The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Optimizing the stability and electrical transport properties of CeNbO4+δ-based oxide ceramics by regulating oxygen ion content

CeNbO_4+δ ceramics have attracted extensive research interest because of their unique mixed ion-electron transport characteristics and interesting structure-functional characteristics caused by the difference in oxygen ion content. Although the change of oxygen ion content brings rich redox properties, it also causes serious crystal transformation and abnormal electrical transport properties. In order to obtain stable structure and excellent electrical transport properties, the directional regulation of the oxygen ion content has been realized through introducing Al₂O₃ and high temperature aging. After 600 h of aging at 1073 K, the prepared composite ceramics not only obtain a stable structure without crystal transformation, but also show good negative temperature coefficient (NTC) thermistor characteristics in the temperature range of 473 K–1273 K, in which the linear fitting maximum Pearson's r of the relationship between lnρ and 1000/T can reach 99.97%. The proposed method provides a new thought for the design and application of high-temperature electronic ceramics.     

Corrosion behaviour of an industrial shot-peened and coated automotive spring steel AISI 9254

A high-strength low-alloy steel, AISI 9254 (54SiCr6), is widely used for suspension spring production in the automotive industry. In this work, industrially manufactured zinc phosphate coated helical springs are subjected to detailed microstructural and surface analysis for better understanding of corrosion evolution. The material’s free corrosion potential and anodic/cathodic behaviour were investigated in NaCl solutions and corrosion propagation mechanisms were studied using potentiostatic polarisation on cross-sectional and external surfaces. The bulk material is fully martensite with uniformly distributed MnS inclusions, while the spring surface has a 2–3?μm mechanically deformed region introduced by shot-peening and a thin zinc phosphate coating. The corrosion open circuit potential of bulk material and shot-peened spring surface was about –0.7V_SCE without significant difference, while phosphated surface is more noble (more positive potential). MnS inclusions, stimulating the anodic attack in the steel, influence corrosion propagation and pit morphology to a large extent that can have an impact on the spring performance.     

From Oxadiazole to Triazole Analogues: Optimization toward a Dual Orexin Receptor Antagonist with Improved in vivo Efficacy in Dogs

The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone ( 6 ), a compound which emerged from our in-house research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (f_u brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone ( 42 ), a DORA with improved in vivo efficacy compared to 6 .     

基于双声表面波器件的引信加速度传感器

In view of the shortcomings of silicon micro acceleration sensor based on piezoresistive effect and capacitance principle, such as temperature drift, low resolution and poor anti-interference ability, a fuze acceleration sensor based on dual SAW devices is proposed. The sensor adopts a dual saw device structure, one is coated with a sensitive film for measurement, the other is an uncoat- ed reference channel for compensation of environmental temperature, pressure, humidity and other factors. The experimental results show that the maximum linear error is only 1.6%, the sensitivity is 54.3Hz/g, and the maximum hysteresis error is less than 1%. Compared with piezoresistive accelerometer and capacitive accelerometer, the linear error of the accelerometer is small, the sensitivi- ty is high, and it has strong anti-interference ability.     

Enzymolysis reaction kinetics and thermodynamics of rapeseed protein with sequential dual‐frequency ultrasound pretreatment

We evaluated the effect of sequential dual‐frequency ultrasound (SDFU) pretreatments on rapeseed protein enzymolysis, using alcalase as a model enzyme. Hydrolysed protein concentrations, enzymolysis kinetics and thermodynamic parameters were investigated. The results showed that the hydrolysed rapeseed protein concentration following SDFU pretreatments was higher compared to that of the control for up to 75 min of enzymolysis at various substrate concentrations of 5–25 g L^?1; both control and SDFU pretreatment groups showed first‐order reaction kinetics. Compared to the control, the Michaelis–Menten constant (K_M) value decreased remarkably by 17.61%, while an increase in the binding frequency between enzyme and substrate (K_A) by 10.47% was observed. The thermodynamic parameters, enthalpy, entropy and activation energy were reduced in the SDFU pretreatment group compared to the control by 31.78%, 18.0% and 29.56%, respectively. SDFU pretreatment showed little effect on Gibbs free energy at the various temperatures studied.     

Sarcopenia: Molecular Pathways and Potential Targets for Intervention

Aging is associated with sarcopenia. The loss of strength results in decreased muscle mass and motor function. This process accelerates the progressive muscle deterioration observed in older adults, favoring the presence of debilitating pathologies. In addition, sarcopenia leads to a decrease in quality of life, significantly affecting self-sufficiency. Altogether, these results in an increase in economic resources from the National Health Systems devoted to mitigating this problem in the elderly, particularly in developed countries. Different etiological determinants are involved in the progression of the disease, including: neurological factors, endocrine alterations, as well as nutritional and lifestyle changes related to the adoption of more sedentary habits. Molecular and cellular mechanisms have not been clearly characterized, resulting in the absence of an effective treatment for sarcopenia. Nevertheless, physical activity seems to be the sole strategy to delay sarcopenia and its symptoms. The present review intends to bring together the data explaining how physical activity modulates at a molecular and cellular level all factors that predispose or favor the progression of this deteriorating pathology.     

时效工艺对纳米结构2297铝锂合金力学性能与微观组织的影响

采用535 ℃×2 h固溶制度,将热锻态2297铝锂合金固溶水淬后冷轧,冷轧压下量为95%,然后将轧制样品在不同温度(120~190 ℃)和时间(0~80 h)范围内进行时效处理。采用拉伸、扫描电镜(SEM)和透射电镜(TEM)等测试方法,分析时效温度和时间对铝锂合金组织与性能的影响。结果表明:时效前的大塑性变形能获得纳米结构组织,能促进T₁相均匀细小地析出,缩短合金达到峰时效的时间,最终成功制备了高强高塑性铝锂合金。在120~140 ℃温区内时效时,时效温度越高,达到峰时效的时间越短、强度越高。140 ℃达到峰时效时间缩短为40 h,此时合金的抗拉强度、屈服强度和伸长率分别为525 MPa、478 MPa和7.7%,主要强化相为细小的T₁相。在170~190 ℃温区内时效时,时效温度越高,达到峰时效的时间越短,但抗拉强度与屈服强度迅速下降。170 ℃时效8 h达到峰时效状态,此时合金的抗拉强度、屈服强度和伸长率分别是503 MPa、462 MPa和5.0%,主要强化相仍为T₁相,但已经明显粗化。     

相界面对双相钛合金层裂孔洞形核的影响

利用一级轻气炮对TC4双相钛合金进行加载, 获得初期的层裂状态, 在加载中采用多普勒激光干涉测速技术对样品自由面粒子速度进行测试。在软回收经过加载的样品之后, 借助于金相显微镜、X射线断层扫描、纳米压痕等检测手段进行多维分析, 探讨了相界面对孔洞形核位置的影响。结果表明, 孔洞绝大部分都在α相内形核, 而不是如准静态损伤理论预测的形核于α/β相界面。这是由于相界面的反射与透射作用, 当冲击波从高阻抗α相传入到低阻抗β相时, 会在α相内产生拉伸脉冲, 当拉伸脉冲足够大时, 导致在α相内产生孔洞。