Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model

Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its progression.Antioxidant peptides may thus present therapeutic potential for PD.In this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for Cath-KP.In vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant properties.Using the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway activation.Both focal adhesion kinase(FAK)and p38 were also identified as regulatory elements.In the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated dyskinesia.To the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress.These findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.

基于断裂力学的腐蚀钢丝疲劳S-N曲线研究

高强冷拔钢丝因其优异的力学性能被广泛应用于缆索承重结构,服役过程中钢丝腐蚀与断裂威胁着结构安全。钢丝腐蚀后表面的蚀坑因应力集中效应易产生疲劳裂纹,因此腐蚀钢丝剩余疲劳寿命主要取决于裂纹的扩展阶段,且裂纹扩展受到腐蚀程度(初始损伤)的显著影响。精确表征腐蚀程度并准确评估服役期钢丝腐蚀后的剩余寿命,仍是亟待解决的维修难题。首先采用蚀坑最大深度表征钢丝腐蚀程度,以应力强度因子幅作为裂纹扩展驱动力指标,基于断裂力学的Paris公式建立受拉钢丝裂纹扩展理论模型,进而推导腐蚀钢丝的疲劳S-N曲线。大量既有的腐蚀钢丝疲劳试验结果与理论预测值的比较验证了所提理论模型及疲劳S-N曲线的合理性和有效性。含多个蚀坑的钢丝裂纹扩展有限元模拟表明,等效单裂纹适用于多腐蚀坑钢丝疲劳寿命的简化分析。参数分析表明,蚀坑深度和腐蚀环境是腐蚀钢丝疲劳强度的关键影响因素,而应力比和疲劳加载频率影响较小,所提出的S-N曲线在钢丝常规服役条件下适用于评估其剩余寿命,可得到合理的预测结果。基于断裂力学所提的理论方法和疲劳S-N曲线可为腐蚀钢丝的疲劳强度和寿命评估提供参考。

2022年四川芦山M_(S)6.1地震前应力状态研究

为研究2022年6月1日四川芦山M_(S)6.1地震的孕育和发生过程,采用CAP方法反演了2013年芦山M_(S)7.0主震及M_(S)≥5.0余震的震源机制解,并基于应力张量方差与b值时空分布特征,探讨了芦山M_(S)6.1地震的力学机制和震源区的应力状态。结果表明:2022年芦山M_(S)6.1地震震源机制表现出与2013年芦山M_(S)7.0主震和5级余震相似的逆冲型破裂特征,压应力轴方位与龙门山断裂带南段区域应力场一致。2013年芦山M_(S)7.0地震后震中及附近的应力张量方差和b值长期处于低值状态,2022年芦山M_(S)6.1地震前震中及附近出现了应力张量方差和b值的低值异常,表明芦山余震区处于较高的应力水平。分析认为:巴颜喀拉块体持续东向运动受到华南块体的阻挡,震中所在区域长期受挤压逆冲作用,从而使芦山余震区长期处于应力积累的状态,芦山M_(S)6.1地震也是在这种动力学背景下发生的。

乌什 M_(S)7.1地震序列及应力降特征研究

研究乌什M_(S)7.1地震序列时间和空间变化以及震源参数特征,结果表明地震余震主要分布在主震北东和南西两侧,展布与迈丹断裂的走向基本吻合。目前序列b值为0.67,h值为1.3,p值为1.28。震源机制解为逆冲型,应力降处于低值水平,序列衰减基本正常。此次地震为主震—余震型,最大余震为M_(S)5.8地震。

A novel binary effective medium model to describe the prepeak stressstrain relationship of combined bodies of rock-like material and rock

