Electroacupuncture pretreatment inhibits ferroptosis and inflammation after middle cerebral artery occlusion in rats by activating Nrf2.

OBJECTIVE: Electroacupuncture (EA) pretreatment can effectively increase the tolerance of the brain to ischemic stroke. The mechanism of ischemic tolerance induced by EA is related to Nrf2, but its specific mechanism has not been elucidated. This paper was designed to explore the effect of EA pretreatment on brain injury and the related mechanisms. METHODS: Rats were pretreated with EA before middle cerebral artery occlusion (MCAO) modeling. The symptoms of neurological deficit and the volume of cerebral infarction were measured. The levels of inflammatory factors, oxidative stress-related factors, LPO, ROS, and Fe2+ were evaluated by the corresponding kits. Cell apoptosis was determined through TUNEL staining. The mRNA expression of inflammatory factors was examined by RT-qPCR, and the protein expression of ferroptosis-related factors, pyroptosis-related proteins, Keap1, Nrf2, HO-1, and NQO1 by western blotting. RESULTS: EA pretreatment improved the symptoms of neurological deficit and reduced the volume of cerebral infarction. EA pretreatment significantly inhibited oxidative stress, inflammatory response, ferroptosis, pyroptosis, and apoptosis in brain tissues of MCAO rats. Mechanistically, EA pretreatment could activate Nrf2 expression and reduce Keap1 expression. CONCLUSION: EA pretreatment reduced inflammation and oxidative stress and inhibited ferroptosis by activating Nrf2 expression, ultimately delaying the development of ischemic stroke.

Synthesis and pharmacodynamic evaluation of Dihydropteridone derivatives against PDCoV in vivo and in vitro.

Porcine Delta Coronavirus (PDCoV) infection can induce serious dehydration, diarrhea and even death of piglets, which has caused huge losses to the breeding industry. PDCoV has been reported to have the potential for cross species transmission, and even reports of infecting humans have emerged. At present, there are still no effective prevention and control measures for PDCoV. In this study, we have designed and synthesized a series of unreported Dihydropteridone derivatives. All of these compounds were evaluated for the against PDCoV in vivo and in vitro for the first time. In this study, antiviral activity (17.34 ± 7.20 µM) and low cytotoxicity (>800 µM) was found in compound W8. Compound W8 exerts antiviral effect on PDCoV by inhibiting cell apoptosis and inflammatory factors caused by virus infection in vitro. In addition, lung and small intestinal lesions caused by PDCoV infection in mice could be significantly reduced by compound W8. These findings highlight the potential of compound W8 as a valuable therapeutic option against PDCoV infection, and lay a foundation for further research and development in this field.

Multispecies transcriptomics identifies SIKE as a MAPK repressor that prevents NASH progression.

Nonalcoholic fatty liver (NAFL) remains relatively benign, but high-risk to end-stage liver diseases become highly prevalent when it progresses into nonalcoholic steatohepatitis (NASH). Our current understanding of the development of NAFL to NASH remains insufficient. In this study, we revealed MAP kinase (MAPK) activation as the most notable molecular signature associated with NASH progression across multiple species. Furthermore, we identified suppressor of IKKε (SIKE) as a conserved and potent negative controller of MAPK activation. Hepatocyte-specific overexpression of Sike prevented NASH progression in diet- and toxin-induced mouse NASH models. Mechanistically, SIKE directly interacted with TGF-ß-activated kinase 1 (TAK1) and TAK1-binding protein 2 (TAB2) to interrupt their binding and subsequent TAK1-MAPK signaling activation. We found that indobufen markedly up-regulated SIKE expression and effectively improved NASH features in mice and macaques. These findings identify SIKE as a MAPK suppressor that prevents NASH progression and provide proof-of-concept evidence for targeting the SIKE-TAK1 axis as a potential NASH therapy.

Low-Temperature and Fast-Charge Sodium Metal Batteries.

