31 research outputs found
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<sub><i>n</i></sub> 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<sub><i>n</i></sub> 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
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>-PÂ(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-(dimethylÂamino)Âethyl
methacrylate (DMAEMA) and reduction-cleavable coumarin methacrylate
(CMA) monomer. PHEMAPOSS-<i>b</i>-PÂ(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 tetraphenylÂporphyrin 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