Combined bodies of rock-like material and rock are widely encountered in geotechnical engineering,such as tunnels and mines.The existing theoretical models describing the stress-strain relationship of a combined body lack a binary feature.Based on effective medium theory,this paper presents the governing equation of the“elastic modulus”for combined and single bodies under triaxial compressive tests.A binary effective medium model is then established.Based on the compressive experiment of concretegranite combined bodies,the feasibility of determining the stress threshold based on crack axial strain is discussed,and the model is verified.The model is further extended to coal-rock combined bodies of more diverse types,and the variation laws of the compressive mechanical parameters are then discussed.The results show that the fitting accuracy of the model with the experimental curves of the concretegranite combined bodies and various types of coal-rock combined bodies are over 95%.The crack axial strain method can replace the crack volumetric strain method,which clarifies the physical meanings of the model parameters.The variation laws of matrix parameters and crack parameters are discussed in depth and are expected to be more widely used in geotechnical engineering.

Neuroprotective effects of curculigoside against Alzheimer’s disease via regulation oxidative stress mediated mitochondrial dysfunction in L-Glu-exposed HT22 cells and APP/PS1 mice

Curculigoside(CCG)is a phenolic glycoside compound extracted from the root of a natural plant called Curculigo orchioides Gaertn.In this study,the neuroprotective effect of CCG through oxidative stress mediated mitochondrial dysfunction on L-glutamate(L-Glu)-damaged hippocampal neuron cell line(HT22)and APPswe/PSEN1dE9 transgenic(APP/PS1)mice were investigated.Observably,CCG in L-Glu-damaged HT22 cells suppressed apoptosis,reduced the accumulation of reactive oxygen species,balanced the mitochondrial membrane potential and prevented the over-influx of calcium.In APP/PS1 mice,4-week CCG administration significantly improved their memory and behavioral impairments,enhanced the function of cholinergic system,reduced the deposition of Aβand neurofibrillary fiber tangles caused by tau phosphorylation,and suppressed the development and progression of oxidative stress in brains of APP/PS1 mice.Based on the screening of proteomic analysis on hippocampus,CCG were confirmed that it could regulate the expression levels of proteins related to mitochondrial dysfunction,mainly through activating on AMPK/Nrf2 signaling,in APP/PS1 mice and L-Glu-exposed HT22 cells.CCG has a prominent neuroprotective effect on regulate the AMPK/Nrf2-mediated mitochondrial dysfunction in cells APP/PS1 mice support CCG is a potentially potent drug for AD treatment and merits further investigation.

Apparent stress as an indicator of stress meta-instability:The 2021 M_(S)6.4 Yangbi earthquake in Yunnan,China

Investigating spatiotemporal changes in crustal stress associated with major earthquakes has implications for understanding seismogenic processes.However,in individual earthquake cases,the characteristics of the stress after it reaches its maximum value are rarely discussed.In this study,we use the 2021 M_S6.4 Yangbi earthquake in Yunnan,China and events of magnitudes M_L≥3.0 occurred in the surrounding area in the previous 11 years to investigate the spatiotemporal evolution of apparent stress.The results indicate that apparent stress began to increase in January 2015 and reached a maximum in January 2020.Apparent stress then remained at a high level until October 2020,after which it declined considerable.We suggest that the stress was in the accumulation stage from January 2015 to January 2020,and entered the meta-instability stage after October 2020.During the meta-instability stage,the zone of decreasing stress expanded continuously and the apparent stress increased around the Yangbi earthquake source region.These features are generally consistent with the results of laboratory rock stress experiments.We propose that apparent stress can be a good indicator for determining whether the stress at a specific location has entered the meta-instability stage and may become the epicenter of an impending strong earthquake.