Low-temperature operation of sodium metal batteries (SMBs) at the high rate faces challenges of unstable solid electrolyte interphase (SEI), Na dendrite growth, and sluggish Na+ transfer kinetics, causing a largely capacity curtailment. Herein, low-temperature and fast-charge SMBs are successfully constructed by synergetic design of the electrolyte and electrode. The optimized weak-solvation dual-salt electrolyte enables high Na plating/stripping reversibility and the formation of NaF-rich SEI layer to stabilize sodium metal. Moreover, an integrated copper sulfide electrode is in situ fabricated by directly chemical sulfuration of copper current collector with micro-sized sulfur particles, which significantly improves the electronic conductivity and Na+ diffusion, knocking down the kinetic barriers. Consequently, this SMB achieves the reversible capacity of 202.8 mAh g-1 at -20 °C and 1 C (1 C = 558 mA g-1 ). Even at -40 °C, a high capacity of 230.0 mAh g-1 can still be delivered at 0.2 C. This study is encouraging for further exploration of cryogenic alkali metal batteries, and enriches the electrode material for low-temperature energy storage.

TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase.

Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.

A ddPCR platform based on a microfluidic chip with a dual-function flow-focusing structure for sample-to-result DNA quantification analysis.

Droplet digital PCR (ddPCR) is a powerful method for absolute nucleic acid quantification with high precision and accuracy. However, complicated operational steps have hampered the use and diffusion of ddPCR. Therefore, an automated, easy-to-use, low-sample-consumption, and portable ddPCR platform is urgently needed. This paper proposes a microfluidic ddPCR platform based on a microfluidic chip that can realize the sample-to-result function by switching the rotary valve, achieving the dual function of the flow-focusing structure for droplet generation and readout. Sample, generation oil, and analysis oil were pre-added to the reservoirs. Droplets were generated due to focusing flow, and after passing through the integrated temporary storage bin in the rotary valve, the droplets and oil subsequently entered the collecting tube, improving the droplet-to-oil volume ratio for enhanced thermal cycle performance. Droplets with an average diameter of 107.44 µm and a CV of 2.38% were generated using our chip under the optimal pressures. High-performance thermal cycling was achieved through improvements of the droplet-to-oil volume ratio of the sample, the integrated heating lid, the pure copper heating base, and the temperature-controlling algorithm. Gradient quantification experiments were conducted for the HER2 and CEP17 genes extracted from breast cancer cells, yielding strong linear correlations with R2 values of 0.9996 for FAM and 0.9989 for CY5. Moreover, pronounced linearity was obtained between the detected concentrations of HER2 and CEP17, indicated by a slope of 1.0091 and an R2 of 0.9997, signifying consistent HER2 : CEP17 ratios across various sample dilutions. The outcomes of the quantitative analysis, encompassing the dynamic range and the consistency of the HER2 : CEP17 ratio using our ddPCR platform, meet the standards required for breast cancer assessment and therapy. Our ddPCR platform is automated, portable, and capable of stable droplet generation, high-efficiency amplification, realization of the sample-to-result function based on dual-function flow-focusing structure, and accuracy absolute quantification, underscoring its significant potential for ddPCR analysis in clinical diagnostics.

A Novel Intelligent Fault Diagnosis Method for Self-Priming Centrifugal Pumps.

The real-time diagnostic monitoring of self-priming centrifugal pumps is essential to ensure their safe operation. Nevertheless, owing to the intricate structure and complex operational conditions inherent in such pumps, existing fault diagnosis methods encounter challenges in effectively extracting crucial fault feature information and accurately identifying fault types. Consequently, this paper introduces an intelligent fault diagnosis method tailored for self-priming centrifugal pumps. The approach amalgamates refined time-shift multiscale fluctuation dispersion entropy, cosine pairwise-constrained supervised manifold mapping, and adaptive chaotic Aquila optimization support vector machine techniques. To begin with, refined time-shift multiscale fluctuation dispersion entropy is employed to extract fault-related features, adeptly mitigating concerns related to entropy domain deviations and instability. Subsequently, the application of cosine pairwise-constrained supervised manifold mapping serves to reduce the dimensionality of the extracted fault features, thereby bolstering the efficiency and precision of the ensuing identification process. Ultimately, the utilization of an adaptive chaotic Aquila optimization support vector machine facilitates intelligent fault classification, leading to enhanced accuracy in fault identification. The experimental findings unequivocally affirm the efficacy of the proposed method in accurately discerning among various fault types in self-priming centrifugal pumps, achieving an exceptional recognition rate of 100%. Moreover, it is noteworthy that the average correct recognition rate achieved by the proposed method surpasses that of five existing intelligent fault diagnosis techniques by a significant margin, registering a notable increase of 15.97%.

