Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer

BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.

Frequency Domain Fatigue Evaluation on SCR Girth-Weld Based on Structural Stress

The Steel Catenary Riser(SCR)is a vital component for transporting oil and gas from the seabed to the floating platform.The harsh environmental conditions and complex platform motion make the SCR’s girth-weld prone to fatigue failure.The structural stress fatigue theory and Master S-N curve method provide accurate predictions for the fatigue damage on the welded joints,which demonstrate significant potential and compatibility in multi-axial and random fatigue evaluation.Here,we propose a new frequency fatigue model subjected to welded joints of SCR under multiaxial stress,which fully integrates the mesh-insensitive structural stress and frequency domain random process and transforms the conventional welding fatigue technique of SCR into a spectrum analysis technique utilizing structural stress.Besides,a full-scale FE model of SCR with welds is established to obtain the modal structural stress of the girth weld and the frequency response function(FRF)of modal coordinate,and a biaxial fatigue evaluation about the girth weld of the SCR can be achieved by taking the effects of multi-load correlation and pipe-soil interaction into account.The research results indicate that the frequency-domain fatigue results are aligned with the time-domain results,meeting the fatigue evaluation requirements of the SCR.

Impact of comorbid subthreshold depressive symptoms on cancerrelated fatigue and complications in adults with leukemia

BACKGROUND Patients not only experience symptoms caused by cancer but also suffer from the accompanying psychological pain.Therefore,these patients do not have high quality of life.According to the World Health Organization,the incidence of leukemia in China in 2020 was 5.1/100000,the mortality rate was 3.3/100000,and the prevalence rate was 16.7/100000.Therefore,it is important to examine the influence of comorbid subthreshold depressive symptoms on leukemia patients.AIM To determine the impact of comorbid subthreshold depressive symptoms on cancer-related fatigue and complications in leukemia patients,thereby providing a basis for early diagnosis and treatment in clinical practice.METHODS A questionnaire survey was conducted among leukemia patients admitted to a tertiary hospital in Xi'an,Shaanxi Province,China,from August 2022 to December 2023.Patients with a score>16 on the Chinese Classification of Mental Disorders(CCMD-3)and a Hamilton Depression Rating Scale score of 8-17 were classified as the subthreshold depressive group(n=95),while 100 leukemia patients admitted during the same period were classified as the control group.Data were collected using Epidata 3.1 software,and comparisons were made between the two groups regarding general clinical data,the Piper Fatigue Scale(PFS),the Pittsburgh Sleep Quality Index(PSQI),the Numeric Rating Scale for pain assessment,laboratory indicators,and the occurrence of complications.RESULTS In this survey,120 leukemia patients with depression were preliminarily screened,95 patients with subthreshold depression were ultimately selected as the subthreshold depression group,and 100 leukemia patients admitted during the same period were enrolled as the normal group.Comparison of basic clinical data between the two groups revealed no significant differences in age,sex,body mass index,cognitive function,or comorbidity with other chronic diseases.However,there were statistically significant differences in the use of radiotherapy and regular exercise between the two groups(P<0.05).Comparisons of scales and laboratory indicators revealed no significant differences in albumin or PSQI scores between the two groups,but there were statistically significant differences in pain scores,PSQI scores,PFS scores,hemoglobin levels,and C-reactive protein levels(P<0.05).Spearman’s correlation analysis indicated that cancer-related fatigue was correlated with age,hemoglobin levels,C-reactive protein levels,pain,and regular exercise among leukemia patients with subthreshold depression.Multivariate regression analysis revealed that advanced age,combined radiotherapy,pain,and low hemoglobin levels were risk factors for cancer-related fatigue in leukemia patients with comorbid subthreshold depression,while regular exercise was a protective factor against cancer-related fatigue.Follow-up comparisons revealed a significantly lower overall incidence of complications in the control group(4%)than in the depressive group(24.21%;P<0.001).CONCLUSION Leukemia patients with comorbid subthreshold depressive symptoms experience more severe cancer-related fatigue and a higher incidence of complications.These findings may be related to advanced age,combined radiotherapy,pain,and low hemoglobin levels,while regular exercise may effectively alleviate symptoms.

