Macrochirality of Self-Assembled and Co-assembled Supramolecular Structures of a Pair of Enantiomeric Peptides

Although macrochirality of peptides’ supramolecular structures has been found to play important roles in biological activities, how macrochirality is determined by the molecular chirality of the constituted amino acids is still unclear. Here, two chiral peptides, Ac-LKLHLHLQLKLLLVLFLFLALK-NH2 (KK-11) and Ac-DKDHDHDQDKDL DVDFDFDADK-NH2 (KKd-11), which were composed entirely of either L- or D-amino acids, were designed for studying the chiral characteristics of the supramolecular microstructures. It was found that monocomponent KK-11 or KKd-11 self-assembled into right- or left-handed helical nanofibrils, respectively. However, when they co-assembled with concentration ratios varied from 1:9 to 9:1, achiral nanowire-like structures were formed. Both circular dichroism and Fourier transform infrared spectra indicated that the secondary structures changed when the peptides co-assembled. MD simulations indicated that KK-11 or KKd-11 exhibited a strong propensity to self-assemble into right-handed or left-handed nanofibrils, respectively. However, when KK-11 and KKd-11 were both presented in a solution, they had a higher probability to co-assemble instead of self-sort. MD simulations indicated that, in their mixtures, they formed nanowires without handedness feature, a good agreement with experimental observation. Our results shed light on the molecular mechanisms of the macrochirality of peptide supramolecular microstructures

Zinc finger and SCAN domain containing 1, ZSCAN1, is a novel stemness-related tumor suppressor and transcriptional repressor in breast cancer targeting TAZ

IntroductionCancer stem cells (CSCs) targeted therapy holds the potential for improving cancer management; identification of stemness-related genes in CSCs is necessary for its development.MethodsThe Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets were used for survival analysis. ZSCAN1 correlated genes was identified by Spearman correlation analysis. Breast cancer stem-like cells (BCSLCs) were isolated by sorting CD44+CD24- cells from suspension cultured breast cancer (BC) spheroids. The sphere-forming capacity and sphere- and tumor-initiating capacities were determined by sphere formation and limiting dilution assays. The relative gene expression was determined by qRT-PCR, western blot. Lentivirus system was used for gene manipulation. Nuclear run-on assay was employed to examine the levels of nascent mRNAs. DNA pull-down and Chromatin immunoprecipitation (ChIP) assays were used for determining the interaction between protein and target DNA fragments. Luciferase reporter assay was used for evaluating the activity of the promoter.Results and discussionZSCAN1 is aberrantly suppressed in BC, and this suppression indicates a bad prognosis. Ectopic expression of ZSCAN1 inhibited the proliferation, clonogenicity, and tumorigenicity of BC cells. ZSCAN1-overexpressing BCSLCs exhibited weakened stemness properties. Normal human mammary epithelial (HMLE) cells with ZSCAN1 depletion exhibited enhanced stemness properties. Mechanistic studies showed that ZSCAN1 directly binds to -951 ~ -925bp region of WWTR1 (encodes TAZ) promoter, inhibits WWTR1 transcription, thereby inhibiting the stemness of BCSCs. Our work thus revealed ZSCAN1 as a novel stemness-related tumor suppressor and transcriptional repressor in BC

Effects of different altitudes on the structure and properties of potato starch

The main element influencing the quality of potato starch is the environment. To investigate the effects of different altitude cultivation locations on the molecular structure and physicochemical properties of starch, two potato varieties, Jiusen No.1 B1 and Qingshu No.9 B2, were planted in three different altitude zones: A1 at low altitude (Chongzhou 450 m), A2 at middle altitude (Xichang 2800 m), and A3 at high altitude (Litang 3650 m). The results showed that the average volume, number, surface area diameter, average branched polymerization degree, crystallinity, and gelatinization temperature of two potato granules in high altitude areas were significantly lower than those in middle and low altitude areas were, and the gelatinization performance of potato starch was affected according to the correlation of starch structure characteristics. Potato starch with more short-branched chains and less long branched chains resulted in a lower gelatinization temperature in high altitude areas. The results showed that Jiusen No. 1 and Qingshu No. 9 were mainly affected by accumulated radiation and accumulated rainfall in Litang, a high altitude area, and by effective accumulated temperature in Xichang, a middle altitude area. This study quantified the influence of meteorological factors on the main starch quality of potato tubers. The results can be used as a theoretical basis for the scientific planting of high-quality potatoes

Impact of Government Environmental Regulations on Remanufacturing Supply Chain with Multi-Subject Responsibility for Recycling and Disposal

