Modulation of intramolecular freedom for tuning fluorescence imaging and photooxidation of amyloid-β aggregates.

Alzheimer's disease (AD) is distinguished by amyloid-β (Aβ) deposition and plaque formation, prompting significant interest in fluorescence imaging and photooxidation of Aβ aggregates for diagnostic and intervention purposes. However, the molecular engineering required to modulate fluorescence imaging and photooxidation of Aβ presents notable challenges. Here, we present the design of four small molecules (BTD-SZ, BTD-YD, BTD-TA-SZ, and BTD-TA-YD) aimed at investigating the influence of intramolecular freedom of movement on imaging and photooxidation.

3D Laser Writing of Low-Loss Cross-Section-Variable Type-I Optical Waveguide Passive/Active Integrated Devices in Single Crystals.

Optical waveguides fabricated in single crystals offer crucial passive/active optical components for photonic integrated circuits. Single crystals possess inherent advantages over their amorphous counterpart, such as lower optical losses in visible-to-mid-infrared band, larger peak emission cross-section, higher doping concentration. However, the writing of Type-I positive refractive index modified waveguides in single crystals using femtosecond laser technology presents significant challenges.

Inhaled delivery of cetuximab-conjugated immunoliposomes loaded with afatinib: A promising strategy for enhanced non-small cell lung cancer treatment.

Afatinib (AT), an FDA-approved aniline-quinazoline derivative, is a first-line treatment for metastatic non-small cell lung cancer (NSCLC). Combining it with cetuximab (CX), a chimeric human-murine derivative immunoglobulin-G1 monoclonal antibody (mAb) targeting the extracellular domain of epidermal growth factor receptor (EGFR), has shown significant improvements in median progression-free survival. Previously, we developed cetuximab-conjugated immunoliposomes loaded with afatinib (AT-MLP) and demonstrated their efficacy against NSCLC cells (A549 and H1975).

Localized Temperature Engineering Enables Writing of Heterostructures in Glass for Polarized Photoluminescence of Perovskites.

Metal halide perovskite (MHP) structures that exhibit polarized photoluminescence (PL) have attracted significant interest in fabricating light field regulation elements for display, imaging, and information storage applications. We report a three-dimensional direct lithography of heterostructures for controllable polarized PL inside glass by laser-induced localized temperature engineering. The heterostructures consisted of oriented periodic structures (OPSs) and MHP nanocrystals, and the mechanism for hierarchical distribution of heterostructures was illustrated.

Toward a10 dB net-gain waveguide amplifier in an Er-Yb co-doped phosphate glass.

High-gain materials and high-quality structures are the two main conditions that determine the amplification performance of optical waveguides. However, it has been hard to balance each other, to date. In this work, we demonstrate breakthroughs in both glass optical gain and optical waveguide structures.

Rofecoxib derivatives as NIR fluorescent probes for mitochondrial viscosity and in vivo imaging of Aβ plaques.

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder for which the underlying causes remain largely unknown. Therefore, the development of imaging agents capable of detecting biomarkers associated with this disease is crucial. Dual-functional probes are particularly important as they can track two biomarkers at the same time and examine their interaction.

Development of cyclopeptide inhibitors of cGAS targeting protein-DNA interaction and phase separation.

Cyclic GMP-AMP synthase (cGAS) is an essential sensor of aberrant cytosolic DNA for initiating innate immunity upon invading pathogens and cellular stress, which is considered as a potential drug target for autoimmune and autoinflammatory diseases. Here, we report the discovery of a class of cyclopeptide inhibitors of cGAS identified by an in vitro screening assay from a focused library of cyclic peptides. These cyclopeptides specifically bind to the DNA binding site of cGAS and block the binding of dsDNA with cGAS, subsequently inhibit dsDNA-induced liquid phase condensation and activation of cGAS.

Development and evolution of human glutaminyl cyclase inhibitors (QCIs): an alternative promising approach for disease-modifying treatment of Alzheimer's disease.

Human glutaminyl cyclase (hQC) is drawing considerable attention and emerging as a potential druggable target for Alzheimer's disease (AD) due to its close involvement in the pathology of AD via the post-translational pyroglutamate modification of amyloid-β. A recent phase 2a study has shown promising early evidence of efficacy for AD with a competitive benzimidazole-based QC inhibitor, PQ912, which also demonstrated favorable safety profiles. This finding has sparked new hope for the treatment of AD.

