Rational Design of Hierarchical “Ceramic‐in‐Polymer” and “Polymer‐in‐Ceramic” Electrolytes for Dendrite‐Free Solid‐State Batteries

Solid polymer electrolytes as one of the promising solid‐state electrolytes have received extensive attention due to their excellent flexibility. However, the issues of lithium (Li) dendrite growth still hinder their practical applications in solid‐state batteries (SSBs). Herein, composite electrolytes from “ceramic‐in‐polymer” (CIP) to “polymer‐in‐ceramic” (PIC) with different sizes of garnet particles are investigated for their effectiveness in dendrite suppression. While the CIP electrolyte with 20 vol% 200 nm Li_6.4La₃Zr_1.4Ta_0.6O₁₂ (LLZTO) particles (CIP‐200 nm) exhibits the highest ionic conductivity of 1.6 × 10^?4 S cm^?1 at 30 °C and excellent flexibility, the PIC electrolyte with 80 vol% 5 µm LLZTO (PIC‐5 µm) shows the highest tensile strength of 12.7 MPa. A sandwich‐type composite electrolyte (SCE) with hierarchical garnet particles (a PIC‐5 µm interlayer sandwiched between two CIP‐200 nm thin layers) is constructed to simultaneously achieve dendrite suppression and excellent interfacial contact with Li metal. The SCE enables highly stable Li plating/stripping cycling for over 400 h at 0.2 mA cm^?2 at 30 °C. The LiFePO₄/SCE/Li cells also demonstrate excellent cycle performance at room temperature. Fabricating sandwich‐type composite electrolytes with hierarchical filler designs can be an effective strategy to achieve dendrite‐free SSBs with high performance and high safety at room temperature.     

Introgression lines of Solanum sitiens,a wild nightshade of the Atacama Desert,in the genome of cultivated tomato

The wild tomato relative Solanum sitiens is a xerophyte endemic to the Atacama Desert of Chile and a potential source of genes for tolerance to drought, salinity and low‐temperature stresses. However, until recently, strong breeding barriers prevented its hybridization and introgression with cultivated tomato, Solanum lycopersicum L. We overcame these barriers using embryo rescue, bridging lines and allopolyploid hybrids, and synthesized a library of introgression lines (ILs) that captures the genome of S. sitiens in the background of cultivated tomato. The IL library consists of 56 overlapping introgressions that together represent about 93% of the S. sitiens genome: 65% in homozygous and 28% in heterozygous (segregating) ILs. The breakpoints of each segment and the gaps in genome coverage were mapped by single nucleotide polymorphism (SNP) genotyping using the SolCAP SNP array. Marker‐assisted selection was used to backcross selected introgressions into tomato, to recover a uniform genetic background, to isolate recombinant sub‐lines with shorter introgressions and to select homozygous genotypes. Each IL contains a single S. sitiens chromosome segment, defined by markers, in the genetic background of cv. NC 84173, a fresh market inbred line. Large differences were observed between the lines for both qualitative and quantitative morphological traits, suggesting that the ILs contain highly divergent allelic variation. Several loci contributing to unilateral incompatibility or hybrid necrosis were mapped with the lines. This IL population will facilitate studies of the S. sitiens genome and expands the range of genetic variation available for tomato breeding and research.     

密码子优化策略在异源蛋白表达中的应用

酶在医疗和生物药物方面有着广泛的应用,不仅可以用来治疗各种疾病,还在临床诊断和人体健康等方面有着重要的影响。利用微生物来表达异源蛋白已经成为获取酶最简单快速的方法。为获得高浓度和高质量的异源蛋白,常用的方法是对基因序列进行密码子优化。传统的密码子优化策略主要基于密码子偏好性和GC含量,忽略了翻译动力学和代谢水平等复杂多样的变化因素。文中从基因水平、转录水平、翻译水平、翻译后水平以及代谢水平等多方面考虑出发,提供了一个较为全面的密码子优化策略,主要包括密码子偏好性、密码子协调性、密码子敏感性、调整基因序列结构以及一些其他影响因素。同时对每种策略的内容、理论支持以及应用范围等方面作了全面的总结,并将各策略的优缺点进行了系统的比较,为异源蛋白表达提供了全方位、多层次、多选择的优化策略,也为酶工业和生物药物等方面提供参考。     

Fullerene nanoparticles for the treatment of ulcerative colitis

Ulcerative colitis (UC) is a long-term, recurrent inflammatory bowel disease for which no effective cure is yet available in the clinical setting. Repairing the barrier dysfunction of the colon and reducing intestinal inflammation are considered key objectives to cure UC. Here we demonstrate a novel therapeutic strategy based on a C₆₀ fullerene suspension (C₆₀FS) to treat dinitrobenzene sulfonic acid-induced UC in an animal model. C₆₀FS can repair the barrier dysfunction of UC and effectively promote the healing of ulcers; it also manifests better treatment effects compared with mesalazine enema. C₆₀FS can reduce the numbers of basophils in the blood of UC rats and mast cells in the colorectal tissue, thereby effectively alleviating inflammation. The expression of H1R, H4R, and VEGFR2 receptors in colorectal tissues is inhibited by C₆₀FS, and the levels of histamine and prostaglandin in the rat blood are reduced. This work presents a reliable strategy based on fullerene to cure UC and provides a novel guide for UC treatment.

