关于COVID-19、膜脂质与公众健康（网络首发、推荐阅读）

冠状病毒具有一层脂质膜。虽然复制需要劫持宿主的RNA工具来合成病毒体蛋白，但必须将其包裹在脂质膜中，促其萌生以扩展感染。最近研究表明，某些必需脂肪酸可以抑制其复制活性。脂质膜通常被认为是水溶物的脂肪屏障，但它对细胞和亚细胞的功能是高度有序和组分特异性的，其对病毒外壳可能也有最佳的特异性。虽然复制中DNA、RNA和蛋白质组成不受饮食影响，但脂质膜受其影响。此外，自1960年代以来，人们就知道男性对这些必需脂肪酸和膜完整性不足的敏感性高于女性。有证据表明，花生四烯酸和二十二碳六烯酸具有抗病毒、免疫、抗炎、控制血压和消退素活性，因此，迫切需要考察它们在Covid-19预防和治疗中的地位，也需重新评估现行的膳食指导。当前，有关脑、神经、血管和免疫系统等富含膜系统对脂质需求还尚未被详细认识。毫无疑问，这些脂质在几百万年来塑造人类基因组方面具有重要意义，因此，如果这些膜脂质失衡将会使人类面临机体紊乱和感染风险，且男性比女性风险更大。     

Furan fatty acid concentrations in tea infusions prepared from green,black, and herbal teas

Furan fatty acids (FuFAs) are valuable antioxidants with highly effective radical scavenging properties which are widely distributed at low levels in food. Previous research indicated that tea is a valuable source of FuFAs. However, tea is only consumed in form of infusions. To fill this gap, we prepared infusions from different herbal, green, and black teas. Initial measurements with GC-MSMS of tea verified previous findings that 11-(3,4-dimethyl-5-penylfuran-2-yl)-undecanoic acid (11D5) was the prevalent FuFA in tea matrix. Therefore, 11D5 was quantified in tea infusions by means of UHPLC-MSMS equipment after mild alkaline hydrolysis. While herbal tea infusions were low or free of FuFAs, 11D5 was detectable in all samples of green and black tea infusions. Amounts of 11D5 were higher in green tea than in black tea. Moreover, Darjeeling tea infusions were by ~30% richer in 11D5 than black and green teas from other regions. Each cup of green and black tea infusion may provide 20–60 μg 11D5, which is about 5% of the amounts found in tea samples. Spread over the day, regular tea consumption may contribute to the intake of valuable FuFAs.     

Design,Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2–5.4 μM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.     

The Structures of Gd(III) Chelates Conjugated at the Periphery of 3-(1’-Hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) Have a Significant Impact on the Imaging and Therapy of Cancer

3-(1’-Hexyloxyethyl)-3-devinyl-pyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll-a derivative currently undergoing human clinical trials, was conjugated at various peripheral positions (position-17 or 20) of HPPH with either Gd(III)-aminobenzyl-DTPA (Gd(III) DTPA) or Gd(III)-aminoethylamido-DOTA (Gd(III) DOTA). The corresponding conjugates were evaluated for in vitro PDT efficacy, T₁, T₂ relaxivities, in vivo fluorescence, and MR imaging under similar treatment parameters. Among these analogs, the water-soluble Gd(III)-aminoethylamido-DOTA linked at position-17 of HPPH, i. e., HPPH-17-Gd(III) DOTA, demonstrated strong potential for tumor imaging by both MR and fluorescence, while maintaining the PDT efficacy in BALB/c mice bearing Colon-26 tumors (7/10 mice were tumor free on day 60). In contrast to Gd(III) DTPA (Magnevist) and Gd(III) DOTA (Dotarem), the HPPH-Gd(III) DOTA retains in the tumor for a long period of time (24 to 48 h) and provides an option of fluorescence-guided cancer therapy. Thus, a single agent can be used for cancer-imaging and therapy. However, further detailed pharmacokinetic, pharmacodynamic, and toxicological studies of the conjugate are required before initiating Phase I human clinical trials.     

Task-Independent Spiking Central Pattern Generator: A Learning-Based Approach

Neural Processing Letters - Legged locomotion is a challenging task in the field of robotics but a rather simple one in nature. This motivates the use of biological methodologies as solutions to...     

CMC jackets for metallic pipes – A novel approach to prevent the creep deformation of thermo-mechanically loaded metals

Steel materials suffer extensive creep by the application at temperatures of about 700?°C and pressures about 350?bar in a power plant environment. The presented concept overwraps a steel pipe with a ceramic matrix composite (CMC) jacket in order to support the steel pipe and provide high temperature strength. Finite Element simulations show the influence of the wall thickness of CMC jacket and the coefficient of thermal expansion (CTE) on circumferential stresses within the hybrid metal ceramic pipe. Suitable fiber and matrix materials were studied, composites fabricated and mechanical properties determined. Finally, a prototype was designed in order to confirm the feasibility of the concept. The lifetime of a pure steel pipe was increased by more than four-fold by the additional CMC jacket.     

Dichroic nanocomposites based on polymers and metallic particles: from biology to materials science

Dichroic nanocomposites change their colors when they are viewed through a turning polarizer. In the case of polymer matrices containing inorganic nanoparticles, this color effect originates in anisotropic structures of inorganic moieties, such as uniaxially oriented linear assemblies of spherical nanoparticles or parallel oriented nanorods. The orientation of the particles or particle assemblies, respectively, is induced by the polymer matrix, either through oriented elongated hollow spaces or drawing. Matrices based on biopolymers (e.g. cellulose, polypeptides, chitin) as well as synthetic polymers (e.g. polyethylene, poly(vinyl alcohol)) have been employed. The dichroic colors have been generated so far mainly by silver or gold particles (including nanorods), but also other metals and occasionally also semiconductors (metalloids). Notably, dichroism is also disclosed in optical absorption spectra recorded with polarized light. Dichroism in biopolymer‐based objects with incorporated nanoparticles has been exploited for the cognition of biological fine structures, while dichroic films with technical polymers as matrices have been considered as optical switches in bicolored liquid crystal displays and authenticity cachets for documents, banknotes and packaging films. In this context, micropatterning of dichroic nanocomposites, which has been achieved by local heating procedures of materials composed of metal nanorods, is also of interest. © 2017 Society of Chemical Industry     

A Pyropheophorbide Analogue Containing a Fused Methoxy Cyclohexenone Ring System Shows Promising Cancer-Imaging Ability

Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1′-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the ¹²⁴I isotope). The PET imaging ability and ex vivo biodistribution of [¹²⁴I] 4 were compared with the well-studied methyl [3-(¹²⁴1′-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [¹²⁴I] 2 ) and [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [¹²⁴I] 4 containing a fused methoxy cyclohexenone ring system showed excellent tumor contrast with time (72>48>24 h post-injection). Ex vivo biodistribution results indicate that relative to the current clinical standard [¹⁸F]FDG and [¹²⁴I] 2 in 2 % ethanol formulation, [¹²⁴I] 4 , at the same radioactive dose (25 μCi per mouse), showed higher tumor uptake at 24 h post-injection and longer tumor retention. In biological environments, compound 4 showed lower fluorescence and lower singlet oxygen yield than 2 , which is possibly due to higher aggregation caused by the presence of a fused cyclohexenone ring system, resulting in limited in vitro/in vivo PDT efficacy. Therefore, the chlorophyll-a analogue [¹²⁴I] 4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types—brain, renal carcinomas, pancreas—in which [¹⁸F]FDG shows limitations.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.