Efficient treatment of surfactant containing wastewater by photocatalytic ozonation with BiPO4 nanorods.

In this study, monoclinic BiPO4 nanorods were fabricated by one-pot solvothermal method. Its catalytic capability in photocatalytic ozonation process was tested by degradation and mineralization of sodium dodecyl benzene sulfonate (SDBS) solution. The results demonstrated that the TOC removal rate was dramatically improved to 90.0% at 75 min for UV/O3/BiPO4 process, which was 4.9 and 3.8 times more than that of UV/BiPO4 and O3. Moreover, the pseudo-first-order kinetic constant (0.337 min-1) and mineralization rate (90.0%) for SDBS degradation using BiPO4 in UV/O3 process were 1.6 and 1.3 times as great as that of conventional TiO2 photocatalyst (0.206 min-1, 67.3%). The influence of BiPO4 dosage, O3 concentration initial pH and coexisted ions on SDBS degradation in UV/O3/BiPO4 process were also investigated. The outcome of quenching studies illustrated both ·OH and h+ contributed prominently to SDBS degradation in UV/O3/BiPO4 process, implying that high valence band position of BiPO4 could promote the synergism between photocatalysis and ozonation. The degradation pathway of SBDS was proposed by combination of intermediates analysis and DFT calculation. Real carwash wastewater was chosen as typical surfactant containing wastewater to explore the practical application of UV/O3/BiPO4 technology. During 30 min, COD and LAS removal efficiency reached 59.7% and 70.6%, respectively. The quality indices of effluent could meet the requirements for reuse of carwash water in Water Quality Standard for Urban Miscellaneous Use in China. Energy consumption in the process was calculated as 13.9 kW h m-3, which was about 3.6 and 2.2 times less than that of UV/BiPO4 and O3 process, respectively. The results suggest that UV/O3/BiPO4 system has an application potential for surfactant containing wastewater treatment or recycle.

Mussel Foot Protein Inspired Tape-Type Adhesive with Water-Responsive, High Conformal, Tough, and On-Demand Detachable Adhesion to Wet Tissue.

Wet adhesion is highly demanded in noninvasive wound closure, tissue repair, and biomedical devices, but it is still a big challenge for developing biosafe and tough wet bioadhesives due to low or even nonadhesion in the wet state for conventional adhesives. Inspired by the wet-adhesion-contributing factors of mussel foot proteins, a water-responsive dry robust tissue adhesive PAGU tape is made with thickness of <0.5 mm through fast UV-initiated copolymerization of acrylic acid (AA), gelatin (Gel), and hexadecenyl-1,2-catechol (UH). The tape shows strong cohesive mechanical properties and strong interfacial adhesion bonds. Upon application onto wet tissue, the adhesive tape can conform to the tissue, quickly dry tissue surface through absorbing surface/interfacial water and then allows formation of interfacial bonding with a high interfacial toughness of ≈818 J m-2 . Furthermore, it can be readily detached by treating with aq. urea solution. A highly efficient avenue is provided here for producing conformable, tough, and easy detachable wet bioadhesive tapes.

TSAb Modulates Microglia M1 Polarization via Activation of the TSHR-Mediated NF-κB Signaling Pathway.

