Structured Cerium-Manganese Catalysts Supported on Nickel Foam for Toluene Oxidation by Electric Internal Heating.

Structured catalysts are widely used in catalytic oxidation of gaseous pollutants, hot catalysis is usually needed to assist the reaction in the catalytic process. Herein, a Ce-modified manganese oxide octahedral molecular sieves (Ce-OMS-2) structured catalyst supported on foam nickel was prepared through impregnation process. A systematically quantitative testing on the toluene catalytic oxidation effectiveness of this structured catalyst was conducted through catalyst evaluation device, combining a series of characterization methods, such as XRD and SEM, the structure-activity relationship was established. Assisted with electric internal heating and ozone oxidation environments, this structured catalyst exhibits excellent catalytic oxidation performance for oxidative decomposition of toluene even under high humidity conditions. The results showed that the ozone-coupled structured nickel foam catalyst increased the decomposition efficiency of toluene from 25 % (without catalyst and heating) to 55 % (with catalyst and without heating) and the electric internal heating can significantly improve the reactivity and moisture resistance of the structured nickel-foam catalyst, at 90 % RH and 40000 h-1, 50000 ppb O3 and 40 mg/m3 toluene was maintained 100 % catalytic efficiency. The high-efficiency non-precious metal-based electrothermal catalyst prepared herein is expected to have certain enlightenment for the purification of VOCs.

Carbonic Anhydrase-Embedded Hydrogen-Bonded Organic Frameworks Coating for Facilitated Offshore CO2 Fixation.

Exhausted emission of carbon dioxide (CO2 ) from ships or offshore platforms has become one of the major contributors to global carbon emissions. Enzymes such as carbonic anhydrase (CA) have been widely used for CO2 mineralization because of their high catalytic rate. However, CA in seawater is easy to inactivate and difficult to reuse. Immobilization would be a feasible solution to address the stability issue, which, however, may cause an increase of internal diffusion resistance and reduced catalytic activity. In this regard, design of high-performance biocatalysts for acquiring high catalytic activity and stability of CA is highly desirable. Herein, a monolithic catalyst of Filler-CA@Lys-HOF-1 (FCLH) was prepared by chemical sorption of CA on the surface of the Filler followed by the coating of Lys-HOF-1. The highest catalytic activity of FCLH was obtained by regulating the amount of HOF-1 monomer added. Due to the protection of Lys-HOF-1, the FCLH showed good tolerance against acidity and salinity, which could retain about 80.2 % of the original activity after 9 h incubation in simulated seawater. The catalytic activity of FCLH could retain 85.4 % of the initial activity after 10 cycles. Hopefully, our study can provide a promising biocatalyst for CO2 mineralization, which may drive down carbon emissions when used for CO2 capture and conversion on offshore platforms.

Competing Si2CH4-H2 and SiCH2-SiH4 Channels in the Bimolecular Reaction of Ground-State Atomic Carbon (C(3Pj)) with Disilane (Si2H6, X1A1g) under Single Collision Conditions.

The bimolecular gas-phase reaction of ground-state atomic carbon (C(3Pj)) with disilane (Si2H6, X1A1g) was explored under single-collision conditions in a crossed molecular beam machine at a collision energy of 36.6 ± 4.5 kJ mol-1. Two channels were observed: a molecular hydrogen elimination plus Si2CH4 (reaction 1) pathway and a silane loss channel along with the formation of SiCH2 (reaction 2), with branching ratios of 20 ± 3 and 80 ± 4%, respectively. Both channels involved indirect scattering dynamics via long-lived Si2CH6 reaction intermediate(s); the latter eject molecular hydrogen and silane in "molecular" elimination channels within the rotational plane of the fragmenting intermediate nearly perpendicularly to the total angular momentum vector. These molecular elimination channels are associated with tight exit transition states as reflected in a significant electron rearrangement as visible from the chemical bonding in the light reaction products molecular hydrogen and silane. Once these hydrogenated silicon-carbide clusters are formed within the inner envelope of carbon stars such as of IRC + 10216, the stellar wind can drive both Si2CH4 and SiCH2 to the outside sections of the envelope, where they can be photolyzed. This is of particular importance to unravel potential formation pathways to disilicon monocarbide (Si2C) observed recently in the circumstellar shell of IRC + 10216.

