The 3C-like protease (3CLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV) cleaves 11 sites in the polyproteins, including its own N- and C-terminal autoprocessing sites, by ...recognizing P4–P1 and P1′. In this study, we determined the crystal structure of 3CLpro with the C-terminal prosequence and the catalytic-site C145A mutation, in which the enzyme binds the C-terminal prosequence of another molecule. Surprisingly, Phe at the P3′ position Phe(P3′) is snugly accommodated in the S3′ pocket. Mutations of Phe(P3′) impaired the C-terminal autoprocessing, but did not affect N-terminal autoprocessing. This difference was ascribed to the P2 residue, Phe(P2) and Leu(P2), in the C- and N-terminal sites, as follows. The S3′ subsite is formed by Phe(P2)-induced conformational changes of 3CLpro and the direct involvement of Phe(P2) itself. In contrast, the N-terminal prosequence with Leu(P2) does not cause such conformational changes for the S3′ subsite formation. In fact, the mutation of Phe(P2) to Leu in the C-terminal autoprocessing site abolishes the dependence on Phe(P3′). These mechanisms explain why Phe is required at the P3’ position when the P2 position is occupied by Phe rather than Leu, which reveals a type of subsite cooperativity. Moreover, the peptide consisting of P4–P1 with Leu(P2) inhibits protease activity, whereas that with Phe (P2) exhibits a much smaller inhibitory effect, because Phe(P3′) is missing. Thus, this subsite cooperativity likely exists to avoid the autoinhibition of the enzyme by its mature C-terminal sequence, and to retain the efficient C-terminal autoprocessing by the use of Phe(P2).
An adaptive neural network dynamic surface control method for strict feedback non‐linear systems with model uncertainty is proposed in this paper. The uncertain parts are approached by RBF neural ...network; meanwhile, the virtual controller is designed to make system stable according to dynamic surface control. The method of Lyapunov is used to prove the stability and convergence of the system. The simulation results prove the feasibility of this controller and prove that the controller has an advantage to approach the uncertain non‐linear system and make system have well convergence and traceability.
A simplified adaptive neural network dynamic surface control method for strict feedback non‐linear systems with model uncertainty is proposed in this paper.
► Tea tree oil (TTO) vapor treatment alleviated gray mold and soft rot in strawberries. ► TTO vapor treatment maintained a higher quality of freshness than untreated fruit in storage. ► Spore ...germination and mycelial growth of Botrytis cinerea and Rhizopus stolonifer were inhibited by TTO. ► TTO induced H2O2 levels and SOD, PAL, POD and β-1,3-glucanase activities in strawberries.
The purpose of this study was to investigate the effect of tee tree oil (TTO) against the main fungal disease in strawberries and a possible mechanism for the effects. TTO vapor exhibited a higher activity against spore germination and mycelial growth of Botrytis cinerea and Rhizopus stolonifer under in vitro conditions. TTO vapors at 0.9g/L significantly reduced artificially inoculated gray mold and soft rot in vivo, and treated strawberries maintained a fresher quality than untreated strawberries during storage. In addition, this treatment also enhanced the resistance of strawberries against B. cinerea, which caused a higher hydrogen peroxide (H2O2) level and activities of superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), peroxidase (POD) and β-1,3-glucanase during the first period of incubation. These results indicate that TTO can reduce fruit decay, possibly by inhibiting pathogen growth directly and inducing disease resistance indirectly, and TTO vapor may provide an alternative means of controlling disease in strawberries.
The low response rate and adaptive resistance of PD‐1/PD‐L1 blockade demands the studies on novel therapeutic targets for cancer immunotherapy. We discovered that a novel immune checkpoint TIGIT ...expressed higher than PD‐1 in many tumors especially anti‐PD‐1 resistant tumors. Here, mirror‐image phage display bio‐panning was performed using the d‐enantiomer of TIGIT synthesized by hydrazide‐based native chemical ligation. d‐peptide DTBP‐3 was identified, which could occupy the binding interface and effectively block the interaction of TIGIT with its ligand PVR. DTBP‐3 showed proteolytic resistance, tumor tissue penetrating ability, and significant tumor suppressing effects in a CD8+ T cell dependent manner. More importantly, DTBP‐3 could inhibit tumor growth and metastasis in anti‐PD‐1 resistant tumor model. This is the first d‐peptide targeting TIGIT, which could serve as a potential candidate for cancer immunotherapy.