2024年新疆乌什M_(S)7.1地震发震断层产状及其动力学探讨

大地震发生后,断层面产状快速确定对震后趋势判定具有重要参考价值。本文收集2024年新疆乌什M_(S)7.1地震序列的震源机制数据,对多家机构计算的该地震震源机制解进行中心解求解后,对震源机制的节面进行聚类分析,去掉噪声点的震源机制得到两簇结果,发现标准差较小的第二簇中心节面可能为发震断层面。然后,为进一步通过断层面与应力场关系验证可能的发震断层面,收集了该地区历史震源机制资料,反演得到乌什地震震源区的构造应力场,发现该地区受到NW—SE向的挤压应力和近垂直向的拉张应力;将应力场分别投影到两簇节面上,发现标准差较小的第二簇中心节面处于剪应力较大区域,并且正应力也有利于该中心节面破裂。综合其他资料分析,本研究推测2024年新疆乌什M_(S)7.1地震发震断层为NW向、低倾角断层,走向为244.62°,倾角为46.19°。

Interplay between microglia and environmental risk factors in Alzheimer's disease

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

Bushen Yizhi Formula regulates the IRE1αpathway to alleviate endoplasmic reticulum stress in an Alzheimer’s disease rat model

While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD.

Deep tectonics and seismogenic mechanisms of the seismic source zone of the Jishishan M_(s)6.2 earthquake on December 18,2023,at the northeast margin of the Tibetan Plateau

On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong earthquakes to occur through the release of overlying rigid crustal stresses.However,it is unlikely that an earthquake of comparable or larger magnitude would occur in the short term(e.g.,in one year)at the Jishishan east margin fault.

Chloride Resistance of Concrete under Complex Stress and Environment

The presence of stress is shown to have a significant impact on chloride ions in concrete. Reinforced concrete is usually durable and cost-effective which has resulted in its widespread use for construction, however, the concrete subjected to environment and load has become increasingly apparently that attacked by aggressive agents such as chloride ion. In this study, the coupling influences are stress effects and environmental problems on the coastline concrete durability have been investigated. A series of cyclic of a wet-dry cycle and submersion tests were performed onto the stressed concrete to obtain an understanding of the physical mechanisms causing the accumulation of chlorides in the interior pores of concrete under different stress types and exposure environments, based on the same duration. Specimens were prepared and subjected to NaCl solution in a wet-dry cycle and submersion, the chloride in the tension zone is gradual with increasing the stress level, as well as the chloride ion in the wet-dry cycle, is increasing the number of cycles. The apparent diffusion coefficient of each specimen was calculated respectively, the profile of concentration at a different section of tension and compression zones were presented in influence factors of the number of cycles, the length of drying phase, and periodic wetting cycles with sodium solution was discussed. After employed Fick’s second law, the results suggested Da in a wet-dry cycle is much higher than the Da in submersion zones.

2023年甘肃积石山M_(S)6.2地震对周围断层的应力影响及对余震的触发作用

2023年12月18日,甘肃省临夏州积石山县发生M_(S)6.2地震,震中位于拉脊山断裂带。为深度剖析本次地震对周围断层和后续地震的静态库仑破裂应力影响,文章基于地震破裂模型参数和弹性半空间模型,计算积石山M_(S)6.2地震在周围主要断层上不同深度产生的静态库仑破裂应力变化,并评估这些应力变化对未来地震危险性的影响。结果显示:本次地震使青海南山—循化南山断裂、拉脊山北缘断裂和拉脊山南缘断裂部分区域的库仑破裂应力显著增加,青海南山—循化南山断裂东段的库仑破裂应力增加远超出静态应力触发阈值,并达到了0.022 MPa,表现出较高地震危险性;其他断层也呈现出不同程度的库仑应力变化,拉脊山北缘断裂和拉脊山南缘断裂部分区域的应力卸载量达到了万帕,青海南山—循化南山断裂除东段外的其他分段和庄浪河断裂的应力卸载量达到了百帕。对不同震源深度下断层库仑破裂应力变化进行对比分析,发现深度变化对此次地震库仑破裂应力变化模式影响很大。文章还计算了本次地震在较大余震断层面上的库仑破裂应力,结果表明:甘肃积石山M_(S)6.2地震在后续三次M_(S)≥4地震的断层面上产生的库仑破裂应力分别为0.024 MPa、0.033 MPa和0.034 MPa,均超过触发阈值(0.01 MPa),表明M_(S)6.2地震对这三次地震具有明显的触发作用。文章可为该地区未来地震可能性与危险性的评估提供一定的参考。

