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[Application,troubles,and growth secrets to individualized homeopathy preparations].
Two-dimensional materials provide a secluded space for bone formation and preserve the growth of surrounding tissues, thus playing a crucial role in guided bone regeneration (GBR). Graphene oxide (GO) has been widely employed in GBR due to its good mechanical and hydrophilic properties. A single GO membrane, however, does not provide a friendly environment for osteogenic cell adhesion. With their adjustable mechanical properties and excellent biocompatibility, composite membranes can simulate the multicomponent structure of an extracellular matrix for cell adhesion. To obtain two-dimensional membranes with appropriate mechanical strength and sufficient biocompatibility, GO-based composite membranes simultaneously containing chitosan (CS) and hydroxyapatite (HAP) were first prepared using one-step vacuum filtration and a biomimetic mineralization method. CS and HAP improved the mechanical strength and surface hydrophilicity of the membranes. In addition, moderate addition of HAP enhanced the adhesion, differentiation, and mineralization of osteoblasts. The prepared composite membranes were then implanted into a calvarial defect model to evaluate their osteogenic induction effects in vivo. Microcomputed tomography observation and histological analysis indicate that GO/CS/HAP composite membranes can accelerate bone regeneration without the contribution of endogenous cytokines. GO/CS/HAP composite membranes with unique biomimetic porous structures, superior mechanical properties, and excellent bone regeneration capacity are potential materials for application in GBR.Regenerated silk fibroin (RSF) has been regarded as a very promising biomaterial for the preparation of microfluidic devices. However, the facile and low-cost fabrication of three-dimensional (3D) RSF microfluidic devices is still a great challenge. Herein, we developed a tape-mask-assisted multiple-step etching technique to fabricate 3D microfluidic devices based on water-annealed RSF films. Several rounds of tape adhesion- or peeling-etching cycles need to be conducted to produce 3D features on the RSF films with the LiBr aqueous solution as the etchant. The water-annealed RSF films could be effectively etched with 1.0 g·mL-1 LiBr solution at 60 °C. The shape, width, and height of the 3D structures could be precisely tailored by controlling the mask pattern, etching conditions, and the number of etchings. Using the tape adhesion- and peeling-assisted multiple-etching techniques, the convex-pyramid-shaped and the concave-step-shaped structures could be successfully prepared on the RSF films, respectively. The RSF-film-based 3D micromixers and microfluidic separator were also manufactured with the proposed approach, exhibiting excellent liquid mixing and size-dependent particle sorting capabilities, respectively. The enzymatic degradation of RSF-film-based devices was also investigated to show their environmental friendliness. This work may not only provide a facile and low-cost method for the fabrication of RSF-based 3D microfluidic devices but also extend the applications of RSF in the fields of biomedical and chemical analysis.The self-assembly of cyclodextrins (CDs) with various guest polymers and small molecules has been intensively investigated for several decades, and it has still increasingly attracted wide attention to construct well-defined microstructures for the uses in biomedicine, sensors, environments, and nanorobotics. While most of the self-assembly of CDs involves the presence of guests, we recently discovered that α-CDs and γ-CDs could be self-assembled between themselves without the incorporation of any guests simply by elevating the temperature of their N,N-dimethylformamide (DMF) solution. In this work, we further found that α-CDs could self-assemble or reorganize in DMF into hexagonal rods simply by directly drying out the α-CD DMF solution. The α-CDs were self-assembled in the guest-free solution triggered by solvent evaporation. The X-ray powder diffraction results confirmed that they possessed a columnar structure, combined with the absence of guests in the strategy, and the cavities of CDs were not filled with guest molecules, but some water molecules may exist. The rods could be formed in various concentrations from 0.001 to 0.08 g/mL with drying temperatures ranging from 80 to 140 °C. The finding of this work shows the exceptional possibility of CDs to form well-defined microstructures without the engagement of guest molecules.Oxygen-dependent photodynamic therapy (PDT) could exacerbate tumor hypoxia to induce the upregulation of hypoxia-inducible factor-1α (HIF-1α), which would promote tumor growth and metastasis. In this paper, a self-remedied nanomedicine is developed based on a photosensitizer and a HIF-1α inhibitor to surmount the Achilles' heel of PDT for enhanced antitumor efficacy. Specifically, the nanomedicine (designated as CYC-1) is prepared by the self-assembly of chlorine e6 (Ce6) and 3-(5'-hydroxy-methyl-2'-furyl)-1-benzylindazole (YC-1) through π-π stacking and hydrophobic interactions. Of special note, carrier-free CYC-1 holds an extremely high drug loading rate and avoids excipient-triggered adverse reactions. Intravenously administered CYC-1 prefers to accumulate in the tumor tissue for effective cellular uptake. More importantly, it is verified that CYC-1 is capable of inhibiting the HIF-1α activity, thereby improving its PDT efficacy on tumor suppression. Besides, CYC-1 has the overwhelming superiority in restraining tumor proliferation over the combined administration of Ce6 and YC-1, which highlights the advantage of this self-remedied strategy in drug delivery and tumor therapy. This study sheds light on the development of self-delivery nanomedicine for efficient PDT against malignancies.Epilepsy detection and focus location are urgent issues that need to be solved in epilepsy research. A cortex conformable and fine spatial accuracy electrocorticogram (ECoG) sensor array, especially for real-time detection of multicortical functional regions and