Size-Dependent Optical Properties of Aluminum Nanoparticles: From Classical to Quantum Description

The absorption spectra of a series of tetrahedral-shaped aluminum nanoparticles (ANPs) with side lengths ranging from <i>L</i> = 1.4 to 141.4 nm have been calculated. The size-dependent evolution of structures and spectra has been demonstrated. The plasmon resonance of ANPs is highly sensitive to the particle size and spans a wide spectral region from ultraviolet to visible. As <i>L</i> increases from 70 to 141 nm, an apparent spectral red shift is still observed, although their spectral line shapes do not change much. For the small clusters Al_<i>n</i> with <i>n</i> ≤ 560 (or with <i>L</i> ≤ 3.68 nm), their absorption spectra have been calculated by both the real-time time-dependent density functional theory (RT-TDDFT) scheme and the finite difference time domain (FDTD) classical electrodynamics method, whereas for the larger nanoparticles, their absorption spectra have only been calculated by the FDTD method. Al_<i>n</i> with <i>n</i> ≤ 560 has two main absorption bands attributed to two kinds of localized surface plasmon resonance modes, vertexes and edges, revealed by the corresponding induced electron densities. RT-TDDFT and FDTD approaches produce obvious spectral differences, and RT-TDDFT predicts more intensive low-energy absorption bands and broader high-energy bands than FDTD. The effect of geometrical relaxation on the absorption spectra of small clusters is visible, which tends to blue shift and broaden the spectra. The smaller the cluster, the larger is the geometrical change

π–π Stacking Mediated Chirality in Functional Supramolecular Filaments

While a great diversity of peptide-based supramolecular filaments have been reported, the impact of an auxiliary segment on the chiral assembly of peptides remains poorly understood. Herein we report on the formation of chiral filaments by the self-assembly of a peptide-drug conjugate containing an aromatic drug camptothecin (CPT) in a computational study. We find that the chirality of the filament is mediated by the π–π stacking between CPTs, not only by the well-expected intermolecular hydrogen bonding between peptide segments. Our simulations show that π–π stacking of CPTs governs the early stages of the self-assembly process, while a hydrogen bonding network starts at a relatively later stage to contribute to the eventual morphology of the filament. Our results also show the possible presence of water within the core of the CPT filament. These results provide very useful guiding principles for the rational design of supramolecular assemblies of peptide conjugates with aromatic segments

Design and Construction of Supramolecular Nanobeacons for Enzyme Detection

Molecular beacons are typically water-soluble molecules that can convert specific chemical reactions or binding events into measurable optical signals, providing a noninvasive means to help understand cellular and subcellular activities at the molecular level. However, the soluble form of the current molecular beacon design often leads to their poor stability and facile degradation by nonspecific enzymes, and as a result, this undesired activation could give rise to false signals and thus poses a limitation for accurate detection of enzymatic activities. Here we report a proof-of-concept design and synthesis of a new type of supramolecular nanobeacon that is resistant to nonspecific enzymatic degradation in the self-assembled state but can be effectively cleaved by the target enzyme in the monomeric form. Our results show that the nanobeacon with a GFLG peptide linker could serve as an indicator for the presence of a lysosomal enzyme, cathepsin B

Data_Sheet_2_Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis.docx

Background and aimsAlthough iron homeostasis has been associated with liver function in many observational studies, the causality in this relationship remains unclear. By using Mendelian Randomization analyses, we aimed to evaluate the genetic effects of increased systemic iron levels on the risk of liver injury and various liver diseases. Moreover, in light of the sex-dependent iron regulation in human beings, we further estimated the sex-specific effect of iron levels in liver diseases.MethodsIndependent single nucleotide polymorphisms associated with systemic iron status (including four indicators) at the genome-wide significance level from the Genetics of Iron Status (GIS) Consortium were selected as instrumental variables. Summary data for six liver function biomarkers and five liver diseases were obtained from the UK Biobank, the Estonian Biobank, the eMERGE network, and FinnGen consortium. Mendelian Randomization assessment of the effect of iron on liver function and liver diseases was conducted.ResultsGenetically predicted iron levels were positively and significantly associated with an increased risk of different dimensions of liver injury. Furthermore, increased iron status posed hazardous effects on non-alcoholic fatty liver disease, alcoholic liver disease, and liver fibrosis/cirrhosis. Sex-stratified analyses indicated that the hepatoxic role of iron might exist in NAFLD and liver fibrosis/cirrhosis development among men. No significantly causal relationship was found between iron status and viral hepatitis.ConclusionOur study adds to current knowledge on the genetic role of iron in the risk of liver injury and related liver diseases, which provides clinical and public health implications for liver disease prevention as iron status can be modified.</p

Enhanced Cellular Entry and Efficacy of Tat Conjugates by Rational Design of the Auxiliary Segment

