In this work, we demonstrate that porous MgACC microspheres could be prepared in liposome solution containing zwitterionic and anionic lipids. We find that the lipid molecules incorporated into MgACC ...could be as high as 10 mass%. Because hydrophobic drugs are lipophilic, the porous MgACC has been exploited as the carriers of hydrophobic drugs. Using lecithin as the source of lipids and N‐(rhodamine‐6G)lactam‐ethylenediamine (R6GNCCN) as the model of hydrophobic drugs, the optimal loading capacity was found to be ca. 1.4 mass%. The release of R6GNCCN to a phosphate buffer at pH 7.4 was over 90% within 5 hr. The drug release profile could be attenuated by encapsulating the MgACC core by a CaP shell.
Lipid vesicles are used to facilitate the incorporation of hydrophobic drugs into the porous microspheres of Mg‐stabilized amorphous calcium carbonate (MgACC). Upon the dissolution of MgACC in the solution, the release of the drug molecules is triggered.
Huntington’s disease (HD) belongs to protein misfolding disorders associated with polyglutamine (polyQ)-rich mutant huntingtin (mHtt) protein inclusions. Currently, it is indicated that the ...aggregation of polyQ-rich mHtt participates in neuronal toxicity and dysfunction. Here, we designed and synthesized a polyglutamine-specific gold nanoparticle (AuNP) complex, which specifically targeted mHtt and alleviated its toxicity. The polyglutamine-specific AuNPs were prepared by decorating the surface of AuNPs with an amphiphilic peptide (JLD1) consisting of both polyglutamine-binding sequences and negatively charged sequences. By applying the polyQ aggregation model system, we demonstrated that AuNPs–JLD1 dissociated the fibrillary aggregates from the polyQ peptide and reduced its β-sheet content in a concentration-dependent manner. By further integrating polyethyleneimine (PEI) onto AuNPs–JLD1, we generated a complex (AuNPs–JLD1–PEI). We showed that this complex could penetrate cells, bind to cytosolic mHtt proteins, dissociate mHtt inclusions, reduce mHtt oligomers, and ameliorate mHtt-induced toxicity. AuNPs–JLD1–PEI was also able to be transported to the brain and improved the functional deterioration in the HD Drosophila larva model. Our results revealed the feasibility of combining AuNPs, JLD1s, and cell-penetrating polymers against mHtt protein aggregation and oligomerization, which hinted on the early therapeutic strategies against HD.
TAR DNA-binding protein (TDP-43) was identified as the major ubiquitinated component deposited in the inclusion bodies in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration ...with ubiquitin-positive inclusions (FTLD-U) in 2006. Later on, numerous ALS-related mutations were found in either the glycine or glutamine/asparagine-rich region on the TDP-43 C-terminus, which hinted on the importance of mutations on the disease pathogenesis. However, how the structural conversion was influenced by the mutations and the biological significance of these peptides remains unclear. In this work, various peptides bearing pathogenic or de novo designed mutations were synthesized and displayed their ability to form twisted amyloid fibers, cause liposome leakage, and mediate cellular toxicity as confirmed by transmission electron microscopy (TEM), circular dichroism (CD), Thioflavin T (ThT) assay, Raman spectroscopy, calcein leakage assay, and cell viability assay. We have also shown that replacing glycines with prolines, known to obstruct β-sheet formation, at the different positions in these peptides may influence the amyloidogenesis process and neurotoxicity. In these cases, GGG308PPP mutant was not able to form beta-amyloid, cause liposome leakage, nor jeopardized cell survival, which hinted on the importance of the glycines (308-310) during amyloidogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The amyloidogenic core in the TAR DNA-binding protein (TDP-43) C-terminal fragment has been characterized with its chemical, biochemical, and structural properties delineated. Various properties of ...the core sequence, including membrane impairment ability and the seeding effect, have also been studied.
We report the incorporation of salicylaldehyde derivatives onto the hydrazine-tagged amyloidogenic peptides by forming photoisomerizable hydrazones. These hydrazones with positive photochromism are ...photostable under physiological conditions and enable photoswitching without the addition of external reductants or high-power irradiation. By applying superresolution microscopy, we were able to distinguish polymorphic nanoscopic structures of the hydrazone-incorporated peptides in vitro under different buffer conditions. Moreover, the additive-free condition in our platform allows the exploration of detailed amyloid aggregate morphologies in live cells.
The amyloidogenic core in the TAR DNA-binding protein (TDP-43) C-terminal fragment has been characterized with its chemical, biochemical, and structural properties delineated. Various properties of ...the core sequence, including membrane impairment ability and the seeding effect, have also been studied.
The amyloidogenic core peptide derived from the TDP-43 C-terminus can disrupt the liposome membrane and induce nascent TDP-43 aggregation.
Taiwanese Hokkien is declining in use and status due to a language shift towards Mandarin in Taiwan. This is partly why it is a low resource language in NLP and speech research today. To ensure that ...the state of the art in speech processing does not leave Taiwanese Hokkien behind, we contribute a 1.5-hour dataset of Taiwanese Hokkien to ML-SUPERB's hidden set. Evaluating ML-SUPERB's suite of self-supervised learning (SSL) speech representations on our dataset, we find that model size does not consistently determine performance. In fact, certain smaller models outperform larger ones. Furthermore, linguistic alignment between pretraining data and the target language plays a crucial role.
The integration of graphene and other two-dimensional (2D) materials with existing silicon semiconductor technology is highly desirable. This is due to the diverse advantages and potential ...applications brought about by the consequent miniaturization of the resulting electronic devices. Nevertheless, such devices that can operate at very high frequencies for high-speed applications are eminently preferred. In this work, we demonstrate a vertical graphene base hot-electron transistor that performs in the radio frequency regime. Our device exhibits a relatively high current density (∼200 A/cm2), high common base current gain (α* ∼ 99.2%), and moderate common emitter current gain (β* ∼ 2.7) at room temperature with an intrinsic current gain cutoff frequency of around 65 GHz. Furthermore, cutoff frequency can be tuned from 54 to 65 GHz by varying the collector-base bias. We anticipate that this proposed transistor design, built by the integrated 2D material and silicon semiconductor technology, can be a potential candidate to realize extra fast radio frequency tunneling hot-carrier electronics.
Two-dimensional (2D) materials have attracted huge attention due to their unique properties and potential applications. Since wafer scale synthesis of 2D materials is still in nascent stages, ...scientists cannot fully rely on traditional semiconductor techniques for related research. Delicate processes from locating the materials to electrode definition need to be well controlled. In this article, a universal fabrication protocol required in manufacturing nanoscale electronics, such as 2D quasi-heterojunction bipolar transistors (Q-HBT), and 2D back-gated transistors are demonstrated. This protocol includes the determination of material position, electron beam lithography (EBL), metal electrode definition, et al. A step by step narrative of the fabrication procedures for these devices are also presented. Furthermore, results show that each of the fabricated devices has achieved high performance with high repeatability. This work reveals a comprehensive description of process flow for preparing 2D nano-electronics, enables the research groups to access this information, and pave the way toward future electronics.
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