INTRODUCTION: Thyrotropin receptor-stimulating antibody (TSAb) is a pathogenic antibody in the serum of patients with Graves' disease. The binding of TSAb to thyroid-stimulating hormone receptor (TSHR) in non-thyroid tissue may be associated with the occurrence and development of Graves' disease-related complications. However, only few studies have been conducted on the effects of TSAb on the brain, and the pathogenesis of acute hyperthyroidism myopathy (ATM) is unclear. Therefore, this study aimed to explore the effect of TSAb on the polarization of BV-2 cells in the brain and its possible mechanism and provide a basic experimental basis for ATM. METHODS: BV-2 cells were treated with different concentrations of TSAb. The relative survival rate of BV-2 cells was determined using the CCK-8 assay; the migration ability of BV-2 cells was detected using the Transwell migration assay; and the expression levels of M1/M2 polarization markers (CD86, inducible nitric oxide synthase [iNOS], CD206, and arginase 1 [Arg-1]), TSHR, tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) protein in BV-2 cells were measured using WB. RESULTS: Compared with the negative control group, the proliferative activity of BV-2 cells was significantly increased in the 20, 50, and 100 ng/mL TSAb groups, and the migration ability of BV-2 cells was significantly enhanced in the 50 and 100 ng/mL TSAb groups. The expression levels of M1 polarization markers (CD86 and iNOS), TSHR, TNF-α, and NF-κB protein in BV-2 cells treated with 50 and 100 ng/mL TSAb for 24 h were significantly upregulated, whereas those of M2 polarization markers (CD206 and Arg-1) significantly decreased. CONCLUSIONS: TSAb can induce abnormal activation of microglia, polarize to the M1 phenotype, and promote the inflammatory cascade reaction, in which TSHR plays a key role in NF-κB activation and proinflammatory cytokine release.

Water-driven noninvasively detachable wet tissue adhesives for wound closure.

Tissue adhesive with on-demand detachment feature is critically important since it can minimize hurt to patient when it is stripped away. Herein, a water-driven noninvasively detachable wet tissue adhesive hydrogel (w-TAgel) was produced by UV-initiated radical copolymerization of N-isopropylacrylamide (NIPAM), acrylamide (AAm), gelatin methacrylate (GelMA), and urushiol. As a w-TAgel, its robust and tough mechanical property makes it suitable for dynamic wound tissue. The polyurushiol segments of it are crucial to the formation of tough adhesion interface with various wet tissues, while polyNIPAM units play an indispensable role in on-demand detachment via thermo-responsive swelling behavior because the hydrophobic aggregation among isopropyl groups is destroyed upon water treatment with temperature of 25 â€‹°C or less. Additionally, it exhibits multiple merits including good hemocompatibility, cytocompatibility as well as pro-coagulant activity and hemostasis. Therefore, our w-TAgel with strong adhesion and facile detachment is an advanced prospective dressing for wound closure and rapid hemostasis. The wet tissue adhesion and water-driven detachable mechanism may shed new light on the development of on-demand noninvasively detachable wet tissue adhesives.

Design, synthesis and bioactivity evaluation of favorable evodiamine derivative scaffold for developing cancer therapy.

Natural product evodiamine is one of the most privileged scaffolds in drug discovery and is suitable for derivatization, which can be conducted quickly for structure optimization and structure-activity relationship research. In this work, a comprehensive SAR study on evodiamine scaffold with N14-3'-fluorophenyl substituted was completed, and compounds with high anti-tumor activity and good inhibitory effect on Top1 and Top2 were screened out. Tested evodiamine derivatives exhibited excellent broad-spectrum anti-tumor activity. Among them, compound 8b revealed 55.15% and 55.50% inhibition for Top1 and Top2 at 25 µM, as well as 0.16 and 0.13 µM IC50 value for MGC-803 and SGC-7901 cells, respectively; compound 9a revealed 70.50% and 71.81% inhibition for Top1 and Top2 at 25 µM, as well as 0.22 and 0.27 µM IC50 value for MGC-803 and SGC-7901 cells, respectively. The further biological evaluation showed that they could functionally induce apoptosis, significantly arrest the cell cycle at the G2/M phase, and markedly inhibit cell proliferation, migration and invasion. In addition, compound 9a performed a tumor inhibitory rate of 36.35% and showed no apparent toxicity in vivo. Overall, these optimized protocols will advance the progression of cancer chemotherapy and can be used to expand the options for screening therapeutic cancer drugs.

Design, Synthesis, and Biological Evaluation of Novel Evodiamine Derivatives as Potential Antihepatocellular Carcinoma Agents.

