BACKGROUND Rectal cancer management is currently evolving with the advent of different neoadjuvant treatment strategies and organ preservation strategies.A significant proportion of patients could achieve complete cli...BACKGROUND Rectal cancer management is currently evolving with the advent of different neoadjuvant treatment strategies and organ preservation strategies.A significant proportion of patients could achieve complete clinical response after neoadjuvant treatment,which often translates to pathologic complete response(pCR)as assessed on surgical specimens after curative intent surgery.Endoscopy plays a significant role in assessing treatment response to neoadjuvant therapies.AIM To explore the role of endoscopy in predicting subsequent pCR after neoadjuvant treatment in rectal cancer patients.METHODS An extensive literature review was undertaken to identify the criteria used for assessment of endoscopic response and their ability to predict pCR.RESULTS Fifteen studies were identified through literature review.The most commonly used endoscopic criteria for evaluation included the presence of a flat white scar and the absence of nodularity or telangiectasia.Information on the timing of endoscopic assessment in relation to neoadjuvant treatment protocols were also extracted from the studies.In most studies,the diagnostic accuracy for predicting pCR exceeded 0.8.The main limitations identified were the retrospective design of included studies included and a moderate risk of bias.CONCLUSION Endoscopy can be a key prognostic factor in predicting pCR to neoadjuvant treatment in rectal cancer despite significant limitations in currently available data.展开更多
The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell d...The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.展开更多
Imaging plays a crucial role in the evaluation of hepatocellular carcinoma(HCC)treatment response.Contrast enhanced computed tomography and magnetic resonance imaging with extra-cellular or hepatobiliary contrast agen...Imaging plays a crucial role in the evaluation of hepatocellular carcinoma(HCC)treatment response.Contrast enhanced computed tomography and magnetic resonance imaging with extra-cellular or hepatobiliary contrast agents are the imaging techniques of choice.Contrast enhanced ultrasound is a promising technique.In this paper,we describe radiological techniques,imaging findings after HCC treatment,and the criteria of response evaluation.The utility of the structured report is also evaluated.展开更多
This paper presents a new type of triangular Sharp Eagle wave energy converter(WEC)platform.On the basis of the linear potential flow theory and the finite element analysis method,the hydrodynamic performance and stru...This paper presents a new type of triangular Sharp Eagle wave energy converter(WEC)platform.On the basis of the linear potential flow theory and the finite element analysis method,the hydrodynamic performance and structural response of the platform are studied,considering the actual platform motion and free surface rise under extreme sea states.First,the effects of the wave frequency and direction on the wave-induced loads and dynamic responses were examined.The motion at a wave direction angle of 0°is relatively low.On this basis,the angle constrained by the two sides of the Sharp Eagle floaters should be aligned with the main wave direction to avoid significant platform motion under extreme sea states.Additionally,the structural response of the platform,including the wave-absorbing floaters,is investigated.The results highlighted that the conditions or locations where yielding,buckling,and fatigue failures occur were different.In this context,the connection area of the Sharp Eagle floaters and platform is prone to yielding failure under oblique wave action,whereas the pontoon and side of the Sharp Eagle floaters are prone to buckling failure during significant vertical motion.Additionally,fatigue damage is most likely to occur at the connection between the middle column on both sides of the Sharp Eagle floaters and the pontoons.The findings of this paper revealed an intrinsic connection between wave-induced loads and the dynamic and structural responses of the platform,which provides a useful reference for the improved design of WECs.展开更多
Both acceleration and pseudo-acceleration response spectra play important roles in structural seismic design.However,only one of them is generally provided in most seismic codes.Therefore,many studies have attempted t...Both acceleration and pseudo-acceleration response spectra play important roles in structural seismic design.However,only one of them is generally provided in most seismic codes.Therefore,many studies have attempted to develop conversion models between the acceleration response spectrum(SA)and the pseudo-acceleration response spectrum(PSA).Our previous studies found that the relationship between SA and PSA is affected by magnitude,distance,and site class.Subsequently,we developed an SA/PSA model incorporating these effects.However,this model is suitable for cases with small and moderate magnitudes and its accuracy is not good enough for cases with large magnitudes.This paper aims to develop an efficient SA/PSA model by considering influences of magnitude,distance,and site class,which can be applied to cases not only with small or moderate magnitudes but also with large ones.For this purpose,regression analyses were conducted using 16,660 horizontal seismic records with a wider range of magnitude.The magnitude of these seismic records varies from 4 to 9 and the distances vary from 10 to 200 km.These ground motions were recorded at 338 stations covering four site classes.By comparing them with existing models,it was found that the proposed model shows better accuracy for cases with any magnitudes,distances,and site classes considered in this study.展开更多
The source region of the Yellow River(SRYR),with its semi-humid to semi-arid climate,is crucial for understanding water resource dynamics.Precipitation is key for replenishing surface water and balancing the ecosystem...The source region of the Yellow River(SRYR),with its semi-humid to semi-arid climate,is crucial for understanding water resource dynamics.Precipitation is key for replenishing surface water and balancing the ecosystem’s water cycle.However,the soil moisture response to precipitation across climate zones and soil layers remains poorly understood due to limited long-term data.This study examines the response of soil moisture to precipitation at multiple time scales in the SRYR,using data from Maqu,Mado,Ngoring Lake sites,and the Maqu monitoring network(MMN),along with CN05.1 precipitation and GLEAM v3.8a soil moisture data.Results show that the semi-humid area requires more precipitation to trigger soil moisture responses compared to the semi-arid area in the SRYR.Surface soil at Maqu,MMN,Ngoring Lake,and Mado sites require at least 8.6,8.4,5.2,and 2.84 mm of precipitation,respectively,for effective replenishment.Significant responses to precipitation events were observed in soil layers at 40 cm and above in the semi-humid area,while at 20 cm and above in the semi-arid area.Precipitation volume is the primary factor influencing soil moisture,affecting both the increment and time lag to maximum moisture.Precipitation intensity and pre-rain moisture have no direct effect.In the central SRYR,accumulated precipitation has a greater impact.Root-zone soil moisture has a weaker correlation with precipitation compared to surface soil moisture but persists longer,responding for up to 10 days,while surface soil moisture responds more immediately but only lasts about 5 days.展开更多
