Effect of N-o-nitrobenzylation on conformation and membrane permeability of linear peptides.

In this study, we explored the potential of the photoremovable o-nitrobenzyl (oNB) group as a tool to manipulate the membrane permeability and regulate the conformation of linear peptides by means of experimental and computational studies. We found that the introduction of one or more oNB groups markedly increased the permeability and altered the conformation, as compared to the corresponding unmodified peptides. We thoroughly investigated the impact of peptide length, number of oNB group, oNB insertion position, and introduction of N- and C-terminal protecting groups on the passive membrane permeability by means of parallel artificial membrane permeability assay (PAMPA). Photoreaction of peptides containing one or two oNB groups proceeded cleanly in moderate to high yields, releasing the unprotected parent linear peptide. The oNB-modified peptides showed a cis/trans conformational equilibrium, while after photolysis, the unprotected linear peptides showed only the trans-amide conformation. Furthermore, a comprehensive comparison of oNB-modified peptides and N-methylated peptides was conducted, encompassing conformational analysis and physicochemical properties. N-Substituted peptides favored a folded-like structure, which may contribute to the improvement in permeability.

Antitumor activity of galaxamide involved in cell apoptosis and stemness by inhibiting Wnt/ß-catenin pathway in cervical cancer.

Our previous work reported that galaxamide, a cyclopeptide extracted from the seaweed Galaxaura filamentosa, showed antiproliferative activity against HeLa cells by MTT assay. In this study, the growth-inhibitory effects of galaxamide in HeLa cells and xenograft mouse models were investigated. It was found galaxamide significantly inhibited cell growth, colony formation, migration, and invasion and induced cell apoptosis by inhibiting the Wnt signaling pathway in HeLa cells. RNA sequencing revealed that galaxamide regulated stemness by Wnt6 signaling pathway in HeLa cells. By analyzing The Cancer Genome Atlas database, Wnt6 was found to be negatively/positively correlated with stemness- and apoptosis-related genes in human cervical cancer. Cancer stem-like cells (CSCs) isolated and enriched from HeLa cells demonstrated elevated Wnt6 and ß-catenin genes compared with nonstem HeLa cells. After galaxamide treatment, CSCs showed abrogation of sphere-forming ability, along with inhibition of stemness-related and Wnt pathway genes. Galaxamide treatment was also accompanied by the induction of apoptosis in HeLa cells, which was consistent with the results in BALB/c nude mice. Our results provide evidence that suppression of stemness by downregulating the Wnt signaling pathway is the molecular mechanism by which galaxamide effectively inhibits cell growth and induces apoptosis in cervical cancer cells.

Active droplet driven by a collective motion of enclosed microswimmers.

Active fluids containing self-propelled particles are relevant for applications such as self-mixing, micropumping, and targeted drug delivery. With a confined boundary, active fluids can generate bulk flow inside the system, which has the potential to create self-propelled active matter. In this study, we propose that an active droplet is driven by a collective motion of enclosed microswimmers. We show that the droplet migrates via the flow field generated by the enclosed microswimmers; moreover, the locomotion direction depends on the swimming mode of these internal particles. The locomotion mechanism of the droplet can be well explained by interfacial velocity, and the locomotion velocity shows good agreement with the Lighthill-Blake theory. These findings are essential to understand the interplay between the motion of self-propelled particles and the bulk motion response of active matter.

A comprehensive evaluation of single nucleotide polymorphisms associated with hepatocellular carcinoma risk in Asian populations: A systematic review and network meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been inconsistently associated with hepatocellular carcinoma (HCC) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with HCC in the Asian population. METHODS: Databases were searched to identify association studies of SNPs and HCC in Asians published through January 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on 41 studies (13,167 patients with HCC and 15,886 noncancer controls). Network meta-analysis and Thakkinstian's algorithm were used to select the most appropriate genetic model, along with false positive report probability (FPRP) for noteworthy associations. RESULTS: Eleven SNPs meeting the inclusion criteria were tested for association with HCC, including CCND1 rs9344, PTGS2 rs689466, IL18 rs187238 and rs1946518, KIF1B rs17401966, MDM2 rs2279744, MIR146A rs2910164, MIR149 rs2292832, MIR196A2 rs11614913, MIR499A rs3746444, and TGFB1 rs1800469. A significant increase for HCC risk was observed for MDM2 rs2279744, and the dominant (pooled OR = 1.59, 95% CI: 1.26-2.00) and codominant (pooled OR = 1.37, 95% CI: 1.18-1.60) models were determined to be the most appropriate models. MIR499A rs3746444 also showed a significant association with HCC risk under the allele contrast model (pooled OR = 1.36, 95% CI: 1.05-1.77). Only the significance of MDM2 rs2279744 was noteworthy (FPRP < 0.2). CONCLUSIONS: MDM2 rs2279744 is associated with HCC susceptibility in Asians, and the dominant and codominant models are likely the most appropriate models to estimate HCC risk.

Bandgap engineering of PbTe ultra-thin layers by surface passivations.

We calculate the electronic structures of the PbTe (1 1 1) ultra-thin films by performing the first-principles calculations. The PbTe (1 1 1) ultra-thin films possess direct or indirect band gaps depending sensitively on surface passivations with hydrogen or halogen atoms, and the band gaps depend sensitively on the passivation elements. The bandgaps of PbTe (1 1 1) ultra-thin films with hydrogen passivations can be tuned from 15 meV to 65 meV by applying external strains, making PbTe ultra-thin films promising candidates for optoelectronic device applications in terahertz regime.

Synthesis of P-Doped and NiCo-Hybridized Graphene-Based Fibers for Flexible Asymmetrical Solid-State Micro-Energy Storage Device.

Fiber supercapacitors (FSCs) are promising energy storage devices in portable and wearable smart electronics. Currently, a major challenge for FSCs is simultaneously achieving high volumetric energy and power densities. Herein, the microscale fiber electrode is designed by using carbon fibers as substrates and capillary channels as microreactors to space-confined hydrothermal assembling. As P-doped graphene oxide/carbon fiber (PGO/CF) and NiCo2 O4 -based graphene oxide/carbon fiber (NCGO/CF) electrodes are successfully prepared, their unique hybrid structures exhibit a satisfactory electrochemical performance. An all-solid-state PGO/CF//NCGO/CF flexible asymmetric fiber supercapacitor (AFSC) based on the PGO/CF as the negative electrode, NCGO/CF hybrid electrode as the positive electrode, and poly(vinyl alcohol)/potassium hydroxide as the electrolyte is successfully assembled. The AFSC device delivers a higher volumetric energy density of 36.77 mW h cm-3 at a power density of 142.5 mW cm-3 . In addition, a double reference electrode system is adopted to analyze and reduce the IR drop, as well as effectively matching negative and positive electrodes, which is conducive for the optimization and improvement of energy density. For the AFSC device, its better flexibility and electrochemical properties create a promising potential for high-performance micro-supercapacitors. Furthermore, the introduction of the double reference electrode system provides an interesting method for the study on the electrochemical performances of two-electrode systems.