Xihuang pills induce apoptosis in hepatocellular carcinoma by suppressing phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin pathway.

BACKGROUND: The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin (PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills (XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma (HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHP-associated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway. AIM: To confirm the effect of XHP on HCC and the possible mechanisms involved. METHODS: The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS). Cell-based experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP (0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay. Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction (RT-qPCR), respectively. Third, Western blotting and RT-qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway. Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed. RESULTS: The following 12 compounds were identified in XHP using high-resolution mass spectrometry: Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-ß-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-ß-boswellic acid, 5ß-androstane-3,17-dione, and 3-acetyl-11-keto-ß-boswellic acid. The cell viability assay results showed that treatment with 0.625 mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose- and time-dependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract (0.625 mg/mL). Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins (e.g., caspase-9 and caspase-3). The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights. CONCLUSION: XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3. Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.

[Research progress on precious Tibetan medicine formula in prevention and treatment of central nervous system diseases].

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.

[Mechanism of Tibetan medicine Ershiwuwei Songshi Pills in regulating intestinal flora and improving non-alcoholic steatohepatitis].

This study aimed to investigate the effect of Tibetan medicine Ershiwuwei Songshi Pills(ESP) on the intestinal flora of non-alcoholic steatohepatitis(NASH) mice. Forty-eight male C57 BL/6 mice were randomly divided into the control group, model(methionine-choline-deficient, MCD) group, high-(0.8 g·kg~(-1)), medium-(0.4 g·kg~(-1)), and low-dose(0.2 g·kg~(-1)) ESP groups, and pioglitazone(PGZ, 10 mg·kg~(-1)) group, with eight mice in each group. Mice in the control group were fed with normal diet, while those in the remaining five groups with MCD diet for five weeks for inducing NASH. During modeling, they were gavaged with the corresponding drugs. The changes in body mass, daily water intake, and daily food intake were recorded. At the end of the experiment, the liver tissues were collected and stained with hematoxylin-eosin(HE) for observing the pathological changes, followed by oil red O staining for observing fat accumulation in the liver. The levels of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and triglyceride(TG) in liver tissue were measured. The changes in intestinal flora of mice were determined using 16 S rRNA high-throughput sequencing technology. The results showed that compared with the model group, the high-, medium-and low-dose ESP groups and the PGZ group exhibited significantly lowered AST and ALT in serum and TG in liver tissues and alleviated hepatocellular steatosis and fat accumulation in the liver. As demonstrated by 16 S rRNA sequencing, the abundance index and diversity of intestinal flora decreased in the model group, while those increased in the ESP groups. Besides, the Firmicutes to Bacteroidetes ratio decreased at the phylum level. In the alteration of the composition of intestinal flora, ESP reduced the abundance of Erysipelotrichia and Faecalibaculum but increased the abundance of Desulfovibrionaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. This study has revealed that ESP has a protective effect against NASH induced by MCD diet, which may be related to its regulation of the changes in intestinal flora, alteration of the composition of intestinal flora, and inhibition of the intestinal dysbiosis.

[Ershiwuwei Shanhu Pills regulate Akt/mTOR/GSK-3ß signaling pathway to alleviate Alzheimer's disease mice].

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3ß signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3ß in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3ß in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3ß signaling pathway.

[Mechanism of Tibetan medicine Ershiwuwei Shanhu Pills on scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway].

