Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.     

水杨酸处理诱导采后甜瓜抗坏血酸-还原型谷胱甘肽循环代谢清除过氧化氢的作用及机制

目的：研究抗坏血酸（ascorbic acid，AsA）-还原型谷胱甘肽（reduced glutathione，GSH）循环代谢在水杨酸处理采后甜瓜诱导的过量H2O2清除过程中的作用。方法：用4 mmol/L水杨酸浸泡‘玉金香’厚皮甜瓜10 min，测定处理后果实常温贮藏过程中丙二醛（malondialdehyde，MDA）含量，分析活性氧的积累水平、超氧化物歧化酶（superoxide dismutase，SOD）和过氧化氢酶（catalase，CAT）活力，以及AsA-GSH循环过程相关酶活力及产物和底物含量。结果：水杨酸处理降低了果实MDA含量，第10天处理组MDA含量较对照组降低14.6%；显著提高了果实O2－·的产生速率和H2O2含量（P＜0.05），其中处理后第2天O2－·的产生速率高出同期对照组的1.9 倍，第6天H2O2含量高出对照组果实29.7%；提高了果实SOD活力，但抑制了CAT活力，说明H2O2的清除可能是依赖于除酶促系统外的其他系统。此外，水杨酸处理提高了果实抗坏血酸过氧化物酶、单脱氢抗坏血酸过氧化物酶、脱氢抗坏血酸还原酶和谷胱甘肽还原酶的活力，增加了AsA和氧化型谷胱甘肽的含量，降低了脱氢抗坏血酸和GSH的含量。结论：水杨酸处理诱导了厚皮甜瓜果实的氧爆，抑制了MDA产生，由水杨酸诱导产生的过量H2O2主要依靠AsA-GSH循环系统清除。     

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe³⁺ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe³⁺ was adsorbed in PDA NPs at pH values close to which Fe(OH)₃ begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe³⁺. Otherwise, it was demonstrated that Fe³⁺ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca²⁺ content, and that when Fe³⁺ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe³⁺ and doxorubicin may constitute a good approach to target breast tumors.     

Theoretical study on a kind of cyclization mechanism of boron trichloride and hexamethyldisilazane to form the borazine ring for SiBCN ceramics precursor

Borazine rings act as a pivotal part in siliconboroncarbonitride ceramics (SiBCN) for high-temperature stability and great resistance to crystallization. A detailed investigation of the ring formation mechanism will guide the design and synthesis of SiBCN to meet application requirements under extreme conditions. Boron trichloride (BCl₃) and hexamethyldisilazane (HN(SiMe₃)₂) are common raw materials for the synthesis of precursors for SiBCN. In this paper, quantum chemical calculation was used to study the cyclization reaction mechanism between BCl₃ and HN(SiMe₃)₂ to form trichloroborazine (TCBZ) at the MP2/6-31G (d,p) level of theory. We discussed the structure properties, reaction pathways, energy barriers, reaction rates, and other aspects in detail. The results show that BCl₃ and HN(SiMe₃)₂ alternately participate in the reaction process, accompanied by the release of trimethylchlorosilane (TMCS), and that the entire reaction shows an absolute advantage in terms of energy. In the Step by step reaction, lower reaction barriers are formed due to the introduction of BCl₃ with more heat released compared to that for the introduction of HN(SiMe₃)₂. The final single-molecule cyclization and TMCS elimination steps are found to be faster compared to all previous bimolecular reactions.     

Psychrophilic hydrogen production from petrochemical wastewater via anaerobic sequencing batch reactor: techno-economic assessment and kinetic modelling

Independent hydrogen production from petrochemical wastewater containing mono-ethylene glycol (MEG) via anaerobic sequencing batch reactor (ASBR) was extensively assessed under psychrophilic conditions (15–25 °C). A lab-scale ASBR was operated at pH of 5.50, and different organic loading rates (OLR) of 1.00, 1.67, 2.67, and 4.00 gCOD/L/d. The hydrogen yield (HY) progressed from 134.32 ± 10.79 to 189.09 ± 22.35 mL/gMEG_initial at increasing OLR from 1.00 to 4.00 gCOD/L/d. The maximum hydrogen content of 47.44 ± 3.60% was achieved at OLR of 4.0 gCOD/L/d, while methane content remained low (17.76 ± 1.27% at OLR of 1.0 gCOD/L/d). Kinetic studies using four different mathematical models were conducted to describe the ASBR performance. Furthermore, two batch-mode experiments were performed to optimize the nitrogen supplementation as a nutrient (C/N ratio), and assess the impact of salinity (as gNaCl/L) on hydrogen production. HY substantially dropped from 62.77 ± 4.09 to 6.02 ± 0.39 mL/gMEG_initial when C/N ratio was increased from 28.5 to 114.0. Besides, the results revealed that salinity up to 10.0 gNaCl/L has a relatively low inhibitory impact on hydrogen production. Eventually, the cost/benefit analysis showed that environmental and energy recovery revenues from ASBR were optimized at OLR of 4.0 gCOD/L/d (payback period of 7.13 yrs).     

A comparative study on hygroscopic and physiochemical properties of chicken powders obtained by different drying methods

Abstract

Different drying methods (spray drying (SD), vacuum drying (VD), microwave vacuum drying (MVD), and infrared vacuum drying (IFVD)) were applied in order to compare the hygroscopicity behavior of chicken powders. The hygroscopicity curves and glass transition temperature were used to evaluate the influence of ambient humidity and temperature on moisture absorption of powders. The results showed that the chicken powder dried by MVD had the lowest moisture absorption, followed by IFVD, VD, and SD. The hygroscopicity of SD chicken powders was different from other three kinds of chicken powders due to the physical properties of particles and the changes of protein secondary structure as detected by the Fourier transform-infrared spectrometer. For the three vacuum drying methods, the difference of protein secondary structure was the main reason of differences in hygroscopicity. Although MVD chicken powders were slightly inferior to SD chicken powders in taste, MVD chicken powders were the best in terms of smell and color as suggested by instrumental sensory parameter evaluations. It was found that MVD had a positive effect on reducing moisture absorption and maintaining sensory quality of chicken powders.     

Advancements in the Development of non-BET Bromodomain Chemical Probes

The bromodomain and extra terminal (BET) family of bromodomain-containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high-quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non-BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non-BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non-BET bromodomains as tractable therapeutic targets.     

碳脱氧在钢包顶渣改质中的应用

 为了进一步降低夹杂物缺陷并提高产品质量,基于碳脱氧进行了钢包顶渣改质的研究。冷轧产品的生产工艺为铁水预处理→转炉→RH精炼→连铸,为减少钢中夹杂物质量分数,需要进行钢包顶渣改质,同时降低钢包顶渣TFe质量分数。采用粒碳部分替代铝渣球的方法进行基于碳脱氧工艺的钢包顶渣改质,试验结果表明,顶渣改质效果良好,在顶渣TFe质量分数、中间包钢水游离氧明显降低的同时铸坯中Al₂O₃夹杂物得到优化;“30 kg粒渣+铝渣球”工艺降低生产成本5.16元/t(钢)。