Design and Dynamic Analysis of the Recirculating Planetary Roller Screw Mechanism

The recirculating planetary roller screw mechanism(RPRSM)is a transmission mechanism that engages the screw and nut threaded by multiple grooved rollers.In this paper,frstly,the design method of RPRSM nut threadless area is proposed,and the equations related to the structural parameters of nut threadless area are derived.On this basis,the cross-section design method of roller,screw and nut is constructed according to the actual situation of engagements between the screw/nut and the roller.By adjusting the gap between the two beveled edges and that between the arc and the beveled edge,the accuracy of the thread engagements between the screw/nut and the roller can be improved.Secondly,to ensure the engagements of the screw/nut and the roller,the distance equation from the center surface of the diferent rollers to the end surface of cam ring is given.Thirdly,combined with the working principle and structural composition of RPRSM,the component model is established according to its relevant structural parameters,and the virtual assembly is completed.Finally,the 3D model is imported into the ADAMS simulation software for multi-rigid body dynamics.The dynamic characteristic is analyzed,and the simulated values are compared with the theoretical values.The results show that the contact forces between the screw/nut and the roller are sinusoidal,mainly due to the existence of a small gap between the roller and the carrier.The maximum collision forces between the roller and cam ring are independent from load magnitude.Normally,the collision force between the roller and the carrier increases as the load increases.When RPRSM is in the transmission process,the roller angular speed in nut threadless area begins to appear abruptly,and the position of the maximum change is at the contact between the roller and the convex platform of cam ring.The design of the nut threadless area and the proposed virtual assembly method can provide a theoretical guidance for RPRSM research,as well as a reference for overall performance optimization.

Circulating tumor DNA genomic profiling reveals the complicated olaparib-resistance mechanism in prostate cancer salvage therapy: A case report

BACKGROUND The poly(ADP-ribose)polymerase(PARP)inhibitor olaparib has displayed superior clinical effect in metastatic castration-resistant prostate cancer(mCRPC)patients with the homologous recombination repair(HRR)genes mutations.However,when a patient’s tumor tissue volume is insufficient for genomic profiling of HRR gene mutations,circulating tumor DNA(ctDNA)may be useful in helping to determine and monitor the efficacy of olaparib,as well as in abiraterone-combination treatment,and for understanding any resistance mechanism related to such mutations.CASE SUMMARY A 61-year-old man who was diagnosed with metastatic prostate adenocarcinoma was initially hormone sensitivity,showing high Gleason score(5+5=10)and absolute positive rate(14/14 biopsied specimens).Following failure of several standard therapies,the patient progressed to mCRPC.Surprisingly,the patient showed good response to olaparib-abiraterone-prednisone combination treatment(an androgen-deprivation therapy,provided as the‘final choice’in China).Serum total prostate-specific antigen(TPSA)level reduced and symptoms remitted for 4 months.However,thereafter,serum TPSA levels began slowly increasing,indicating development of olaparib resistance.Subsequent comprehensive genomic profiling of ctDNA, screening 508 cancer-related genes by next-generation sequencing,identified 10 somatic variants as well as 3 copy number alterations. Two identified reversemissense mutations in partner and localizer of BRCA2 (PALB2) may have recovered the readingframe, restoring function of the primary germline PALB2 mutation and causing resistance to thePARP inhibitor olaparib.CONCLUSIONReverse mutations in PALB2, discovered via genomic profiling of ctDNA, may represent apotential resistance mechanism against olaparib in mCRPC.

Circulating tumor cells: Biological features and survival mechanisms

Circulating tumor cells(CTCs)are neoplastic cells that are detached from primary tumors and enter circulation.Enumeration and characterization of CTCs are of significance in cancer diagnosis,prognosis,and treatment monitoring.CTC survival in the bloodstream is a limiting step for the development of metastases in distant organs.Recent technological advances,especially in single-cell molecular analyses have uncovered heterogeneous CTC survival mechanisms.Undergoing epithelial-to-mesenchymal transition(EMT),increasing stem cell-like properties,and forming cell clusters enable CTCs to adapt to the harsh microenvironment of the circulation.Expressing and releasing several immunosuppressive molecules help CTCs escape from anti-cancer immune mechanisms.This review article summarizes the biological characteristics of CTCs and focuses on the recent understanding of the mechanisms by which CTCs survive in circulation.Additionally,the clinical and therapeutic implications of CTCs are discussed.

Decoding molecular mechanisms:brain aging and Alzheimer's disease

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

Contribution of mechanical forces to structural synaptic plasticity:insights from 3D cellular motility mechanisms

Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).