The multifrequency voltage(MFV)stress,including switching impulses and harmonics,commonly appearing in the modern power system will stimulate the multifrequency impedance dynamics behaviours of electrical insulation.T...The multifrequency voltage(MFV)stress,including switching impulses and harmonics,commonly appearing in the modern power system will stimulate the multifrequency impedance dynamics behaviours of electrical insulation.Therefore,this article presents a novel concept of insulation resilience response(IRR)by employing polymer insulation materials,which may be extended to electrical insulation resilience(EIR).The focus is on understanding reversible recovery performance and supporting physics-informed condition assessment for electrical insulation exposed to MFV.The underlying physical mechanisms and modelling methodologies are integrated to characterise the IRR behaviours of polymer insulation systems.The multifrequency dielectric/impedance properties of different resin dielectrics under diverse temperatures are comparatively investigated as proofofconcept cases.Furthermore,multidimensional sensitivity indicators are developed to quantify the electrical insulation resilience behaviour.A radar plot representation integrating resilience sensitivity indicators qualitatively assesses the IRR behaviours of polymer insulation systems.Additionally,a quantification methodology,including the resilience index(RI)and time-varied RI(TVRI),is proposed for the reversible recovery performance analysis for electrical insulation,respectively.Ultimately,an application-oriented framework derived from TVRI is provided to analyse the recovery performance evolution behaviours of electrical insulation under complex operating conditions.This offers a key theoretical foundation for insulation performance characterisation and condition analysis for high-voltage power equipment.展开更多
Background The potential of exercise as a concurrent therapy for actively treated primary tumors has been suggested by emerging preclinical and observational studies.However,clinical trials regarding this question are...Background The potential of exercise as a concurrent therapy for actively treated primary tumors has been suggested by emerging preclinical and observational studies.However,clinical trials regarding this question are scarce.Therefore,we conducted a randomized controlled trial investigating the effects of aerobic or resistance exercise concomitant to neoadjuvant chemotherapy(NACT)on tumor size.Methods In the BENEFIT study(German title:Bewegung bei neoadjuvanter chemotherapie zur verbesserung der fitness),patients with breast cancer scheduled for NACT were randomly assigned to supervised resistance training(RT,n=60)or aerobic training(AT,n=60)twice weekly during NACT or to a waitlist control group(WCG,n=60).The primary outcome,“change in tumor size”,as well as the secondary clinical outcomes pathologic complete response(pCR),type of surgery(breast conserving/mastectomy),axillary lymph node dissection(ALND,yes/no),premature discontinuation of chemotherapy(yes/no),and relative dose intensity(RDI)were derived from clinical records.Due to the highly skewed distribution,the primary outcome was categorized.Multiple(ordinal)logistic regression analyses were performed.Results Overall,there was no significant difference in post-intervention tumor size between RT or AT and WCG.However,there was a significant effect modification by hormone receptor(HR)status(P_(interaction)=0.030).Among patients with HR+tumors,results suggest a beneficial effect of AT on tumor shrinkage(odds ratio(OR)=2.37,95%confidence interval(95%CI):0.97‒5.78),on pCR(OR=3.21,95%CI:0.97‒10.61);and on ALND(OR=3.76,95%CI:0.78‒18.06)compared to WCG.The effects of RT were slightly less pronounced.For HR−subtypes,beneficial effects on RDI were found for AT(OR=3.71,95%CI:1.20‒11.50)and similarly for RT(OR=2.58,95%CI:0.88‒7.59).Both AT and RT had favorable effects on premature discontinuation of chemotherapy(OR(no vs.yes)=2.34,95%CI:1.10‒5.06),irrespective of tumor receptor status.Conclusion While there was no significant effect on the primary outcome in the overall group,aerobic and resistance exercise concomitant to NACT seem to beneficially affect tumor shrinkage and pCR,reduce the need for ALND among patients with HR+breast cancers,and prevent low RDI among patients with HR–breast cancers.These results warrant confirmation in further trials.展开更多
Objective:Pathologic complete response(pCR)following neoadjuvant therapy(NAT)for gastric cancer(GC)is rare but associated with a favorable prognosis.This study aims to reassess the optimal response population(ORP)foll...Objective:Pathologic complete response(pCR)following neoadjuvant therapy(NAT)for gastric cancer(GC)is rare but associated with a favorable prognosis.This study aims to reassess the optimal response population(ORP)following NAT by evaluating the prognostic outcomes associated with various T and N stages,utilizing multicenter data from China.Methods:Patients who underwent NAT following radical gastrectomy at 10 tertiary hospitals in China between2008 and 2021 were included.The ORP was introduced to explore the disease-free survival(DFS),overall survival(OS),recurrence patterns,and influencing factors following propensity score matching(PSM).Results:A total of 1,076 patients were enrolled in this study(median follow-up period:60 months).We defined ORP as a pCR or tumor infiltration of the mucosal or submucosal layer without lymph node metastasis(pCR or yp T1N0)after NAT.The ORP group comprised 136 patients(12.6%),while the non-ORP group comprised 940patients(87.4%).After applying a 1:4 PSM,we obtained an ORP group of 136 patients and non-ORP group of 544patients.Survival analysis demonstrated that both the 3-year OS(before PSM:89.0%vs.55.0%,P<0.001;after PSM:89.0%vs.55.4%,P<0.001)and DFS(before PSM:85.8%vs.49.7%,P<0.001;after PSM:85.8%vs.50.6%,P<0.001)were significantly superior in the ORP group compared to that in the non-ORP group.Remarkably,adjuvant chemotherapy did not impact the prognosis of patients in the ORP group(3-year OS:89.0%vs.89.7%,P=0.988;3-year DFS:84.9%vs.89.7%,P=0.700).Conclusions:This study reevaluates patients with ORP following NAT,providing a more comprehensive and accurate depiction of the potential beneficiary group and survival outcomes in patients with locally advanced GC.展开更多
Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4;however,the mechanisms underlying this association remain poorly understood.Here we prospectively followed 191 healthy...Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4;however,the mechanisms underlying this association remain poorly understood.Here we prospectively followed 191 healthy,vaginally born,term infants from birth to 15 months,using a systems vaccinology approach to assess the effects of antibiotic exposure on immune responses to vaccination.Exposure to direct neonatal but not intrapartum antibiotics was associated with significantly lower antibody titres against various polysaccharides in the 13-valent pneumococcal conjugate vaccine and the Haemophilus influenzae type b polyribosylribitol phosphate and diphtheria toxoid antigens in the combined 6-in-1 Infanrix Hexa vaccine at 7 months of age.Blood from infants exposed to neonatal antibiotics had an inflammatory transcriptional profile before vaccination;in addition,faecal metagenomics showed reduced abundance of Bifidobacterium species in these infants at the time of vaccination,which was correlated with reduced vaccine antibody titres 6 months later.In preclinical models,responses to the 13-valent pneumococcal conjugate vaccine were strongly dependent on an intact microbiota but could be restored in germ-free mice by administering a consortium of Bifidobacterium species or a probiotic already widely used in neonatal units.Our data suggest that microbiota-targeted interventions could mitigate the detrimental effects of early-life antibiotics on vaccine immunogenicity.展开更多
BACKGROUND Although the 2021 Chinese Clinical Practice Guidelines for Enhanced Recovery after Surgery(ERAS)provide recommendations for ERAS in gastrointestinal surgery,the clinical application of standard ERAS nursing...BACKGROUND Although the 2021 Chinese Clinical Practice Guidelines for Enhanced Recovery after Surgery(ERAS)provide recommendations for ERAS in gastrointestinal surgery,the clinical application of standard ERAS nursing models is challenging due to the variety of diseases involved in gastrointestinal surgery and the com-plex factors contributing to patient stress responses.Moreover,stress responses are more severe in older adult patients.Therefore,precision medicine is required to improve the quality of nursing care and promote postoperative recovery in gastrointestinal surgery.and demonstrate nursing benefits through clinical practice.METHODS This randomized clinical trial first established an evidence-based nursing ERAS protocol in older adult patients based on literature related to perioperative nursing measures for gastrointestinal surgery stress response.Next,392 older adult patients who underwent gastrointestinal surgery and were admitted to our hospital between December 2021 and June 2023 were categorized into two groups to receive evidence-based(study group)or conventional(control group)ERAS nursing models,respectively.Intraoperative physiological parameters during surgery and postoperative recovery indicators were compared between the groups.RESULTS Among 64 domestic and international studies,the stress responses of older adult patients mainly included emotional anxiety,sleep disorders,gastrointestinal discomfort,physical weakness,pain,and swelling.The appropriate nursing interventions included comprehensive psychological counseling,pre-and postoperative nutritional support,temperature control,pain management,and rehabilitation training.Compared with the control group,the study group showed lower heart rate,mean arterial pressure,blood glucose level,and adrenaline level;shorter duration of drainage tube placement,time to first flatus,time to first ambulation,and postoperative hospital stay;lower anxiety scores on postoperative day 3;and lower incidences of postoperative infection,obstruction,poor wound healing,and gastrointestinal reactions were lower in the study group(all P<0.05).CONCLUSION The evidence-based nursing measures targeting stress responses based on the conventional ERAS nursing model resulted in stable intraoperative physiological parameters during surgery,promoted postoperative recovery,and reduced the incidence of complications.展开更多
The occurrence of top-down(TD)cracking has gradually become a prevalent issue in semi-rigid base asphalt pavements after prolonged service.A coupled simulation model integrating the finite difference method(FDM)and di...The occurrence of top-down(TD)cracking has gradually become a prevalent issue in semi-rigid base asphalt pavements after prolonged service.A coupled simulation model integrating the finite difference method(FDM)and discrete element method(DEM)was employed to investigate the mechanical behavior of asphalt pavement containing a pre-existing TD crack.The mesoscopic parameters of the model were calibrated based on the mixture modulus and the static mechanical response on the MLS66 test road.Finally,an analysis was performed to assess how variations in TD crack depth and longitudinal length affect the distribution patterns of transverse tensile stress,vertical shear stress,and vertical compressive stress.The results indicate that the vertical propagation of TD crack significantly increases both the tensile stress value and range on the middle surface,while the longitudinal development of TD crack has minimal impact.This phenomenon may result in more severe fatigue failure on the middle surface.With the vertical and longitudinal development of TD crack,the vertical shear stress and compressive stress show obvious"two-stage"characteristics.When the crack's vertical length reaches 40 mm,there is a sharp increase in stress on the upper surface.As the crack continues to propagate vertically,the growth of stress on the upper surface becomes negligible,while the stress in the middle and lower layers increased significantly.Conversely,for longitudinal development of TD crack,any changes in stress are insignificant when their length is less than 180 mm;however,as they continue to develop longitudinally beyond this threshold,there is a sharp increase in stress levels.These findings hold great significance for understanding pavement structure deterioration and maintenance behavior associated with TD crack.展开更多
The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with...The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.展开更多
Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elu...Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.展开更多
A deep-sea mining riser is a crucial component of the system used to lift seafloor mineral resources to the vessel.It is prone to damage and failure because of harsh environmental conditions and internal fluid erosion...A deep-sea mining riser is a crucial component of the system used to lift seafloor mineral resources to the vessel.It is prone to damage and failure because of harsh environmental conditions and internal fluid erosion.Furthermore,damage can impact the response characteristics of the riser,but varying environmental loadings easily mask it.Thus,distin-guishing between riser damage and environmental effects poses a considerable challenge.To address this issue,a cantilevered model is created for a deep-sea mining riser via the concentrated mass method,and a time-domain analytical strategy is developed.The vortex-induced vibration(VIV)response characteristics of the riser are initially examined,considering various damage conditions and flow velocities.The study results revealed four primary observations:(a)effective tension can serve as a reliable indicator for identifying damage at lower velocities;(b)there are noticeable differences in displacement between the healthy and damaged risers in the in-line direction rather than the cross-flow direction;(c)frequency characteristics can more effectively distinguish the damage conditions at high flow velocities,with the mean square frequency and frequency variance being more effective than the centroid frequency and root variance frequency;(d)displacement differences are more sensitive to damage occurring near the top and bottom of the riser,while both velocity variations and structural damage can influence displacements,especially in regions between modal nodes.The vibrational behavior and damage indicators are clarified for structural health monitoring of deep-sea mining risers during lifting operations.展开更多
Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic m...Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.展开更多
β-Ga_(2)O_(3),as one of the important 4th generation semiconductors,is widely used in solar-blind ultraviolet(UV)detectors with a short detection range of 200-280 nm benefiting from its ultra-wide bandgap,strong radi...β-Ga_(2)O_(3),as one of the important 4th generation semiconductors,is widely used in solar-blind ultraviolet(UV)detectors with a short detection range of 200-280 nm benefiting from its ultra-wide bandgap,strong radiation resistance,and excellent chemical and thermal stabilities.Here,a self-powered photodetector(PD)based on an Ag/β-Ga_(2)O_(3) Schottky heterojunction was designed and fabricated.Through a subtle design of electrodes,the pyro-phototronic effect was discovered,which can be coupled to the common photovoltaic effect and further enhance the performance of the PD.Compared to traditional Ga_(2)O_(3)-based PD,the as-used PD exhibited a self-driving property and a broadband response beyond the bandgap lim-itations,ranging from 200 nm(deep UV)to 980 nm(infrared).Moreover,the photoresponse time was greatly shrunk owing to the coupling effect.Under laser irradiation,with a wavelength of 450 nm and a power density of 8 mW cm-2,the photocurrent could be improved by around 41 times compared with the sole photovoltaic effect.Besides,the performances of the Schottky PD were enhanced at both high and low temperatures.The device also possessed long-term working stability.This paper not only re-veals basic physics lying in the 4th generation semiconductor Ga_(2)O_(3) but also sheds light on the multi-encryption transmission of light information using this PD.展开更多
As the mine depth around the world increases,the temperature of the surrounding rock of the mining workface increases significantly.To control the heat hazards,the hot water in the mining floor is developed during min...As the mine depth around the world increases,the temperature of the surrounding rock of the mining workface increases significantly.To control the heat hazards,the hot water in the mining floor is developed during mining to decrease the min-ing workface temperature while also developing geothermal energy.This method is called the co-exploitation of mine and geothermal energy(CMGE).The geothermal development may precipitate the large-scale failure of the nearby fault zone during the mining process.However,the evolution of shear slide and shear failure of fault under geothermal production/rein-jection during mining is missing.Therefore,a fully-coupled hydraulic mechanism(HM)double-medium model for CMGE was developed based on the measured data of the Chensilou mine.A comparative analysis of the mechanical response of fault between CMGE and single mining was conducted.The disturbance of geothermal production pressure and reinjection pressure under mining on fault stability were respectively expounded.The results indicate that:(1)The disturbance of geo-thermal reinjection amplifies the disturbance of mining on fault stability.The amplified effect resulted in a normal stress drop of the fault,further leading to a substantial increase in shear slide distance,failure area,and cumulative seismic moment of fault compared with the single mining process.(2)As the distance of reinjection well to the fault decreases,the fault failure intensity increases.Setting the production well within the fault is advantageous for controlling fault stability under CMGE.(3)The essence of the combined disturbance of CMGE on the nearby fault is the overlay of tensile stress disturbance on the fault rock mass of the mining and geothermal reinjection.Though the geothermal reinjection causes a minor normal stress drop of fault,it can result in a more serious fault failure under CMGE.This paper supplies a significant gap in understanding thenearby faults failure under CMGE.展开更多
BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD....BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.展开更多
The DDR(DNA damage response)is an essential cellular mechanism that detects and repairs DNA lesions to maintain genomic stability.Dysregulation of DDR pathways is frequently observed in human tumors,leading to increas...The DDR(DNA damage response)is an essential cellular mechanism that detects and repairs DNA lesions to maintain genomic stability.Dysregulation of DDR pathways is frequently observed in human tumors,leading to increased genomic instability and promoting tumor progression.Consequently,targeting DDR mechanisms has emerged as a promising therapeutic strategy in oncology.This review provides an overview of the major DDR pathways,highlighting the roles of key proteins involved in various DDR processes.A detailed understanding of these molecular mechanisms has paved the way for the development of targeted antitumor agents,including inhibitors of PARP1,ATM,ATR,CHK1,CHK2,DNA-PK,and WEE1.Additionally,the significant challenges in the development of DDR inhibitors are examined,including tumor microenvironment heterogeneity,resistance mechanisms,issues with selectivity and toxicity,and the complexities associated with clinical trial design.Finally,future directions and emerging strategies to improve DDR-targeted therapies are discussed.These strategies include biomarker-driven precision medicine,novel combination therapies,advanced drug delivery systems,and the potential application of artificial intelligence to optimize treatment outcomes.展开更多
文摘BACKGROUND Rectal cancer management is currently evolving with the advent of different neoadjuvant treatment strategies and organ preservation strategies.A significant proportion of patients could achieve complete clinical response after neoadjuvant treatment,which often translates to pathologic complete response(pCR)as assessed on surgical specimens after curative intent surgery.Endoscopy plays a significant role in assessing treatment response to neoadjuvant therapies.AIM To explore the role of endoscopy in predicting subsequent pCR after neoadjuvant treatment in rectal cancer patients.METHODS An extensive literature review was undertaken to identify the criteria used for assessment of endoscopic response and their ability to predict pCR.RESULTS Fifteen studies were identified through literature review.The most commonly used endoscopic criteria for evaluation included the presence of a flat white scar and the absence of nodularity or telangiectasia.Information on the timing of endoscopic assessment in relation to neoadjuvant treatment protocols were also extracted from the studies.In most studies,the diagnostic accuracy for predicting pCR exceeded 0.8.The main limitations identified were the retrospective design of included studies included and a moderate risk of bias.CONCLUSION Endoscopy can be a key prognostic factor in predicting pCR to neoadjuvant treatment in rectal cancer despite significant limitations in currently available data.
