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.     

退火工艺对激光选区熔化成形Ti6Al4V合金组织及室温力学性能的影响

以Ti6Al4V球形粉末为原料,利用激光选区熔化成形方法制备了Ti6Al4V合金试样,采用光学显微镜、扫描电镜及力学性能测试等手段,研究了退火工艺对Ti6Al4V合金室温力学性能及组织的影响规律。结果表明: SLM成形沉积态Ti6Al4V合金室温抗拉强度超过1200 MPa,而平均断后伸长率仅为4.0%;在650 ℃下进行真空退火处理,合金的抗拉强度仍保持在1200 MPa左右,规定塑性延伸强度R_p0.2高于1150 MPa,但试样的断后伸长率<10%;而在750及800 ℃下进行真空退火处理,合金试样的抗拉强度降至1100 MPa左右,规定塑性延伸强度高于1050 MPa,伸长率达到甚至超过10%,材料的综合强韧性得到明显提升。随着真空退火加热温度和保温时间的增加,SLM成形Ti6Al4V合金原始β晶界逐渐变模糊,晶粒趋向于等轴化。与此同时,快速冷却转变的α′针状马氏体未出现明显地粗化。     

Use of polymers for taste-masking pediatric drug products

Many drugs are bitter and overcoming this bitter taste is a major barrier in developing a successful product, especially for pediatric patients. Approaches to mask taste include changing taste perception, creating a physical barrier to separate the drug from interacting with taste buds, and changing drug solubility. This review is focused on polymers and the different ways these materials are used to achieve taste masking. Attention is given to systems that are easily swallowed, as swallowability is another concern in developing palatable products for pediatrics. Variables that should be considered when selecting a taste-masking approach are also presented.     

A High Capacity All Solid-State Li-Sulfur Battery Enabled by Conversion-Intercalation Hybrid Cathode Architecture

As demands for electrochemical energy storage continue to rise, alternative electrochemistries to conventional Li-ion batteries become more appealing. Here, an intercalation-conversion hybrid cathode that combines intercalation-type VS₂ with conversion-type sulfur chemistry to construct high performance solid-state lithium-sulfur batteries is reported. The layered VS₂ nanomaterial features Li-ion transport channels, metallic conductivity, and active capacity contribution, all of which provide an ideal platform for the solid state S/Li₂S redox couple to unlock its high gravimetric capacity. The S/VS₂/Li₃PS₄ hybrid cathode composite is prepared by a facile, low-cost, and low-energy mechanical blending process. The S/VS₂/Li₃PS₄|Li₃PS₄|Li/In (or Li) all-solid-state cell exhibits sulfur utilization of ≈85%, with a Coulombic efficiency of close to 100%. High areal capacity up to 7.8 mA h cm⁻² with an active material loading (S/VS₂) as high as 15.5 mg cm⁻² is achieved.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Commercial farmers’ strategies to control water resources in South Africa: an empirical view of reform

This article shows how large-scale commercial farmers, individually and collectively, are responding to land and water reform processes in the Thukela River basin, KwaZulu-Natal, South Africa. With a high degree of innovative agency, commercial farmers have effectively executed four strategies, enabling them to adapt and use their access to resources to neutralize multiple water reform efforts that once promised to be catalysts for inclusive change in the post-apartheid era. It is likely that policy alone will not facilitate the envisioned transformation, if local practices are not sufficiently understood and anticipated by the governmental officials charged with the implementation of water reform processes.     

1Cr18Ni9Ti激光选区熔化成形工艺参数对致密度的影响

采用正交试验,结合典型缺陷形成原因和微观组织,研究了激光选区熔化成形工艺参数(激光功率、扫描速度和扫描间距)对1Cr18Ni9Ti不锈钢致密度的影响,分析了各工艺参数对致密度的影响规律。结果表明,粉末熔化的能量输入密度主要取决于激光功率和扫描速度;在激光功率325~340 W、扫描速度1 000~1 200 mm/s、扫描间距0.12 mm的工艺参数下,SLM技术可制备致密度高于99.9%的1Cr18Ni9Ti不锈钢零件。采用优化后的SLM工艺参数成形1Cr18Ni9Ti不锈钢试棒的力学性能优于QJ501A-98标准,抗拉强度Rm≥709 MPa,屈服强度Rp0.2≥547 MPa,断后伸长率A≥41%。