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.     

Achieving fabrication of highly transparent Y2O3 ceramics via air pre-sintering by deionization treatment of suspension

An easy albeit quite effective deionization suspension treatment was adopted to alleviate the detrimental effects related to the hydrolysis of Y₂O₃ in an aqueous medium. Fabrication of highly transparent Y₂O₃ ceramics with a fine grain size via air pre-sintering and post–hot isostatic pressing (HIP) treatment without using any sintering additive was achieved using the treated suspensions. The hydrolysis issue of Y₂O₃ powder in an aqueous medium was effectively alleviated by using deionization treatment, and a well-dispersed suspension with a low concentration of dissolved Y³⁺ species was obtained. The dispersed suspensions were consolidated by the centrifugal casting method, and the green bodies derived from the suspension of 35.0 vol% solid loading showed an improved homogeneity with a relative density of 52.1%. Fully dense Y₂O₃ transparent ceramic with high transparency was obtained by pre-sintering consolidated green compacts at a low temperature of 1400°C for 16 h in air followed by a post-HIP treatment at 1550°C for 2 h under 200 MPa pressure. The sample had a fine average grain size of 690 nm. The in-line transmittance of the sample reached 83.3% and 81.8% at 1100 nm and 800 nm, respectively, very close to the theoretical values of Y₂O₃.     

Public perceptions on artificial intelligence driven disaster management: Evidence from Sydney,Melbourne and Brisbane

In recent years, artificial intelligence (AI) is being increasingly utilised in disaster management activities. The public is engaged with AI in various ways in these activities. For instance, crowdsourcing applications developed for disaster management to handle the tasks of collecting data through social media platforms, and increasing disaster awareness through serious gaming applications. Nonetheless, there are limited empirical investigations and understanding on public perceptions concerning AI for disaster management. Bridging this knowledge gap is the justification for this paper. The methodological approach adopted involved: Initially, collecting data through an online survey from residents (n = 605) of three major Australian cities; Then, analysis of the data using statistical modelling. The analysis results revealed that: (a) Younger generations have a greater appreciation of opportunities created by AI-driven applications for disaster management; (b) People with tertiary education have a greater understanding of the benefits of AI in managing the pre- and post-disaster phases, and; (c) Public sector administrative and safety workers, who play a vital role in managing disasters, place a greater value on the contributions by AI in disaster management. The study advocates relevant authorities to consider public perceptions in their efforts in integrating AI in disaster management.     

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.     

一种植物油中苯并（a）芘含量测定的固相萃取前处理方法

为了建立一种准确性高、成本低的植物油中苯并(a)芘测定的样品前处理方法，基于GB 5009.7—2016以自制氧化铝柱为固相萃取柱，采用单因素试验对称样量、洗脱剂量、洗脱流速、吸附剂存放时间、吸附剂量这5个影响植物油中苯并（a）芘洗脱的因素进行研究，优化前处理条件，并对测定方法进行考察。结果表明：优化的前处理条件为称样量0.100 0 g、洗脱剂量120 mL、吸附剂（氧化铝）量22 g、洗脱流速1滴/2 s、吸附剂存放时间少于12周；方法检出限为0.2 μg/L，样品加标回收率为94.23%～100.00%，RSD为1.20%～7.36%；同一样品测定结果与SGS测定值接近，相对平均偏差为2.36%～3.50%。说明本试验方法测定结果准确，可应用于油脂企业植物油中痕量苯并（a）芘的测定。     

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.