A comparative study of the anti-fatigue activity of extracts from different parts of Cistanche tubulosa(Schenk)Wight

Objective:To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa(Schenk)Wight(C.tubulosa,Rou Cong Rong),focusing on central and exercise-induced fatigue in mice.This study investigated the pharmacological effects of the total oligosaccharides,polysaccharides,and phenylethanoid glycosides(CPhGs)extracted from C.tubulosa.Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue.The mice were treated with different extracts of C.tubulosa,and their effects were assessed using behavioral tests to measure exercise capacity,learning,and memory function.Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels,liver and muscle glycogen storage,and various fatigue-related biomarkers.Results: This study found that treatment with C.tubulosa extract improved exercise capacity,learning,and memory in mice.Total oligosaccharides from C.tubulosa enhanced adrenocorticotropic hormone,cholinesterase,and thyroid-stimulating hormone levels,reduced cortisol levels in central fatigue models,and ameliorated biochemical markers of exercise-induced fatigue,including lowering lactic acid,blood urea nitrogen,and malondialdehyde levels.Among the tested extracts,the total oligosaccharides showed the most comprehensive anti-fatigue effects.Conclusion: The anti-fatigue effects of C.tubulosa,particularly those of its total oligosaccharides,are pronounced in both central and exercise-induced fatigue.These effects are mediated by the regulation of neurotransmitter levels,enhancement of glycogen storage,and improvement of antioxidant enzyme activity,suggesting potential therapeutic benefits in fatigue-related conditions.

The heterogeneity of tumor-associated macrophages and strategies to target it

Tumor-associated macrophages(TAMs)are emerging as targets for tumor therapy because of their primary role in promoting tumor progression.Several studies have been conducted to target TAMs by reducing their infiltration,depleting their numbers,and reversing their phenotypes to suppress tumor progression,leading to the development of drugs in preclinical and clinical trials.However,the heterogeneous characteristics of TAMs,including their ontogenetic and functional heterogeneity,limit their targeting.Therefore,in-depth exploration of the heterogeneity of TAMs,combined with immune checkpoint therapy or other therapeutic modalities could improve the efficiency of tumor treatment.This review focuses on the heterogeneous ontogeny and function of TAMs,as well as the current development of tumor therapies targeting TAMs and combination strategies.

Research progress of tumor-associated macrophages in immune checkpoint inhibitor tolerance in colorectal cancer

The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.

MicroRNA-206 as a promising epigenetic approach to modulate tumor-associated macrophages in hepatocellular carcinoma

This letter comments on the recently published manuscript by Huang et al in the World Journal of Gastroenterology,which focused on the immunomodulatory effect of Calculus bovis on hepatocellular carcinoma(HCC)tumor microenvironments(TME)by inhibiting M2-tumor-associated macrophage(M2-TAM)polarization via Wnt/β-catenin pathway modulation.Recent research highlights the crucial role of TAMs and their polarization towards the M2 phenotype in promoting HCC progression.Epigenetic regulation,particularly through microRNAs(miR),has emerged as a key factor in modulating immune responses and TAM polarization in the TME,influencing treatment responses and tumor progression.This editorial focuses on miR-206,which has been found to inhibit HCC cell proliferation and migration and promote apoptosis.Moreover,miR-206 enhances anti-tumor immune responses by promoting M1-polarization of Kupffer cells,facilitating CD8+T cell recruitment and suppressing liver cancer stem cell expansion.However,challenges remain in understanding the precise mechanisms regulating miR-206 and its potential as a therapeutic agent.Targeting epigenetic mechanisms and improving strategies,whether through pharmacological or genetic approaches,offer promising avenues to sensitize tumor cells to chemotherapy.Understanding the intricate interactions between cancer and non-coding RNA regulation opens new avenues for developing targeted therapies,potentially improving HCC prognosis.

Abnormally activated wingless/integrated signaling modulates tumor-associated macrophage polarization and potentially promotes hepatocarcinoma cell growth

In this article,we comment on the article by Huang et al.The urgent development of new therapeutic strategies targeting macrophage polarization is critical in the fight against liver cancer.Tumor-associated macrophages(TAMs),primarily of the M2 subtype,are instrumental in cellular communication within the tumor microenvironment and are influenced by various signaling pathways,including the wingless/integrated(Wnt)pathway.Activation of the Wnt signaling pathway is pivotal in promoting M2 TAMs polarization,which in turn can exacerbate hepatocarcinoma cell proliferation and migration.This manuscript emphasizes the burgeoning significance of the Wnt signaling pathway and M2 TAMs polarization in the pathogenesis and progression of liver cancer,highlighting the potential therapeutic benefits of inhibiting the Wnt pathway.Lastly,we point out areas in Huang et al’s study that require further research,providing guidance and new directions for similar studies.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii.Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components,namely quercetin,β-sitosterol,stigmasterol,7-Omethylluteolin-6-C-beta-glucoside_qt,atropine,and glycitein,were identified to have potency in improving exercise fatigue via multiple pathways,such as the PI3K-Akt,neuroactive ligand-receptor interaction,IL-17,TNF,and MAPK signaling pathways.The immunofluorescence results indicated that quercetin,a significant active component in Fructus lycii,increased the mean staining area of 2-NBDG,TMRM,and MitoTracker,and decreased the area of CellRox compared to the control.Furthermore,the protein expression levels of p-38 MAPK,p-MAPK,p-JNK,p-PI3K,and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways.Among these,quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress.The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Concerting magnesium implant degradation facilitates local chemotherapy in tumor-associated bone defect

Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects,substantial tumor recurrence,and long-lasting bone reconstruction post tumor resection.Magnesium and its alloys have recently emerged in clinics as orthopedics implantable metals but mostly restricted to mechanical devices.Here,by deposition of calcium-based bilayer coating on the surface,a Mg-based composite implant platform is developed with tailored degradation characteristics,simultaneously integrated with chemotherapeutic(Taxol)loading capacity.The delicate modulation of Mg degradation occurring in aqueous environment is observed to play dual roles,not only in eliciting desirable osteoinductivity,but allows for modification of tumor microenvironment(TME)owing to the continuous release of degradation products.Specifically,the sustainable H2 evolution and Ca2+from the implant is distinguished to cooperate with local Taxol delivery to achieve superior antineoplastic activity through activating Cyt-c pathway to induce mitochondrial dysfunction,which in turn leads to significant tumor-growth inhibition in vivo.In addition,the local chemotherapeutic delivery of the implant minimizes toxicity and side effects,but markedly fosters osteogenesis and bone repair with appropriate structure degradation in rat femoral defect model.Taken together,a promising intraosseous administration strategy with biodegradable Mg-based implants to facilitate tumor-associated bone defect is proposed.

Microstructure evolution and enhanced fatigue behavior in the Mg-10Li-5Zn-0.5Er alloys micro-alloyed with Yb

In this paper,(0.2-1 wt%)Yb was added to improve the tensile properties and high-cycle fatigue behavior of the as-cast and as-extruded Mg-10Li-5Zn-0.5Er alloys.It is found that Yb mainly affects the mechanical properties of the alloy by changing the grain size,type and morphology of the second phases.Yb mainly exists in the formation of Mg_(2)Yb and Mg-Zn-Yb phases in the metallographic structure.With the addition of Yb,the grains are refined and these Yb-containing phases replace the large-sized MgLiZn phase to be enriched at the grain boundaries.While the addition of excess Yb reduces the number of small-sized MgLiZn phases in the grain,thus reducing the alloys’mechanical performance.After extrusion,the small-sized MgLiZn phase is refined and the number increases,which effectively improves the tensile and fatigue strength of the alloy.The fatigue strength is mainly affected by the number and morphology of the second phase,positively correlated with the strength.Balanced in grain size and number and size of second phases,the extruded alloy with 0.2Yb added exhibits excellent mechanical properties with the yield strength,ultimate tensile strength and elongation of 292 MPa,303 MPa and 11.7%,and an fatigue strength of 130 MPa.

Effects of orientation on the fatigue crack growth behaviors of the ZK60 magnesium alloy in air and PBS

Strong anisotropic corrosion and mechanical properties caused by specimen orientations greatly limit the applications of wrought magnesium alloys.To investigate the influences of specimen orientation,the corrosion tests and(corrosion)fatigue crack growth tests were conducted.The rolled and transverse surfaces of the materials show distinct corrosion rate differences in the stable corrosion stage,but the truth is the opposite for the initial stage of corrosion.In air,specimen orientations have a significant influence on the plastic deformation mechanisms near the crack tip,which results in different fatigue fracture surfaces and cracking paths.Compared with R-T specimens,N-T specimens show a slower fatigue crack growth(FCG)rate in air,which can be attributed to crack closure effects and deformation twinning near the crack tip.The corrosion environment will not significantly change the main plastic deformation mechanisms for the same type of specimen.However,the FCG rate in phosphate buffer saline(PBS)is one order of magnitude higher than that in air,which is caused by the combined effects of hydrogen-induced cracking and anodic dissolution.Owing to the similar corrosion rates at crack tips,the specimens with different orientations display close FCG rates in PBS.