CO_(2)分压对S135钢在CO_(2)/H_(2)S共存体系中腐蚀行为的影响

为了给井下油气管材的选择和腐蚀预测模型的建立提供理论依据,利用高温高压反应釜进行S135钢在CO_(2)/H_(2)S共存体系中的腐蚀模拟试验,采用失重法、恒载荷法、X射线衍射(XRD)、扫描电镜(SEM)、能谱(EDS)、三维轮廓扫描仪等手段研究了CO_(2)分压对S135钢在温度100℃、CO_(2)/H_(2)S共存体系中腐蚀行为的影响及规律。结果表明,随CO_(2)分压升高,S135钢的腐蚀速率增大,屈服强度损伤加剧,CO_(2)分压为5,10,15,20 MPa时,其屈服强度(σs)损伤率分别为1.4%、3.6%、4.5%和15.9%;抗拉强度(σb)损伤率分别为1.2%、3.4%、5.2%和15.4%。S135钢在低CO_(2)分压下发生全面腐蚀,随CO_(2)分压增大发展为以全面腐蚀为主,辅以局部腐蚀。应力腐蚀裂纹在萌生阶段以局部阳极溶解作用(点蚀)为主,随CO_(2)分压增大应力腐蚀裂纹更易生长,应力腐蚀敏感性增加,加剧了基体的腐蚀进程。

基于潮汐附加构造应力的2013年灯塔M_(S)5.1地震射出长波辐射变化分析

针对2013年1月23日辽宁灯塔M_(S)5.1地震,利用引潮力附加构造应力(Additional Tectonic Stress Caused By Tidal Force,ATSCTF)计算模型,计算得到震中位置(41.5°N,123.2°E)在地震前5周以及震后3周(2012年12月16日—2013年2月15日)的ATSCTF变化。地震发生时,ATSCTF垂直方向分量处于高相位点附近,显示引潮力对本次正断层走滑型地震具有诱发作用。以ATSCTF变化周期的各低相位点时间(2012年12月19日、2013年1月4日、2013年1月18日、2013年2月2日)数据分别为背景,各周期期后数据分别与背景逐日相减,计算研究区(36°N~46°N,118°E~128°E)范围内,National Oceanic and Atmospheric Administration(NOAA)卫星射出长波辐射数据(Outgoing Long Wave Radiation,OLR)在各ATSCTF周期时段分布及其变化。结果显示,无震的ATSCTF变化的A、B、D周期,震中附近OLR无变化;发震的ATSCTF变化的C周期,在空间上,该地区震前OLR仅震中及其南侧区域发生了显著连续升高变化过程,在时间上经历了初始微异常→异常加强→高峰→衰减→发震→平静的演化过程,与岩石应力加载—破裂经历:初始微动破裂→扩张破裂→应力闭锁→地震爆发→平静的力学演化过程中各阶段红外辐射特征一致;显示引潮力对处于临界状态的活动断层具有诱发作用,而OLR是地震构造应力应变过程辐射表征。

C-phycocyanin shows neuroprotective effect against rotenone-induced Parkinson’s disease in mice

