Upregulation of rate-limiting enzymes in cholesterol metabolism by PKCδ mediates endothelial apoptosis in diabetic wound healing.

Diabetic foot ulcer (DFU) is a prevalent complication of diabetes that poses significant challenges in terms of treatment and management. It is characterized by heightened endothelial apoptosis and impaired angiogenesis. In this study, we aimed to investigate the role of protein kinase Cδ (PKCδ) in regulating endothelial apoptosis in diabetic wounds by promoting cholesterol biosynthesis. The expression of PKCδ was increased in human umbilical vascular endothelial cells (HUVECs) cultivated in high glucose medium and skin tissue isolated from diabetic mice. High glucose-induced HUVECs apoptosis was reduced by PKCδ inhibition with siRNA or rottlerin. RNA-seq identified two enzymes, 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), as the downstream of PKCδ. PKCδ knockdown or inhibition suppressed the expression of HMGCS1 and HMGCR and lowered free cholesterol (FC) levels. Cholesterol restored high glucose-induced apoptosis in siRNA- or rottlerin-treated HUVECs. In vivo use of rosuvastatin calcium, an inhibitor of HMGCR, downregulated free cholesterol levels and accelerated the wound healing process. In conclusion, PKCδ expression in endothelial cells was activated by high glucose, which subsequently upregulates the expression of two enzymes catalyzing cholesterol biosynthesis, HMGCS1 and HMGCR. Enhanced cholesterol biosynthesis raises free cholesterol levels, promotes endothelial apoptosis, and finally delays wound healing.

Scalable multi-dimensional topological deformation actuators for active object identification.

Rarely are bionic robots capable of rapid multi-dimensional deformation and object identification in the same way as animals and plants. This study proposes a topological deformation actuator for bionic robots based on pre-expanded polyethylene and large flake MXene, inspired by the octopus predation behavior. This unusual, large-area topological deformation actuator (easily reaching 800 cm2 but is not constrained to this size) prepared by large-scale blow molding and continuous scrape coating exhibits different distribution states of molecular chains at low and high temperatures, causing the actuator's deformation direction to change axially. With its multi-dimensional topological deformation and self-powered active object identification capabilities, the actuator can capture objects like an octopus. The contact electrification effect assists the actuator to identify the type and size of the target object during this multi-dimensional topological deformation that is controllable and designable. This work demonstrates the direct conversion of light energy into contact electrical signals, introducing a new route for the practicality and scaling of bionic robots.

The Investigation of the Influence of a Cu2O Buffer Layer on Hole Transport Layers in MAPbI3-Based Perovskite Solar Cells.

The passivation engineering of the hole transport layer in perovskite solar cells (PSCs) has significantly decreased carrier accumulation and open circuit voltage (Voc) loss, as well as energy band mismatching, thus achieving the goal of high-power conversion efficiency. However, most devices incorporating organic/inorganic buffer layers suffer from poor stability and low efficiency. In this article, we have proposed an inorganic buffer layer of Cu2O, which has achieved high efficiency on lower work function metals and various frequently used hole transport layers (HTLs). Once the Cu2O buffer layer was applied to modify the Cu/PTAA interface, the device exhibited a high Voc of 1.20 V, a high FF of 75.92%, and an enhanced PCE of 22.49% versus a Voc of 1.12 V, FF of 69.16%, and PCE of 18.99% from the (PTAA/Cu) n-i-p structure. Our simulation showed that the application of a Cu2O buffer layer improved the interfacial contact and energy alignment, promoting the carrier transportation and reducing the charge accumulation. Furthermore, we optimized the combinations of the thicknesses of the Cu2O, the absorber layer, and PTAA to obtain the best performance for Cu-based perovskite solar cells. Eventually, we explored the effect of the defect density between the HTL/absorber interface and the absorber/ETL interface on the device and recommended the appropriate reference defect density for experimental research. This work provides guidance for improving the experimental efficiency and reducing the cost of perovskite solar cells.

A strategy for identifying effective and risk compounds of botanical drugs with LC-QTOF-MS and network analysis: A case study of Ginkgo biloba preparation.

Botanical drugs have unique advantages in the treatment of complex diseases. In order to ensure the efficacy and safety of botanical drugs, ascertaining the effective and risk compounds is quite necessary. However, the conventional identification method is laborious, time-consuming, and inefficient. In this work, a 3-steps strategy was presented to rapidly identify the effective and risk compounds of botanical drugs, and a Ginkgo biloba preparation, Shu-Xue-Ning injection (SXNI), was taken as a case study. Firstly, mass spectral molecular networking was used to rapidly identify the compounds of SXNI. Secondly, three networks (i.e. the compound-target network, the indication-related biomolecule network, and the adverse drug reaction-related biomolecule network) are constructed. Finally, a novel network analysis algorithm was used to predict the effective and risk compounds in SXNI. By this strategy, a total of 138 compounds were identified including the firstly reported terpenoid glycosides and lignan glycosides. Among them 71 compounds were predicted as effective ones, and 42 compounds as risk ones. Especially, 31 compounds relevant to both efficacy and safety should be scientifically controlled during manufacturing. In addition, ten pathways were enriched to preliminarily explain the action mechanism of SXNI. This strategy for MS data analysis can be applied to provide important basis for the manufacturing and quality control, as well as valuable points for research on the pharmacological mechanisms of botanical drugs.

