CDK5R1 promotes Schwann cell proliferation, migration, and production of neurotrophic factors via CDK5/BDNF/TrkB after sciatic nerve injury.

Cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) is necessary for central nervous system development and neuronal migration. At present, there are few reports about the role of CDK5R1 in peripheral nerve injury, and these need to be further explored. The CCK-8 and EdU assay was performed to examine cell proliferation. The migration ability of Schwann cells was tested by the cell scratch test. The apoptosis of Schwann cells was detected by flow cytometry. Sciatic nerve injury model in rats was established by crush injury. The sciatic function index (SFI) and the paw withdrawal mechanical threshold (PWMT) were measured at different time points. The results revealed that overexpression of CDK5R1 promoted the proliferation and migration of Schwann cells, and inhibited the apoptosis. Further studies found that pcDNA3.1-CDK5R1 significantly upregulated the expression of CDK5, BDNF and TrkB. More importantly, CDK5R1 promoted the recovery of nerve injury in rats. In addition, the CDK5 mediated BDNF/TrkB pathway was involved in the molecular mechanism of CDK5R1 on Schwann cells. It is suggested that the mechanism by which CDK5R1 promotes functional recovery after sciatic nerve injury is by CDK5 mediated activation of BDNF/TrkB signaling pathways.

Discovery of benzofuran-2-carboxylic acid derivatives as lymphoid tyrosine phosphatase (LYP) inhibitors for cancer immunotherapy.

Lymphoid-tyrosine phosphatase (LYP) is mainly expressed in the immune system and plays an important role in the T-cell receptor (TCR) signaling pathway and tumor immunity. Herein, we identify benzofuran-2-carboxylic acid as a potent pTyr mimic and design a new series of new LYP inhibitors. The most active compound, D34 and D14, reversibly inhibits LYP (Ki = 0.93 µM and 1.34 µM) and possess a certain degree of selectivity toward other phosphatases. Meanwhile, D34 and D14 regulate the TCR signaling by specifically inhibiting LYP. In particular, D34 and D14 significantly suppress tumor growth in an MC38 syngeneic mouse model by boosting antitumor immunity, including activation of T-cell and inhibition of M2 macrophage polarization. Moreover, treatment of D34 or D14 upregulate PD-1/PD-L1 expression, which can be leveraged with PD-1/PD-L1 inhibition to augment immunotherapy. In summary, our study demonstrates the feasibility of targeting LYP for cancer immunotherapy and provides new lead compounds for further drug development.

LncRNA HAGLR promotes the proliferation, migration, and neurotrophic factor production of Schwann cells via miR-204/CDK5R1 after sciatic nerve injury.

Peripheral nerve injury induces motor and sensory defects and has serious impacts on patients' quality of life. Schwann cells (SCs) are the major glial cells in the peripheral nervous system and play important roles in the repair and regeneration of peripheral nerves. Long noncoding RNA HAGLR has been reported to be highly expressed in neurons and to promote neuronal differentiation but its expression decreases after nerve injury, suggesting that HAGLR may be involved in the process of nerve injury repair. This study aimed to investigate the role and mechanism of HAGLR in neural repair functions of SCs. We found that HAGLR promoted SC proliferation and migration and facilitated the secretion of neurotrophic factors. Furthermore, HAGLR functions as a competing endogenous RNA to regulate CDK5R1 expression via sponging miR-204. Overexpression of miR-204 or silencing of CDK5R1 partially abolished the promoting effect of HAGLR on SCs. Moreover, overexpression of HAGLR promoted the functional recovery of sciatic nerve crush (SNC) model rats. In summary, HAGLR promoted SC proliferation, migration, neurotrophic factor production, and facilitated functional recovery of SNC rats via miR-204/CDK5R1. Therefore, it may provide a potential therapeutic target for peripheral nerve repair and regeneration.

Effects of Valence States of Working Cations on the Electrochemical Performance of Sodium Vanadate.