Research on Driver’s Fatigue Detection Based on Information Fusion

Driving fatigue is a physiological phenomenon that often occurs during driving.After the driver enters a fatigued state,the attentionis lax,the response is slow,and the ability todeal with emergencies is significantly reduced,which can easily cause traffic accidents.Therefore,studying driver fatigue detectionmethods is significant in ensuring safe driving.However,the fatigue state of actual drivers is easily interfered with by the external environment(glasses and light),which leads to many problems,such as weak reliability of fatigue driving detection.Moreover,fatigue is a slow process,first manifested in physiological signals and then reflected in human face images.To improve the accuracy and stability of fatigue detection,this paper proposed a driver fatigue detection method based on image information and physiological information,designed a fatigue driving detection device,built a simulation driving experiment platform,and collected facial as well as physiological information of drivers during driving.Finally,the effectiveness of the fatigue detection method was evaluated.Eye movement feature parameters and physiological signal features of drivers’fatigue levels were extracted.The driver fatigue detection model was trained to classify fatigue and non-fatigue states based on the extracted features.Accuracy rates of the image,electroencephalogram(EEG),and blood oxygen signals were 86%,82%,and 71%,separately.Information fusion theory was presented to facilitate the fatigue detection effect;the fatigue features were fused using multiple kernel learning and typical correlation analysis methods to increase the detection accuracy to 94%.It can be seen that the fatigue driving detectionmethod based onmulti-source feature fusion effectively detected driver fatigue state,and the accuracy rate was higher than that of a single information source.In summary,fatigue drivingmonitoring has broad development prospects and can be used in traffic accident prevention and wearable driver fatigue recognition.

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

A critical review of wheel/rail high frequency vibration-induced vibration fatigue of railway bogie in China

Purpose–This review aims to give a critical view of the wheel/rail high frequency vibration-induced vibration fatigue in railway bogie.Design/methodology/approach–Vibration fatigue of railway bogie arising from the wheel/rail high frequency vibration has become the main concern of railway operators.Previous reviews usually focused on the formation mechanism of wheel/rail high frequency vibration.This paper thus gives a critical review of the vibration fatigue of railway bogie owing to the short-pitch irregularities-induced high frequency vibration,including a brief introduction of short-pitch irregularities,associated high frequency vibration in railway bogie,typical vibration fatigue failure cases of railway bogie and methodologies used for the assessment of vibration fatigue and research gaps.Findings–The results showed that the resulting excitation frequencies of short-pitch irregularity vary substantially due to different track types and formation mechanisms.The axle box-mounted components are much more vulnerable to vibration fatigue compared with other components.The wheel polygonal wear and rail corrugation-induced high frequency vibration is the main driving force of fatigue failure,and the fatigue crack usually initiates from the defect of the weld seam.Vibration spectrum for attachments of railway bogie defined in the standard underestimates the vibration level arising from the short-pitch irregularities.The current investigations on vibration fatigue mainly focus on the methods to improve the accuracy of fatigue damage assessment,and a systematical design method for vibration fatigue remains a huge gap to improve the survival probability when the rail vehicle is subjected to vibration fatigue.Originality/value–The research can facilitate the development of a new methodology to improve the fatigue life of railway vehicles when subjected to wheel/rail high frequency vibration.

Thermal fatigue and wear of compacted graphite iron brake discs with various thermomechanical properties

The increase in payload capacity of trucks has heightened the demand for cost-effective yet high performance brake discs.In this work,the thermal fatigue and wear of compacted graphite iron brake discs were investigated,aiming to provide an experimental foundation for achieving a balance between their thermal and mechanical properties.Compacted graphite iron brake discs with different tensile strengths,macrohardnesses,specific heat capacities and thermal diffusion coefficients were produced by changing the proportion and strength of ferrite.The peak temperature,pressure load and friction coefficient of compacted graphite iron brake discs were analyzed through inertia friction tests.The morphology of thermal cracks and 3D profiles of the worn surfaces were also discussed.It is found that the thermal fatigue of compacted graphite iron discs is determined by their thermal properties.A compacted graphite iron with the highest specific heat capacity and thermal diffusion coefficient exhibits optimal thermal fatigue resistance.Oxidization of the matrix at low temperatures significantly weakens the function of alloy strengthening in hindering the propagation of thermal cracks.Despite the reduced hardness,increasing the ferrite proportion can mitigate wear loss resulting from low disc temperatures and the absence of abrasive wear.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Improving fatigue properties of normal direction ultrasonic vibration assisted face grinding Inconel 718 by regulating machined surface integrity