The d‐peptide DTBP‐3 was identified, which could effectively block TIGIT/PVR interaction. DTBP‐3 could inhibit tumor growth and metastasis in anti‐PD‐1 resistant tumor model and could serve as a potential candidate for cancer immunotherapy.
Aromatic–aromatic interactions between natural aromatic amino acids Phe, Tyr, and Trp play crucial roles in protein–protein recognition and protein folding. However, the function of such interactions ...in the preparation of different dimensional, ordered protein superstructures has not been recognized. Herein, by a combination of the directionality of the symmetry axes of protein building blocks and the strength of the aromatic–aromatic interactions coming from a group of aromatic amino acid residues, we built an engineering strategy to construct protein superlattices. Based on this strategy, substitution of single amino acid residue Glu162 around the C 4 rotation axes near the outer surface of 24-mer ferritin nanocage with Phe, Tyr, and Trp, respectively, resulted in 2D and 3D protein superlattices where protein cages are aligned along the C 4 axes, imposing a fixed disposition of neighboring ferritins. The self-assembly of these superlattices is reversible, which can be tuned by external stimuli (salt concentration or pH). Moreover, these superlattices can serve as biotemplates for the fabrication of 2D and 3D inorganic nanoparticle arrays.
•Chitosan combined with clove oil showed in vitro synergistic antifungal activity against P. digitatum.•The combined treatment caused alterations in P. digitatum hyphal morphology and disruption of ...cell membranes.•The combined coating did show synergistic effects with artificial green mold on mandarins.•A combined coating improved the activities of PAL and chitinase at the later stage of incubation.
The antifungal activity of chitosan combined with clove oil against Penicillium digitatum, the causal agent of citrus green mold, was tested in vitro and in vivo. Chitosan combined with clove oil inhibited mycelial growth more than individual treatments, which was related to the greater release of cellular material and the largest alterations in hyphal morphology of P. digitatum. However, compared to chitosan alone, 1% chitosan coatings combined with various amounts of clove oil (0.5, 1 or 2mL/L) showed no greater ability in controlling decay development on artificially inoculated citrus fruit. 1% chitosan combined with 0.5mL/L clove oil appeared to slightly reduce lesion diameter and enhanced the activities of defense enzymes, including chitinase and phenylalanine ammonia-lyase at the later stages of incubation. This study indicated that the synergistic antifungal activity of chitosan-clove oil observed in in vitro studies was not found in in vivo tests. Therefore, the data suggest that a coating of 1% chitosan alone, not combined with clove oil, can effectively contribute to the control of green mold on citrus fruit.
Twisted bilayer systems with discrete magic angles, such as twisted bilayer graphene featuring moiré superlattices, provide a versatile platform for exploring novel physical properties. Here, we ...discover a class of superflat bands in general twisted bilayer systems beyond the low-energy physics of magic-angle twisted counterparts. By considering continuous lattice dislocation, we obtain intrinsic localized states, which are spectrally isolated at lowest and highest energies and spatially centered around the AA stacked region, governed by the macroscopic effective energy potential well. Such localized states exhibit negligible inter-cell coupling and support the formation of superflat bands in a wide and continuous parameter space, which can be mimicked using a twisted bilayer nanophotonic system. Our finding suggests that general twisted bilayer systems can realize continuously tunable superflat bands and the corresponding localized states for various photonic, phononic, and mechanical waves.
