The role of miR-128 and MDFI in cardiac hypertrophy and heart failure: Mechanistic.

Heart failure (HF) prognosis depends on various regulatory factors; microRNA-128 (miR-128) is identified as a regulator of cardiac fibrosis, contributing to HF. MyoD family inhibitor (MDFI), which is reported to be related with Wnt/ß-catenin pathway, is supposed to be regulated by miR-128. This study investigates the interaction between miR-128 and MDFI in cardiomyocyte development and elucidates its role in heart injury. Gene expression profiling assessed miR-128's effect on MDFI expression in HF using qPCR and Western blot analysis. Luciferase assays studied the direct interaction between miR-128 and MDFI. MTT, transwell, and immunohistochemistry evaluated the effects of miR-128 and MDFI on myocardial cells in mice HF. Genescan and luciferase assays validated the interaction between miR-128 and MDFI sequences. miR-128 mimics significantly reduced MDFI expression at mRNA and protein levels with decrease rate of 55%. Overexpression of miR-128 promoted apoptosis with the increase rate 65% and attenuated cardiomyocyte proliferation, while MDFI upregulation significantly enhanced proliferation. Elevated miR-128 levels upregulated Wnt1 and ß-catenin expression, whereas increased MDFI levels inhibited these expressions. Histological analysis with haematoxylin and eosin staining revealed that miR-128 absorption reduced MDFI expression, hindering cell proliferation and cardiac repair, with echocardiography showing corresponding improvements in cardiac function. Our findings suggest miR-128 interacts with MDFI, playing a crucial role in HF management by modulating the Wnt1/ß-catenin pathway. Suppression of miR-128 could promote cardiomyocyte proliferation, highlighting the potential value of the miR-128/MDFI interplay in HF treatment.

Cancer-associated fibroblast infiltration in osteosarcoma: the discrepancy in subtypes pathways and immunosuppression.

Introduction: Osteosarcoma (OS), the primary malignant bone tumor, has a low survival rate for recurrent patients. Latest reports indicated that cancer-associated fibroblasts (CAFs) were the main component of tumor microenvironment, and would generate a variable role in the progression of tumors. However, the role of CAFs is still few known in osteosarcoma. Methods: The processed RNA-seq data and the corresponding clinical and molecular information were retrieved from the Cancer Genome Atlas Program (TCGA) database and processed data of tumor tissue was obtained from Gene Expression Omnibus (GEO) database. Xcell method was used in data processing, and Gene set variation analysis (GSVA) was used to calculates enrichment scores. Nomogram was constructed to evaluate prognostic power of the predictive model. And the construction of risk scores and assessment of prognostic predictive were based on the LASSO model. Results: This study classified Cancer Genome Atlas (TCGA) cohort into high and low CAFs infiltrate phenotype with different CAFs infiltration enrichment scores. Then TOP 9 genes were screened as prognostic signatures among 2,488 differentially expressed genes between the two groups. Key prognostic molecules were CGREF1, CORT and RHBDL2 and the risk score formula is: Risk-score = CGREF1*0.004 + CORT*0.004 + RHBDL2*0.002. The signatures were validated to be independent prognostic factors to predict tumor prognosis with single-factor COX and multi-factor COX regression analyses and Norton chart. The risk score expression of risk score model genes could predict the drug resistance, and significant differences could be found between the high and low scoring groups for 17-AAG, AZD6244, PD-0325901 and Sorafenib. Discussion: To sum up, this article validated the prediction role of CAF infiltration in the prognosis of OS, which might shed light on the treatment of OS.

The soldiers needed to be awakened: Tumor-infiltrating immune cells.

