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.     

Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.     

Targeted editing of intronic-splicing silencer enhancement of SMN2 Exon 7 inclusion by CRISPR/Case 9

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value.     

纳米级超声造影剂的理论研究进展

为了克服超声造影剂中微米级气泡尺寸较大的局限性,大量研究人员对超声应用的替代造影剂(纳米级造影剂)进行了研究。随着生物纳米技术的飞速发展,纳米级超声造影剂在诊断与治疗领域有着广阔的发展前景。与超声造影剂中的微米级气泡相比,纳米级造影剂粒径较小,渗透能力极强,可以通过血管内皮间隙,进而可以实现血管外病变部位的显影。文中详细论述了超声造影剂在超声作用下的行为以及2种主要的纳米级造影剂:纳米气泡和纳米液滴造影剂,对其理论研究进展进行了总结,并提出了目前仍存在的一些问题及其未来的研究方向。     

CuO-SiO2气凝胶@TiO2纳米纤维无牺牲剂光催化还原CO2

采用溶胶-凝胶法制备CuO-SiO2复合气凝胶,通过在气凝胶孔道内填充TiCl4,然后将其气相水解,得到了在CuO-SiO2气凝胶表面生长了高结晶度的TiO2纳米纤维(CuO-SiO2@TiO2),纤维直径～16 nm.通过XPS、UPS、UV-Vis DRS、荧光光谱(PL)等表征了材料的结构及光电性能.结果表明,制备的CuO-SiO2@TiO2对可见光有明显吸收,且荧光强度较商用TiO2(P25)大幅降低,光生电子-空穴对更加稳定.再在纳米纤维上负载CuO,所得CuO-SiO2@TiO2/CuO在可见光区的荧光强度进一步增强.以300 W氙灯为光源,分别以CuO-SiO2@TiO2及CuO-SiO2@TiO2/CuO为催化剂,无牺牲剂条件下光催化还原CO2,4 h后甲醇产率分别为1304.0及1589.0μmol/g-cat,转换频率(TOF)分别为0.038及0.046 h–1.循环实验表明,纳米纤维具有较好的光催化稳定性,经过4次光催化循环实验后,CuO-SiO2@TiO2/CuO的保留率～94％,甲醇产率可达1472.0μmol/g-cat,TOF为0.042 h–1.     

Box-Behnken Design a Key Tool to Achieve Optimized PCL/Gelatin Electrospun Mesh

Hybrid electrospun nanofibers of polycaprolactone (PCL)/gelatin are considered as drug-delivery systems for increasing the treatment efficacy in superficial (skin) wounds. Continuous delivery of therapeutic agents, skin extracellular matrix similarity, management of wound exudate, and antimicrobial barrier effect are the major advantages of electrospun nanofibers in skin applications. Additionally, combining the favorable properties of PCL and gelatin, regarding their biocompatibility, biodegradability and mechanical performance have been revealed promising parameters to be considered for blend in hybrid structures. However, the usual optimization protocol of nanofibers’ production in electrospinning is based on the observation of one-variable-at-time being this methodology expensive and time-consuming. Therefore, in this research work, a statistical model based on four input variables namely, the flow rate, the needle-working distance, the applied voltage, and the ratio of PCL in the solution, is developed to predict the behavior of nanofibers. The performance of nanofibers is monitored by measurements of fiber's diameter, mesh's thickness, and mesh's permeability. Overall, the model showed to be statistically significant (p-value < 0.05) and an independent analysis validated the predicted response for optimal condition. Finally, a delivery study is performed to evaluate the electrospun mesh performance as a drug carrier.     

基于现代审美下的赣傩艺术元素分析与设计应用

目的 赣傩艺术元素内容丰富并保存完整,是研究我国古代赣傩地区文化与艺术的珍贵史料.研究赣傩艺术元素的提取及衍生图案的设计方法,在设计应用中表达赣傩傩面具、选取傩舞形和构筑傩庙魂,能给当代赣傩艺术元素的产品设计以指引.方法 通过直接引用、形意结合和局部强化的设计方法,增厚其丰富内涵、设计个性和主题意蕴.通过现代化审美中"绿色化、感性化、地域化"的要求,遵循"以退为进,化繁为简""多元并存,个性体现"的原则,强化赣傩艺术元素的独特风格.结论 用现代的手法,将特色的赣傩艺术元素植入到理性的产品设计中去,使赣傩艺术元素与现代设计思想有机结合.在继承传统文化与现代流行中找到契合点,深入挖掘赣傩艺术元素蕴含的文化精神、文化胸怀和文化自信,使中华传统文化在现代审美下进行创新再现.     

梯度铝蜂窝夹芯板的力学行为

梯度分层铝合金蜂窝板是一种有效的吸能结构,本工作在梯度铝蜂窝结构的基础上根据梯度率的概念,通过改变蜂窝芯层的胞壁长度,设计了4种质量相同、梯度率不同的铝蜂窝夹芯结构。通过准静态压缩实验,并结合非线性有限元模拟准静态及冲击态下梯度铝蜂窝夹芯结构的变形情况及其力学性能,分析对比了相同质量下梯度铝蜂窝夹芯结构在准静态下的变形模式以及冲击载荷下分层均质蜂窝结构和不同梯度率的分层梯度蜂窝结构的动态响应和能量吸收特性。结果表明:在准静态压缩过程中,铝蜂窝梯度夹芯板的变形具有明显的局部化特征,蜂窝芯的变形为低密度优先变形直至密实,层级之间的密实化应变差随芯层密度的增大而逐渐减小;在高速冲击下,梯度蜂窝板并非严格按照准静态过程中逐级变形直至密实,而是在锤头冲击惯性及芯层密度的相互作用下整体发生的线弹性变形、弹性屈曲、塑性坍塌及密实化;另外,在本工作所设计的梯度率中,当梯度率为γ₁=0.0276时,梯度蜂窝夹芯板的吸能性达到最好,相较于同等质量下的均质蜂窝夹芯板,能量吸收提高了10.63%。     

Microbial susceptibility of various polymers and evaluation of thermoplastic elastomers with antimicrobial additives

The incursion of microbial growth on polymeric products can deteriorate their performance and lead to the development of undesirable staining and odors. A growing trend in the industry has aimed to reduce microbial populations on high-touch surfaces via the use of antimicrobials to protect material aesthetics and durability or to prevent the spread of pathogenic microorganisms. In this study, a variety of plastic substrates (30 unique polymer compounds), including poly(acrylonitrile-co-butadiene-co-styrene), poly(butylene terephthalate), poly(etherimide), various thermoplastic elastomers (TPEs), poly(carbonates), and poly(amides), were screened for susceptibility to microbial attack using American Society for Testing and Materials (ASTM) G21 (fungi susceptibility), Japanese Industrial Standard (JIS) Z2801, and modified ASTM E1428-15a (bacterial susceptibility) test standards. TPEs were determined to be most susceptible to microbial attack under the appropriate environmental conditions. Subsequent studies assessed the use of an antimicrobial additive, zinc pyrithione (ZPT), for potential efficacy in a variety of TPE blends for diverse target market applications. ZPT proved to be very effective in protecting TPEs, reducing Staphylococcus aureus and Escherichia coli populations by 99.9% or more in JIS Z2801 testing and inhibiting fungal growth (rating = 0) according to the ASTM G21 standard.