and[45°/0°/0°/45°],respectively,attain the highest peak load,whereas[45°/45°/0°/0°]s and[45°/45°/45°/45°]combinations possess the most gradual decrease in the load.展开更多
The rising frequency of extreme disaster events seriously threatens the safe and secure operation of the regional integrated electricity-natural gas system(RIENGS).With the growing level of coupling between electric a...The rising frequency of extreme disaster events seriously threatens the safe and secure operation of the regional integrated electricity-natural gas system(RIENGS).With the growing level of coupling between electric and natural gas systems,it is critical to enhance the load restoration capability of both systems.This paper proposes a coordinated optimization strategy for resilience-enhanced RIENGS load restoration and repair scheduling and transforms it into a mixed integer second-order cone programming(MISOCP)model.The proposed model considers the distribution network reconfiguration and the coordinated repair strategy between the two systems,minimizing the total system load loss cost and repair time.In addition,a bi-directional gas flow model is used to describe the natural gas system,which can provide the RIENGS with more flexibility for load restoration during natural gas system failure.Finally,the effectiveness of the proposed approach is verified by conducting case studies on the test systems RIENGS E13-G7 and RIENGS E123-G20.展开更多
基金National Natural Science Foundation of China,No.U20A20403This study was conducted in accordance with the Animal Ethics Committee of the Institute of Antler Science and Product Technology,Changchun Sci-Tech University(AEC No:CKARI202309).
文摘BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.
基金supported by the Novo Nordisk Foundation(NNF180C0034936)the Lundbeck Foundation(R380-2021-1262)(to CD and JN)。
文摘Loss of plasma membrane integrity can compromise cell functioning and viability.To countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the emergence of vital membrane processes(Cooper and McNeil,2015).This relationship between basic cellular functioning and membrane repair highlights the fundamental significance of preserving membrane integrity for cellular life.
基金financially supported by the Science and Technology Commission Foundation of Shanghai(Grant Nos.22DZ1208903,20DZ2251900)the National Natural Science Foundation of China(Grant No.51679134)。
文摘A new scour countermeasure using solidified slurry for offshore foundation has been proposed recently.Fluidized solidified slurry is pumped to seabed area around foundation for scour protection or pumped into the developed scour holes for scour repair as the fluidized material solidifies gradually.In the pumping operation and solidification,the engineering behaviors of solidified slurry require to be considered synthetically for the reliable application in scour repair and protection of ocean engineering such as the pumpability related flow value,flow diffusion behavior related rheological property,anti-scour performance related retention rate in solidification and bearing capacity related strength property after solidification.In this study,a series of laboratory tests are conducted to investigate the effects of mix proportion(initial water content and binder content)on the flow value,rheological properties,density,retention rate of solidified slurry and unconfined compressive strength(UCS).The results reveal that the flow value increases with the water content and decreases with the binder amount.All the solidified slurry exhibits Bingham plastic behavior when the shear rate is larger than 5 s^(-1).The Bingham model has been employed to fit the rheology test results,and empirical formulas for obtaining the density,yield stress and viscosity are established,providing scientific support for the numerical assessment of flow and diffusion of solidified slurry.Retention rate of solidified slurry decreases with the water flow velocity and flow value,which means the pumpability of solidified slurry is contrary to anti-scour performance.The unconfined compressive strength after solidification reduces as the water content increases and binder content decreases.A design and application procedure of solidified soil for scour repair and protection is also proposed for engineering reference.
基金Research and Development Program of China(2023YFD1400200)the Natural Science Foundation of Fujian Province,China(2022J01125)+2 种基金the Fujian Key Laboratory for Monitoring and Integrated Management of Crop Pests,China(MIMCP-202301)the Fujian Provincial Science and Technology Key Project,China(2022NZ030014)the National Natural Science Foundation of China(NSFC31871914).