This study aims to investigate the mechanism of the Tibetan medicine Ershiwuwei Shanhu Pills(ESP) in improving scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway. ICR mice were randomized into blank group, model group, low-dose(200 mg·kg~(-1)), medium-dose(400 mg·kg~(-1)), and high-dose(800 mg·kg~(-1)) ESP groups, and donepezil hydrochloride group. The learning and memory impairment was induced in mice by intraperitoneal injection of scopola-mine. The learning and memory abilities of mice were detected by Morris water maze test, and the damage of hippocampal neurons and cortical neurons was detected based on Nissl staining. The expression of neuron specific nuclear protein(NeuN) in hippocampus and cortex of mice was determined by immunofluorescence assay, and the content of acetylcholine(Ach) and the activity of acetylcholines-terase(AchE) in hippocampus of mice by kits. Moreover, the content of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in serum of mice was detected. The content of Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase 1(HO-1) in hippocampus was determined by Western blot. The results showed that there were significant differences in the trajectory map of mice among different groups in the behavioral experiment. Moreover, the latency of ESP groups decreased significantly compared with that in the model group. The hippocampal neurons in the high-dose ESP group were significantly more than those in the model group and the cortical neurons in the high-dose and medium-dose ESP groups were significantly more than those in the model group. The expression of NeuN in the model group was significantly decreased compared with that in the blank group, and the expression in the ESP groups was significantly higher than that in the model group. The AchE activity and MDA level were significantly decreased, and Ach content and levels of SOD, CAT, and T-AOC in the ESP groups were significantly increased in the ESP groups compared with those in the model group. The expression of Keap1 in the model group was significantly increased compared with that in the blank group, and the Keap1 expression increased insignificantly in ESP groups compared with that in the model group. The expression of Nrf2 and HO-1 was significantly lower in the model group than in the blank group, and the expression was significantly higher in the medium-dose ESP group than in the model group. In conclusion, ESP protected mice against the scopolamine-induced learning and memory impairment by regulating the Keap1/Nrf2/HO-1 signaling pathway.

Shuyu pills inhibit immune escape and enhance chemosensitization in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by dysregulation of the immune microenvironment and the development of chemoresistance. Specifically, expression of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis, an immune checkpoint, may lead to tumour immune escape, resulting in disease progression. The latest research shows that tumour immune escape may be caused by the upregulation of PD-L1 mediated by hypoxia-inducible factor-1 alpha (HIF-1α), and simultaneous inhibition of HIF-1α and PD-L1 has the potential to enhance the host's antitumour immunity. Moreover, inhibition of the PD-1/PD-L1 axis may mitigate tumour chemoresistance. Shuyu pills (SYPs) contain immunity-enhancing and antitumour components, making them a potential HCC treatment. AIM: To investigate the efficacy of SYPs for HCC treatment via simultaneous HIF-1α and PD-L1 inhibition and the mechanism involved. METHODS: A subcutaneous xenograft tumour model was first established in BALB/c nude mice by the subcutaneous injection of 1 × 107 SMMC-7721 cells. Male mice (male, 5 weeks old; n = 24) were then randomly divided into the following four groups (n = 6): Control (0.9% normal saline), SYP (200 mg/kg), SYP + cisplatin (DDP) (200 mg/kg + 5 mg/kg DDP weekly via intraperitoneal injection), and DDP (5 mg/kg cisplatin weekly via intraperitoneal injection). The dose of saline or SYPs for the indicated mouse groups was 0.2 mL/d via intragastric administration. The tumour volumes and body weights of the mice were measured every 2 d. The mice were euthanized by cervical dislocation after 14 d of continuous treatment, and the xenograft tissues were excised and weighed. Western blot assays were used to measure the protein expression of HIF-1α, PD-1, PD-L1, CD4+ T cells, and CD8+ T cells in HCC tumours from mice. Quantitative reverse transcription polymerase chain reaction was used for real-time quantitative detection of PD-1, PD-L1, and HIF-1α mRNA expression. An immunofluorescence assay was conducted to examine the expression of CD4+ T cells and CD8+ T cells. RESULTS: Compared to mice in the control group, those in the SYP and SYP + DDP groups exhibited reduced tumour volumes and tumour weights. Moreover, the protein and mRNA expression levels of the oncogene HIF-1α and that of the negative immunomodulatory factors PD-1 and PD-L1 were decreased in both the SYP and SYP + DDP groups, with the decrease effects being more prominent in the SYP + DDP group than in the SYP group (HIF-1α protein: Control vs SYP, P = 0.0129; control vs SYP + DDP, P = 0.0004; control vs DDP, P = 0.0152, SYP + DDP vs DDP, P = 0.0448; HIF-1α mRNA: control vs SYP, P = 0.0009; control vs SYP + DDP, P < 0.0001; control vs DDP, P = 0.0003, SYP vs SYP + DDP, P = 0.0192. PD-1 protein: Control vs SYP, P = 0.0099; control vs SYP + DDP, P < 0.0001, SPY vs SYP + DDP, P = 0.0009; SYP + DDP vs DDP, P < 0.0001; PD-1 mRNA: control vs SYP, P = 0.0002; control vs SYP + DDP, P < 0.0001; control vs DDP, P = 0.0003, SPY vs SYP + DDP, P = 0.0003; SYP + DDP vs DDP, P = 0.0002. PD-L1 protein: control vs SYP, P < 0.0001; control vs SYP + DDP, P < 0.0001; control vs DDP, P < 0.0001, SPY vs SYP + DDP, P = 0.0040; SYP + DDP vs DDP, P = 0.0010; PD-L1 mRNA: Control vs SYP, P < 0.0001; control vs SYP + DDP, P < 0.0001; control vs DDP, P < 0.0001, SPY vs SYP + DDP, P < 0.0001; SYP + DDP vs DDP, P = 0.0014). Additionally, the quantitative and protein expression levels of CD4+ T cells and CD8+ T cells were simultaneously upregulated in the SYP + DDP group, whereas only the expression of CD4+ T cells was upregulated in the SYP group. (CD4+ T cell quantitative: Control vs SYP + DDP, P < 0.0001, SYP vs SYP + DDP, P = 0.0005; SYP + DDP vs DDP, P = 0.0002. CD4+ T cell protein: Control vs SYP, P = 0.0033; Control vs SYP + DDP, P < 0.0001; Control vs DDP, P = 0.0021, SYP vs SYP + DDP, P = 0.0004; SYP + DDP vs DDP, P = 0.0006. Quantitative CD8+ T cells: Control vs SYP + DDP, P = 0.0013; SYP vs SYP + DDP, P = 0.0347; SYP + DDP vs DDP, P = 0.0043. CD8+ T cell protein: Control vs SYP + DDP, P < 0.0001; SYP vs SYP + DDP, P < 0.0001; SYP + DDP vs DDP, P < 0.0001). Finally, expression of HIF-1α was positively correlated with that of PD-1/PD-L1 and negatively correlated with the expression of CD4+ T cells and CD8+ T cells. CONCLUSION: SYPs inhibit immune escape and enhance chemosensitization in HCC via simultaneous inhibition of HIF-1α and PD-L1, thus inhibiting the growth of subcutaneous xenograft HCC tumours.