With the emergence of a large number of waste electronic products and the enhancement of social awareness of environmental protection, the recycling of waste electronic products has become one of the pressing issues of social concern. Government environmental regulation is an important policy to promote the development of the remanufacturing industry. In this paper, we study the government levies recycling and disposal fees on original products for environmental governance and establish two game models based on the perspective of maximizing social welfare with no government regulation and a tripartite liability system. The optimal decisions on wholesale, retail prices and quantity of original and remanufactured products, as well as the recycling and disposal fee are analyzed under both models. Based on the numerical results, the impact of the main parameter (such as the responsibility sharing ratio) on the decisions and profits of the parties is discussed. The results show that (1) the wholesale and retail prices of remanufactured products are not affected by government regulation; (2) the tripartite liability system can increase the output of remanufactured products and reduce the output of original products while cutting the profits of remanufacturing supply chain members, and increasing social welfare; (3) government’s optimal recycling and disposal fee is not related to the sharing ratio. The study can provide practitioners with suggestions for ways to develop environmental regulation

The incorporation of cationic property and immunopotentiator in poly (lactic acid) microparticles promoted the immune response against chronic hepatitis B

Biodegradable microparticles (MPs) as vaccine adjuvants have sparked the passion of researchers in recent decades. However, it is still a huge challenge to develop an efficient vaccine delivery system to reverse chronic hepatitis B (CHB). Herein, we integrated a physiochemical merit and an immunopotentiator property in poly (lactic acid) (PLA) MPs and verified the therapeutic effect on CHB model mice. We prepared uniform MPs with insertion of cationic lipid didodecyldimethylammonium bromide (DDAB), which endowed a physiochemical merit for MPs. Such a DDAB-PLA (DP) group raised the recruitment of immune cells to the injection site along with the secretion of chemokines and pro-inflammatory cytokines, promoting the activation of antigen-presenting cells (APCs). Further combination of stimulator of interferon genes (STING) agonist 5,6-dimethylxanthenone-4-acetic acid (DMXAA) (DP-D) elevated 5.8-fold higher interferon regulatory factor 7 (IRF-7) expression compared to that for DP group. The DP group showed preferred lysosome escape advantage, which was in line with the DMXAA release behavior and the intracellular target of DMXAA. In addition, DP-D vaccine augmented the IFN-gamma secreting splenocytes and motivated Th1-biased antibodies in a more efficient way than that for the DP group. In the CHB model, the MPs based vaccines achieved 50% HBsAg seroconversion rate, and HBcAg in the liver also got a reduction. DP-D produced higher amount of memory T/B cells to confer protection in a sustained manner. Present work thus provided a promising strategy, via integrating a fine-tuned physiochemical property and an immunopotentiator virtue in the MPs, which synergistically reinforced both humoral and cellular immune responses against CHB

New Practice of E-Commerce Platform: Evidence from Two Trade-In Programs

In the context of developing the digital platform economy, trade-in programs have become an effective strategy for e-commerce platforms to stimulate consumption. Many head e-commerce platforms have launched their own trade-in programs. However, the existing research on trade-in programs is still stuck in the traditional trade-in model. The purpose of this study is to explore whether there is a new and more beneficial trade-in program. In this paper, we construct the Stackelberg game model between a brand owner and a B2C e-commerce platform under two trade-in programs and use optimization theory to obtain the equilibrium results of the model. The results indicate that the performance improvement of the new-generation product will promote the increase in two-generation products’ price under traditional trade-in programs, the price of the new-generation product will increase, and the price of the previous-generation product will decrease under new trade-in programs. The brand owner always prefers traditional trade-in to new trade-in. However, the e-commerce platform prefers traditional trade-in to new trade-in just when the previous-generation product is durable enough and the performance improvement of a new-generation product is small enough; otherwise, it prefers new trade-in to traditional trade-in. These findings are beneficial to the operational practices of e-commerce platforms and brand owners

New Practice of E-Commerce Platform: Evidence from Two Trade-In Programs

In the context of developing the digital platform economy, trade-in programs have become an effective strategy for e-commerce platforms to stimulate consumption. Many head e-commerce platforms have launched their own trade-in programs. However, the existing research on trade-in programs is still stuck in the traditional trade-in model. The purpose of this study is to explore whether there is a new and more beneficial trade-in program. In this paper, we construct the Stackelberg game model between a brand owner and a B2C e-commerce platform under two trade-in programs and use optimization theory to obtain the equilibrium results of the model. The results indicate that the performance improvement of the new-generation product will promote the increase in two-generation products’ price under traditional trade-in programs, the price of the new-generation product will increase, and the price of the previous-generation product will decrease under new trade-in programs. The brand owner always prefers traditional trade-in to new trade-in. However, the e-commerce platform prefers traditional trade-in to new trade-in just when the previous-generation product is durable enough and the performance improvement of a new-generation product is small enough; otherwise, it prefers new trade-in to traditional trade-in. These findings are beneficial to the operational practices of e-commerce platforms and brand owners

Development of a molecular feature-based survival prediction model of ovarian cancer using the deep neural network

202304 bcwwVersion of RecordSelf-fundedEarly releaseCC, In Press, Corrected Proof, need replace Vo