Triptorelin nanoparticle-loaded microneedles for use in assisted reproductive technology.

Triptorelin is a first-line drug for assisted reproductive technology (ART), but the low bioavailability and frequent subcutaneous injection of triptorelin impair the quality of life of women preparing to become pregnant. We report silk fibroin (SF)-based microneedles (MNs) for transdermal delivery of triptorelin-loaded nanoparticles (NPs) to improve bioavailability and achieve safe and efficacious self-administration of triptorelin. Triptorelin was mixed into an aqueous solution of SF with shear force to prepare NPs to control the release and avoid the degradation of triptorelin by enzymes in the skin.

A rapid-crosslinking antimicrobial hydrogel with enhanced antibacterial capabilities for improving wound healing.

One of the main reasons impeding wound healing is wound infection caused by bacterial colonization with a continuous stage of inflammation. Traditional wound treatments like gauze are being replaced by tissue adhesives with strong wet tissue adhesion and biocompatibility. Herein, a fast-crosslinking hydrogel is developed to achieve both strong antimicrobial properties and excellent biocompatibility.

Nanoparticle drug delivery systems for synergistic delivery of tumor therapy.

Nanoparticle drug delivery systems have proved anti-tumor effects; however, they are not widely used in tumor therapy due to insufficient ability to target specific sites, multidrug resistance to anti-tumor drugs, and the high toxicity of the drugs. With the development of RNAi technology, nucleic acids have been delivered to target sites to replace or correct defective genes or knock down specific genes. Also, synergistic therapeutic effects can be achieved for combined drug delivery, which is more effective for overcoming multidrug resistance of cancer cells.

High-order mode waveguide amplifier with high mode extinction ratio written in an Er-doped phosphate glass.

Inscription of fiber-compatible active waveguides in high-gain glass, followed by direct interconnection with few-mode fibers, is one of the most promising solutions for all-optical mode-division multiplexing. In this work, based on the femtosecond laser writing technique, we propose a general fabrication scheme for inscribing high-order mode waveguides in glass, by carefully tailoring the cross-section of the waveguides to match the mode intensity distribution via an improved multi-scan approach. Specifically, we design and fabricate two kinds of waveguides, namely, LP-mode waveguide and LP-mode waveguide in a highly Er-doped phosphate glass, enabling the insertion loss of the waveguides to be as low as 1.

Hyaluronic acid-modified redox-sensitive hybrid nanocomplex loading with siRNA for non-small-cell lung carcinoma therapy.

A novel hyaluronic acid (HA)-modified hybrid nanocomplex HA-SeSe-COOH/siR-93C@PAMAM, which could efficiently deliver siRNA into tumor cells via a redox-mediated intracellular disassembly, was constructed for enhanced antitumor efficacy. Thereinto, siR-93C (siRNA) and positive PAMAM were firstly mixed into the electrostatic nano-intermediate, and then diselenide bond (-SeSe-)-modified HA was coved to shield excessive positive charges. This hybrid nanocomplex displayed uniform dynamic sizes, high stability, controlled zeta potential and narrow PDI distribution.

Charge reversal nano-systems for tumor therapy.

Surface charge of biological and medical nanocarriers has been demonstrated to play an important role in cellular uptake. Owing to the unique physicochemical properties, charge-reversal delivery strategy has rapidly developed as a promising approach for drug delivery application, especially for cancer treatment. Charge-reversal nanocarriers are neutral/negatively charged at physiological conditions while could be triggered to positively charged by specific stimuli (i.

Silk fibroin double-layer microneedles for the encapsulation and controlled release of triptorelin.

A double-layer silk fibroin microneedles (SF-MNs) was proposed for the transdermal delivery of triptorelin. Two-step pouring and centrifugation were employed to prepare SF-MNs. Triptorelin was wrapped in MNs in the form of microcrystals with a size of ∼1 μm.

Knowledge-Based Reasoning Network for Relation Detection.

With the rapid growth of large-scale knowledge bases (KBs), knowledge base question answering (KBQA) has attracted increasing attention recently. Relation detection plays an important role in the KBQA system, which finds a compatible answer by analyzing the semantics of questions and querying and reasoning with multiple KB triples. Significant progress has been made by deep neural networks.