Design, synthesis, and anti-respiratory syncytial virus potential of novel 3-(1,2,3-triazol-1-yl)furoxazine-fused benzimidazole derivatives.

Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in infants, children, and older persons. Currently, the only approved anti-viral chemotherapeutic drug for RSV treatment is ribavirin aerosol; however, its significant toxicity has led to restricted clinical use. In a previous study, we developed various benzimidazole derivatives against RSV. In this study, we synthesised 3-azide substituted furoxazine-fused benzimidazole derivatives by sulfonylation and azide substitution of the 3-hydroxyl group of the furoxazine-fused benzimidazole derivatives. Subsequently, a series of 3-(1,2,3-triazol-1-yl)-substituted furoxazine-fused benzimidazole derivatives were synthesised using the classical click reaction. Biological evaluations of the target compounds indicated that compound 4a-2 had higher activity against RSV (EC50 = 12.17 µM) and lower cytotoxicity (CC50 = 390.64 µM). Compound 4a-2 exerted anti-viral effects against the RSV Long strain by inhibiting apoptosis and the elevation of reactive oxygen species (ROS) and inflammatory factors caused by viral infection in vitro. Additionally, the clinical symptoms of the virus-infected mice were markedly relieved, and the viral load in the lung tissues was dramatically decreased. The biosafety profile of compound 4a-2 was also favourable, showing no detectable adverse effects on any of the major organs in vivo. These findings underscore the potential of compound 4a-2 as a valuable therapeutic option for combating RSV infections while also laying the foundation for further research and development in the field.

Experimental and theoretical study on the photoionization of styrene.

This study employed a vacuum ultraviolet synchrotron radiation source and reflectron time-of-flight mass spectrometry (TOF-MS) to investigate the photoionization and dissociation of styrene. By analyzing the photoionization mass spectrum and efficiency curve alongside G3B3 theoretical calculations, we determined the ionization energy of the molecular ion, appearance energy of fragment ions, and relevant dissociation pathways. The major ion peaks observed in the photoionization mass spectra of styrene correspond to C8 H8 + , C8 H7 + and C6 H6 + . The ionization energy of styrene is measured as 8.46 ± 0.03 eV, whereas the appearance energies of C8 H7 + and C6 H6 + are found to be 12.42 ± 0.03 and 12.22 ± 0.03 eV, respectively, in agreement with theoretical values. The main channel for the photodissociation of styrene molecular ions is the formation of benzene ions, whereas the dissociation channel that loses hydrogen atoms is the secondary channel. Based on the experimental results and empirical formulas, the required dissociation energies (Ed ) of C8 H7 + , C8 H6 + and C6 H6 + are calculated to be (3.96 ± 0.06), (4.00 ± 0.06) and (3.76 ± 0.06) eV, respectively. Combined with related thermochemical parameters, the standard enthalpies of formations of C8 H8 + , C8 H7 + , C8 H6 + and C6 H6 + are determined to be 964.2, 1346.3, 1350.2 and 1327.0 kJ/mol, respectively. Based on the theoretical study, the kinetic factors controlling the styrene dissociation reaction process are determined by using the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. This provides a reference for further research on the atmospheric photooxidation reaction mechanism of styrene in atmospheric and interstellar environments.

The influence of national policies on the evolution of industrial design education in China.

This study systematically describes research trends of "industrial design education in China" using bibliometrics mapping from 1992 to 2021. This study aims to sort out industrial design education's historical flow in China and analyze its intrinsic links with Chinese national policies. A combination of quantitative and qualitative methods is used to describe and analyze this study. A technique that combines policy historical analysis with a bibliometric review based on Citespace's knowledge mapping is used in this research. The study was conducted on 492 ″Industrial Design Education" papers included in the core collection database of the China National Knowledge Infrastructure between 1992 and 2021. The results obtained from this study are 1) Research on industrial design education in China has grown steadily over the past three decades and remained high-quality level; 2) The three main research themes are "Chinese culture," "interdisciplinary cooperation" and "government, industry, academia and research" cooperation; 3) Innovation and entrepreneurship, evaluation system, Interdisciplinary, new engineering, and new liberal arts are the research hot spots of Chinese core journals; 4) Interdisciplinary construction in the context of new engineering, assessment system research in the context of high-quality development, and innovation and entrepreneurship education in the context of creative industry development are the future research directions.