Comparison of Clinical and Radiological Outcomes Between Upper Fibular Curvature and Non-Curvature with Medial Knee Osteoarthritis Following Proximal Fibular Osteotomy: A Retrospective Cohort Study with Minimum 2-Year Follow-up.

OBJECTIVE: To evaluate and compare the clinical and radiographic outcomes of proximal fibular osteotomy (PFO) in treating medial knee osteoarthritis (KOA) patients with upper fibular curvature and non-curvature. METHODS: A retrospective cohort study was performed. From January 2016 to January 2017, a total of 51 patients (nine males and 42 females) at a mean age of 63.7 years (range 48-79 years) with medial KOA who underwent PFO procedure at the Third Hospital of Hebei Medical University were included in the study. The patients were divided into the two groups, namely curvature group (28 patients, six males and 22 females, aged 62.6 ± 7.7 years) and non-curvature group (23 patients, three males and 20 females, aged 64.5 ± 7.6 years). Perioperative parameters and Kellgren-Lawrence classification were recorded and analyzed in the two groups, respectively. All patients were followed up at 1, 3, 6, and 12 months at the first year of post-operation, and then every 6 months from the second year of post-operation. A telephone survey with standard questionnaire survey, including Visual Analog Scale (VAS) score and Hospital for Special Surgery (HSS) scoring system, was used to evaluate postoperative clinical outcomes. Radiological results were assessed using the femorotibial angle (FTA), hip-knee-ankle angle (HKA), and settlement value of medial tibial platform (MTP) in the two groups. RESULTS: The average follow-up periods of the curvature group and the non-curvature group were 34.8 ± 6.1 and 33.9 ± 5.4 months, respectively. There were no significant differences between the two groups of demographic data in terms of number of patients, age, body mass index (BMI), gender, KOA side, and Kellgren-Lawrence classification (P > 0.05). The VAS scores of the curvature group and non-curvature group were (3.53 ± 1.62 vs 3.68 ± 1.43 at 1 month, 3.46 ± 0.79 vs 3.57 ± 0.66 at 3 months, and 2.43 ± 0.88 vs 2.83 ± 0.94 at 6 months, both P > 0.05), while significant differences were found from 12 months post-operation (1.54 ± 0.72 vs 2.03 ± 0.85 at 12 months, and 1.04 ± 0.69 vs 1.74 ± 0.75 at 24 months, both P < 0.05). The HSS scores of the curvature group and non-curvature group were (79.67 ± 5.14 vs 78.25 ± 6.37 at 1 month, 84.65 ± 3.76 vs 83.18 ± 3.64 at 3 months, and 86.27 ± 3.13 vs 85.49 ± 3.25 at 6 months, both P > 0.05), while significant differences were found from 12 months post-operation (90.64 ± 4.32 vs 87.71 ± 5.63 at 12 months, and 92.93 ± 2.07 vs 90.06 ± 2.08 at 24 months, both P < 0.05). In addition, the FTA and settlement value of the curvature group were lower than the non-curvature group (177.18 ± 1.52 vs 178.35 ± 1.86, and 5.29 ± 1.74 vs 6.49 ± 2.09, both P < 0.05) while the HKA were higher than the non-curvature group (175.32 ± 2.34 vs 173.83 ± 2.64, P < 0.05) at the final follow-up. CONCLUSIONS: Medial KOA patients with upper fibular curvature is an optimal surgical indication for PFO surgery, with the advantages of pain relief, better functional recovery, and alignment correction.