基金supported by the National Institutes of Health(Grants P30 CA036727 and R01 CA258621)and funding from the University of Nebraska Medical Center Graduate Studies Assistantship.
文摘The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.
文摘Imaging plays a crucial role in the evaluation of hepatocellular carcinoma(HCC)treatment response.Contrast enhanced computed tomography and magnetic resonance imaging with extra-cellular or hepatobiliary contrast agents are the imaging techniques of choice.Contrast enhanced ultrasound is a promising technique.In this paper,we describe radiological techniques,imaging findings after HCC treatment,and the criteria of response evaluation.The utility of the structured report is also evaluated.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFC3003805)Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.2022356)Guangzhou Basic and Applied Basic Research Project(Grant No.2023A04J0955).
文摘This paper presents a new type of triangular Sharp Eagle wave energy converter(WEC)platform.On the basis of the linear potential flow theory and the finite element analysis method,the hydrodynamic performance and structural response of the platform are studied,considering the actual platform motion and free surface rise under extreme sea states.First,the effects of the wave frequency and direction on the wave-induced loads and dynamic responses were examined.The motion at a wave direction angle of 0°is relatively low.On this basis,the angle constrained by the two sides of the Sharp Eagle floaters should be aligned with the main wave direction to avoid significant platform motion under extreme sea states.Additionally,the structural response of the platform,including the wave-absorbing floaters,is investigated.The results highlighted that the conditions or locations where yielding,buckling,and fatigue failures occur were different.In this context,the connection area of the Sharp Eagle floaters and platform is prone to yielding failure under oblique wave action,whereas the pontoon and side of the Sharp Eagle floaters are prone to buckling failure during significant vertical motion.Additionally,fatigue damage is most likely to occur at the connection between the middle column on both sides of the Sharp Eagle floaters and the pontoons.The findings of this paper revealed an intrinsic connection between wave-induced loads and the dynamic and structural responses of the platform,which provides a useful reference for the improved design of WECs.
基金National Natural Science Foundation of China under Grant No.52278135。
文摘Both acceleration and pseudo-acceleration response spectra play important roles in structural seismic design.However,only one of them is generally provided in most seismic codes.Therefore,many studies have attempted to develop conversion models between the acceleration response spectrum(SA)and the pseudo-acceleration response spectrum(PSA).Our previous studies found that the relationship between SA and PSA is affected by magnitude,distance,and site class.Subsequently,we developed an SA/PSA model incorporating these effects.However,this model is suitable for cases with small and moderate magnitudes and its accuracy is not good enough for cases with large magnitudes.This paper aims to develop an efficient SA/PSA model by considering influences of magnitude,distance,and site class,which can be applied to cases not only with small or moderate magnitudes but also with large ones.For this purpose,regression analyses were conducted using 16,660 horizontal seismic records with a wider range of magnitude.The magnitude of these seismic records varies from 4 to 9 and the distances vary from 10 to 200 km.These ground motions were recorded at 338 stations covering four site classes.By comparing them with existing models,it was found that the proposed model shows better accuracy for cases with any magnitudes,distances,and site classes considered in this study.
基金supported by the National Natural Science Foundation of China(Grant No.42325502,and 42275045)the West Light Foundation of the Chi-nese Academy of Sciences(Grant No.xbzg-zdsys-202215)+1 种基金the Sci-ence and Technology Research Plan of Gansu Province(Grant Nos.23JRRA654 and 20JR10RA070)iLEAPs(Integrated Land Ecosystem-Atmosphere Processes Study).
文摘The source region of the Yellow River(SRYR),with its semi-humid to semi-arid climate,is crucial for understanding water resource dynamics.Precipitation is key for replenishing surface water and balancing the ecosystem’s water cycle.However,the soil moisture response to precipitation across climate zones and soil layers remains poorly understood due to limited long-term data.This study examines the response of soil moisture to precipitation at multiple time scales in the SRYR,using data from Maqu,Mado,Ngoring Lake sites,and the Maqu monitoring network(MMN),along with CN05.1 precipitation and GLEAM v3.8a soil moisture data.Results show that the semi-humid area requires more precipitation to trigger soil moisture responses compared to the semi-arid area in the SRYR.Surface soil at Maqu,MMN,Ngoring Lake,and Mado sites require at least 8.6,8.4,5.2,and 2.84 mm of precipitation,respectively,for effective replenishment.Significant responses to precipitation events were observed in soil layers at 40 cm and above in the semi-humid area,while at 20 cm and above in the semi-arid area.Precipitation volume is the primary factor influencing soil moisture,affecting both the increment and time lag to maximum moisture.Precipitation intensity and pre-rain moisture have no direct effect.In the central SRYR,accumulated precipitation has a greater impact.Root-zone soil moisture has a weaker correlation with precipitation compared to surface soil moisture but persists longer,responding for up to 10 days,while surface soil moisture responds more immediately but only lasts about 5 days.
