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The mechanism and origins of site-selectivity of Rh2(S-tfpttl)4-catalyzed C(sp3)–H bond aminations were studied using density functional theory (DFT) calculations. The synergistic combination of the dirhodium complex Rh2(S-tfpttl)4 with tert-butylphenol sulfamate TBPhsNH2 composes a pocket that can access both tertiary and benzylic C–H bonds. The nonactivated tertiary C–H bond was selectively aminated in the presence of an electronically activated benzylic C–H bond. Both singlet and triplet energy surfaces were investigated in this study. The computational results suggest that the triplet stepwise pathway is more favorable than the singlet concerted pathway. In the hydrogen atom abstraction by Rh–nitrene species, which is the rate- and site-selectivity-determining step, there is an attractive π–π stacking interaction between the phenyl group of the substrate and the phthalimido group of the ligand in the tertiary C–H activation transition structure. By contrast, such attractive interaction is absent in the benzylic C–H amination transition structure. Therefore, the DFT computational results clearly demonstrate how the synergistic combination of the dirhodium complex with sulfamate overrides the intrinsic preference for benzylic C–H amination to achieve the amination of the nonactivated tertiary C–H bond.

By using the finite element method and a “coarse to fine” two-stage genetic algorithm as the forward calculation method and the inverse search scheme, respectively, we perform both the unconstrained and constrained optimal design of the unit cell topology of the two-dimensional square-latticed solid phononic crystals (PnCs), to maximize the relative widths of the gaps between the adjacent energy bands of the PnCs. In the constrained optimizations, the maximization is subjected to the constraint of a predefined average density. In the numerical results, the variation patterns of the optimized structures with the order of the bandgap for both the out-plane shear and the in-plane mixed elastic wave modes are presented, and the effects of both the material contrast and the predefined average density on the obtained optimal structures are discussed.

Autophagy, a conserved cellular degradation and recycling process, can be enhanced by nutrient depletion, oxidative stress or other harmful conditions to maintain cell survival. 6-Hydroxydopamine/ascorbic acid (6-OHDA/AA) is commonly used to induce experimental Parkinson’s disease (PD) lesions by causing oxidative damage to dopaminergic neurons. Activation of autophagy has been observed in the 6-OHDA-induced PD models. However, the mechanism and exact role of autophagy activation in 6-OHDA PD model remain inconclusive. In this study, we report that autophagy was triggered via mucolipin 1/calcium/calcineurin/TFEB (transcription factor EB) pathway upon oxidative stress induced by 6-OHDA/AA. Interestingly, overexpression of TFEB alleviated 6-OHDA/AA toxicity. Moreover, autophagy enhancers, Torin1 (an mTOR-dependent TFEB/autophagy enhancer) and curcumin analog C1 (a TFEB-dependent and mTOR-independent autophagy enhancer), significantly rescued 6-OHDA/AA-induced cell death in SH-SY5Y cells, iPSC-derived DA neurons and mice nigral DA neurons. The behavioral abnormality of 6-OHDA/AA-treated mice can also be rescued by Torin 1 or C1 administration. The protective effects of Torin 1 and C1 can be blocked by autophagy inhibitors like chloroquine (CQ) or by knocking down autophagy-related genes TFEB and ATG5. Taken together, this study supports that TFEB-mediated autophagy is a survival mechanism during oxidative stress and pharmacological enhancement of this process is a neuroprotective strategy against oxidative stress-associated PD lesions.

Background Flavonoids have strong free radical scavenging and antioxidant capacity. The high abundance of flavonoids in Chinese prickly ash peels have many benefits to human health. In this study, ‘Hancheng Dahongpao’, a main cultivar, was taken as materials to investigate the flavonoids biosynthesis mechanism of Zanthoxylum bungeanum Maxim at three key development stages by integration of metabolomics and transcriptomics analysis. Results A total of 19 differentially accumulated metabolites were identified, the key flavonoids compounds were kaempferol, quercetin and their glycoside derivatives, and two major anthocyanins (peonidin O-hexoside and peonidin 3-O-glucoside). 5 gene networks/modules including 15 important candidate genes were identified, which was highly correlated with flavonoids. Among these genes, ZM-163828 and ZM-184209 were strongly correlated with kaempferol and quercetin, and ZM-125833 and ZM-97481 were controlled the anthocyanins biosynthesis. Moreover, it was shown that MYB-ZM1, MYB-ZM3, MYB-ZM5, MYB-ZM6 and MYB-ZM7 coordinately controlled flavonoids accumulation through regulating the structural genes. Conclusions Generally, this study systematically revealed the flavonoids metabolic pathways and candidate genes involved in flavonoids biosynthesis and laid a foundation for the potential targets for the breeding of new valuable Chinese prickly ash cultivars.