Supercapacitors have received much attention as large-scale energy storage devices for high power density and ultralong cycling life. In this work, sodium vanadate Na0.76V6O15/poly(3,4-ethylenedioxythiophene) (PEDOT) nanocables with deficient bridge oxygen at the interface (denoted Vo••-PNVO) have been tailored for supercapacitors through the in situ polymerization of 3,4-ethylenedioxythiophene and studied using three different electrolytes. Experiments and theoretical calculations reveal that all Na+, Zn2+, and Al3+ ions appear as hydrates in aqueous solutions but insert into the crystal structure as Na+ ions and Zn2+-H2O and Al3+-H2O hydrates, respectively. In comparison with the Zn2+-H2O and Al3+-H2O hydrates, Na+ ions with a smaller radius diffuse more quickly in Vo••-PNVO. Thus, Vo••-PNVO delivers better charge storage capability and stability when an electrolyte with Na+ ions is used. The results strongly suggest that an electrostatic interaction is significant in determining transport properties and storage capacities, rather than hydrate radii or valence states.

Ultrasensitive microfluidic immunosensor with stir bar enrichment for point-of-care test of Staphylococcus aureus in foods triggered by DNAzyme-assisted click reaction.

This work demonstrated an ultrasensitive and simple microfluidic immunosensor for point-of-care test of Staphylococcus aureus (S. aureus) based on the stir bar enrichment and DNAzyme-assisted click reaction. Initially, S. aureus was enriched by the 4-mercaptophenylboronic acid-functionalized stir bar. The yolk antibody (immunoglobulin Y) and copper-labeled polydopamine nanoparticles were then specifically conjugated with the captured target. The Cu(II) was released under acidic conditions and effectively catalyzed the copper-catalyzed azide-alkyne cycloaddition (CuAAC) between the alkyne group-labeled DNAzyme and the streptavidin-biotin-azido with the assistance of DNAzyme. Finally, the DNAzyme-streptavidin complexes were detected by microfluidic chips to quantify S. aureus. Under optimum conditions, this immunosensor showed good detection performances toward S. aureus within 10 to 2.5 × 104 CFU/mL with a limit of detection of 3 CFU/mL. Moreover, the satisfying detection results of real samples of animal origin also implied that this immunosensor owned great potential in practical applications.

Rapid and sensitive detection of Staphylococcus aureus by using a long-period fiber grating immunosensor coated with egg yolk antibody.

The rapid and reliable detection of bacteria plays an important role in clinical and veterinary practice. A stable, label free, compact, and sensitive long-period fiber grating (LPFG) sensor based on egg yolk antibody (IgY) was proposed for the detection of Staphylococcus aureus (S. aureus). LPFG was fabricated with laser writing technology, and specific IgY was further immobilized on the grating region and then combined with the corresponding bacteria. S. aureus was detected by tracking the change of resonance wavelength in the LPFG transmission spectrum caused by bacteria-antibody interaction induced by the increase of biological cover thickness and density after the immune reaction. The testing results showed that the proposed sensor was selective and sensitive to S. aureus measurement, and the detection limit is approximately 33 CFU/ml. The proposed antibody immobilization method is very simple, and the optical fiber can be manufactured in batch to reduce the cost. The detection time of the sensor is around 20 min, which is fast and suitable for detection. The assay was successfully applied for the quantitative analysis of S. aureus in natural waters and met the needs of on-site screening trace pathogenic bacteria in food safety control.

Interphases, Interfaces, and Surfaces of Active Materials in Rechargeable Batteries and Perovskite Solar Cells.

The ever-increasing demand for clean sustainable energy has driven tremendous worldwide investment in the design and exploration of new active materials for energy conversion and energy-storage devices. Tailoring the surfaces of and interfaces between different materials is one of the surest and best studied paths to enable high-energy-density batteries and high-efficiency solar cells. Metal-halide perovskite solar cells (PSCs) are one of the most promising photovoltaic materials due to their unprecedented development, with their record power conversion efficiency (PCE) rocketing beyond 25% in less than 10 years. Such progress is achieved largely through the control of crystallinity and surface/interface defects. Rechargeable batteries (RBs) reversibly convert electrical and chemical potential energy through redox reactions at the interfaces between the electrodes and electrolyte. The (electro)chemical and optoelectronic compatibility between active components are essential design considerations to optimize power conversion and energy storage performance. A focused discussion and critical analysis on the formation and functions of the interfaces and interphases of the active materials in these devices is provided, and prospective strategies used to overcome current challenges are described. These strategies revolve around manipulating the chemical compositions, defects, stability, and passivation of the various interfaces of RBs and PSCs.