Failure mechanism and infrared radiation characteristic of hard siltstone induced by stratification effect

The deformation in sedimentary rock induced by train loads has potential threat to the safe operation of tunnels. This study investigated the influence of stratification structure on the infrared radiation and temporal damage mechanism of hard siltstone. The uniaxial compression tests, coupled with acoustic emission(AE) and infrared radiation temperature(IRT) were conducted on siltstones with different stratification effects. The results revealed that the stratigraphic structure significantly affects the stress-strain response and strength degradation characteristics. The mechanical parameters exhibit anisotropy characteristics, and the stratification effect exhibits a negative correlation with the cracking stress and peak stress. The failure modes caused by the stratification effect show remarkable anisotropic features, including splitting failure(Ⅰ: 0°-22.50°, Ⅱ: 90°), composite failure(45°), and shearing failure(67.50°). The AE temporal sequences demonstrate a stepwise response characteristic to the loading stress level. The AE intensity indicates that the stress sensitivity of shearing failure and composite failure is generally greater than that of splitting failure. The IRT field has spatiotemporal migration and progressive dissimilation with stress loading and its dissimilation degree increases under higher stress levels. The stronger the stratification effect, the greater the dissimilation degree of the IRT field. The abnormal characteristic points of average infrared radiation temperature(AIRT) variance at local stress drop and peak stress can be used as early and late precursors to identify fracture instability. Theoretical analysis shows that the competitive relationship between compaction strengthening and fracturing damage intensifies the dissimilation of the infrared thermal field for an increasing stress level. The present study provides a theoretical reference for disaster warnings in hard sedimentary rock mass.

Microdynamic mechanical properties and fracture evolution mechanism of monzogabbro with a true triaxial multilevel disturbance method

The far-field microdynamic disturbance caused by the excavation of deep mineral resources and underground engineering can induce surrounding rock damage in high-stress conditions and even lead to disasters.However,the mechanical properties and damage/fracture evolution mechanisms of deep rock induced by microdynamic disturbance under three-dimensional stress states are unclear.Therefore,a true triaxial multilevel disturbance test method is proposed,which can completely simulate natural geostress,excavation stress redistribution(such as stress unloading,concentration and rotation),and subsequently the microdynamic disturbance triggering damaged rock failure.Based on a dynamic true triaxial test platform,true triaxial microdynamic disturbance tests under different frequency and amplitudes were carried out on monzogabbro.The results show that increasing amplitude or decreasing frequency diminishes the failure strength of monzogabbro.Deformation modulus gradually decreases during disturbance failure.As frequency and amplitude increase,the degradation rate of deformation modulus decreases slightly,disturbance dissipated energy increases significantly,and disturbance deformation anisotropy strengthens obviously.A damage model has been proposed to quantitatively characterize the disturbance-induced damage evolution at different frequency and amplitude under true triaxial stress.Before disturbance failure,the micro-tensile crack mechanism is dominant,and the micro-shear crack mechanism increases significantly at failure.With the increase of amplitude and frequency,the micro-shear crack mechanism increases.When approaching disturbance failure,the acoustic emission fractal dimension changes from a stable value to local large oscillation,and finally increases sharply to a high value at failure.Finally,the disturbance-induced failure mechanism of surrounding rock in deep engineering is clearly elucidated.

Antagonism effect of residual S triggers the dual-path mechanism for water oxidation

Transition metal chalcogenides(TMCs)are recognized as pre-catalysts,and their(oxy)hydroxides derived from electrochemical reconstruction are the active species in the water oxidation.However,understanding the role of the residual chalcogen in the reconstructed layer is lacking in detail,and the corresponding catalytic mechanism remains controversial.Here,taking Cu_(1-x)Co_(x)S as a platform,we explore the regulating effect and existence form of the residual S doped into the reconstructive layer for oxygen evolution reaction(OER),where a dual-path OER mechanism is proposed.First-principles calculations and operando~(18)O isotopic labeling experiments jointly reveal that the residual S in the reconstructive layer of Cu_(1-x)Co_(x)S can wisely balance the adsorbate evolution mechanism(AEM)and lattice oxygen oxidation mechanism(LOM)by activating lattice oxygen and optimizing the adsorption/desorption behaviors at metal active sites,rather than change the reaction mechanism from AEM to LOM.Following such a dual-path OER mechanism,Cu_(0.4)Co_(0.6)S-derived Cu_(0.4)Co_(0.6)OSH not only overcomes the restriction of linear scaling relationship in AEM,but also avoids the structural collapse caused by lattice oxygen migration in LOM,so as to greatly reduce the OER potential and improved stability.