In the tumor microenvironment, tumor-infiltrating immune cells (TIICs) are a key component. Different types of TIICs play distinct roles. CD8+ T cells and natural killer (NK) cells could secrete soluble factors to hinder tumor cell growth, whereas regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) release inhibitory factors to promote tumor growth and progression. In the meantime, a growing body of evidence illustrates that the balance between pro- and anti-tumor responses of TIICs is associated with the prognosis in the tumor microenvironment. Therefore, in order to boost anti-tumor response and improve the clinical outcome of tumor patients, a variety of anti-tumor strategies for targeting TIICs based on their respective functions have been developed and obtained good treatment benefits, including mainly immune checkpoint blockade (ICB), adoptive cell therapies (ACT), chimeric antigen receptor (CAR) T cells, and various monoclonal antibodies. In recent years, the tumor-specific features of immune cells are further investigated by various methods, such as using single-cell RNA sequencing (scRNA-seq), and the results indicate that these cells have diverse phenotypes in different types of tumors and emerge inconsistent therapeutic responses. Hence, we concluded the recent advances in tumor-infiltrating immune cells, including functions, prognostic values, and various immunotherapy strategies for each immune cell in different tumors.

An Inducible Nitric Oxide Synthase Dimerization Inhibitor Prevents the Progression of Osteoarthritis.

Objective: Osteoarthritis (OA) is a degenerative joint disease. Excessive nitric oxide (NO) mediates the chondrocyte inflammatory response, apoptosis, and extracellular matrix (ECM) degradation during the occurrence and development of OA. NO in chondrocytes is mainly produced by inducible nitric oxide synthase (iNOS). The aim of this study was to design and synthesize an iNOS dimerization inhibitor and evaluate its effects on chondrocyte inflammation and articular cartilage injury in OA via in vitro and in vivo experiments. Design: The title compound 22o was designed, synthesized, and screened based on a previous study. The effects of different concentrations (5, 10, and 20 µM) of compound 22o on chondrocyte inflammatory response and ECM anabolism or catabolism were evaluated by Western blot and real-time quantitative reverse transcription-polymerase chain reaction using the rat chondrocyte model of IL-1ß-induced OA. Furthermore, different doses (40 and 80 mg/kg) of compound 22o were administered by gavage to a rat OA model induced by anterior cruciate ligament transection (ACLT), and their protective effects on the articular cartilage were evaluated by histopathology and immunohistochemistry. Results: Compound 22o showed effective iNOS inhibitory activity by inhibiting the dimerization of iNOS. It inhibited the IL-1ß-induced expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase 3 (MMP3) in the chondrocytes, decreased NO production, and significantly increased the expression levels of the ECM anabolic markers, aggrecan (ACAN), and collagen type II (COL2A1). Gavage with compound 22o was found to be effective in the rat OA model induced by ACLT, wherein it regulated the anabolism and catabolism and exerted a protective effect on the articular cartilage. Conclusions: Compound 22o inhibited the inflammatory response and catabolism of the chondrocytes and reduced articular cartilage injury in the rat OA model, indicating its potential as a disease-modifying OA drug.

Ultrasonic-assisted extraction of polyphenolic compounds from Paederia scandens (Lour.) Merr. Using deep eutectic solvent: optimization, identification, and comparison with traditional methods.

Ultrasonic-assisted extraction (UAE) coupled with deep eutectic solvent (DES) is a novel, efficient and green extraction method for phytochemicals. In this study, the effects of 16 DESs coupled with UAE on the extraction rate of polyphenols from Paederia scandens (Lour.) Merr. (P. scandens), an edible and medicinal herb, were investigated. DES synthesised with choline chloride and ethylene glycol at a 1:2 M ratio resulted in the highest extractability. Moreover, the effects of extraction parameters were investigated by using a two-level factorial experiment followed by response surface methodology The optimal parameters (water content in DES of 49.2%, the actual ultrasonic power of 72.4 W, and ultrasonic time of 9.7 min) resulted in the optimal total flavonoid content (TFC) (27.04 mg CE/g DW), ferric-reducing antioxidant power (FRAP) value (373.27 µmol Fe(Ⅱ)E/g DW) and 2,2'-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid radical (ABTS+) value (48.64 µmol TE/g DW), closely matching the experimental results. Furthermore, a comparison study demonstrated that DES-UAE afforded the higher TFC and FRAP value than traditional extraction methods. 36 individual polyphenolic compounds were identified and quantified by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) in P. scandens extracts, and of which 30 were found in the extracts obtained by DES-UAE. Additionally, DES-UAE afforded the highest sum of individual polyphenolic compound content. These results revealed that DES-UAE enhanced the extraction efficiency for polyphenols and provided a scientific basis for further processing and utilization of P. scandens.