Study on the source of magnetic properties of three novel boratopolyoxovanadates via two-dimensional infrared correlation spectroscopy.

Three novel polyoxovanadoborates namely [V12B18O46(OH)14(H2O)0.75]·20.5H2O 1, Na2[V12B18O48(OH)12(H2O)0.5]·26.5H2O 2 and Cd0.5{[Na(H2O)2]2[Na(H2O)]2[Na(H2O)3]2V12B18O53(OH)7(H2O)0.5}·11H2O 3 have been hydrothermally synthesized and structurally characterized. The boratopolyoxovanadate cage [V12B18O60] backbones in 1-3 are constructed by the combination of two hexameric oxovanadate units [V6O9] and one puckered [B18O42] ring via sharing O atoms. All three compounds were obtained under alkaline conditions, and the cluster anions were all [V12B18O60]. But the cations were different, it is inferred that the protonation of the three compound cluster ions is different, respectively [V12B18O46(OH)14(H2O)0.75] in 1, [V12B18O48(OH)12(H2O)0.5]2- in 2 and [V12B18O53(OH)7(H2O)0.5]7- in 3. The V oxidation states ratio of VIV to VV were 2:1 confirmed by valence bond calculation and XPS. We studied the magnetic properties of three compounds by two methods: The variable temperature magnetic susceptibility and the 2D IR COS under magnetic perturbation. From the 2D IR COS under magnetic perturbation map, it is showed that all three: (1) the presence of VIV. (2) Certain quasi-aromaticity from B3O3 six-membered ring. (3) The difference of protonation and the charge of the cluster anions. This work enriches the theory of two-dimensional correlation spectroscopy and also provides a new approach to the study of magnetic materials.

Magnetic stir bars with hyperbranched aptamer as coating for selective, effective headspace extraction of trace polychlorinated biphenyls in soils.

It is challenging to greatly increase of the extraction selectivity and efficiency by stir bar sorptive extraction of ultra-trace polychlorinated biphenyls (PCBs) in complex environmental matrix, e.g., soils. To fulfill this purpose, one of the critical works is to prepare some coatings with high selectivity, adsorptive capacity and reusability. It is also important to develop some green, simple methods for preperation the coatings. In this work, a kind of highly efficient and bioactive coating based on hyperbranched aptamer (HB-Apt) was constructed via hybridization chain reaction (HCR). Then, the HB-Apt was coated on a magnetic stir bar and applied to headspace extraction of PCB72 and PCB106 in soils. The core-shell gold magnetic particles (Fe3O4@AuNPs, AuMNPs for short) was employed as the substrate to immobilize the HB-Apt. The extracted PCBs on the stir bar could be easily eluted in ethanol by stirring, and then sampled in gas chromatography-mass spectrometry (GC-MS) for qualification. The ultra-low detection limit (0.003-0.005 ng•g-1), good linearity (0.01-500 ng•g-1, R2≥0.994) and reproducibility (RSD: 4.58-6.53%) were obtained. Compared with the common aptamer coating, the HB-Apt coating exhibited good selectivity and higher extraction capacity. The results might be related to the fact that there are more aptamer fragments grated on the HB-Apt coating than those of the common aptamer coating. The magnetic stir bar can not only be employed for easy headspace extraction, but also facilitate separation and elution. Moreover, the coating could be recycled for at least 60 times before recoveries of the PCB72 and PCB106 in the spiked samples drop below 90%. All these indicated that the assay is simple, robust, environment friendly and promising for detection of trace PCBs in complex environmental samples.

Interface Engineering V2 O5 Nanofibers for High-Energy and Durable Supercapacitors.