Conjugation with a cell penetrating peptide such as Tat presents an effective approach to improve the intracellular accumulation of molecules with low membrane permeability. This strategy, however, leads to a reduced cellular entry of molecules that can cross cell membrane effectively. We report here that covalent linkage of an additional hydrophobic unit that mimics a hydrophobic domain near the Tat sequence can further improve the cellular uptake of the parental conjugate into cancer cells regardless of the membrane permeability of the unconjugated molecule. Both fluorescent imaging and flow cytometry measurements confirmed the effect of palmitoylation on the increased internalization of the Tat conjugates with either 5-carboxyfluorescein (5-FAM), a nonmembrane penetrating dye, or doxorubicin, an anticancer cancer drug that can readily diffuse across cell membranes. In the case of the Tat–doxorubicin conjugate, palmitoylation improves the conjugate’s anticancer activity in both drug sensitive and resistant cervical cancer cell lines. We further demonstrate that modification of a Tat–5-FAM conjugate with a hydrophobic quencher could not only efficiently quench the fluorescence outside of cancer cell but also facilitate its entry into MCF-7 breast cancer cells. These results highlight the importance of rational molecular design of using peptide conjugation chemistry in cancer therapeutics and diagnostics

Data_Sheet_1_Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis.XLSX

Background and aimsAlthough iron homeostasis has been associated with liver function in many observational studies, the causality in this relationship remains unclear. By using Mendelian Randomization analyses, we aimed to evaluate the genetic effects of increased systemic iron levels on the risk of liver injury and various liver diseases. Moreover, in light of the sex-dependent iron regulation in human beings, we further estimated the sex-specific effect of iron levels in liver diseases.MethodsIndependent single nucleotide polymorphisms associated with systemic iron status (including four indicators) at the genome-wide significance level from the Genetics of Iron Status (GIS) Consortium were selected as instrumental variables. Summary data for six liver function biomarkers and five liver diseases were obtained from the UK Biobank, the Estonian Biobank, the eMERGE network, and FinnGen consortium. Mendelian Randomization assessment of the effect of iron on liver function and liver diseases was conducted.ResultsGenetically predicted iron levels were positively and significantly associated with an increased risk of different dimensions of liver injury. Furthermore, increased iron status posed hazardous effects on non-alcoholic fatty liver disease, alcoholic liver disease, and liver fibrosis/cirrhosis. Sex-stratified analyses indicated that the hepatoxic role of iron might exist in NAFLD and liver fibrosis/cirrhosis development among men. No significantly causal relationship was found between iron status and viral hepatitis.ConclusionOur study adds to current knowledge on the genetic role of iron in the risk of liver injury and related liver diseases, which provides clinical and public health implications for liver disease prevention as iron status can be modified.</p

Regression analysis.

<p>Regression analysis.</p

Cellular Uptake and Cytotoxicity of Drug–Peptide Conjugates Regulated by Conjugation Site

Conjugation of anticancer drugs to hydrophilic peptides such as Tat is a widely adopted strategy to improve the drug’s solubility, cellular uptake, and potency against cancerous cells. Here we report that attachment of an anticancer drug doxorubicin to the <i>N</i>- or <i>C</i>-terminal of the Tat peptide can have a significant impact on their cellular uptake and cytotoxicity against both drug-sensitive and drug-resistant cancer cells. We observed higher cellular uptake by both cell lines for <i>C</i>-terminal conjugate relative to the <i>N</i>-terminal analogue. Our results reveal that the <i>C</i>-terminal conjugate partially overcame the multidrug resistance of cervical cancer cells, while the <i>N</i>-terminal conjugate showed no significant improvement in cytotoxicity when compared with free doxorubicin. We also found that both <i>N</i>- and <i>C</i>-conjugates offer a mechanism to circumvent drug efflux associated with multidrug resistance

Hollow Polymeric Capsules from POSS-Based Block Copolymer for Photodynamic Therapy

A novel amphiphilic diblock copolymer, PHEMAPOSS-<i>b</i>-P­(DMAEMA-<i>co</i>-CMA), was prepared via reversible addition–fragmentation chain transfer (RAFT) polymerization, where PHEMAPOSS block was first synthesized using a methacrylate monomer based on polyhedral oligomeric silsesquioxane (HEMAPOSS), and PHEMAPOSS was further utilized to prepare the block copolymer via RAFT copolymerization of 2-(dimethyl­amino)­ethyl methacrylate (DMAEMA) and reduction-cleavable coumarin methacrylate (CMA) monomer. PHEMAPOSS-<i>b</i>-P­(DMAEMA-<i>co</i>-CMA) could self-assemble in water to form spherical micelles with POSS core and stimuli-responsive shell. The micelles were cross-linked by photodimerization of coumarin, and then hollow polymeric capsules could be finally obtained via etching the POSS core in the solution of hydrofluoric acid (HF). The morphologies of the micelles and hollow polymeric capsules were well characterized by TEM, SEM, and DLS. The hollow polymeric capsules are responsive to typical physiological stimuli such as pH, and redox potential, and could be further utilized in the encapsulation and release of tetraphenyl­porphyrin tetrasulfonic acid hydrate (TPPS) for photodynamic therapy (PDT). The <i>in vitro</i> release of TPPS-loaded polymeric capsules allowed a relatively low TPPS release at pH = 7.4. However, a burst release of TPPS was observed in the presence of 10 mM glutathione (GSH) at pH = 5.5. Confocal laser scanning microscopy (CLSM) confirmed that TPPS-loaded polymeric capsules could well improve the internalization rate in MCF-7 cells. According to the result of MTT assay, TPPS-loaded polymeric capsules demonstrated efficient PDT efficacy and low dark toxicity toward MCF-7 cells. Thus, TPPS-loaded polymeric capsules have presented potential application in PDT

Correlation analysis between CSE and job burnout (r).

<p>Correlation analysis between CSE and job burnout (r).</p