文摘The conserved DNA damage repair complex,MMS21-SMC5/6(Methyl methane sulfonate 21-Structural maintenance of chromosomes 5/6),has been extensively studied in yeast,animals,and plants.However,its role in phytopathogenic fungi,particularly in the highly destructive rice blast fungus Magnaporthe oryzae,remains unknown.In this study,we functionally characterized the homologues of this complex,MoMMS21 and MoSMC5,in M.oryzae.We first demonstrated the importance of DNA damage repair in M.oryzae by showing that the DNA damage inducer phleomycin inhibited vegetative growth,infection-related development and pathogenicity in this fungus.Additionally,we discovered that MoMMS21 and MoSMC5 interacted in the nuclei,suggesting that they also function as a complex in M.oryzae.Gene deletion experiments revealed that both MoMMS21 and MoSMC5 are required for infection-related development and pathogenicity in M.oryzae,while only MoMMS21 deletion affected growth and sensitivity to phleomycin,indicating its specific involvement in DNA damage repair.Overall,our results provide insights into the roles of MoMMS21 and MoSMC5 in M.oryzae,highlighting their functions beyond DNA damage repair.
基金supported by grants from the Innovation and Cultivation Fund Project of the Seventh Medical Center,PLA General Hospital(No.QZX-2023-7)Postdoctoral Science Foundation of China(No.2021M691649)Postdoctoral Science Foundation of Jiangsu Province(No.2021K524C).
文摘Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.
基金supported by the National Key Research and Development Program(2019YFC1606704)the Key Research and Development Program of Shaanxi Province(2022NY-013)+1 种基金National Natural Science Foundation of China(31801653)the Natural Science Foundation of Shaanxi Province(2019JQ-722).
文摘Probiotics participate in various physiological activities and contribute to body health.However,their viability and bioefficacy are adversely affected by gastrointestinal harsh conditions,such as gastric acid,bile salts and various enzymes.Fortunately,encapsulation based on various nanomaterials shows tremendous potential to protect probiotics.In this review,we introduced some novel encapsulation technologies involving nanomaterials in view of predesigned stability and viability,selective adhesion,smart release and colonization,and efficacy exertion of encapsulated probiotics.Furthermore,the interactions between encapsulated probiotics and the gastrointestinal tract were summarized and analyzed,with highlighting the regulatory mechanisms of encapsulated probiotics on intestinal mechanical barrier,chemical barrier,biological barrier and immune barrier.This review would benefit the food and pharmaceutical industries in preparation and utilization of multifunctional encapsulated probiotics.
基金financially supported by National Natural Science Foundation of China(52374288,52204298)Young Elite Scientists Sponsorship Program by China Association for Science and Technology(2022QNRC001)+2 种基金National Key Research and Development Program of China(2022YFC3900805-4/7)Hunan Provincial Education Office Foundation of China(No.21B0147)Collaborative Innovation Centre for Clean and Efficient Utilization of Strategic Metal Mineral Resources,Found of State Key Laboratory of Mineral Processing(BGRIMM-KJSKL-2017-13)。
文摘Spent battery recycling has received considerable attention because of its economic and environmental potential.A large amount of retired graphite has been produced as the main electrode material,accompanied by a detailed exploration of the repair mechanism.However,they still suffer from unclear repair mechanisms and physicochemical evolution.In this study,spent graphite was repaired employing three methodologies:pickling-sintering,pyrogenic-recovery,and high-temperature sintering.Owing to the catalytic effect of the metal-based impurities and temperature control,the as-obtained samples displayed an ordered transformation,including the interlayer distance,crystalline degree,and grain size.As anodes of lithium ions batteries,the capacity of repaired samples reached up to 310 mA h g^(-1)above after 300loops at 1.0 C,similar to that of commercial graphite.Meanwhile,benefitting from the effective assembly of carbon atoms in internal structure of graphite at>1400℃,their initial coulombic efficiency were>87%.Even at 2.0 C,the capacity of samples remained approximately 244 mA h g^(-1)after 500 cycles.Detailed electrochemical and kinetic analyses revealed that a low temperature enhanced the isotropy,thereby enhancing the rate properties.Further,economic and environmental analyses revealed that the revenue obtained through suitable pyrogenic-recovering manners was approximately the largest value(5500$t^(-1)).Thus,this study is expected to clarify the in-depth effect of different repair methods on the traits of graphite,while offering all-round evaluations of repaired graphite.