Supercapacitors (SCs) with high power density and long cycling span life are demanding energy storage devices that will be an attractive power solution to modern electronic and electrical ...applications. Numerous theoretical and experimental works have been devoted to exploring various possibilities to increase the functionality and the specific capacitance of electrodes for SCs. Non-carbon two-dimensional (2D) materials have been considered as encouraging electrode candidates for their chemical and physical advantages such as tunable surface chemistry, high electronic conductivity, large mechanical strength, more active sites, and dual non-faradaic and faradaic electrochemical performances. Besides, these 2D materials also play particular roles in constructing highway channels for fast ion diffusion. This concise review summarizes cutting-edge progress of some representative 2D non-carbon materials for the aqueous electrolyte-based SCs, including transition metal oxides (TMOs), transition metal hydroxides (TMHs), transition metal chalcogenides (TMCs), MXenes, metal-organic frameworks (MOFs) and some emerging materials. Different synthetic methods, effective structural designs and corresponding electrochemical performances are reviewed in detail. And we finally present a detailed discussion of the current intractable challenges and technical bottlenecks, and highlight future directions and opportunities for the development of next-generation high-performance energy storage devices.
This review summarizes some recent advances of 2D non-carbon transition metal oxides (TMOs), transition metal hydroxides (TMHs), transition metal chalcogenides (TMCs), MXenes and metal-organic frameworks (MOFs) as high-performance supercapacitor electrode materials. Display omitted
•Cooking methods affect the nutritional quality of red cabbage.•Fresh-cut red cabbage could retain the highest nutrition.•Steaming with less water and cooking time was recommended to use in Asian ...cuisine.
The aim of this work is to investigate the effects of domestic cooking methods, including steaming, microwave heating, boiling and stir-frying on the nutritional quality of red cabbage. Compared with fresh-cut red cabbage, all cooking methods were found to cause significant reduction in anthocyanin and total glucosinolates contents. Moreover, steaming resulted in significantly greater retention of vitamin C and DPPH radical-scavenging activity, while stir-frying and boiling, two popular Chinese cooking methods, led to significant losses of total phenolic, vitamin C, DPPH radical-scavenging activity, and total soluble sugar as well as reducing sugars. Normally, red cabbage consumed fresh in salads could maintain the highest nutrition. However, considering the habits of Asian cuisine, it is recommended to use less water and less cooking time, such as steaming based on our present results, so as to retain the optimum benefits of the health-promoting compounds.
Chemokine (CC motif) ligand 18 (CCL18) is involved in remodeling of the tumor microenvironment and plays critical roles in oncogenesis, invasiveness, and metastasis. We previously investigated the ...overexpression of CCL18 in primary oral squamous cell carcinoma (OSCC) tissues and its association with advanced clinical stage in OSCC patients. However, the underlying mechanisms of this CCL18‐derived activity remains unidentified. This study showed exogenous CCL18 increased cell migration and invasion and induced cell epithelial–mesenchymal transition (EMT), and that E‐cadherin, an epithelial marker, decreased and N‐cadherin, a mesenchymal marker, increased, compared to negative control in OSCC cells. Furthermore, we detected that CCL18 induced the acquisition of cancer stem(‐like) cell characteristics in oral cancer cells, but also found a significantly positive correlation between the expression of CCL18 and Bmi‐1 (P < 0.001) in OSCC surgical specimens by immunohistochemistry analysis. The expression of octamer‐binding transcription factor 4 and Bmi‐1 were significantly upregulated, and proportions of aldehyde dehydrogenasehigh+ cells and CD133+ cells were markedly increased in CCL18‐treated cells compared to untreated cells. Sphere formation ability was observably enhanced when cells were continually exposed to high levels of CCL18. Moreover, CCL18 upregulated Slug expression by stimulating the mammalian target of rapamycin (mTOR) signaling pathway in OSCC cell lines. Inhibition of the mTOR pathway by INK128, or Slug knockdown by RNA interference, reversed CCL18‐induced EMT and the stemness response at both molecular and functional levels. In conclusion, our data suggested that CCL18 upregulated Slug expression to promote EMT and stem cell‐like features by activating the mTOR pathway in oral cancer. These findings provide new potential targets for the early diagnosis and treatment of OSCC.
The study provided evidence that elevated CCL18 induced migration, invasion, epithelial‐mesenchymal transition (EMT), and the obtain of cancer stem‐cell like characteristics in OSCC cells. Moreover, we found that these CCL18‐derived responses were initiated by Slug overexpression via stimulating the mTOR signaling pathway in OSCC.
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