Styrene-Acrylic Emulsion with "Transition Layer" for Damping Coating: Synthesis and Characterization.

In order to study the dynamic mechanical properties of styrene-acrylic latex with a core/shell structure, a variety of latexes were synthesized by semi-continuous seeded emulsion polymerization based on "particle design" with the same material. The latexes were characterized by rotary viscosimeter, dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), transmission electron microscope (TEM), dynamic mechanical analysis (DMA), and universal testing machine. The effects of difference at the glass transition temperature () of core and shell and the introduction of the "transition layer" on the damping and mechanical properties of latex film were studied.

Design and Discovery of Natural Cyclopeptide Skeleton Based Programmed Death Ligand 1 Inhibitor as Immune Modulator for Cancer Therapy.

Blockade of immune checkpoint PD-1/PD-L1 facilitates the rescue of immune escapes of tumor cells. Though various monoclonal antibodies have been approved for clinical therapy, the development of small molecular inhibitors lags behind antibodies partially owing to the challenges of protein-protein interaction (PPI) blocker design. In this work, we adopted the skeleton of natural cyclopeptidic antibiotics gramicidin S as the start point for PD-1/PD-L1 inhibitor exploring and discovered a series of novel cyclopeptides that could interfere with the PPI of PD-1/PD-L1 based on several rounds of structural design and optimization.

Raloxifene alleviates amyloid-β-induced cytotoxicity in HT22 neuronal cells via inhibiting oligomeric and fibrillar species formation.

Raloxifene, a selective estrogen receptor modulator, displays benefits for Alzheimer's disease (AD) prevention in postmenopausal women as hormonal changes during menopause have the potential to influence AD pathogenesis, but the underlying mechanism of its neuroprotection is not entirely clear. In this study, the effects of raloxifene on amyloid-β (Aβ) amyloidogenesis were evaluated. The results demonstrated that raloxifene inhibits Aβ aggregation and destabilizes preformed Aβ fibrils through directly interacting with the N-terminus and middle domains of Aβ peptides.

Manipulating Polymer Donors Toward a High-Performance Polymer Acceptor Based On a Fused Perylenediimide Building Block With a Built-In Twisting Configuration.

A novel fused perylene diimide (PDI)-based polymer electron acceptor (PFPDI-BDF) with a built-in twisting configuration was constructed for application in all-polymer solar cells (all-PSCs). To shed light on the compatibility of the FPDI polymer acceptor and to identify a suitable polymer donor for device applications, we considered herein to investigate three polymer donors (PBDB-T, PTB7-Th, and PCPDTFBT) with different optical and electronic properties as well as polymer chain packing behavior for comparing the device performance. After being fabricated with PFPDI-BDF, polymer donor PBDB-T with a wide band gap showed a decent power conversion efficiency (PCE) of 4.

EAPB: entropy-aware path-based metric for ontology quality.

Background: Entropy has become increasingly popular in computer science and information theory because it can be used to measure the predictability and redundancy of knowledge bases, especially ontologies. However, current entropy applications that evaluate ontologies consider only single-point connectivity rather than path connectivity, and they assign equal weights to each entity and path.

Results: We propose an Entropy-Aware Path-Based (EAPB) metric for ontology quality by considering the path information between different vertices and textual information included in the path to calculate the connectivity path of the whole network and dynamic weights between different nodes.

An ontology-driven clinical decision support system (IDDAP) for infectious disease diagnosis and antibiotic prescription.

Background: The available antibiotic decision-making systems were developed from a physician's perspective. However, because infectious diseases are common, many patients desire access to knowledge via a search engine. Although the use of antibiotics should, in principle, be subject to a doctor's advice, many patients take them without authorization, and some people cannot easily or rapidly consult a doctor.

Dissociation of haemolytic and oligomer-preventing activities of gramicidin S derivatives targeting the amyloid-β N-terminus.

The intrinsic haemolysis of an amyloid-β (Aβ) N-terminal targeting gramicidin S derivative was successfully dissociated from its Aβ oligomer-preventing activities via Ala-scanning-based regulation of molecular amphiphilicity. The representative analogue DGR-7 shows low toxicity but significant efficiency in preventing Aβ oligomers and reducing amyloid plaques in APP/PS1 transgenic AD mice.