Objective:To investigate the neuroprotective effect of C-phycocyanin in a mouse model of rotenone-induced Parkinson’s disease.Methods:C-phycocyanin(50 mg/kg,i.p.,daily)was administered to rotenone(30 mg/kg,p.o.,daily)treated mice for 28 days.Behavioral studies(Y-maze,rotarod,round beam walk,and wire-hang tests)were carried out to assess neurobehavioral deficits.Glutathione and malondialdehyde were determined in both serum and striatal tissue.Molecular proteins(AKT,AMPK,NF-κB,BDNF,and alpha-synuclein)in the striatum were estimated using ELISA.Histopathological analyses(hematoxylin and eosin stainning as well as Nissl staining)were carried out to assess structural abnormalities in the striatum.Results:C-phycocyanin significantly increased BDNF levels and decreased alpha-synuclein levels.It also slightly upregulated AMPK and AKT levels without significant difference compared with the rotenone group.Additionally,rotenone-induced elevated oxidative stress and structural abnormalities in the striatum were markedly mitigated by C-phycocyanin.Conclusions:C-phycocyanin might have potential neuroprotective effects against Parkinson’s disease.Further studies are warranted to verify its efficacy and to understand the molecular mechanisms behind the neuroprotective effects of C-phycocyanin in Parkinson’s disease.

Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases

Aging is a natural phenomenon characterized by a progressive decline in physiological integrity,leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases,including cardiovascular diseases,osteoporosis,cancer,diabetes,and neurodegeneration.Aging is considered the major risk factor for Parkinson’s and Alzheimer’s disease develops.Likewise,diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative disorders.Currently,no treatment can effectively reverse these neurodegenerative pathologies.However,some antidiabetic drugs have opened the possibility of being used against neurodegenerative processes.In the previous framework,Vanadium species have demonstrated a notable antidiabetic effect.Our research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic syndrome.The results suggest that these polyoxidovanadates induce neuronal and cognitive restoration mechanisms.This review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain,constituting a therapeutic alternative for aging and neurodegenerative diseases.

The pathogenesis of Parkinson’s disease and crosstalk with other diseases

In China,Parkinson’s disease(PD)is the second most prevalent central nervous system(CNS)degenerative illness affecting middle-aged and older persons.Movement disorders including resting tremor,bradykinesia,myotonia,postural instability,and gait instability are the predominant clinical symptoms.The two main types of PD are sporadic and familial,with sporadic PD being the more prevalent of the two.The environment,genetics,mitochondrial dysfunction,oxidative stress,inflammation,protein aggregation and misfolding,loss of trophic factors,cell death,and gut microbiota may all have a role in the etiology of PD.PD is inversely connected with other cancers and positively correlated with COVID-19,diabetes mellitus(DM),melanoma,and ischemic heart disease(IHD)risk.Delaying disease progression,managing motor and non-motor symptoms,and avoiding and controlling dysfunction in the middle and later phases of the disease are the key areas of research and development for its therapy.Presently,the development and progression of PD can be slowed down by using conventional pharmacology,natural items,and innovative technology.This article reviews the pathogenesis of PD,its correlations with other non-genetic diseases,and the research progress of drugs and technologies for alleviating PD.

基于等效结构应力法的高强钢焊接结构低温主S-N曲线

现有的疲劳S-N曲线已不再适用于北极的低温环境,为了评估北极海洋工程设备材料的低温疲劳寿命,有必要建立金属结构尤其是焊接结构的低温疲劳S-N曲线。本文基于等效结构应力法,计算出Q690高强钢管环焊缝的主S-N曲线,并通过共振疲劳试验对该方法进行了验证。在此基础上,结合大量的高强钢焊接结构试验结果,将温度敏感因子c引入到低温疲劳主S-N曲线的推导中,首次建立了基于低温金属焊接结构的主S-N曲线,并对文献中的疲劳S-N试验数据和ASME中的修正方法进行了对比和验证。结果表明,等效结构应力法能够较准确地计算出焊缝疲劳S-N曲线,推导出的金属焊接结构低温主S-N曲线与试验曲线吻合较好,能够满足低温地区工程要求,可为高强钢焊接结构在北极地区低温环境中的广泛应用提供理论指导。该方法可以为金属焊接结构的低温疲劳研究节省大量的成本,减少非标准试验操作造成的不必要的误差。这对北极海洋工程设备的设计、安全运行和疲劳评估具有重要意义。