Investigation of Damage Reduction When Dry-Drilling Aramid Fiber-Reinforced Plastics Based on a Three-Point Step Drill.

Aramid fiber-reinforced plastic (AFRP) is widely used in bullet-proof and armor structures, and is difficult to drill because of the high-toughness aramid fibers with ductile fracturing-differently from carbon fiber. Therefore, drilling quality cannot be ensured by the drilling used for carbon fiber-reinforced plastic, and frequently, delamination and burrs occur in the drilling process. This article first established a two-dimensional cutting model for analyzing the fiber deformation and material interface cracking. According to the model, reducing the thrust force and the radial force of the edge on the fibers is an effective way to reduce the fiber deformation, and a three-point step drill is proposed further. Comparative experiments were carried out among twist drilling, candle core drilling and three-point step drilling under three drilling parameters. The results show that the three-point step drill changed the traditional cutting behavior on the drill-exit material into a compound process. Finally, the AFRP was cut effectively with the novel drill with a small thrust force, and the delamination and "burrs area" were reduced through different drilling parameters. In summary, the three-point step drill can drill the AFRP without delamination and burrs with 0.02 mm/rev, which provides a new solution of cost-effective production for AFRP manufacturers.

MicroRNA-708 prevents ethanol-induced hepatic lipid accumulation and inflammatory reaction via direct targeting ZEB1.

Alcoholic liver disease (ALD) was a global liver disease which divided into liver inflammation, fatty liver, alcoholic hepatitis or cirrhosis. Abnormal expression levels of some microRNAs (miRNA) family members often lead to ALD and other liver diseases. MicroRNA-708 (miR-708) was known to suppress the proliferation and metastasis of hepatocellular carcinoma (HCC), but its role in the progression of ALD was not clear. In this study, the expression level of miR-708 was down-regulated in ethanol-induced L0-2 cells. ZEB1 could decrease the PPAR-α expression while increase the SREBP-1 expression. Meanwhile, the expression levels of TNF-α and IL-6 were up-regulated by ZEB1. Of note, ZEB1 aggravated the apoptotic rate of L0-2 cells induced by ethanol via inhibiting p-AKT and p-mTOR of AKT/mTOR signaling pathway. What's more, it was demonstrated that miR-708 family members particularly target ZEB1 3'-UTR regions and can down-regulate the expression level of ZEB1 in L0-2 cells. Sum up, these results indicated that miR-708 might inhibit the liver inflammation and lipid accumulation by targeting ZEB1 via regulating AKT/mTOR signaling pathway.

A nanosystem loaded with perfluorohexane and rose bengal coupled upconversion nanoparticles for multimodal imaging and synergetic chemo-photodynamic therapy of cancer.