文摘Repairs of corroded high-pressure pipelines are essential for fluids transportation under high pressure.One of the methods used in their repairs is the use of layered composites.The composite used must have the necessary strength.Therefore,the experiments and analytical solutions presented in this paper are performed according to the relevant standards and codes,including ASME PCC-2,ASME B31.8S,ASME B31.4,ISO 24817 and ASME B31.G.In addition,the experimental tests are replicated numerically using the finite element method.Setting the strain gauges at different distances from the defect location,can reduce the nonlinear effects,deformation,and fluctuations due to the high pressure.The direct relationship between the depth of an axial defect and the stress concentration is observed at the inner side edges of the defect.Composite reparation reduces the non-linearities related to the sharp variation of the geometry and a more reliable numerical simulation could be performed.
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financially supported by Science and Technology Major Project of Changsha,China(No.kh2401034)the Fundamental Research Funds for the Central Universities of Central South University(No.CX20230182)the National Key Research and Development Project of China(No.2019YFA0709002)。
文摘Additive friction stir deposition(AFSD)is a novel structural repair and manufacturing technology has become a research hotspot at home and abroad in the past five years.In this work,the microstructural evolution and mechanical performance of the Al-Mg-Si alloy plate repaired by the preheating-assisted AFSD process were investigated.To evaluate the tool rotation speed and substrate preheating for repair quality,the AFSD technique was used to additively repair 5 mm depth blind holes on 6061 aluminum alloy substrates.The results showed that preheat-assisted AFSD repair significantly improved joint bonding and joint strength compared to the control non-preheat substrate condition.Moreover,increasing rotation speed was also beneficial to improve the metallurgical bonding of the interface and avoid volume defects.Under preheating conditions,the UTS and elongation were positively correlated with rotation speed.Under the process parameters of preheated substrate and tool rotation speed of 1000 r/min,defect-free specimens could be obtained accompanied by tensile fracture occurring in the substrate rather than the repaired zone.The UTS and elongation reached the maximum values of 164.2MPa and 13.4%,which are equivalent to 99.4%and 140%of the heated substrate,respectively.
基金the National Key Research and Development Program of China(No.2020YFC1107501)the National Natural Science Foundation of China(No.51971222,51801220)+4 种基金the Natural Science Foundation of Liaoning Province of China(No.2020-MS-001)the Dong Guan Innovative Research Team Program(No.2020607134012)the Military Translational Medicine Fund of Chinese PLA General Hospital(ZH19008)Capital’s Funds for Health Improvement and Research(CFH 2022-2-5051)the Dong Guan Science and Technology Service Network Initiative(20201600200042)。
文摘Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation,the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures.In the present work,degradable magnesium(Mg)alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4±0 absorbable suture as control.The shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4,8,and 12 weeks after operation.The Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to failure.Gross observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture groups.In the histological analysis,for Mg alloy suture groups,chondrocytes appear to proliferate at 4 weeks postoperatively,and the tendon-bone interface showed an orderly structural transition zone at 8 weeks postoperatively.The collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed,where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous enthesis.In vivo degradation of the magnesium alloy wire was completed within 12 weeks.The results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.
基金supported by the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(2023C03033,2024C03200).