Regarding the Regulatory Sandbox Route and Mechanism for Governance of Artificial Intelligence

The main challenge in AI governance today is striking a balance between controlling AI dangers and fostering AI innovation.Regulators in a number of nations have progressively extended the regulatory sandbox,which was first implemented in the banking sector,to AI governance in an effort to reduce the conflict between regulation and innovation.The AI regulatory sandbox is a new and feasible route for AI governance in China that not only helps to manage the risks of technology application but also prevents inhibiting AI innovation.It keeps inventors'trial-and-error tolerance space inside the regulatory purview while offering a controlled setting for the development and testing of novel AI that hasn't yet been put on the market.By providing full-cycle governance of AI with the principles of agility and inclusive prudence,the regulatory sandbox offers an alternative to the conventional top-down hard regulation,expost regulation,and tight regulation.However,the current system also has inherent limitations and practical obstacles that need to be overcome by a more rational and effective approach.To achieve its positive impact on AI governance,the AI regulatory sandbox system should build and improve the access and exit mechanism,the coordination mechanism between the sandbox and personal information protection,and the mechanisms of exemption,disclosure,and communication.

Circulating tumor DNA in liquid biopsy: Current diagnostic limitation

With the rapid development of science and technology,cell-free DNA(cfDNA)is rapidly becoming an important biomarker for tumor diagnosis,monitoring and prognosis,and this cfDNA-based liquid biopsy technology has great potential to become an important part of precision medicine.cfDNA is the total amount of free DNA in the systemic circulation,including DNA fragments derived from tumor cells and all other somatic cells.Tumor cells release fragments of DNA into the bloodstream,and this source of cfDNA is called circulating tumor DNA(ctDNA).cfDNA detection has become a major focus in the field of tumor research in recent years,which provides a new opportunity for non-invasive diagnosis and prognosis of cancer.In this paper,we discuss the limitations of the study on the origin and dynamics analysis of ctDNA,and how to solve these problems in the future.Although the future faces major challenges,it also con-tains great potential.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Hybrid model for BOF oxygen blowing time prediction based on oxygen balance mechanism and deep neural network

The amount of oxygen blown into the converter is one of the key parameters for the control of the converter blowing process,which directly affects the tap-to-tap time of converter. In this study, a hybrid model based on oxygen balance mechanism (OBM) and deep neural network (DNN) was established for predicting oxygen blowing time in converter. A three-step method was utilized in the hybrid model. First, the oxygen consumption volume was predicted by the OBM model and DNN model, respectively. Second, a more accurate oxygen consumption volume was obtained by integrating the OBM model and DNN model. Finally, the converter oxygen blowing time was calculated according to the oxygen consumption volume and the oxygen supply intensity of each heat. The proposed hybrid model was verified using the actual data collected from an integrated steel plant in China, and compared with multiple linear regression model, OBM model, and neural network model including extreme learning machine, back propagation neural network, and DNN. The test results indicate that the hybrid model with a network structure of 3 hidden layer layers, 32-16-8 neurons per hidden layer, and 0.1 learning rate has the best prediction accuracy and stronger generalization ability compared with other models. The predicted hit ratio of oxygen consumption volume within the error±300 m^(3)is 96.67%;determination coefficient (R^(2)) and root mean square error (RMSE) are0.6984 and 150.03 m^(3), respectively. The oxygen blow time prediction hit ratio within the error±0.6 min is 89.50%;R2and RMSE are0.9486 and 0.3592 min, respectively. As a result, the proposed model can effectively predict the oxygen consumption volume and oxygen blowing time in the converter.

Instability mechanism of mining roadway passing through fault at different angles in kilometre-deep mine and control measures of roof cutting and NPR cables

The angle α between the fault strike and the axial direction of the roadway produces different damage characteristics. In this paper, the research methodology includes theoretical analyses, numerical simulations and field experiments in the context of the Daqiang coal mine located in Shenyang, China. The stability control countermeasure of "pre-splitting cutting roof + NPR anchor cable"(PSCR-NPR) is simultaneously proposed. According to the different deformation characteristics of the roadway, the faults are innovatively classified into three types, with α of type I being 0°-30°, α of type II being 30°-60°, and α of type III being 60°-90°. The full-cycle stress evolution paths during mining roadway traverses across different types of faults are investigated by numerical simulation. Different pinch angles α lead to high stress concentration areas at different locations in the surrounding rock. The non-uniform stress field formed in the shallow surrounding rock is an important reason for the instability of the roadway. The pre-cracked cut top shifted the high stress region to the deep rock mass and formed a low stress region in the shallow rock mass. The high prestressing NPR anchor cable transforms the non-uniform stress field of the shallow surrounding rock into a uniform stress field. PSCR-NPR is applied in the fault-through roadway of Daqiang mine. The low stress area of the surrounding rock was enlarged by 3-7 times, and the cumulative convergence was reduced by 45%-50%. It provides a reference for the stability control of the deep fault-through mining roadway.

Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

Molecular Mechanism and Molecular Design of Lubricating Oil Antioxidants

To overcome the limitations of traditional experimental“trial and error”methods in lubricant additive design,a new molecular design method based on molecular structure parameters is established here.The molecular mechanism of the antioxidant reaction of hindered phenol,diphenylamine,and alkyl sulfide are studied via molecular simulations.Calculation results show that the strong electron-donating ability and high hydrogen-donating activity of the antioxidant molecule and the low hydrogen-abstracting activity of free radicals formed after dehydrogenation are the internal molecular causes of the shielding of phenol and diphenylamine from scavenging peroxy free radicals,and the strong electron-donating ability is the internal molecular cause of the high activity of thioether in decomposing alkyl hydrogen peroxide.Based on this antioxidant molecular mechanism,a molecular design rule of antioxidant is proposed,namely“high EHOMO,large Q(S),low bond dissociation energy BDE(O—H)and BDE(N—H)”.Two new antioxidants,PAS-I and PAS-II,are designed and prepared by chemical bonding of hindered phenol,diphenylamine,and sulfur atoms.Experimental results show that these antioxidants both have excellent antioxidant effects in lubricating oil,and that PAS-II is the superior antioxidant,consistent with theoretical predictions.

Recent research progress in the mechanism and suppression of fusion welding-induced liquation cracking of nickel based superalloys

Nickel-based superalloys are extensively used in the crucial hot-section components of industrial gas turbines,aeronautics,and astronautics because of their excellent mechanical properties and corrosion resistance at high temperatures.Fusion welding serves as an effective means for joining and repairing these alloys;however,fusion welding-induced liquation cracking has been a challenging issue.This paper comprehensively reviewed recent liquation cracking,discussing the formation mechanisms,cracking criteria,and remedies.In recent investigations,regulating material composition,changing the preweld heat treatment of the base metal,optimizing the welding process parameters,and applying auxiliary control methods are effective strategies for mitigating cracks.To promote the application of nickel-based superalloys,further research on the combination impact of multiple elements on cracking prevention and specific quantitative criteria for liquation cracking is necessary.

Deactivation mechanism for water splitting:Recent advances

Hydrogen(H_(2)) has been regarded as a promising alternative to fossil-fuel energy.Green H_(2) produced via water electrolysis(WE)powered by renewable energy could achieve a zero-carbon footprint.Considerable attention has been focused on developing highly active catalysts to facilitate the reaction kinetics and improve the energy efficiency of WE.However,the stability of the electrocatalysts hampers the commercial viability of WE.Few studies have elucidated the origin of catalyst degradation.In this review,we first discuss the WE mechanism,including anodic oxygen evolution reaction(OER)and cathodic hydrogen evolution reaction(HER).Then,we provide strategies used to enhance the stability of electrocatalysts.After that,the deactivation mechanisms of the typical commercialized HER and OER catalysts,including Pt,Ni,RuO_(2),and IrO_(2),are summarized.Finally,the influence of fluctuating energy on catalyst degradation is highlighted and in situ characterization methodologies for understanding the dynamic deactivation processes are described.

Preliminary discussion on the ignition mechanism of exploding foil initiators igniting boron potassium nitrate

Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ignition mechanism of EFIs directly igniting pyrotechnics.An oscilloscope,a photon Doppler velocimetry,and a plasma spectrum measurement system were employed to obtain information of electric characteristics,impact pressure,and plasma temperature.The results of the electric characteristics and the impact pressure were inconsistent with ignition results.The only thing that the ignition success tests had in common was that their plasma all had a relatively long period of high-temperature duration(HTD).It eventually concludes that the ignition mechanism in this research is the microconvection heat transfer rather than the shock initiation,which differs from that of exploding foil initiators detonating explosives.Furthermore,the methods for evaluating the ignition success of semiconductor bridge initiators are not entirely applicable to the tests mentioned in this paper.The HTD is the critical parameter for judging the ignition success,and it is influenced by two factors:the late time discharge and the energy of the electric explosion.The longer time of the late time discharge and the more energy of the electric explosion,the easier it is to expand the HTD,which improves the probability of the ignition success.