基金supported by the Science and Technology Project of State Grid Corporation of China(Grant 5500-202455120A-1-1-ZN).
文摘The multifrequency voltage(MFV)stress,including switching impulses and harmonics,commonly appearing in the modern power system will stimulate the multifrequency impedance dynamics behaviours of electrical insulation.Therefore,this article presents a novel concept of insulation resilience response(IRR)by employing polymer insulation materials,which may be extended to electrical insulation resilience(EIR).The focus is on understanding reversible recovery performance and supporting physics-informed condition assessment for electrical insulation exposed to MFV.The underlying physical mechanisms and modelling methodologies are integrated to characterise the IRR behaviours of polymer insulation systems.The multifrequency dielectric/impedance properties of different resin dielectrics under diverse temperatures are comparatively investigated as proofofconcept cases.Furthermore,multidimensional sensitivity indicators are developed to quantify the electrical insulation resilience behaviour.A radar plot representation integrating resilience sensitivity indicators qualitatively assesses the IRR behaviours of polymer insulation systems.Additionally,a quantification methodology,including the resilience index(RI)and time-varied RI(TVRI),is proposed for the reversible recovery performance analysis for electrical insulation,respectively.Ultimately,an application-oriented framework derived from TVRI is provided to analyse the recovery performance evolution behaviours of electrical insulation under complex operating conditions.This offers a key theoretical foundation for insulation performance characterisation and condition analysis for high-voltage power equipment.
基金supported by an intramural proof of concept grant of the NCT Heidelberg.
文摘Background The potential of exercise as a concurrent therapy for actively treated primary tumors has been suggested by emerging preclinical and observational studies.However,clinical trials regarding this question are scarce.Therefore,we conducted a randomized controlled trial investigating the effects of aerobic or resistance exercise concomitant to neoadjuvant chemotherapy(NACT)on tumor size.Methods In the BENEFIT study(German title:Bewegung bei neoadjuvanter chemotherapie zur verbesserung der fitness),patients with breast cancer scheduled for NACT were randomly assigned to supervised resistance training(RT,n=60)or aerobic training(AT,n=60)twice weekly during NACT or to a waitlist control group(WCG,n=60).The primary outcome,“change in tumor size”,as well as the secondary clinical outcomes pathologic complete response(pCR),type of surgery(breast conserving/mastectomy),axillary lymph node dissection(ALND,yes/no),premature discontinuation of chemotherapy(yes/no),and relative dose intensity(RDI)were derived from clinical records.Due to the highly skewed distribution,the primary outcome was categorized.Multiple(ordinal)logistic regression analyses were performed.Results Overall,there was no significant difference in post-intervention tumor size between RT or AT and WCG.However,there was a significant effect modification by hormone receptor(HR)status(P_(interaction)=0.030).Among patients with HR+tumors,results suggest a beneficial effect of AT on tumor shrinkage(odds ratio(OR)=2.37,95%confidence interval(95%CI):0.97‒5.78),on pCR(OR=3.21,95%CI:0.97‒10.61);and on ALND(OR=3.76,95%CI:0.78‒18.06)compared to WCG.The effects of RT were slightly less pronounced.For HR−subtypes,beneficial effects on RDI were found for AT(OR=3.71,95%CI:1.20‒11.50)and similarly for RT(OR=2.58,95%CI:0.88‒7.59).Both AT and RT had favorable effects on premature discontinuation of chemotherapy(OR(no vs.yes)=2.34,95%CI:1.10‒5.06),irrespective of tumor receptor status.Conclusion While there was no significant effect on the primary outcome in the overall group,aerobic and resistance exercise concomitant to NACT seem to beneficially affect tumor shrinkage and pCR,reduce the need for ALND among patients with HR+breast cancers,and prevent low RDI among patients with HR–breast cancers.These results warrant confirmation in further trials.
基金supported by the construction funds for“high-level hospitals and clinical specialties”of Fujian Province(No.[2021]76)。
文摘Objective:Pathologic complete response(pCR)following neoadjuvant therapy(NAT)for gastric cancer(GC)is rare but associated with a favorable prognosis.This study aims to reassess the optimal response population(ORP)following NAT by evaluating the prognostic outcomes associated with various T and N stages,utilizing multicenter data from China.Methods:Patients who underwent NAT following radical gastrectomy at 10 tertiary hospitals in China between2008 and 2021 were included.The ORP was introduced to explore the disease-free survival(DFS),overall survival(OS),recurrence patterns,and influencing factors following propensity score matching(PSM).Results:A total of 1,076 patients were enrolled in this study(median follow-up period:60 months).We defined ORP as a pCR or tumor infiltration of the mucosal or submucosal layer without lymph node metastasis(pCR or yp T1N0)after NAT.The ORP group comprised 136 patients(12.6%),while the non-ORP group comprised 940patients(87.4%).After applying a 1:4 PSM,we obtained an ORP group of 136 patients and non-ORP group of 544patients.Survival analysis demonstrated that both the 3-year OS(before PSM:89.0%vs.55.0%,P<0.001;after PSM:89.0%vs.55.4%,P<0.001)and DFS(before PSM:85.8%vs.49.7%,P<0.001;after PSM:85.8%vs.50.6%,P<0.001)were significantly superior in the ORP group compared to that in the non-ORP group.Remarkably,adjuvant chemotherapy did not impact the prognosis of patients in the ORP group(3-year OS:89.0%vs.89.7%,P=0.988;3-year DFS:84.9%vs.89.7%,P=0.700).Conclusions:This study reevaluates patients with ORP following NAT,providing a more comprehensive and accurate depiction of the potential beneficiary group and survival outcomes in patients with locally advanced GC.