     

A new metabolite with a new substitution pattern from the seeds of the Chinese Yew, Taxus mairei

A new taxoid metabolite with a new substitution pattern was isolated from the methanol extract of the seeds of Taxus mairei, and its structure was established as 5alpha,15-dihydroxy-7beta,9alpha-diacetoxy-11(15-->1)abeo-taxa-4(20),11-dien-13-one (1) on the basis of spectral analysis including (1)H- and (13)C-NMR, HMQC, HMBC, NOESY, and confirmed by HR-FAB mass spectrometry.     

Chronic Sleep Restriction Induces Aβ Accumulation by Disrupting the Balance of Aβ Production and Clearance in Rats

Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD) pathogenesis, and growing evidence has shown that poor sleep quality is one of the risk factors for AD, but the mechanisms of sleep deprivation leading to AD have still not been fully demonstrated. In the present study, we used wild-type (WT) rats to determine the effects of chronic sleep restriction (CSR) on Aβ accumulation. We found that CSR-21d rats had learning and memory functional decline in the Morris water maze (MWM) test. Meanwhile, Aβ₄₂ deposition in the hippocampus and the prefrontal cortex was high after a 21-day sleep restriction. Moreover, compared with the control rats, CSR rats had increased expression of β-site APP-cleaving enzyme 1 (BACE1) and sAPPβ and decreased sAPPα levels in both the hippocampus and the prefrontal cortex, and the BACE1 level was positively correlated with the Aβ₄₂ level. Additionally, in CSR-21d rats, low-density lipoprotein receptor-related protein 1 (LRP-1) levels were low, while receptor of advanced glycation end products (RAGE) levels were high in the hippocampus and the prefrontal cortex, and these transporters were significantly correlated with Aβ₄₂ levels. In addition, CSR-21d rats had decreased plasma Aβ₄₂ levels and soluble LRP1 (sLRP1) levels compared with the control rats. Altogether, this study demonstrated that 21 days of CSR could lead to brain Aβ accumulation in WT rats. The underlying mechanisms may be related to increased Aβ production via upregulation of the BACE1 pathway and disrupted Aβ clearance affecting brain and peripheral Aβ transport.

     

Long noncoding RNA growth arrest-specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR-dependent manner

Malignant glioma is a severe type of brain tumor with a grim prognosis. The occurrence of resistance compromises the efficacy of chemotherapy for glioma. Long noncoding RNA growth arrest-specific 5 (GAS5) has recently become an attractive target for cancer therapy by regulating cell growth, invasion, and migration. Nevertheless, its role in glioma chemoresistance remains elusive. In the current study, the expression of GAS5 was decreased in glioma cell lines, and lower levels of GAS5 were observed in U138 and LN18 glioma cells that had low sensitivity to cisplatin. Functional assay confirmed that knockdown of GAS5 enhanced cell resistance to cisplatin in U87 cells, which had a relatively high expression of GAS5. Conversely, elevation of GAS5 increased cell sensitivity to cisplatin in U138 cells that had a relatively low expression of GAS5. Mechanistically, cisplatin exposure evoked excessive autophagy concomitant with an increase in autophagy-related LC3II expression and a decrease in autophagy substrate p62 expression, which was reversely muted after GAS5 overexpression. In addition, GAS5 restored cisplatin-inhibited mammalian target of rapamycin (mTOR) activation. Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5-mediated depression in cisplatin-evoked autophagy. Notably, blocking the mTOR pathway also attenuated GAS5-increased sensitivity to cisplatin in U138 cells. Cumulatively, these findings indicate that GAS5 may blunt the resistance of glioma cells to cisplatin by suppressing excessive autophagy through the activation of mTOR signaling, implying a promising therapeutic strategy against chemoresistance in glioma.     

Opioid activity of synthetic deltorphin II analogues and their spin labeled derivatives

Deltorphin II (Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH₂, Del II), an endogenous linear heptapeptide, is a highly selective agonist of the -opioid receptor. To study the effect of the position 4 residue (Glu) on the opioid activity of Del II, we designed and synthesized three analogues of Del II by solid-phase peptide synthesis. They were [Val⁴,Glu⁵]Del II, [Val⁴,Glu⁶]Del II and [Gly⁴,Glu⁷]Del II. To study the effect of spin labeling on peptide bioactivities, all the peptides were labeled using a free radical. The labeling material was a stable nitrogen–oxygen free radical which was linked to the N-terminal via an amide bond. We investigated the opioid bioactivities of these analogues both in vivo and in vitro, and concluded that the differences in opioid activity of Del II and its analogues were due to structural differences. When the Glu residue is at position 5 or 6, the internal hydrogen bonds in Del II are affected and there is a change in three-dimensional structure and opioid activity. The antinociceptive activity of all the peptides decreased after spin labeling. This indicates that the stable nitrogen–oxygen free radical is a dual-function spin-labeling molecule.