Synthesis and pharmacodynamic evaluation of naphthalene derivatives against influenza A virus in vitro and in vivo.

Influenza A virus is a highly mutable pathogenic pathogen that could cause a global pandemic. It is necessary to find new anti-influenza drugs to resist influenza epidemics due to the seasonal popularity of a certain area every year. Naphthalene derivatives had potential antiviral activity. A series of naphthalene derivatives were synthesized via the metal-free intramolecular hydroarylation reactions of alkynes. Evaluation of their biological efficacy showed that compound 2-aminonaphthalene 4d had better antiviral activity in vitro than ribavirin. By studying the mechanism of action of 2-aminonaphthalene 4din vivo and in vitro, we found that 4d had antiviral activity to three different subtype influenza viruses of A/Weiss/43 (H1N1), A/Virginia/ATCC2/2009 (H1N1) and A/California/2/2014 (H3N2). Compound 4d had the best effect after viral adsorption, and mainly played in the early stage of virus replication. 2-Aminonaphthalene 4d could reduce the replication of virus by inhibiting the NP and M proteins of virus. Compound 4d cut down ROS accumulation, autophagy and apoptosis induced by influenza virus. Inflammatory response mediated by RIG-1 pathway were suppressed in the cell and mice. In addition, the pathological changes of lung tissue and virus titer in mice were reduced by the administration of 4d. Therefore, naphthalene derivative 4d is a potential drug for the treatment of influenza A virus infection.

Synthesis and evaluation of alkoxy-substituted enamides against influenza A virus in vitro and in vivo.

Alkoxy-substituted enamides are often used as synthetic intermediates due to their special reactivity. To the best our knowledge, the biological activity of alkoxy-substituted amines has never been reported so far. We have synthesized a series of alkoxy-substituted enamides to study their anti-influenza A virus activity in vitro and in vivo. Among these compounds, compound E-2o had the best antiviral activity (EC50 = 2.76 ± 0.67 µM) and low cytotoxicity (CC50 = 662.87 ± 24.85 µM). The mechanism of action of this compound was preliminarily explored by us. It alleviated the cytopathic effects and cell death caused by different subtypes of influenza A virus. Different drug delivery methods and timed dosing experiments had shown that E-2o had the best therapeutic effect and mainly played a role in the early stages of virus replication. The expansion of influenza viruses in cells was inhibited by reducing ROS accumulation, cell apoptosis, and autophagy. Alkoxy-substituted enamide E-2o reduced the production of interferon and other pro-inflammatory factors in the RIG-Ⅰ pathway and its downstream NF-κB was induced by influenza A virus in vitro and in vivo. It avoided damage in the mice which was caused by excessive inflammatory factors. In addition, the weight loss and lung lesion damage in mice caused by influenza virus were improved by compound E-2o. Therefore, Alkoxy-substituted enamide E-2o could inhibit the replication of influenza viruses in vivo and in vitro, and has the potential to be developed into a drug for treating influenza.

Necroptosis inhibits autophagy by regulating the formation of RIP3/p62/Keap1 complex in shikonin-induced ROS dependent cell death of human bladder cancer.