A local electric field is induced to engineer the interface of vanadium pentoxide nanofibers (V2 O5 -NF) to manipulate the charge transport behavior and obtain high-energy and durable supercapacitors. The interface of V2 O5 -NF is modified with oxygen vacancies (Vö) in a one-step polymerization process of polyaniline (PANI). In the charge storage process, the local electric field deriving from the lopsided charge distribution around Vö will provide Coulombic forces to promote the charge transport in the resultant Vö-V2 O5 /PANI nanocable electrode. Furthermore, an ≈7 nm porous PANI coating serves as the external percolated charge transport pathway. As the charge transfer kinetics are synergistically enhanced by the dual modifications, Vö-V2 O5 /PANI-based supercapacitors exhibit an excellent specific capacitance (523 F g-1 ) as well as a long cycling lifespan (110% of capacitance remained after 20 000 cycles). This work paves an effective way to promote the charge transfer kinetics of electrode materials for next-generation energy storage systems.

Tailoring Energy and Power Density through Controlling the Concentration of Oxygen Vacancies in V2O5/PEDOT Nanocable-Based Supercapacitors.

Oxygen vacancies (Vö) play a crucial role in energy storage materials. Oxygen-vacancy-enriched vanadium pentoxide/poly(3,4-ethylenedioxythiophene) (Vö-V2O5/PEDOT) nanocables were prepared through the one-pot oxidative polymerization of PEDOT. PEDOT is used to create tunable concentrations of Vö in the surface layer of V2O5, which has been confirmed by X-ray absorption near edge structure (XANES) analysis and X-ray photoelectron spectroscopy (XPS) measurements. Applied as electrode materials for supercapacitors, the electrochemical performance of Vö-V2O5/PEDOT is improved by the synergistic effects of Vö in V2O5 cores and PEDOT shells with rapid charge transfer and fast Na+ ion diffusion; however, it is compromised subsequently by excessive Vö in consuming more V5+ cations for Faradic reactions. Consequently, the specific capacitance and the energy density of Vö-V2O5/PEDOT nanocables are significantly enhanced when the overall concentration of Vö is 1.3%. The migration of Vö renders an increased capacitance (105% retention) after 10 000 cycles, which is verified and corroborated with density functional theory simulations and XANES analysis. This work provides an illumination for the fabrication of high-performance electrode materials in the energy storage field through Vö.

Beneficial effect of grape seed proanthocyanidin extract in rabbits with steroid-induced osteonecrosis via protecting against oxidative stress and apoptosis.

BACKGROUND: Oxidative damage and apoptosis play dominant roles in the pathogenesis of steroid-induced osteonecrosis (ON). Grape seed proanthocyanidin extract (GSPE) demonstrates antioxidant and antiapoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing steroid-induced ON in rabbits. METHODS: Osteonecrosis was induced by high-dose methylprednisolone (40 mg/kg). Rabbits in the preventive medicine group were treated with 100 mg/kg/day GSPE for 14 consecutive days, and the presence or absence of ON was examined histopathologically. Oxidative damage in bone tissue was assessed by immunohistochemical staining of 8-oxo-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA) levels, and activities of antioxidant enzymes Cu/Zn superoxide dismutase (SOD) and phospholipid hydroperoxide glutathione peroxidase (GSH-Px). Apoptosis was detected via quantitative terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate nick end labelling (TUNEL) staining and activated caspase 3 immunoblotting and activity. RESULTS: GSPE significantly attenuated the changes of immunohistochemical staining of 8-OHdG, MDA levels, and antioxidant enzymes activities, which were caused by methylprednisolone administration. Quantitative TUNEL and caspase 3 assay showed lower apoptosis with GSPE application. Simultaneously, GSPE reduced the incidence of steroid-induced ON in an established rabbit model to 17.6 %, compared with 87.5 % in the steroid-only group. CONCLUSION: These results reveal that GSPE treatment could inhibit oxidative damage and apoptosis to exert beneficial effects on reducing the incidence of steroid-induced ON in rabbit models.

Protective effects of necrostatin-1 on glucocorticoid-induced osteoporosis in rats.

