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There is a relationship between autophagy and the occurrence, maintenance, and progression of several neurodegenerative diseases. The activation of microglia after ischemia contributes to neuronal injury via proinflammatory cytokines and neurotoxic elements. The purpose of this study was to evaluate the function of autophagy in the microglia-mediated death of neuronal cells.Microglial activation by oxygen/glucose deprivation induced both apoptosis and autophagy in neuron-like PC12 cells. Microglia-derived interleukin (IL)-6 induced PC12 cell apoptosis in vitro; however, this effect was inhibited by the autophagy inhibitor chloroquine. Further analysis demonstrated that miR-30d in PC12 cells suppressed microglia-induced PC12 apoptosis and autophagy by directly targeting autophagy protein 5. Moreover, microglia-derived IL-6 activated signal transducer and activator of transcription 3 (STAT3), which can then directly repress miR-30d genes via a conserved STAT3-binding site in its promoter, thereby promoting PC12 cell autophagy and apoptosis.Our study identified IL-6-dependent autophagy-related signaling between microglia and neurons, which contributed to neuronal apoptosis. Importantly, we also provided potential therapeutic targets for ischemic treatment via the interruption of proinflammatory signaling.

The application of distributed acoustic sensing (DAS) in seismology is rapidly expanding due to its ability to perform a large number of high-density measurements, i.e., distributed sensing, without using many point sensors, which is cost-effective. DAS application includes vertical seismic profiling, microseismic measurements, and hydraulic fracturing monitoring and mainly focuses on the event detection capability of DAS data. Febus optics DAS interrogator (A1-R) is continuously running at German Black Forest Observatory (BFO) since May 2021, recording RAW data (selectively stored) or strain-rate data (continuously stored). Our study is in the experimental phase and focuses on testing basic concepts of DAS data, i.e., the effect of gauge-length on the amplitude of measurement and comparing the amplitude of DAS with other seismological sensors such as strain-meter array and a STS2 broadband sensor as well as synthetic simulations. Such comparison is performed using background noise characteristics (power spectral density) and examples of local and regional events that are detectable at the BFO site. In this study, we show examples of strain rate measurements related to local earthquakes recorded by horizontal fiber optic cables, employing two different DAS interrogators, cable types and coupling of the cables to the ground. We compared simultaneous recordings using Febus A1 DAS interrogator and OptoDAS by Febus optic and Alcatel Submarine Networks (ASN), respectively, and, concluded about the frequency and gauge-length dependent sensitivity of recordings in two cases. In addition, we compare the amplitude of DAS recordings, for example of local earthquakes, with the synthetic strain simulated at lower frequency bands using the spectral-element method (Salvus) based on 3D media and analytic approach (Qseis) for 1D model.

Taxol is one of the most famous natural diterpenoids and an important anticancer medicine. Taxol represents a formidable synthetic challenge and has prompted significant interest from the synthetic community. However, in all the previous syntheses of Taxol, there have been no reports of closing the desired eight-membered ring through C1-C2 bond formation. Furthermore, the existence of Taxol-resistant tumors and side effects of Taxol make the development of new approaches to synthesize Taxol and its derivatives highly desirable. Here, we report the asymmetric total synthesis of Taxol using a concise approach through 19 isolated intermediates. The synthetically challenging eight-membered ring was constructed efficiently by a diastereoselective intramolecular SmI2-mediated pinacol coupling reaction to form the C1-C2 bond. The unique biomimetic oxygen ene reaction and the newly developed facile tandem C2-benzoate formation and C13 side chain installation improved the efficiency of the synthesis. The mild oxygen ene reaction under light conditions would be an alternative reaction involved in Taxol biosynthesis. This new convergent approach will allow the diverse creation of Taxol derivatives to enable further biological research.

Understanding the underlying processes associated with the thermo-oxidative performance of the ethylene-propylene-diene monomer (EPDM) is essential for assessing and improving its waterproofing performance in underground infrastructures. To explore the fundamentals of EPDM degradation behavior during thermal oxidation, this paper investigates the effects of hydrocarbon free chain, carbon crosslink, chain scission, hydroxyl, and ether crosslinks, on its kinetics and mechanical properties through molecular dynamics (MD) simulations. Several EPDM thermo-oxidative models were built and verified by comparing the simulation results of oxygen diffusivity, glass transition temperature, and mechanical properties with reported experimental ones. Then the radius of gyration, free volume, density, transport, glass transition, and uniaxial compression performance were investigated via MD simulations. The results show that crosslinking in the thermal oxidation process has a significant influence on the free volume, glass transition temperature, and mechanical properties of the system; the hydroxyl and chain scission mainly interfere with the transport properties; all of these affect the structural conformation.