ß-Hydroxybutyrate impairs the release of bovine neutrophil extracellular traps through inhibiting phosphoinositide 3-kinase-mediated nicotinamide adenine dinucleotide phosphate oxidase reactive oxygen species production.

Ketosis in dairy cows often occurs in the peripartal period and is accompanied by immune dysfunction. High concentrations of ß-hydroxybutyrate (BHB) in peripheral blood during ketosis inhibits the release of neutrophil extracellular traps (NET) and contributes to immune dysfunction. However, the mechanisms whereby BHB affects NET release remains unclear. In this study, 5 healthy peripartal dairy cows (within 3 wk postpartum) with serum BHB concentrations <0.6 mM and glucose concentrations >3.5 mM were used as blood donors. Blood samples were collected before feeding, and the isolated polymorphonuclear neutrophils were incubated with 3 mM BHB for different times. Inhibition of Cit-H3 (citrullinated histone 3) protein abundance, a marker of NET activation, in response to BHB was used to determine an optimal incubation time for in vitro experiments. Four hours was selected as the optimal duration of BHB treatment. Phorbol-12-myristate-13-acetate (PMA) was used to induce the release of NET in vitro. The BHB treatment with or without PMA treatment decreased protein abundance of Cit-H3 and PAD4 (arginine deiminase 4) and increased neutrophil elastase. Immunofluorescence and scanning electron microscope analyses revealed that BHB treatment inhibited PMA-induced NET release. The BHB treatment also decreased double strain DNA content in the supernatant, further confirming the inhibitory effect of BHB on NET release. Furthermore, BHB treatment decreased the level of intracellular reactive oxygen species (ROS), phosphorylation level of p47, and protein abundance of Rac2, suggesting that BHB-induced NET inhibition may have been caused by decreased NADPH oxidase-derived ROS. The phosphorylation level of phosphoinositide 3-kinase (PI3K), an important upstream regulator of NADPH oxidase, was attenuated by BHB treatment. To confirm the involvement of PI3K signaling pathway in BHB-induced NET inhibition, 740Y-P, a potent activator of PI3K signaling pathway, was used. Data indicated that 740Y-P relieved the inhibitory effects of BHB on ROS production and NADPH oxidase activation. Importantly, as revealed by immunofluorescence and scanning electron microscopy analyses, 740Y-P also dampened the inhibitory effect of BHB on NET release and the protein abundance of Cit-H3 and PAD4. Overall, the present study revealed that high concentration of BHB impairs NET release through inhibiting PI3K-mediated NADPH oxidase ROS production. These findings help partly explain the immune dysfunction in cows experiencing negative energy balance or ketosis in early lactation.

Transform Quantization for CNN Compression.

In this paper, we compress convolutional neural network (CNN) weights post-training via transform quantization. Previous CNN quantization techniques tend to ignore the joint statistics of weights and activations, producing sub-optimal CNN performance at a given quantization bit-rate, or consider their joint statistics during training only and do not facilitate efficient compression of already trained CNN models. We optimally transform (decorrelate) and quantize the weights post-training using a rate-distortion framework to improve compression at any given quantization bit-rate. Transform quantization unifies quantization and dimensionality reduction (decorrelation) techniques in a single framework to facilitate low bit-rate compression of CNNs and efficient inference in the transform domain. We first introduce a theory of rate and distortion for CNN quantization and pose optimum quantization as a rate-distortion optimization problem. We then show that this problem can be solved using optimal bit-depth allocation following decorrelation by the optimal End-to-end Learned Transform (ELT) we derive in this paper. Experiments demonstrate that transform quantization advances the state of the art in CNN compression in both retrained and non-retrained quantization scenarios. In particular, we find that transform quantization with retraining is able to compress CNN models such as AlexNet, ResNet and DenseNet to very low bit-rates (1-2 bits).

Operation and robustness analysis of a star-bus optic fiber sensor network.

