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.     

成型温度对PBX装药内部质量及性能的影响

针对压制成型的PBX炸药装药，选择CT无损检测、巴西实验和扫描电镜检测等技术，对比研究了室温和加热两种温度下压制成型的炸药装药内部质量、静态力学性能和细观破坏形式。结果表明，加热压制有利于改善炸药装药的内部质量，可避免产生初始损伤，且提高了装药的力学性能。细观尺度上，室温压制成型的装药主要发生界面脱黏破坏，加热压制成型装药的主要破坏形式是穿晶断裂。     

高面板坝全寿命周期变形控制方法及应用

高面板坝的变形对面板的安全运行有着特别重要的影响，国内外已建的高面板坝工程中，因坝体变形大导致防渗面板挤压破损，坝体渗漏量大的实例较多，不得不降低水库水位进行修复处理，造成较大的经济损失乃至给大坝的长期运行留下安全隐患。通过发生挤压破损的实例分析，发现变形控制缺乏系统性是发生面板挤压破损的主要因素，为预防面板破损，系统提出了“控制坝体总变形，转化有害变形，适应纵向变形”的坝体变形控制方法，并在使用软硬岩混合料筑坝的董箐面板堆石坝中得到的应用，取得了良好效果，该工程运行至今达十余年，未见面板有挤压破损迹象，该方法对建设200 m以上乃至300 m级超高面板坝具有重要借鉴意义。     

A model of PEMFC-battery system to evaluate inner operating status and energy consumption under different energy management strategies

A hybrid system with jointed battery and PEMFC is popular and of great potential in New Energy Vehicle (NEV) application. However, reliability and efficiency remain to be improved for commercial products. To reflect the complicated physics inside the proton exchange membrane fuel cell (PEMFC), the PEMFC model consisting of inner muti-physics process and other accessories was built, then a complete hybrid system was established when a matched battery, DC/DC, regenerative braking were taken into consideration. Based on the above model, the stack state and system performance under standard cycle for heavy duty vehicle-CWTVC were obtained. According to the simulation results, fuel cell states such as pressure, water content and voltage suffers severe oscillation with external load, especially in the highway cycle. Membrane electrode assembly (MEA) suffers from pressure impact with average value of more than 24 kPa in highway cycle. In the aspect of relative humidity, the PEMFC stack is most threatened in road cycle. As for the hybrid system, its efficiency and state of charge (SOC) fluctuation perform worst in urban cycle and road cycle respectively, while its highest efficiency occurs in road test. Operating mode of fuel cell has influence on hybrid system. When 3-level mode of fuel cell output was applied, the efficiency increased to its peak value at medium level of 28 kW and then declined gradually. H₂ consumption had an opposite trend compared to efficiency. In the aspect of battery SOC, it declines in operating process and its fluctuations decreases when medium level got bigger. The 3-level mode and 4-level mode were compared using this model. It can be concluded that although 3-level mode performs slightly better in hybrid system efficiency, H₂ consumption, pressure impact, it does not have absolute advantage over 4-level mode in other indicators.     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Noncentrosymmetric Tetrel Pnictides RuSi4P4 and IrSi3P3: Nonlinear Optical Materials with Outstanding Laser Damage Threshold

Noncentrosymmetric (NCS) tetrel pnictides have recently generated interest as nonlinear optical (NLO) materials due to their second harmonic generation (SHG) activity and large laser damage threshold (LDT). Herein nonmetal-rich silicon phosphides RuSi₄P₄ and IrSi₃P₃ are synthesized and characterized. Their crystal structures are reinvestigated using single crystal X-ray diffraction and ²⁹Si and ³¹P magic angle spinning NMR. In agreement with previous report RuSi₄P₄ crystallizes in NCS space group P1, while IrSi₃P₃ is found to crystallize in NCS space group Cm, in contrast with the previously reported space group C2. A combination of DFT calculations and diffuse reflectance measurements reveals RuSi₄P₄ and IrSi₃P₃ to be wide bandgap (E_g) semiconductors, E_g = 1.9 and 1.8 eV, respectively. RuSi₄P₄ and IrSi₃P₃ outperform the current state-of-the-art infrared SHG material, AgGaS₂, both in SHG activity and laser inducer damage threshold. Due to the combination of high thermal stabilities (up to 1373 K), wide bandgaps (≈2 eV), NCS crystal structures, strong SHG responses, and large LDT values, RuSi₄P₄ and IrSi₃P₃ are promising candidates for longer wavelength NLO materials.     

Systemic Inflammation and the Breakdown of Intestinal Homeostasis Are Key Events in Chronic Spinal Cord Injury Patients

Our aim was to investigate the subset distribution and function of circulating monocytes, proinflammatory cytokine levels, gut barrier damage, and bacterial translocation in chronic spinal cord injury (SCI) patients. Thus, 56 SCI patients and 28 healthy donors were studied. The levels of circulating CD14^+highCD16⁻, CD14^+highCD16⁺, and CD14^+lowCD16⁺ monocytes, membrane TLR2, TLR4, and TLR9, phagocytic activity, ROS generation, and intracytoplasmic TNF-α, IL-1, IL-6, and IL-10 after lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. Serum TNF-α, IL-1, IL-6 and IL-10 levels were measured by Luminex and LPS-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP) and zonulin by ELISA. SCI patients had normal monocyte counts and subset distribution. CD14^+highCD16⁻ and CD14^+highCD16⁺ monocytes exhibited decreased TLR4, normal TLR2 and increased TLR9 expression. CD14^+highCD16⁻ monocytes had increased LPS-induced TNF-α but normal IL-1, IL-6, and IL-10 production. Monocytes exhibited defective phagocytosis but normal ROS production. Patients had enhanced serum TNF-α and IL-6 levels, normal IL-1 and IL-10 levels, and increased circulating LBP, I-FABP, and zonulin levels. Chronic SCI patients displayed impaired circulating monocyte function. These patients exhibited a systemic proinflammatory state characterized by enhanced serum TNF-α and IL-6 levels. These patients also had increased bacterial translocation and gut barrier damage.