文摘Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4;however,the mechanisms underlying this association remain poorly understood.Here we prospectively followed 191 healthy,vaginally born,term infants from birth to 15 months,using a systems vaccinology approach to assess the effects of antibiotic exposure on immune responses to vaccination.Exposure to direct neonatal but not intrapartum antibiotics was associated with significantly lower antibody titres against various polysaccharides in the 13-valent pneumococcal conjugate vaccine and the Haemophilus influenzae type b polyribosylribitol phosphate and diphtheria toxoid antigens in the combined 6-in-1 Infanrix Hexa vaccine at 7 months of age.Blood from infants exposed to neonatal antibiotics had an inflammatory transcriptional profile before vaccination;in addition,faecal metagenomics showed reduced abundance of Bifidobacterium species in these infants at the time of vaccination,which was correlated with reduced vaccine antibody titres 6 months later.In preclinical models,responses to the 13-valent pneumococcal conjugate vaccine were strongly dependent on an intact microbiota but could be restored in germ-free mice by administering a consortium of Bifidobacterium species or a probiotic already widely used in neonatal units.Our data suggest that microbiota-targeted interventions could mitigate the detrimental effects of early-life antibiotics on vaccine immunogenicity.
文摘BACKGROUND Although the 2021 Chinese Clinical Practice Guidelines for Enhanced Recovery after Surgery(ERAS)provide recommendations for ERAS in gastrointestinal surgery,the clinical application of standard ERAS nursing models is challenging due to the variety of diseases involved in gastrointestinal surgery and the com-plex factors contributing to patient stress responses.Moreover,stress responses are more severe in older adult patients.Therefore,precision medicine is required to improve the quality of nursing care and promote postoperative recovery in gastrointestinal surgery.and demonstrate nursing benefits through clinical practice.METHODS This randomized clinical trial first established an evidence-based nursing ERAS protocol in older adult patients based on literature related to perioperative nursing measures for gastrointestinal surgery stress response.Next,392 older adult patients who underwent gastrointestinal surgery and were admitted to our hospital between December 2021 and June 2023 were categorized into two groups to receive evidence-based(study group)or conventional(control group)ERAS nursing models,respectively.Intraoperative physiological parameters during surgery and postoperative recovery indicators were compared between the groups.RESULTS Among 64 domestic and international studies,the stress responses of older adult patients mainly included emotional anxiety,sleep disorders,gastrointestinal discomfort,physical weakness,pain,and swelling.The appropriate nursing interventions included comprehensive psychological counseling,pre-and postoperative nutritional support,temperature control,pain management,and rehabilitation training.Compared with the control group,the study group showed lower heart rate,mean arterial pressure,blood glucose level,and adrenaline level;shorter duration of drainage tube placement,time to first flatus,time to first ambulation,and postoperative hospital stay;lower anxiety scores on postoperative day 3;and lower incidences of postoperative infection,obstruction,poor wound healing,and gastrointestinal reactions were lower in the study group(all P<0.05).CONCLUSION The evidence-based nursing measures targeting stress responses based on the conventional ERAS nursing model resulted in stable intraoperative physiological parameters during surgery,promoted postoperative recovery,and reduced the incidence of complications.
基金supported by National Key R&D Program of China(Grant No.2021YFB2601200)Open Fund of National Engineering Research Center of Highway Maintenance Technology(Changsha University of Science&Technology)(No.kfj230207).
文摘The occurrence of top-down(TD)cracking has gradually become a prevalent issue in semi-rigid base asphalt pavements after prolonged service.A coupled simulation model integrating the finite difference method(FDM)and discrete element method(DEM)was employed to investigate the mechanical behavior of asphalt pavement containing a pre-existing TD crack.The mesoscopic parameters of the model were calibrated based on the mixture modulus and the static mechanical response on the MLS66 test road.Finally,an analysis was performed to assess how variations in TD crack depth and longitudinal length affect the distribution patterns of transverse tensile stress,vertical shear stress,and vertical compressive stress.The results indicate that the vertical propagation of TD crack significantly increases both the tensile stress value and range on the middle surface,while the longitudinal development of TD crack has minimal impact.This phenomenon may result in more severe fatigue failure on the middle surface.With the vertical and longitudinal development of TD crack,the vertical shear stress and compressive stress show obvious"two-stage"characteristics.When the crack's vertical length reaches 40 mm,there is a sharp increase in stress on the upper surface.As the crack continues to propagate vertically,the growth of stress on the upper surface becomes negligible,while the stress in the middle and lower layers increased significantly.Conversely,for longitudinal development of TD crack,any changes in stress are insignificant when their length is less than 180 mm;however,as they continue to develop longitudinally beyond this threshold,there is a sharp increase in stress levels.These findings hold great significance for understanding pavement structure deterioration and maintenance behavior associated with TD crack.
基金National Natural Science Foundation of China under Grant No.51578463。
文摘The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.
基金supported by the Anhui Provincial Natural Science Foundation(Grant No.2308085MH250)the Natural Science Research Project of Anhui Educational Committee(Grant No.2023AH053327)the Scientific Research Fund Project of Anhui Medical University(2020xkj039).
文摘Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.
基金financially supported by the National Key Research and Development Program of China(Grant No.2023YFC2811600)the National Natural Science Foundation of China(Grant Nos.52301349 and 52088102)+1 种基金the Qingdao Post-Doctorate Science Fund(No.QDBSH20220202070)the Major Scientific and Technological Innovation Project of Shandong Province(Grant No.2019JZZY010820).