文摘Cesarean scar pregnancy(CSP)is a rare form of ectopic pregnancy that is defined as a pregnancy sac located within the scar of a previous cesarean section.Recurrent cesarean scar pregnancy(RCSP)is even more uncommon,1 with Hasegawa et al reporting the first RCSP in 2005.2 RCSP is a high-risk pregnancy condition with potential complications that include heavy bleeding,uterine rupture,and maternal shock.The exact incidence rates for CSP and RCSP are unknown,although the incidence of CSP is 1/2656–1/1800 of the total number of cesarean sections,and the incidence of RCSP can reach 6.9%–34.3%.3,4,5 With the promulgation of the second and third child policies in China,an increasing number of patients now manifest fertility needs after cesarean section.With improvements in examination methods and awareness of CSP,we also suspect that the rates of CSP and RCSP may be even higher.Unfortunately,there is no standard treatment for CSP.We herein report a case in which the patient was treated by combined hysteroscopic and laparoscopic uterine repair without scar resection during the third RCSP,and the fourth RCSP occurred 6 months later;the patient then selected expectant management.The outcome was a successful cesarean section delivery of a live baby at 34 weeks of gestation,and the uterus was successfully preserved.Placental pathology was examined after delivery and revealed that the chorionic villi penetrated deeply into the myometrium.
基金Supported by Ministerio de la Produccion de Peru,No.317-PNICP-EC-2014,and No.430-PNICP-PIAP-2014Consejo Nacional de Ciencia Tecnologia e Innovacion Tecnologica,No.196-2015-FONDECYT,No.197-2015-FONDECYT,and No.204-2015-FONDECYT.
文摘BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.
基金supported by the State Key Research Development Program of China(2018YFC0603705)the Fundamental Research Funds for the Central Universities(FRF-IDRYGD22-004).
文摘Filling methods in the mining industry can maximize the recovery of mineral resources and protect the underground and surface environments.In recent years,such methods have been widely used in metal mines where pipeline transportation typically plays a decisive role in the safety and stability of the entirefilling system.Because thefilling slurry contains a large percentage of solid coarse particles,the involved pipeline is typically eroded and often damaged during such a process.A possible solution is the so-called nesting repair technology.In the present study,nesting a 127 mm outer diameter pipeline in 151 mm inner diameter borehole is considered to meet the repair objective.First,by using the rheological theory,the pipeline transmission resistance and self-flow conveying range are calculated under different working conditions.It is shown that the pipeline transmission resistance is larger when the inner diameter of casing is 80 mm,and the limitflow rate of vertical pipeline self-flow is 120 m^(3)/h;moreover,when the pipeline diameter is 100 mm and theflow rate is 140 m^(3)/h,the self-flow conveying can be satisfied in most of the underground−455 m stage.Accordingly,a plan is presented for the nesting repair strategy,based on the installation of a drill bit under the casing and lowering the casing into the borehole as if it were a drill pipe.Finally,the outcomes of such a strategy are verified.Thefillingflow rate range using the new pipelines is found to be in the range from 188.60 to 224.39 m^(3)/h,and its averagefillingflow rate reaches 209.83 m^(3)/h when conveying 2319.6 m long-distance quarry.
基金sponsored by BeiGene.Third-party medical writing assistance was provided by Ghina Yaacoub,MSc,of Ashfield MedComms,an Inizio Company,and funded by BeiGene.
文摘Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
基金Supported by National High Level Hospital Clinical Research Funding,No.2023-NHLHCRF-YYPPLC-TJ-03.
文摘BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.
基金supported by DOD AFIRMⅢW81XWH-20-2-0029 subcontract,UT POC19-1774-13Neuraptive Therapeutics Inc.26-7724-56+1 种基金NIH R01-NS128086 grantsLone Star Paralysis gift(to GDB)。
文摘Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.
基金financially sponsored by Qing Lan Project in Jiangsu Province of China(2023)Scientific Research Project of Taizhou Polytechnic College(TZYKY-22-4).
