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.     

纤维类型及取向对纤维-UHPC基体拔出性能影响研究

纤维与基体之间的粘结能力和机械锚固作用是基体将荷载传递给纤维的决定因素之一,不同类型的纤维和取向在拉拔时的受力形式和破坏形式决定试件承载能力。采用单根纤维拉拔试验探究了纤维类型、取向对超高性能混凝土(UHPC)界面拉伸性能的影响。结果表明:随着纤维取向的增加拔出荷载先增大后减小,在45°时拔出荷载达到最大值；随着纤维取向增加,纤维拔出时对基体破坏面积增大,纤维拔出时对于基体的破坏能力:波纹线>端勾型>直线型。由第一峰值荷载分析,波纹型钢纤维相比于直线型和端勾型钢纤维更容易脱黏。对纤维拔出时进行力学行为分析,波纹型钢纤维和端勾型钢纤维拔出过程中首先发生纤维屈服,随着荷载持续基体产生破坏,直线型钢纤维在拔出过程中最先发生纤维与基体脱黏。     

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。     

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.     

数值堆材料辐照损伤并行动力学蒙特卡罗软件MISA-AKMC的设计与实现

材料辐照损伤模拟是数值堆软件的重要内容。原子动力学蒙特卡罗（AKMC）方法是研究核材料辐照行为的重要手段，可在保持原子级别精度下，有效地扩展模拟的时间尺度到秒甚至年量级。但在面向实际应用需求时，其仍面临内存限制和复杂的计算量等挑战。通过并行计算技术提升计算效率是解决这一挑战的有效手段。本文论述一款并行AKMC程序MISA-AKMC的设计原理与实现技术。MISA-AKMC实现了一种并行KMC模拟框架，重点包括sub-lattice并行算法的实现、加速优化方法、转发通信方法、KMC模型接口等。基于该框架，开发了空位-间隙的演化模型，可实现热老化模拟和析出模拟。通过并行性能测试获得了良好的并行性能，结合算例结果验证说明了MISA-AKMC的正确性和可靠性。     

Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways

The base and nucleotide excision repair pathways (BER and NER, respectively) are two major mechanisms that remove DNA lesions formed by the reactions of genotoxic intermediates with cellular DNA. It is generally believed that small non-bulky oxidatively generated DNA base modifications are removed by BER pathways, whereas DNA helix-distorting bulky lesions derived from the attack of chemical carcinogens or UV irradiation are repaired by the NER machinery. However, existing and growing experimental evidence indicates that oxidatively generated DNA lesions can be repaired by competitive BER and NER pathways in human cell extracts and intact human cells. Here, we focus on the interplay and competition of BER and NER pathways in excising oxidatively generated guanine lesions site-specifically positioned in plasmid DNA templates constructed by a gapped-vector technology. These experiments demonstrate a significant enhancement of the NER yields in covalently closed circular DNA plasmids (relative to the same, but linearized form of the same plasmid) harboring certain oxidatively generated guanine lesions. The interplay between the BER and NER pathways that remove oxidatively generated guanine lesions are reviewed and discussed in terms of competitive binding of the BER proteins and the DNA damage-sensing NER factor XPC-RAD23B to these lesions.     

Centimeter-scale low-damage micromachining on single-crystal 4H–SiC substrates using a femtosecond laser with square-shaped Flat-Top focus spots

Femtosecond (fs) lasers have been proved to be reliable tools for high-precision and high-quality micromachining of ceramic materials. Nevertheless, fs laser processing using a single-mode beam with a Gaussian intensity distribution is difficult to obtain large-area flat and uniform processed surfaces. In this study, we utilize a customized diffractive optical element (DOE) to redistribute the laser pulse energy from Gaussian to square-shaped Flat-Top profile to realize centimeter-scale low-damage micromachining on single-crystal 4H–SiC substrates. We systematically investigated the effects of processing parameters on the changes in surface morphology and composition, and an optimal processing strategy was provided. Mechanisms of the formation of surface nanoparticles and the removal of surface micro-burrs were discussed. We also examined the distribution of subsurface defects caused by fs laser processing by removing a thin surface layer with a certain depth through chemical mechanical polishing (CMP). Our results show that laser-induced periodic surface structures (LIPSSs) covered by fine SiO₂ nanoparticles form on the fs laser-processed areas. Under optimal parameters, the redeposition of SiO₂ nanoparticles can be minimized, and the surface roughness Sa of processed areas reaches 120 ± 8 nm after the removal of a 10 μm thick surface layer. After the laser processing, micro-burrs on original surfaces are effectively removed, and thus the average profile roughness Rz of 2 mm long surface profiles decreases from 920 ± 120 nm to 286 ± 90 nm. No visible micro-pits can be found after removing ~1 μm thick surface layer from the laser-processed substrates.