Evodiamine has many biological activities. Herein, we synthesize 23 disubstituted derivatives of N14-phenyl or the E-ring of evodiamine and conduct systematic structure-activity relationship studies. In vitro antiproliferative activity indicated that compounds F-3 and F-4 dramatically inhibited the proliferation of Huh7 (IC50 = 0.05 or 0.04 µM, respectively) and SK-Hep-1 (IC50 = 0.07 or 0.06 µM, respectively) cells. Furthermore, compounds F-3 and F-4 could double inhibit topoisomerases I and II, inhibit invasion and migration, block the cell cycle to the G2/M stage, and induce apoptosis as well. Additionally, compounds F-3 and F-4 could also inhibit the activation of HSC-T6 and reduce the secretion of collagen type I to slow down the progression of liver fibrosis. Most importantly, compound F-4 (TGI = 60.36%) inhibited tumor growth more significantly than the positive drug sorafenib. To sum up, compound F-4 has excellent potential as a strong candidate for the therapy of hepatocellular carcinoma.

Design, synthesis and bioactivity evaluation of novel evodiamine derivatives with excellent potency against gastric cancer.

Gastric cancer represents a significant health burden worldwide. Previously, inspired by the traditional Chinese medicine Wu-Chu-Yu to treat the spleen and stomach system for thousands of years, we identified N14-phenyl substituted evodiamine derivatives as potential antitumor agents with favorable inhibition on Top1. Herein, structural optimization and structure-activity relationship studies (SARs) led us to discovering a highly active evodiamine derivative compound 6t against gastric cancer. Further anti-tumor mechanism studies revealed that compound 6t played as the inhibition of topoisomerase 1 (Top1), effectively induced apoptosis, obviously arrested the cell cycle at the G2/M phase, and significantly inhibited the migration and invasion of SGC-7901 and MGC-803 cell lines in a dose-dependent manner. Moreover, the compound 6t was low toxicity in vivo and exhibited excellent anti-tumor activity (TGI = 70.12%) in the MGC-803 xenograft models. In summary, compound 6t represents a promising candidate as a potential chemotherapeutic agent against gastric cancer.

Research on PM2.5 Spatiotemporal Forecasting Model Based on LSTM Neural Network.

Accurate monitoring of air quality can no longer meet people's needs. People hope to predict air quality in advance and make timely warnings and defenses to minimize the threat to life. This paper proposed a new air quality spatiotemporal prediction model to predict future air quality and is based on a large number of environmental data and a long short-term memory (LSTM) neural network. In order to capture the spatial and temporal characteristics of the pollutant concentration data, the data of the five sites with the highest correlation of time-series concentration of PM2.5 (particles with aerodynamic diameter ≤2.5 mm) at the experimental site were first extracted, and the weather data and other pollutant data at the same time were merged in the next step, extracting advanced spatiotemporal features through long- and short-term memory neural networks. The model presented in this paper was compared with other baseline models on the hourly PM2.5 concentration data set collected at 35 air quality monitoring sites in Beijing from January 1, 2016, to December 31, 2017. The experimental results show that the performance of the proposed model is better than other baseline models.

Investigation of anti-osteoporosis mechanisms of Rehmanniae Radix Preparata based on network pharmacology and experimental verification.

BACKGROUND: Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate the anti-osteoporosis mechanisms of RRP through network pharmacology. METHODS: The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were verified through pharmacological experiments. RESULTS: According to topological analysis results, AKT1, MAPK1, ESR1, and SRC are critical genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including the estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, MAPK1, ESR1, and SRC1 mRNA in bone tissue to increase bone density. CONCLUSION: This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis and provided new ideas for its clinical application and experimental research.

Design, synthesis and bioactivity study of evodiamine derivatives as multifunctional agents for the treatment of hepatocellular carcinoma.