The inhibition of bone formation has been suggested to play a central role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). Recently, many studies suggested that there may be another mechanism involved in GIOP besides apoptosis. The aim of this study was to investigate the protective effect of Necrostatin-1 on GIOP rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n=10): controls; GIOP rats; GIOP rats pretreated with alendronate; and GIOP rats pretreated with Necrostatin-1. Their bone mineral density (BMD) and body weight were measured at the beginning and at the end of the experiment. TUNEL assay, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to observe the change of cellular morphology induced by Nec-1. The biochemical analysis and histomorphometric analysis were used to evaluate the change of bone formation by Nec-1. RIP-1, RIP-3 and caspase-8 expression were evaluated by immunohistochemistry. We found more TUNEL positive osteocytes and larger lacunae volume in GIOP rats compared with the control group. However, most of the osteocytes displayed a necrotic morphology and mitochondria lesions under TEM. In contrast to alendronate, Necrostatin-1 significantly elevated the level of bone formation markers, while it had no effect on bone resorption markers. Necrostatin-1 also markedly ameliorated trabecular bone. In addition, Necrostatin-1 significantly weaken the immunoreactivity of RIP-1 in GIOP rats while had no effect on RIP-3 and caspase-8. These data suggest, for the first time, that Necrostatin-1 accelerate bone formation of glucocorticoid-induced osteoporosis in rats.

A novel podophyllotoxin derivative (YB-1EPN) induces apoptosis and down-regulates express of P-glycoprotein in multidrug resistance cell line KBV200.

Our group synthesized a new potent anti-tumor podophyllotoxin derivative, YB-1EPN. In our study, we found that it was more potent than etoposide (VP-16). Interestingly, we found that the KBV200 cell line and K562/A02 cell line were rendered resistant towards VP-16 but not towards YB-1EPN. In vitro, both the cytotoxicity of YB-1EPN and its ability to inhibit KBV200 and K562/A02 cells were determined by MTT assay and growth curve. The IC(50) value of YB-1EPN on KBV200 cell was (2.52+/-0.28)microM in contrast to VP-16 (10.1+/-0.220)microM. And YB-1EPN showed a dose-dependent and broad-spectrum antiproliferative activity. Inducing apoptosis by YB-1EPN in KBV200 was assessed by various morphological and biochemical characteristics, including cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA ladder formation. Rates of apoptosis and cell cycle were also checked through flow cytometry. Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect mdr-1,p53,bcl-2,and bax gene expression. Western-blot assay was used to assess P-glycoprotein (P-gp) expression. We found that YB-1EPN could down-regulate expression level of the mdr-1, bcl-2, and up-regulate expression level of p53, and bax mRNA, as compared to the control. These results suggest that YB-1EPN has the potentiality to overcome P-glycoprotein-mediated multidrug resistance in the KBV200 cell line.

L1EPO, a novel podophyllotoxin derivative overcomes P-glycoprotein-mediated multidrug resistance in K562/A02 cell line.

The ineffectiveness of anticancer drugs is frequently observed in cancer chemotherapy. The resistance of tumor cells to various cytotoxic drugs is defined as multidrug resistance (MDR). The purpose of our present study was to investigate the inhibitory effects of L1EPO synthesized by our group on P-glycoprotein (P-gp)-mediated MDR in K562/A02 and KBv200 cell lines, which expressed high levels of P-gp. Both the cytotoxicity of the compound and its ability to inhibit K562/A02 and KBv200 cells were determined by sulforhodamine B sodium salt (SRB) assay. Morphologic apoptosis was detected by Hoechst33342 staining assay. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect mdr-1 gene transcription, and Western blot assay was used to assess P-gp expression. Interestingly, we found that the K562/A02 cell line was rendered resistant toward Adriamycin but not towards L1EPO when compared with the parental cells. Furthermore, L1EPO could down-regulate the mdr-1 gene, and it reduced the expression of P-gp and displayed a perfect dose dependence. Moreover, it had less cytotoxicity in normal human cell lines (fibroblast, VEC), GI(50)>10 micromol/l. Consequently, L1EPO has the potential to overcome P-glycoprotein-mediated MDR in the K562/A02 cell line.