delineating epileptic focus remains a challenge. Here, we fabricated a polydimethylsiloxane (PDMS)-parylene hybrid, flexible micro-ECoG electrode array. The multiwalled carbon nanotubes (MWCNTs)/poly(3,4-ethylenedioxythiophene)poly(styrene sulfonate) (PEDOTPSS) nanocomposite-modified electrode interface significantly improved the sensing performance with low impedance (20.68 ± 6.65 kΩ), stable phase offset, and high sensitivity. The electrophysiological activities of multicortical brain regions (somatosensory cortex, parietal association cortex, and visual cortex) were simultaneously monitored during normal and epileptic statuses. The epileptic ECoG activities spread spatiotemporally from the starting point toward the adjacent cortex. Significant variations of the waveform, power, and frequency band were observed. The ECoG potential (123 ± 23 μV) at normal status was prominently up to 417 ± 87 μV at the spike wave stage. Besides, the power for epileptic activity (11.049 ± 4.513 μW) was 10 times higher than that (1.092 ± 0.369 μW) for normal activity. In addition, the theta frequency band was found to be a characteristic frequency band of epileptic signals. These joint analysis results of multicortical regions indicated that the active micron-scale region on the parietal association cortex was more likely to be the epileptogenic focus. Cortical mapping with high spatial detail provides the accurate delineation of lesions. The flexible micro-ECoG electrode array is a powerful tool for constructing a spatiotemporal map of the cortex. learn more It provides a technical platform for epileptic focus location, biomedical diagnosis, and brain-computer interaction.The short half-life of temozolomide (TMZ) limits its therapeutic effect on highly aggressive glioblastoma (GBM). Few approaches attempting to intervene the metabolic kinetics of TMZ are successful. Herein, we designed anionic copolymers via radical polymerization to prepare polymer-coated small copper nanoclusters, taking advantage of the role of pendent thymine groups as a template. The active and key intermediate of TMZ, typically called 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC), was stabilized by copper under physiological (slightly alkaline) conditions, alleviating concerns associated with spontaneous drug degradation and nonspecific drug activation. Importantly, the complexes formed by MTIC and copper nanoclusters could catalyze the Fenton reaction to generate hydroxyl radicals and also respond to pH and glutathione to release therapeutic MTIC, which allows combined chemotherapy and chemodynamic therapy against GBM cells and paves a way for circumventing the complication of TMZ resistance.As an emerging cancer treatment, Ca2+-loaded nanoagents can disorder intracellular calcium homeostasis to induce cancer cell death. However, the developed Ca2+ nanocarriers are very limited in variety. Herein, we developed a metal oxide based nanoagent, Ca0.35CoO2@ss-SiO2-Ce6 (denoted as CCO@ss-SiO2-Ce6), which not only intensively released Ca2+ but also realized enhanced photothermal and photodynamic therapy. The excellent photothermal conversion efficacy (48.01% at 808 nm laser illumination, 1 W/cm2), high heat-enhanced release rate of Ca2+ (50.09% at pH 4.5), and catalase-mimic activity to generate oxygen as well as the facilitated production of the singlet oxygen all contributed to the enhanced synergistic cancer therapy efficacy. The in vitro and in vivo experiments displayed that CCO@ss-SiO2-Ce6 demonstrated superior biocompatibility and remarkable suppressive tumor growth. This work opens a pathway for fabricating synergistic therapeutic nanoplatforms.Carbon dots (CDs) have become the focus of many studies due to their outstanding optical properties and good biocompatibility. We investigated their potential application to produce a smart and highly efficient yet nontoxic nanovector for gene delivery. This was achieved by conjugating PEI1.8k-functionalized CDs (synthesized by one-step microwave-assisted pyrolysis) with arginine-disulfide linkers to produce CD-PEI1.8k-Arg nanoparticles. This nanovector could deliver p-CRISPR (9.3 kb) into different types of cell lines with higher efficiency compared to native PEI1.8k or PEI25k. CD-PEI1.8k-Arg also maintained its outstanding transfection efficiency at a high serum concentration and low p-CRISPR dose, compared to PEI25k, which was ineffective under those conditions. Additionally, CD-PEI1.8k-Arg could knock out the GFP gene with great efficiency by delivering the required components of CRISPR/Cas9, including a plasmid encoding Cas9, sgRNA targeting GFP, and Cas9/sgRNA ribonucleoproteins (RNPs) into the HEK 293T-GFP cells. Moreover, the nanoparticles showed potential for the local delivery of p-CRISPR into brain tissue. The remarkable properties of CD-PEI1.8k-Arg could enable the development of a safe, highly efficient gene-delivery nanovector for the treatment of various diseases in the near future.Inflammation plays an essential role in the human immune system, and anti-inflammatory compounds are important to promote health. However, the in vitro screening of these compounds is largely dependent on flat biology. Herein, we report our efforts in establishing a 3D inflammation murine macrophage model. Murine macrophage RAW 264.7 cells were cultured on poly(ε-caprolactone) (PCL) scaffolds fabricated through an electrohydrodynamic jetting 3D printer and their behavior were examined. Cells on PCL scaffolds showed a 3D shape and morphology with multilayers and a lower proliferation rate. Moreover, macrophages were not activated by scaffold material PCL and 3D microenvironment. The 3D cells showed greater sensitivity to lipopolysaccharide stimulation with higher production activity of nitric oxide (NO), nitric oxide synthases (iNOS), and cyclooxygenase-2 (COX-2). Additionally, the 3D macrophage model showed lower drug sensitivity to commercial anti-inflammatory drugs including aspirin, ibuprofen, and dexamethasone, and natural flavones apigenin and luteolin with higher IC50 for NO production and lower iNOS and COX-2 inhibition efficacy.
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