This paper proposes a star-bus topology optic fiber sensor network with an efficient mechanism for network communication to accomplish monitoring and protection operations. The master node scans each channel for its healthy conditions with an N * M optical switch, just as in time-division multiplexing, accomplishing a comprehensive monitoring of the whole sensor network. In addition, we analyze the impact of structural parameters on network robustness, then obtain a basic design principle of network topology. We also demonstrate the proposed network's feasibility by multiplexing different fiber sensor systems simultaneously; in addition, an optimized structure is proposed to accomplish the measurement in extreme environments and proved to be effective.

Identification and characterization of two highly homologous lysozymes from red swamp crayfish, Procambarus clarkii.

Lysozyme is an important immune effector in innate immunity against pathogen infection. But the study on the active region of lysozyme is limited. In this study, two highly homologous lysozymes were identified from crayfish (designated as PcLysi4 and PcLysi5). The molecular structures of PcLysi4 and PcLysi5 were predicted by SWISS-MODEL with the structure of lysozyme (PDB accession No. 4PJ2.2.B) as model. The results suggested that the structure of PcLysi4 and PcLysi5 were highly similar, but there were more α-helices at positions (127-139) and longer ß-sheet at positions (49-57) in the structure of PcLysi5 than in that of PcLysi4. The antibacterial and antiviral functions of the two lysozymes were investigated. PcLysi4 and PcLysi5 could promote the bacterial clearance ability of crayfish, and increase the survival rate of Vibrio-infected crayfish. Further study showed that PcLysi5 inhibited WSSV replication, and enhanced the survival rate of WSSV-infected crayfish. There was no evidence that PcLysi4 has an influence on WSSV replication. Furthermore, PcLysi5 was detected to interact with envelope protein VP24 of WSSV. Our results would provide a new reference for the study on active region of lysozyme.

Oxidation of salicylic acid in water by the O3 and UV/O3 processes: removal and reaction byproducts.

In this study, the removal of salicylic acid (SA) in water by ozone (O3) and ultraviolet/ozone (UV/O3) processes was investigated. Results showed that more than 50% of SA (10 mg/L) could be effectively removed after 1 min during these two processes. However, the UV/O3 process was much more effective than the O3 process for SA mineralization, and the total organic carbon reduction after 30 min was 69.5% and 28.1%, respectively. In the two processes, the optimum pH value for SA removal was 4.3, while that for SA mineralization was 10.0. Both bicarbonate and dissolved organic carbon significantly inhibited SA removal during the two processes. Eleven oxidation byproducts were detected in O3 process, but only four byproducts were observed in UV/O3 process. Three hydroxylation aromatic products were identified as the initial byproducts during SA degradation. Glyoxylic acid monohydrate, glycolic acid, and oxalic acid were accumulated in O3 process but not observed in UV/O3 process. Oxalic acid was the only detected small molecular byproduct in UV/O3 process, and it could be further mineralized, thereby indicating that UV/O3 had a greater potential for degrading both SA and its reaction byproducts.

Clinical effectiveness and safety of self-expanding metal stent placement following palliative chemotherapy in patients with advanced esophageal cancer.

PURPOSE: To investigate the effect of prior chemotherapy on self-expanding metal stent (SEMS)-related complications in patients with locally advanced primary esophageal cancer. MATERIALS AND METHODS: Data from patients with locally advanced primary esophageal cancer who received SEMS placement with or without prior chemotherapy were retrospectively reviewed. Patients were grouped according to prior palliative therapy: group A (n = 41) had received SEMS only, and group B (n = 64) had received palliative chemotherapy prior to SEMS placement. Patients' age, stricture length, tumor location, and dysphagia score prior to SEMS placement were evaluated. The overall patient cohort had a median follow-up period of 129 days (range 11-463). Outcomes after SEMS placement, including technical and clinical success rates, the occurrence of complications, and overall survival, were compared. RESULTS: There were no significant differences between the two groups regarding patients' age, stricture length, tumor location, and dysphagia score prior to SEMS placement. SEMS placement was technically successful in all patients, with no procedure-related complications reported. Clinical success was achieved in 95.1% of patients in group A and 96.8% of patients in group B. The duration of stent patency was significantly shorter in group B [162 days; 95% confidence interval (CI) 126.6-198.4 vs. group A (339 days; 95% CI 258.8-419.3], p = 0.001. No significant differences were seen between the two groups regarding dysphagia score improvement [group A (3.15 ± 0.57 to 1.17 ± 0.83; p < 0.001) and group B (3.17 ± 0.80 to 1.14 ± 0.79; p < 0.001); p = 0.66], complications [group A (10/41), and group B (24/64); p = 0.094], or overall survival [the median and mean overall survival periods were 105 (95% CI 30-180) and 132 days (95% CI 97-167), respectively, in group A, and 126 (95% CI 88-164) and 156 days (95% CI 132-180), respectively, in group B; p = 0.592]. CONCLUSION: Prior chemotherapy did not increase the risk of complications following SEMS placement in patients with locally advanced esophageal cancer. SEMS patency was significantly longer in patients who did not receive chemotherapy prior to SEMS placement. LEVEL OF EVIDENCE: Level 4, Case Series.