Theranostics is a new trend integrating diagnostic and therapeutic functions in tumour research. Theranostic nanoparticles enabling both tumour imaging and drug delivery are a promising platform for image-guided cancer therapy. Photodynamic therapy (PDT) has great potential in synergy with traditional chemotherapy but faces great challenges due to hypoxia, poor targeting ability and the limited penetration depth of visible light. To solve these problems, we presented a novel nanosystem of FA/UCNPs-RB/HCPT/PFH@lipid (denoted as FURH-PFH-NPs), with a perfluorohexane (PFH) carrying rich oxygen core and a folic acid-modified lipid shell. The shell contains 10-hydroxycamptothecin (HCPT) and self-fluorescing photosensitizer compounds, namely, upconversion nanoparticles and rose bengal (UCNPs-RB). In this study, FURH-PFH-NPs aggregated in SKOV3 cells (in vitro) and the nude xenograft tumour region when combined with folic acid receptors. When triggered by low-intensity focused ultrasound (LIFU), FURH-PFH-NPs released PFH, UCNPs-RB and HCPT. The above procedure was monitored through multimodal imaging, which simultaneously guided the tumour therapy. UCNPs-RB and PFH promoted the PDT effect under LIFU. Through PDT and HCPT, we obtained better therapeutic effects and good biosafety against SKOV3 nude xenograft tumours. FURH-PFH-NPs combined with LIFU and laser irradiation might be a promising strategy for ovarian cancer.

ZEB1 regulates the activation of hepatic stellate cells through Wnt/ß-catenin signaling pathway.

Zinc finger E-box binding homeobox 1 (ZEB1) (previously known as TCF8), a transcriptional repressor, is a member of the zinc-finger family of proteins. Numerous studies have demonstrated that abnormal expression of ZEB1 in many types of liver disease including hepatocellular carcinoma (HCC). Liver fibrosis is the basis and central link in the progression of liver disease. Thereby, the function of ZEB1 in liver fibrosis has been investigated. The aim of the present study was to investigate the role of ZEB1 in liver fibrosis and to elucidate the mechanism. In this study, we explored the effect of ZEB1 in hepatic stellate cells (HSCs) activation and the regulatory mechanism of the Wnt/ß-catenin signaling pathway. Additionally, ZEB1 positively regulated the expression levels of α-SMA and Col.I in vivo and in vitro, which were correlated with the activated HSCs. Furthermore, overexpression of ZEB1 could inhibit HSCs apoptosis and promote IL-6 and TNF-α secretion in LX-2 cells. Conversely, ZEB1 silencing led to the promotion of cell proliferation and the reduction of IL-6 and TNF-α secretion in LX-2 cells. Mechanically, canonical Wnt/ß-catenin signaling pathway could be regulated by ZEB1. Collectively, the data suggested that ZEB1 might play a significant role in the activation of LX-2 cells, and Wnt/ß-catenin signaling pathway might participate in this progression.

A simple rule of direct reciprocity leads to the stable coexistence of cooperation and defection in the Prisoner's Dilemma game.

The long-term coexistence of cooperation and defection is a common phenomenon in nature and human society. However, none of the theoretical models based on the Prisoner's Dilemma (PD) game can provide a concise theoretical model to explain what leads to the stable coexistence of cooperation and defection in the long-term even though some rules for promoting cooperation have been summarized (Nowak, 2006, Science 314, 1560-1563). Here, based on the concept of direct reciprocity, we develop an elementary model to show why stable coexistence of cooperation and defection in the PD game is possible. The basic idea behind our theoretical model is that all players in a PD game prefer a cooperator as an opponent, and our results show that considering strategies allowing opting out against defection provide a general and concise way of understanding the fundamental importance of direct reciprocity in driving the evolution of cooperation.

Chromatin accessibility contributes to simultaneous mutations of cancer genes.