Topoisomerase has been found extremely high level of expression in hepatocellular carcinoma (HCC) and proven to promote the proliferation and survival of HCC. Cancer-associated fibroblasts (CAFs) as a kind of key reactive stromal cell that abundantly present in the microenvironment of HCC, could enhance the metastatic ability and drug resistance of HCC. Therefore, developing new drugs that address the above conundrums would be of the upmost significant in the fight against HCC. Evodiamine, as a multi-target natural product, has been found to exert various biological activities such as anti-cancer and anti-hepatic fibrosis via blocking topoisomerase, NF-κB, TGF-ß/HGF, and Smad2/3. Inspired by these facts, 15 evodiamine derivatives were designed and synthesized for HCC treatment by simultaneously targeting Topo I and CAFs. Most of them displayed preferable anti-HCC activities on three HCC cell lines and low cytotoxicity on one normal hepatic cell. In particular, compound 8 showed the best inhibitory effect on HCC cell lines and a good inhibition on Topo I in vitro. Meanwhile, it also induced obvious G2/M arrest and apoptosis, and significantly decreased the migration and invasion capacity of HCC cells. In addition, compound 8 down-regulated the expression of type I collagen in the activated HSC-T6 cells, and induced the apoptosis of activated HSC-T6 cells. In vivo studies demonstrated that compound 8 markedly decreased the volume and weight of tumor (TGI = 40.53%). In vitro and in vivo studies showed that its effects were superior to those of evodiamine. This preliminary attempt may provide a promising strategy for developing anti-HCC lead compounds taking effect through simultaneous inhibition on Topo I and CAFs.

[Finite element analysis of different intramedullary fixation methods for the treatment of senile pubic ramus fractures].

OBJECTIVE: To evaluate the biomechanical stability of elastic intramedullary nail in the treatment of pubic ramus fractures by finite element analysis, and to compare the stability of elastic intramedullary nail with cannulated screw intramedullary fixation. METHODS: The CT data of the pelvis of a volunteer were selected, and the three-dimensional model of the pelvis was reconstructed by reverse engineering software and the fracture of the pubic ramus fractures was simulated by osteotomy. The hollow nail model, single elastic nail model and double elastic nailmodel were assembled with different implants respectively. The mesh division, material assignment loading and other steps were carried out in the ANSYS software, and then the calculation was submitted. RESULTS: The overall displacement of the pelvis of the elastic nail model was smaller than that of the cannulated screw model, in which the double elastic nail model had the smallest overall displacement, but the cannulated screw model had the smallest plant displacement and the single elastic nail model had the largest plant displacement. Although the stress of cannulated screw was small, there was obvious stress concentration, the stress of elastic nail was large, but there was no obvious stress concentration, especially the stress distribution of double elastic nail was more uniform and the overall stress of pelvis was the smallest. CONCLUSION: All the three fixation methods can effectively improve the stability of the anterior ring of the pelvis. Among them, there is no significant difference in the overall biomechanical propertiesof hollow nail fixation and double elastic nail fixation, which is better than that of single elastic nail fixation. Elastic nail fixation has the advantages of minimally invasive surgery and good biomechanical stability, so it can be used as a better surgical method for the treatment of pubic ramus fractures.

Effects of Rehmannia glutinosa polysaccharides on bone tissue structure and skeletal muscle atrophy in rats with disuse.

PURPOSE: To study effects of Rehmannia glutinosa polysaccharides (RGP) on bone tissue structure and skeletal muscle atrophy in rats with disuse. METHODS: A rat model of disuse osteoporosis combined with muscle atrophy was established by removing the bilateral ovaries of rats and fixing their hind limbs for a long time. Forty SD rats were administered intragastrically for 12 weeks. The bone histomorphometry parameters and the level of oxidative stress were measured. In addition, the changes of muscle atrophy F-box (MAFbx), muscle RING-finger protein-1 (MuRF1), forkhead box O1 (FOXO1) mRNA expression in skeletal muscle of rats were observed. RESULTS: RGP significantly increased the percentage of fluorescence perimeter and bone mineralization deposition rate of the second lumbar vertebrae of rats. It also significantly increased the wet weight ratio and muscle fiber cross-sectional area of the gastrocnemius muscle of rats. At the same time, RGP significantly increased the levels of super oxide dismutase (SOD) and catalase (CAT) in the skeletal muscle of rats, and reduced the content of malondialdehyde (MDA). Rehmannia glutinosa polysaccharides also significantly reduced the expression levels of FOXO1, MAFbx and MuRF1 mRNA in rat skeletal muscle. CONCLUSIONS: RGP could improve the bone structure of osteoporotic rats. It could also improve muscle that atrophy may be related to the inhibition of FOXO1-mediated ubiquitin-proteasome pathway.