Polyamine-Modified Gold Nanoparticles Readily Adsorb on Cell Membranes for Bioimaging.

The surface modification of nanoparticles (NPs) can enhance cellular and intracellular targeting. A new type of polyamine-modified gold NPs (AuNPs) are designed and synthesized, which can be selectively absorbed onto the cell membrane. AuNPs with an average diameter of 4.0 nm were prepared and modified with polyamine (R-4C) through amidation. In order to detect the distribution of NPs within cells by fluorescence imaging, AuNP@MPA-R-4C was functionalized with fluorescein isothiocyanate (FITC). The fluorescence-labled NPs AuNP@MPA-R-4C-FITC demonstrated minimal cytotoxicity in several cell lines. Both confocal laser scanning microscopy and transmission electron microscopy demonstrated that AuNP@MPA-R-4C-FITC was distributed on the cell membrane. Compared with the free organic dye, the modified AuNPs showed significantly increased accumulation on the cell membrane after treatment for only 10 min. These results suggested that AuNP@MPA-R-4C-FITC can be used as a bioprobe targeting the cell membrane for various biological applications.

The Apoptosis Effect on Liver Cancer Cells of Gold Nanoparticles Modified with Lithocholic Acid.

Functionalized gold nanoparticles (AuNPs) have widely applied in many fields, due to their good biocompatibility, a long drug half-life, and their bioactivity is related to their size and the modified ligands on their surface. Here, we synthesized the AuNPs capped with ligands that possess polyethylene glycol (PEG) and lithocholic acid (LCA) linked by carboxyl groups (AuNP@MPA-PEG-LCA). Our cytotoxicity results indicated that AuNP@MPA-PEG-LCA have better cell selectivity; in other words, it could inhibit the growth of multiple liver cancer cells more effectively than other cancer cells and normal cells. Apoptosis plays a role in AuNP@MPA-PEG-LCA inhibition cell proliferation, which was convincingly proved by some apoptotic index experiments, such as nuclear staining, annexin V-FITC, mitochondrial membrane potential (MMP) analysis, and AO/EB staining experiments. The most potent AuNP@MPA-PEG-LCA were confirmed to efficiently induce apoptosis through a reactive oxygen species (ROS) mediating mitochondrial dysfunction. And AuNP@MPA-PEG-LCA could be more effective in promoting programmed cell death of liver cancer cells.

The delivery of doxorubicin of multifunctional ß-cyclodextrin-modified CdSe/ZnS quantum dots for bioactivity and nano-probing.

The modified quantum dots (QDs) have been used in intracellular probing and drug delivery because of their special chemical and physical properties. In this paper, two ß-cyclodextrin (ß-CD)-modified CdSe/ZnS QDs with strong optical emission properties were synthesized as drug carriers to induce apoptosis. The positively charged l-Arginine (l-Arg) and neutral l-Tryptophan (l-Trp) were selected as ligands to compare the effect of charge on bioactivity of QDs nanoparticles. The in vitro assays revealed that these modified QDs showed good Dox carrier ability and significantly high inhibition rate to cancer cells. Especially, the more positively charged ß-CD-l-Arg-polyamine-coated CdSe/ZnS QDs could effectively deliver the doxorubicin (Dox) into cells and exhibit excellent cell selectivity in cancer versus normal cells. The Dox-loaded QDs could enter intracellular, which showed that the Dox can efficiently go through the membranes at the existence of ß-CD. Several lines of evidence suggest that the Dox-loaded QDs can efficiently induce apoptosis likely related to the production of ROS. We expect that the modified QDs can enhance the amount of hydrophobic antitumor drugs in cells and can also be used as fluorescent imaging agents.

The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy.

Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.

A multi-responsive water-driven actuator with instant and powerful performance for versatile applications.

Mechanical actuators driven by water that respond to multiple stimuli, exhibit fast responses and large deformations, and generate high stress have potential in artificial muscles, motors, and generators. Meeting all these requirements in a single device remains a challenge. We report a graphene monolayer paper that undergoes reversible deformation. Its graphene oxide cells wrinkle and extend in response to water desorption and absorption, respectively. Its fast (~0.3 s), powerful (>100 MPa output stress, 7.5 × 10(5) N kg(-1) unit mass force), and controllable actuation can be triggered by moisture, heat, and light. The graphene monolayer paper has potential in artificial muscles, robotic hands, and electromagnetic-free generators.