Background: Traditional Chinese medicine (TCM) has been widely used in the treatment of human diseases. However, the synergistic effects of multiple TCM prescriptions in the treatment of stroke have not been thoroughly studied. Objective of the study: This study aimed to reveal the mechanisms underlying the synergistic effects of these TCM prescriptions in stroke treatment and identify the active compounds. Methods: Herbs and compounds in the Di-Tan Decoction (DTD), Xue-Fu Zhu-Yu Decoction (XFZYD), and Xiao-Xu-Ming Decoction (XXMD) were acquired from the TCMSP database. SEA, HitPick, and TargetNet web servers were used for target prediction. The compound-target (C-T) networks of three prescriptions were constructed and then filtered using the collaborative filtering algorithm. We combined KEGG enrichment analysis, molecular docking, and network analysis approaches to identify active compounds, followed by verification of these compounds with an oxygen-glucose deprivation and reoxygenation (OGD/R) model. Results: The filtered DTD network contained 39 compounds and 534 targets, the filtered XFZYD network contained 40 compounds and 508 targets, and the filtered XXMD network contained 55 compounds and 599 targets. The filtered C-T networks retained approximately 80% of the biological functions of the original networks. Based on the enriched pathways, molecular docking, and network analysis results, we constructed a complex network containing 3 prescriptions, 14 botanical drugs, 26 compounds, 13 targets, and 5 pathways. By calculating the synergy score, we identified the top 5 candidate compounds. The experimental results showed that quercetin, baicalin, and ginsenoside Rg1 independently and synergistically increased cell viability. Conclusion: By integrating pharmacological and chemoinformatic approaches, our study provides a new method for identifying the effective synergistic compounds of TCM prescriptions. The filtered compounds and their synergistic effects on stroke require further research.

Background Isobutanol is an attractive biofuel with many advantages. Third-generation biorefineries that convert CO2 into bio-based fuels have drawn considerable attention due to their lower feedstock cost and more ecofriendly refining process. Although autotrophic cyanobacteria have been genetically modified for isobutanol biosynthesis, there is a lack of stable and convenient strategies to improve their production. Results In this study, we first engineered Synechococcus elongatus for isobutanol biosynthesis by introducing five exogenous enzymes, reaching a production titer of 0.126 g/L at day 20. It was then discovered that high salinity stress could result in a whopping fivefold increase in isobutanol production, with a maximal in-flask titer of 0.637 g/L at day 20. Metabolomics analysis revealed that high salinity stress substantially altered the metabolic profiles of the engineered S. elongatus. A major reason for the enhanced isobutanol production is the acceleration of lipid degradation under high salinity stress, which increases NADH. The NADH then participates in the engineered isobutanol-producing pathway. In addition, increased membrane permeability also contributed to the isobutanol production titer. A cultivation system was subsequently developed by mixing synthetic wastewater with seawater to grow the engineered cyanobacteria, reaching a similar isobutanol production titer as cultivation in the medium. Conclusions High salinity stress on engineered cyanobacteria is a practical and feasible biotechnology to optimize isobutanol production. This biotechnology provides a cost-effective approach to biofuel production, and simultaneously recycles chemical nutrients from wastewater and seawater.

Frame and rocking wall (FRW) structures have excellent resilient performance during earthquakes. However, the concrete at interfacial corners of rocking walls (RWs) is easily crushed due to local extreme compression during the rocking process. An innovative RW with a curved interface is proposed to prevent interfacial corners from producing local damage, enhancing its earthquake resilient performance (ERP). The precast wall panel with a curved interface is assembled into an integral self-centering hybrid rocking wall (SCRW) by two post-tensioned unbonded prestressed tendons. Moreover, two ordinary energy dissipation steel rebars and two shear reinforcements are arranged to increase the energy dissipation capacity and lateral resistance. Two SCRW specimens and one monolithic reinforced concrete (RC) shear wall (SW) were tested under pseudo-static loading to compare the ERPs of the proposed SCRW and the SW, focusing on studying the effect of the curved interface on the SCRW. The key resilient performance of rocking effects, failure modes, and hysteretic properties of the SCRW were explored. The results show that nonlinear deformations of the SCRW are concentrated along the interface between the SCRW and the foundation, avoiding damage within the SCRW. The restoring force provided by the prestressed tendons can effectively realize self-centering capacity with small residual deformation, and the resilient performance of the SCRW is better than that of monolithic SW. In addition, the curved interface of the SCRW makes the rocking center change and move inward, partially relieving the stress concentration and crush of concrete. The rocking range of the rocking center is about 41.4% of the width of the SCRW.

Non-local extensions of the Standard Model with a non-locality scale ΛNL have the effect of smearing the pointlike vertices of the Standard Model. At energies significantly lower than ΛNL vertices appear pointlike, while beyond this scale all beta functions vanish and all couplings approach a fixed point leading to scale invariance. Non-local SM extensions are ghost free, with the non-locality scale serving as an effective cutoff to radiative corrections of the Higgs mass. We argue that the data expected to be collected at the LHC phase 2 will have a sensitivity to non-local effects originating from a non-locality scale of a few TeV. Using an infinite derivative prescription, we study modifications to heavy vector-boson cross sections that can lead to an enhanced production of boosted Higgs bosons in a region of the kinematic phase space where the SM background is very small.

Snakes have numerous features distinctive from other tetrapods and a rich history of genome evolution that is still obscure. Here, we report the high-quality genome of the five-pacer viper, Deinagkistrodon acutus , and comparative analyses with other representative snake and lizard genomes. We map the evolutionary trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion, and many viper TEs show brain-specific gene expression along with their nearby genes. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes and also functional degeneration of genes associated with vision and hearing. Lineage-specific relaxation of functional constraints on respective Hox and Tbx limb-patterning genes supports fossil evidence for a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we infer that the ZW sex chromosome pair had undergone at least three recombination suppression events in the ancestor of advanced snakes. These results altogether forge a framework for our deep understanding into snakes’ history of molecular evolution. Snakes have many characteristics that distinguish them from their relatives. Here, Yin et al. sequence the genome of the five-pacer viper, Deinagkistrodon acutus , and use comparative genomic analyses to elucidate the evolution of transposable elements, developmental genes and sex chromosomes in snakes.