A semantic-extension-based algorithm for short texts is proposed, by involving the Word2vec and the LDA model, to improve the performance of classification, which is frequently deteriorated by semantic dependencies and scarcity of features. For every keyword within a short text, weighted synonyms and related words can be generated by the Word2Vec and LDA model, respectively, and subsequently be inserted to extend the short text to a reasonable length. We not only have established a criterion by means of similarity estimation to determine whether a sentence should be extended, we designed a scheme to choose the number of extended words. The extended text will be classified. Experimental results show that, the classification performance of the proposed algorithm, in terms of the precision rate, is approximately 5% higher than that of the TF-IDF model and approximately 10% higher than that of the VSM method.

Covering: 2010 to 2020Benzocycloheptane is a fundamental and unique structural motif found in pharmaceuticals and natural products. The total syntheses of natural products bearing the benzocycloheptane subunit are challenging and there are only a few efficient approaches to access benzocycloheptane. Thus, new methods and innovative strategies for preparing such natural products need to be developed. In this review, recent progress in the total syntheses of natural products bearing the benzocycloheptane motif is presented, and key transformations for the construction of benzocycloheptane are highlighted. This review provides a useful guide for those engaged in the syntheses of natural products containing the benzocycloheptane motif.

The southern Central Andes (SCA, 29°S—39°S) orogen is one of the seismically most active regions along the length of the South-American convergent margin, where past earthquakes (e.g., San Juan in 1944, Valdivia M9.5 in 1960 and M8.8 Maule in 2010) have had devastating effects on the population. Past research has extensively focused on linking the occurrence of seismic activity with the stress regime on individual faults at a local scale. In order to more systematically address the relationship between the long-term rheological configuration of the whole lithosphere and the spatial patterns of seismic deformation in the SCA, we computed a 3D model of the expected mechanical strength and rheology (brittle, ductile) of the SCA and adjacent forearc and foreland regions based on an existing 3D model describing the first-order variations of thickness, composition and temperature of geological units forming the upper and subducting plates. We found that the spatial variation in the predicted rheology correlates well with the distribution of seismic deformation in the upper plate, with seismicity bounded to the modelled brittle deformation domain. Moreover, seismic events localize at the transition between mechanically strong and weak domains. This ultimately indicates that the strength of the lithosphere exerts a first-order control on the mechanical stability of the region.In contrast, the results from the rheological model fail to reconcile the observed slab seismicity at depths > 50—70 km, where ductile rheological conditions are expected. In this case, we evaluated possible additional mechanisms triggering these earthquakes, including compaction of sediments at the interface, metamorphic reactions within the oceanic crust and mantle, and slab flexural stresses. To characterize the state of hydration of the mantle related to dehydration reactions and/or sediment compaction, we made use of the Vp/Vs ratio from a seismic tomography model. The majority of the slab seismicity was found to spatially correlate with hydrated areas of the slab and overlying continental mantle, apart from a cluster where the slab attains a sub-horizontal angle. In this region, the correlation between the focal mechanisms of these earthquakes and the slab orientation, suggests that seismicity here is driven by enhanced flexural stresses within the oceanic plate.This contribution showcases the importance of a quantitative characterization of the rheological state of the lithosphere to elucidate the causative dynamics of the spatial distribution of seismicity in the area.

BK7 optical glass has been widely used in modern high-tech fields such as aerospace, automotive, optical precision instruments, electronic information, etc. due to its excellent performance, but its gap between plasticity and hardness is huge, making traditional machining easy to appear sub-surface. Damage and other phenomena, surface quality is difficult to meet the requirements. In this paper, the ultrasonic milling dynamics model was firstly established, and then the multi-factor method was used to detect the longitudinal torsional composite ultrasonic milling and ordinary milling of BK7 optical glass, and the surface roughness and surface topography of different spindle speed, milling speed and milling depth were analyzed. Finally, the laws and mechanisms affecting the quality of the machined surface were obtained. It is found that the surface quality is best when the spindle speed is 3000r/min and the milling depth is 0.2mm; the surface quality of BK7 optical glass decreases with the increase of milling speed. The surface quality and processing efficiency of BK7 optical glass are improved by longitudinal torsional composite ultrasonic vibration milling, and the optimal process parameters for BK7 optical glass longitudinal torsional ultrasonic milling are provided.

Type II intramolecular cycloadditions ([4+2], [4+3], [4+4] and [5+2]) have emerged recently as an efficient and powerful strategy for the construction of bridged ring systems. In general, type II cycloadditions provide access to a wide range of bridged bicyclo[m.n.1] ring systems with high regio- and diastereoselectivity in an easy and straightforward manner. In each section of this review, an overview of the corresponding type II cycloadditions is presented, which is followed by highlights of method development and synthetic applications in natural product synthesis. The goal of this review is to provide a survey of recent advances in the field covering literature up to 2020. The review will serve as a useful reference for organic chemists engaged in the total synthesis of natural products containing bridged bicyclo[m.n.1] ring systems and provide strong stimulus for invention and further advances in this exciting research field.