Fully covered self-expandable esophageal metallic stents in patients with inoperable malignant disease who survived for more than 6 months after stent placement.

OBJECTIVES: To investigate the clinical outcomes of fully covered self-expanding metal stent (FCSEMS) placement in patients with malignant esophageal obstruction who survived longer than 6 months. METHODS: From January 2002 to January 2018, 88 FCSEMS were placed in 64 patients (mean age 62.9 ± 11.6 years; 58 males) with inoperable malignant esophageal obstruction with or without esophago-respiratory fistula. Only patients who survived more than 6 months with FCSEMS in place were included. Data regarding technical and clinical success, complications, reinterventions, stent patency, and patient survival were obtained from a prospectively maintained hospital database. RESULTS: The technical and clinical success rates were 100 % (64/64). During follow-up, the median dysphagia score significantly improved (3.09 ± 0.68 to 1.05 ± 0.60, p < 0.001). The complication rate was 48.8 %. Multivariate analysis revealed that only longer stenting duration was associated with complications [hazard ratio = 1.220, 95 % confidence interval (CI) (1.074-2.760), p = 0.039]. The median follow-up duration was 257 days (range, 181-969). The median stent patency duration was 289 days [95% CI (209.9-368.1)]. The median survival was 254 days [95% CI (219.7-288.3)]. CONCLUSIONS: Our data suggest that esophageal FCSEMS placement is an effective option for patients with malignant dysphagia when survival longer than 6 months is expected. The rate of complications increases with time, and SEMS development is needed to keep up with the advancement in oncological treatment. ADVANCES IN KNOWLEDGE: Fully covered esophageal self-expandable stent placement is effective in patients surviving more than 6 months, however, the rate of complications also increases. SEMS development is needed to cope with the advancement in oncological treatment.

A Novel Full Sense Device to Treat Obesity in a Porcine Model: Preliminary Results.

PURPOSE: To evaluate the technical feasibility, safety, and efficacy of a novel full sense device (FSD) for the treatment of obesity in a porcine model. MATERIALS AND METHODS: The novel FSD comprised a self-expanding metallic esophageal stent connected to a star-shaped nitinol disk. Three types of FSD were used: fully covered (type A), fully covered with barbs (type B), and uncovered with barbs (type C). Nine juvenile pigs were divided into two groups: FSD (n = 6) and control (n = 3). FSD type A was placed in the FSD group. In case of migration, either FSD type B or type C was then randomly placed. Food intake was monitored daily. Weight changes and ghrelin hormone levels were monitored weekly for 12 weeks. RESULTS: FSD placement was technically successful in all pigs. All FSDs except one migrated to the stomach within 1 week after placement. The pig in which the FSD was retained showed decreased food intake in the first week after FSD placement, and there was a difference in the final weight between the FSD pig and control pigs. The percentage of weight gain was 116.6% in the control group and 105.3% in the FSD pig. CONCLUSION: FSD placement under fluoroscopic and endoscopic guidance is technically feasible and safe in a porcine model. The uncovered FSD appears to decrease food intake and reduce the rate of weight gain. However, the high FSD migration rate is not encouraging.