Design, synthesis and bioactivity evaluation of novel N-phenyl-substituted evodiamine derivatives as potent anti-tumor agents.

Natural products are important sources for the development of therapeutic medicine, among which evodia fruit has a wide range of medicinal properties in traditional Chinese medicine. Evodiamine, the main active component of evodia fruit, has various anti-cancer effects and has been proved to be a Topo inhibitor. From our previous attempts of modifying evodiamine, we found that the N14 phenyl substituted derivatives had showed great anti-tumor activity, which prompted us to further explore the novel structures and activities of these compounds. Compound 6f, as a N14 3-fluorinated phenyl substituted evodiamine derivative, showed a certain inhibitory activity against Topo I at 200 µM. By studying its anti-tumor effects in vitro, compound 6f could inhibit proliferation and induce apoptosis, as well as arrest the cell cycle of HGC-27 and HT-29 cell lines at G2/M phase in a concentration-dependent manner. Moreover, compound 6f could inhibit the migration and invasion of HGC-27 cell lines. Meanwhile, compound 6f could induce apoptosis of HGC-27 cells by inhibiting PI3K/AKT pathway. Overall, this work demonstrated that the N14 phenyl-substituted evodiamine derivatives had a good inhibitory effect on tumor cells in vitro, providing a promising strategy for developing potential anticancer agents for the treatment of gastrointestinal tumors.

Melatonin derivatives combat with inflammation-related cancer by targeting the Main Culprit STAT3.

The combination between two well-studied bioactive compounds melatonin and salicylic acid with proper modifications unexpectedly creates a sharp pair of "scissors" cutting off the vicious connection between inflammation and cancer by targeting a key contributor Signal Transducers and Activators of Transcription 3 (STAT3) in the two pathological processes. A representative compound P-3 with IC50 values on each tested cell line ranging from 7.37 to 18.62 µM among the designed melatonin derivatives is equipped with the ability of curbing inflammation-promoting cancer by down-regulating the expression, activation and nuclear translocation of STAT3, breaking the feedforward loop of STAT3 activation by decreasing the expression of pro-tumorigenic cytokines, and inducing cell apoptosis through ROS triggered Cyto-c/Caspase-3 pathway. This study suggests that the melatonin derivative P-3 is likely to become a promising chemical structure for developing the novel anti-cancer agents taking effect through hindering the mutual-promoting processes between inflammation and cancer.

Effects of Rehmannia glutinosa polysaccharides on bone tissue structure and skeletal muscle atrophy in rats with disuse

ABSTRACT Purpose To study effects of Rehmannia glutinosa polysaccharides (RGP) on bone tissue structure and skeletal muscle atrophy in rats with disuse. Methods A rat model of disuse osteoporosis combined with muscle atrophy was established by removing the bilateral ovaries of rats and fixing their hind limbs for a long time. Forty SD rats were administered intragastrically for 12 weeks. The bone histomorphometry parameters and the level of oxidative stress were measured. In addition, the changes of muscle atrophy F-box (MAFbx), muscle RING-finger protein-1 (MuRF1), forkhead box O1 (FOXO1) mRNA expression in skeletal muscle of rats were observed. Results RGP significantly increased the percentage of fluorescence perimeter and bone mineralization deposition rate of the second lumbar vertebrae of rats. It also significantly increased the wet weight ratio and muscle fiber cross-sectional area of the gastrocnemius muscle of rats. At the same time, RGP significantly increased the levels of super oxide dismutase (SOD) and catalase (CAT) in the skeletal muscle of rats, and reduced the content of malondialdehyde (MDA). Rehmannia glutinosa polysaccharides also significantly reduced the expression levels of FOXO1, MAFbx and MuRF1 mRNA in rat skeletal muscle. Conclusions RGP could improve the bone structure of osteoporotic rats. It could also improve muscle that atrophy may be related to the inhibition of FOXO1-mediated ubiquitin-proteasome pathway.