Fatigue properties are crucial for critical aero-engine components in extreme serviceenvironments,which are significantly affected by surface integrity(SI)indexes(especially surface topography,residual stressσ_(res),and microhardness)after machining processes.Normal-direction ultrasonic vibration-assisted face grinding(ND-UVAFG)has advantages in improving the machinability of Inconel 718,but there is a competitive relationship between higher compressiveσ_(res)and higher surface roughness R_(a)in affecting fatigue strength.The lack of a quantitative relationship between multiple SI indexes and fatigue strength makes theindeterminacy of a regulatory strategy for improving fatigue properties.In this work,a model of fatigue strength(σ_f)_(sur)considering multiple SI indexes was developed.Then,high-cycle fatigue tests were carried out on Inconel 718 samples with different SI characteristics,and the influence of ND-UVAFG process parameters on SI was analyzed.Based on SI indexes data,the(σ_f)_(sur)distribution in the grinding surface layer for ND-UVAFG Inconel 718 samples was determined using the developed model,and then the fatigue crack initiation(FCI)sites were furtherpredicted.The predicted FCI sites corresponded well with the experimental results,therebyverifying this model.A strategy for improving the fatigue life was proposed in this work,which was to transfer the fatigue source from the machined surface to the bulk material by controlling the SI indexes.Finally,a critical condition of SI indexes that FCI sites appeared on the surface or in bulk material was given by fitting the predicted results.According to the critical condition,an SI field where FCI sites appeared in the bulk material could be obtained.In this field,thefatigue life of Inconel 718 samples could be improved by approximately 140%.

Effects of Intermittent Hypoxia Exposure on Symptoms of Chronic Fatigue Syndrome in Repeated Restraint Stress and Forced Swimming Induced-Mouse Model

Background: Chronic fatigue syndrome (CFS) shows as its main symptoms debilitating fatigue that is not relieved by physiological rest, depression, inflammation, learning disability and memory impairment. But, intermittent hypoxia, consisting of alternating exposure to hypoxia and normoxia, plays a very important role in improving CFS. However, the essential components for improving learning and memory in CFS patients as well as their mechanism are largely unknown. Objectives: This study aims to analyze the effects of 12% and 15% hypoxia on the expression of alpha tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB) in CFS induced-mouse model for clarifying the effects on the learning and memory function. Methods: A total of 48 type IC mice were used. The CFS mouse model was established using restrained stress and repeated forced swimming. Treatment of CFS was done by exposing CFS mice to intermittent hypoxia at 12% and 15%. The effects of intermittent hypoxia on learning and memory as well as its mechanism of action on inflammation were tested respectively with the Morris test, the SDS page, the immunohistochemistry technique and the Nissl staining. Results: We found that 12% and 15% intermittent hypoxia exposure improved learning capacity and memory of CFS induced-mice. SDS page showed that CFS caused higher TNF-α expression. By exposing CFS mice to 12% and 15% intermittent hypoxia, TNF-α expression decreased significantly, with a much better effect at 15%. Both TNF-α and NF-κB increased in CFS state and decreased after treatment with intermittent hypoxia. Conclusion: Intermittent hypoxia improves learning capacity and memory. It acted by decreasing NF-κB come to down-regulating TNF-α and ameliorates learning capacity and memory impairment in CFS mice.

Fatigue Resistance of RCA Modified Asphalt Based on Dielectric Properties

In order to study the anti-fatigue performance of RCA modified asphalt (RMA),the performance of RMA and 90#matrix asphalt with different modifier content were measured by asphalt penetration,ductility,softening point,Brookfield viscosity,rheological index,infrared spectrum and dielectric constant test.This paper discusses the changes of asphalt basic indexes,fatigue properties and asphalt components based on dielectric properties under different modifier contents,and analyzes the grey correlation degree between components and asphalt pavement performance indexes.The results show that the optimum content of RCA modifier is 16.7%of the asphalt quality according to the penetration,ductility,softening point,Brockfield viscosity,viscosity temperature curve and fatigue life.In the phase angle-strain curve,there is disorder in the latter part of the curve.According to the strain (ε_(d)) corresponding to the disorder point,a new fatigue failure criterion is proposed and proved.Based on the new asphalt fatigue failure criterion,the fatigue prediction model of asphalt mixture is improved,and the fatigue life predicted by the improved fatigue model is compared with the fatigue life obtained by four-point bending fatigue test.The results show that the proposed new asphalt fatigue failure criterion is reasonable,and the fatigue life predicted by the improved asphalt mixture fatigue prediction model is accurate.The research method of classifying asphalt components based on dielectric properties is simple and effective,and the components have a high correlation with the road performance of base asphalt and modified asphalt.