125I implantation under computed tomography guidance to treat patients with recurrent pelvic tumors: Retrospective analysis of clinical results.

OBJECTIVE: The objective of the study was to evaluate computed tomography (CT)-guided 125I implantation for the treatment of recurrent and malignant pelvic tumors. MATERIALS AND METHODS: Fifteen cases of pelvic malignant tumors were studied. Tumor length/diameter was 4-10 cm (average: 6.8 ± 2.3 cm). In patients with pelvic recurrence or metastasis of malignant tumors, comprehensive treatment, including surgery, chemotherapy, or radiotherapy, was performed alongside CT-guided 125I implantation. The follow-up clinical benefit rate, rate of pain relief, quality of life score, and status of any complications were analyzed. RESULTS: The patients were followed up for 6 months after the operation, and evaluation of lesions revealed complete response (CR) in 3/15 cases, partial response (PR) in 8/15 cases, stable disease in 3/15 cases, and progressive disease in 1/15 cases. The total effective rate (CR + PR) was 73.3% (11/15), and the pain relief rate was 86.6% (13/15). No bleeding, pelvic abscesses, intestinal fistulas, intestinal perforations, or other complications were reported. CONCLUSIONS: When using CT-guided 125I implantation, patients with malignant abdominal tumors undergo a convenient operation, sustain little trauma, and have an improved quality of life.

Ultrastructures of Epibiotic Suctorian, Tokophrya huangmeiensis.

Tokophrya species are either free-living or facultative ectosymbiotic suctorians associated with copepods, isopods, mysids, decapods and amphipods. Tokophrya huangmeiensis in particular is found to be epizoic with the redclaw crayfish Cherax quadricarinatus Von Martens, 1868, which has been observed as part of an ongoing investigation of freshwater ciliates biodiversity in Huanggang, Hubei, China (Tahir et al. 2017). This first study on T. huangmeiensis based on morphological features using light microscopy and small subunit ribosomal DNA sequence (Tahir et al. 2017), suggested that more detailed descriptions on the physiological and structural changes of this species should be done. Thus, in this study, we looked at the ultrastructures of T. huangmeiensis using electron microscopy, including both scanning (SEM) and transmission electron microscopy (TEM).

Fluoroscopic Gastroduodenal Stent Placement in 55 Patients with Endoscopic Stent Placement Failure.

PURPOSE: To evaluate the technical feasibility and clinical effectiveness of fluoroscopic self-expandable metal stent (SEMS) placement in malignant gastroduodenal obstructions after failed endoscopic SEMS placement. MATERIALS AND METHODS: Between September 2010 and July 2017, 874 patients underwent endoscopic SEMS placement for dysphagia caused by malignant gastroduodenal obstructions. Endoscopic SEMS placement failed in 55 of 874 patients (6.3%). These patients were referred for fluoroscopic SEMS placement. In case of failed fluoroscopic SEMS placement, combined endoscopic and fluoroscopic SEMS placement was attempted at the same setting. RESULTS: Fluoroscopic SEMS placement was technically successful in 40 of 55 patients (72.7%). Combined endoscopic and fluoroscopic SEMS placement was technically successful in 6 of 15 patients with fluoroscopic SEMS placement failure. Failures in the nine patients were due to complete obstruction (n = 5) and acute angulation at the stricture site (n = 4). The overall technical success rate was 83.6% (46/55). Clinical success was achieved in 95.6% of patients (44/46). Complications occurred in 7 of 46 patients (15.2%), including tumor overgrowth (n = 3), SEMS migration (n = 3), and bleeding (n = 1). The median SEMS patency and patient survival periods were 515 (95% confidence interval (CI), 266.6-761.5) and 83 (95% CI 60.6-105.4) days, respectively. CONCLUSIONS: Fluoroscopic SEMS placement is technically feasible and clinically effective in cases of endoscopic SEMS placement failure. A combined endoscopic and fluoroscopic approach increases the technical success rate after failure of the endoscopic or fluoroscopic approach. LEVEL OF EVIDENCE: Level IV.