文摘A deep-sea mining riser is a crucial component of the system used to lift seafloor mineral resources to the vessel.It is prone to damage and failure because of harsh environmental conditions and internal fluid erosion.Furthermore,damage can impact the response characteristics of the riser,but varying environmental loadings easily mask it.Thus,distin-guishing between riser damage and environmental effects poses a considerable challenge.To address this issue,a cantilevered model is created for a deep-sea mining riser via the concentrated mass method,and a time-domain analytical strategy is developed.The vortex-induced vibration(VIV)response characteristics of the riser are initially examined,considering various damage conditions and flow velocities.The study results revealed four primary observations:(a)effective tension can serve as a reliable indicator for identifying damage at lower velocities;(b)there are noticeable differences in displacement between the healthy and damaged risers in the in-line direction rather than the cross-flow direction;(c)frequency characteristics can more effectively distinguish the damage conditions at high flow velocities,with the mean square frequency and frequency variance being more effective than the centroid frequency and root variance frequency;(d)displacement differences are more sensitive to damage occurring near the top and bottom of the riser,while both velocity variations and structural damage can influence displacements,especially in regions between modal nodes.The vibrational behavior and damage indicators are clarified for structural health monitoring of deep-sea mining risers during lifting operations.
基金supported by the National Natural Science Foundation of China(No.82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)partially supported by Wuhan Kangchuang Biotechnology Co.,Ltd。
文摘Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.
基金supported by the National Natural Science Foundation of China(Grant Nos.52192610 and 52192613)the National Key R&D Project from the Minister of Science and Technology(No.2021YFA1201601)the CAS-TWAS President’s Fellow-ship(A.B).
文摘β-Ga_(2)O_(3),as one of the important 4th generation semiconductors,is widely used in solar-blind ultraviolet(UV)detectors with a short detection range of 200-280 nm benefiting from its ultra-wide bandgap,strong radiation resistance,and excellent chemical and thermal stabilities.Here,a self-powered photodetector(PD)based on an Ag/β-Ga_(2)O_(3) Schottky heterojunction was designed and fabricated.Through a subtle design of electrodes,the pyro-phototronic effect was discovered,which can be coupled to the common photovoltaic effect and further enhance the performance of the PD.Compared to traditional Ga_(2)O_(3)-based PD,the as-used PD exhibited a self-driving property and a broadband response beyond the bandgap lim-itations,ranging from 200 nm(deep UV)to 980 nm(infrared).Moreover,the photoresponse time was greatly shrunk owing to the coupling effect.Under laser irradiation,with a wavelength of 450 nm and a power density of 8 mW cm-2,the photocurrent could be improved by around 41 times compared with the sole photovoltaic effect.Besides,the performances of the Schottky PD were enhanced at both high and low temperatures.The device also possessed long-term working stability.This paper not only re-veals basic physics lying in the 4th generation semiconductor Ga_(2)O_(3) but also sheds light on the multi-encryption transmission of light information using this PD.
基金supported by the Key Project of the National Natural Science Foundation of China(U23B2091)the National Key R&D Program of China(2022YFC2905600)+1 种基金the Youth Project of the National Natural Science Foundation of China(52304104 and 52404157)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZB20240825).
文摘As the mine depth around the world increases,the temperature of the surrounding rock of the mining workface increases significantly.To control the heat hazards,the hot water in the mining floor is developed during mining to decrease the min-ing workface temperature while also developing geothermal energy.This method is called the co-exploitation of mine and geothermal energy(CMGE).The geothermal development may precipitate the large-scale failure of the nearby fault zone during the mining process.However,the evolution of shear slide and shear failure of fault under geothermal production/rein-jection during mining is missing.Therefore,a fully-coupled hydraulic mechanism(HM)double-medium model for CMGE was developed based on the measured data of the Chensilou mine.A comparative analysis of the mechanical response of fault between CMGE and single mining was conducted.The disturbance of geothermal production pressure and reinjection pressure under mining on fault stability were respectively expounded.The results indicate that:(1)The disturbance of geo-thermal reinjection amplifies the disturbance of mining on fault stability.The amplified effect resulted in a normal stress drop of the fault,further leading to a substantial increase in shear slide distance,failure area,and cumulative seismic moment of fault compared with the single mining process.(2)As the distance of reinjection well to the fault decreases,the fault failure intensity increases.Setting the production well within the fault is advantageous for controlling fault stability under CMGE.(3)The essence of the combined disturbance of CMGE on the nearby fault is the overlay of tensile stress disturbance on the fault rock mass of the mining and geothermal reinjection.Though the geothermal reinjection causes a minor normal stress drop of fault,it can result in a more serious fault failure under CMGE.This paper supplies a significant gap in understanding thenearby faults failure under CMGE.
文摘BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.
文摘The DDR(DNA damage response)is an essential cellular mechanism that detects and repairs DNA lesions to maintain genomic stability.Dysregulation of DDR pathways is frequently observed in human tumors,leading to increased genomic instability and promoting tumor progression.Consequently,targeting DDR mechanisms has emerged as a promising therapeutic strategy in oncology.This review provides an overview of the major DDR pathways,highlighting the roles of key proteins involved in various DDR processes.A detailed understanding of these molecular mechanisms has paved the way for the development of targeted antitumor agents,including inhibitors of PARP1,ATM,ATR,CHK1,CHK2,DNA-PK,and WEE1.Additionally,the significant challenges in the development of DDR inhibitors are examined,including tumor microenvironment heterogeneity,resistance mechanisms,issues with selectivity and toxicity,and the complexities associated with clinical trial design.Finally,future directions and emerging strategies to improve DDR-targeted therapies are discussed.These strategies include biomarker-driven precision medicine,novel combination therapies,advanced drug delivery systems,and the potential application of artificial intelligence to optimize treatment outcomes.