文摘The reuse of waste recycled concrete from harsh environments has become a research hotspot in the field of construction.This study investigated the repair effect of carbonation treatment on second-generation recycled fine aggregate(SRFA)obtained from recycled fine aggregate concrete(RFAC)subjected to freeze-thaw(FT)cycles.Before and after carbonation,the properties of SRFA were evaluated.Carbonated second-generation recycled fine aggregate(CSRFA)at five substitution rates(0%,25%,50%,75%,100%)to replace SRFA was used to prepare carbonated second-generation recycled fine aggregate concrete(CSRFAC).The water absorption,porosity and mechanical properties of CSRFAC were tested,and its frost-resisting durability was evaluated.The results showed after carbonation treatment,the physical properties of SRFA was improved and met the requirements of II aggregate.The micro-hardness of the interfacial transition zone and attached mortar in CSRFA was 50.5%and 31.2%higher than that in SRFA,respectively.With the increase of CSRFA replacement rate,the water absorption and porosity of CSRFAC gradually decreased,and the mechanical properties and frost resistance of CSRFAC were gradually improved.Carbonation treatment effectively repairs the damage of SRFA caused by FT cycles and improves its application potential.
基金the financial support by the Council of Scientific&Industrial Research(CSIR)-Research Scheme,India(22/0809/2019-EMR-II)。
文摘Damage caused due to low-velocity impacts in composites leads to substantial deterioration in their residual strength and eventually provokes structural failure.This work presents an experimental investigation on the effects of different patch and parent laminate stacking sequences on the enhancement of impact strength of Carbon Fiber Reinforced Polymers(CFRP)composites by utilising the adhesively bonded external patch repair technique.Damage evolution study is also performed with the aid of Acoustic Emission(AE).Two different quasi-isotropic configurations were selected for the parent laminate,viz.,[45°/45°/0°/0°]s and[45°/0°/45°/0°]s.Quasi Static Indentation(QSI)test was performed on both the pristine laminates,and damage areas were detected by using the C-scan inspection technique.Damaged laminates were repaired by using a single-sided patch of two different configurations,viz.,[45°/45°/45°/45°]and[45°/0°/0°/45°],and employing a circular plug to fill the damaged hole.Four different combinations of repaired laminates with two configurations of each parent and patch laminate were produced,which were further subjected to the QSI test.The results reveal the effectiveness of the repair method,as all the repaired laminates show higher impact resistance compared to the respective pristine laminates.Patches of[45°/0°/0°/45°]configuration when repaired by taking[45°/45°/0°/0°]s and[45°/0°/45°/0°]s as parents exhibited 68%and 73%higher peak loads,respectively,than the respective pristine laminates.Furthermore,parent and patch of configuration[45°/0°/45°/0°]s and[45°/0°/0°/45°],respectively,attain the highest peak load,whereas[45°/45°/0°/0°]s and[45°/45°/45°/45°]combinations possess the most gradual decrease in the load.
基金funded by the Science and Technology Project of State Grid Jilin Electric Power Co.,Ltd.(Project Name:Research onDistributionNetworkResilience Assessment and Improvement Technology for Natural Disaster Areas).
文摘The rising frequency of extreme disaster events seriously threatens the safe and secure operation of the regional integrated electricity-natural gas system(RIENGS).With the growing level of coupling between electric and natural gas systems,it is critical to enhance the load restoration capability of both systems.This paper proposes a coordinated optimization strategy for resilience-enhanced RIENGS load restoration and repair scheduling and transforms it into a mixed integer second-order cone programming(MISOCP)model.The proposed model considers the distribution network reconfiguration and the coordinated repair strategy between the two systems,minimizing the total system load loss cost and repair time.In addition,a bi-directional gas flow model is used to describe the natural gas system,which can provide the RIENGS with more flexibility for load restoration during natural gas system failure.Finally,the effectiveness of the proposed approach is verified by conducting case studies on the test systems RIENGS E13-G7 and RIENGS E123-G20.