[Preparation processes of 3% yttria-stabilized tetragonal zirconia polycrystalline ceramic composite powders coated with nano-sized Al2O3-boron nitride].

OBJECTIVE: In this work, we aim to determine the optimum pH value for the preparation of 3% yttria-stabilized tetragonal zirconia polycrystalline (3Y-TZP)/3%Al2O3 and optimum calcination temperature of Al2O3 precursor and amorphous boron nitride (BN) for Al2O3-BN coating 3Y-TZP powders. METHODS: The 3Y-TZP/3%Al2O3 composite powders were prepared through the heterogeneous precipitation method under different pH values (6.5, 7.5, 8.5, and 9.5) and analyzed through transmission electron microscopy (TEM) to determine the optimum coating morphology. Al2O3 precursor, which was prepared under the optimum pH value, was calcined at different temperatures (800, 1 000, 1 200, and 1 400 ℃). The amorphous BN coating 3Y-TZP/3%Al2O3 powder was prepared via in situ reaction with boric acid and urea (calcined with N2 at 850 ℃ for 5 and 3 h and 800 ℃ for 5 and 3 h). TEM, energy dispersive spectrometry (EDS), and X-ray diffraction (XRD) were performed to characterize the results. RESULTS: The optimum coating morphology was obtained at 8.5 pH. When the Al2O3 precursor was calcined at 1 200 ℃ and coated with BN (calcined with N2 at 800 ℃ for 5 h), the Al-B-O compound was less, and t-ZrO2 was more represented. CONCLUSIONS: The optimum pH value for 3Y-TZP/3%Al2O3 composite preparation is 8.5. For the preparation of Al2O3-BN coating 3Y-TZP powders, the optimum calcination temperature of the Al2O3 precursor and amorphous BN are 1 200 and 800 ℃, respectively.

Alpha-lipoic acid attenuates endoplasmic reticulum stress-induced insulin resistance by improving mitochondrial function in HepG2 cells.

Alpha-lipoic acid (ALA) has been reported to have beneficial effects for improving insulin sensitivity. However, the underlying molecular mechanism of the beneficial effects remains poorly understood. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are considered causal factors that induce insulin resistance. In this study, we investigated the effect of ALA on the modulation of insulin resistance in ER-stressed HepG2 cells, and we explored the potential mechanism of this effect. HepG2 cells were incubated with tunicamycin (Tun) for 6h to establish an ER stress cell model. Tun treatment induced ER stress, mitochondrial dysfunction and insulin resistance. Interestingly, ALA had no significant effect on ER stress signals. Pretreatment of the ER stress cell model with ALA for 24h improved insulin sensitivity, restored the expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and increased intracellular ATP production. Moreover, ALA augmented the ß-oxidation capacity of the mitochondria. Importantly, ALA treatment could decrease oligomycin-induced mitochondrial dysfunction and then improved insulin resistance. Taken together, our data suggest that ALA prevents ER stress-induced insulin resistance by enhancing mitochondrial function.

Pseudo-inverse linear discriminants for the improvement of overall classification accuracies.

This paper studies the learning and generalization performances of pseudo-inverse linear discriminant (PILDs) based on the processing minimum sum-of-squared error (MS(2)E) and the targeting overall classification accuracy (OCA) criterion functions. There is little practicable significance to prove the equivalency between a PILD with the desired outputs in reverse proportion to the number of class samples and an FLD with the totally projected mean thresholds. When the desired outputs of each class are assigned a fixed value, a PILD is partly equal to an FLD. With the customarily desired outputs {1, -1}, a practicable threshold is acquired, which is only related to sample sizes. If the desired outputs of each sample are changeable, a PILD has nothing in common with an FLD. The optimal threshold may thus be singled out from multiple empirical ones related to sizes and distributed regions. Depending upon the processing MS(2)E criteria and the actually algebraic distances, an iterative learning strategy of PILD is proposed, the outstanding advantages of which are with limited epoch, without learning rate and divergent risk. Enormous experimental results for the benchmark datasets have verified that the iterative PILDs with optimal thresholds have good learning and generalization performances, and even reach the top OCAs for some datasets among the existing classifiers.