Somatic mutations of many cancer genes tend to co-occur (termed co-mutations) in certain patterns during tumor initiation and progression. However, the genetic and epigenetic mechanisms that contribute to the co-mutations of these cancer genes have yet to be explored. Here, we systematically investigated the association between the somatic co-mutations of cancer genes and high-order chromatin conformation. Significantly, somatic point co-mutations in protein-coding genes were closely associated with high-order spatial chromatin folding. We propose that these regions be termed Spatial Co-mutation Hotspots (SCHs) and report their occurrence in different cancer types. The conserved mutational signatures and DNA sequences flanking these point co-mutations, as well as CTCF-binding sites, are also enriched within the SCH regions. The genetic alterations that are harboured in the same SCHs tend to disrupt cancer driver genes involved in multiple signalling pathways. The present work demonstrates that high-order spatial chromatin organisation may contribute to the somatic co-mutations of certain cancer genes during tumor development.

Opting out against defection leads to stable coexistence with cooperation.

Cooperation coexisting with defection is a common phenomenon in nature and human society. Previous studies for promoting cooperation based on kin selection, direct and indirect reciprocity, graph selection and group selection have provided conditions that cooperators outcompete defectors. However, a simple mechanism of the long-term stable coexistence of cooperation and defection is still lacking. To reveal the effect of direct reciprocity on the coexistence of cooperation and defection, we conducted a simple experiment based on the Prisoner's Dilemma (PD) game, where the basic idea behind our experiment is that all players in a PD game should prefer a cooperator as an opponent. Our experimental and theoretical results show clearly that the strategies allowing opting out against defection are able to maintain this stable coexistence.

The role of institutional incentives and the exemplar in promoting cooperation.

People on average do not play their individually rational Nash equilibrium (NE) strategy in game experiments based on the public goods game (PGG) that model social dilemmas. Differences from NE behavior have also been observed in PGG experiments that include incentives to cooperate, especially when these are peer-incentives administered by the players themselves. In our repeated PGG experiment, an institution rewards and punishes individuals based on their contributions. The primary experimental result is that institutions which both reward and punish (IRP) promote cooperation significantly better than either institutions which only punish (IP) or which only reward (IR), and that IP has contribution levels significantly above IR. Although comparing their single-round NE strategies correctly predicts which incentives are best at promoting cooperation, individuals do not play these strategies overall. Our analysis shows that other intrinsic motivations that combine conforming behavior with reactions to being rewarded/punished provide a better explanation of observed outcomes. In our experiments, some individuals who display more cooperation than other individuals can be regarded as the exemplars (or leaders). The role of these exemplars in promoting cooperation provides important insights into understanding cooperation in PGG and the effectiveness of institutional incentives at promoting desirable societal behavior.

Transient receptor potential melastatin 7 (TRPM7) contributes to H2O2-induced cardiac fibrosis via mediating Ca(2+) influx and extracellular signal-regulated kinase 1/2 (ERK1/2) activation in cardiac fibroblasts.

Transient receptor potential melastatin 7 (TRPM7), a Ca(2+)-nonselective cation channel, plays a key role in the pathophysiological response of multiple cell types. However, the role of TRPM7 channels in hydrogen peroxide (H2O2)-induced cardiac fibrosis remains unclear. This study aimed to explore whether TRPM7 channels are involved in H2O2-induced cardiac fibrosis and the underlying mechanisms. Our results showed that 2-aminoethoxydiphenylborate (2-APB), which is commonly used to block TRPM7 channels, inhibited H2O2-induced cardiac fibrosis via attenuating the overexpression of important fibrogenic biomarkers and growth factors in cardiac fibroblasts, including collagen type I (Col I), fibronectin (FN), smooth muscle α-actin (α-SMA), connective tissue growth factor (CTGF), and transforming growth factor-ß1 (TGF-ß1). In addition, 2-APB also decreased H2O2-mediated elevation of the concentration of intracellular Ca(2+) ([Ca(2+)]i). Meanwhile, silencing TRPM7 channels by shRNA interference also impaired the increased [Ca(2+)]i and upregulation of Col I, FN, α-SMA, CTGF, and TGF-ß1 induced by H2O2. Furthermore, we found that H2O2-mediated activation of extracellular signal-regulated kinase 1/2 (ERK1/2) decreased in TRPM7-shRNA cells and Ca(2+)-free culture media. These results demonstrated that TRPM7 channels contributed to H2O2-induced cardiac fibrosis and suggested that this contribution may be through mediating Ca(2+) influx and phosphorylation of ERK1/2.