BACKGROUND: Shikonin, a natural naphthoquinone compound, has a wide range of pharmacological effects, but its anti-tumor effect and underlying mechanisms in bladder cancer remain unclear. PURPOSE: We aimed to investigate the role of shikonin in bladder cancer in vitro and in vivo in order to broaden the scope of shikonin's clinical application. STUDY DESIGN AND METHODS: We performed MTT and colony formation to detect the inhibiting effect of shikonin on bladder cancer cells. ROS staining and flow cytometry assays were performed to detect the accumulation of ROS. Western blotting, siRNA and immunoprecipitation were used to evaluate the effect of necroptosis in bladder cancer cells. Transmission electron microscopy and immunofluorescence were used to examine the effect of autophagy. Nucleoplasmic separation and other pharmacological experimental methods described were used to explore the Nrf2 signal pathway and the crosstalk with necroptosis and autophagy. We established a subcutaneously implanted tumor model and performed immunohistochemistry assays to study the effects and the underlying mechanisms of shikonin on bladder cancer cells in vivo. RESULTS: The results showed that shikonin has a selective inhibitory effect on bladder cancer cells and has no toxicity on normal bladder epithelial cells. Mechanically, shikonin induced necroptosis and impaired autophagic flux via ROS generation. The accumulation of autophagic biomarker p62 elevated p62/Keap1 complex and activated the Nrf2 signaling pathway to fight against ROS. Furthermore, crosstalk between necroptosis and autophagy was present, we found that RIP3 may be involved in autophagosomes and be degraded by autolysosomes. We found for the first time that shikonin-induced activation of RIP3 may disturb the autophagic flux, and inhibiting RIP3 and necroptosis could accelerate the conversion of autophagosome to autolysosome and further activate autophagy. Therefore, on the basis of RIP3/p62/Keap1 complex regulatory system, we further combined shikonin with late autophagy inhibitor(chloroquine) to treat bladder cancer and achieved a better inhibitory effect. CONCLUSION: In conclusion, shikonin could induce necroptosis and impaired autophagic flux through RIP3/p62/Keap1 complex regulatory system, necroptosis could inhibit the process of autophagy via RIP3. Combining shikonin with late autophagy inhibitor could further activate necroptosis via disturbing RIP3 degradation in bladder cancer in vitro and in vivo.

Polydopamine-based nanomedicines for efficient antiviral and secondary injury protection therapy.

Viral infections continue to threaten human health. It remains a major challenge to efficiently inhibit viral infection while avoiding secondary injury. Here, we designed a multifunctional nanoplatform (termed as ODCM), prepared by oseltamivir phosphate (OP)-loaded polydopamine (PDA) nanoparticles camouflaged by the macrophage cell membrane (CM). OP can be efficiently loaded onto the PDA nanoparticles through the π-π stacking and hydrogen bonding interactions with a high drug-loading rate of 37.6%. In particular, the biomimetic nanoparticles can accumulate actively in the damaged lung model of viral infection. At the infection site, PDA nanoparticles can consume excess reactive oxygen species and be simultaneously oxidized and degraded to achieve controlled release of OP. This system exhibits enhanced delivery efficiency, inflammatory storm suppression, and viral replication inhibition. Therefore, the system exerts outstanding therapeutic effects while improving pulmonary edema and protecting lung injury in a mouse model of influenza A virus infection.

Targeting peroxisome proliferator-activated receptor γ proteasomal degradation by magnolol is a potential avenue for adipogenesis-mediated metabolic homeostasis.

OBJECTIVE: Adipogenesis has been recognized as an attractive avenue for maintaining systemic homeostasis, with peroxisome proliferator-activated receptor γ (PPARγ) showing predominant roles in this process. This study aims to identify promising drug candidates by targeting PPARγ for adipogenesis-based metabolic homeostasis and to clarify the detailed mechanisms. METHODS: Molecular events contributing to adipogenesis were screened, which identified PPARγ as having the predominant role. Promising agents of adipogenesis agonism were screened using a PPARγ-based luciferase reporter assay. The functional capacity and molecular mechanisms of magnolol were intensively examined using 3T3-L1 preadipocytes and dietary models. RESULTS: This study found that F-box only protein 9 (FBXO9)-mediated lysine 11 (K11)-linked ubiquitination and proteasomal degradation of PPARγ are critically required during adipogenesis and systemic homeostasis. Notably, magnolol was identified as a potent adipogenesis activator by stabilizing PPARγ. The pharmacological mechanisms investigations clarified that magnolol directly binds to PPARγ and markedly interrupts its interaction with FBXO9, leading to a decline in K11-linked ubiquitination and proteasomal degradation of PPARγ. Clinically important, magnolol treatment significantly facilitates adipogenesis in vitro and in vivo. CONCLUSIONS: The downregulation of K11-linked ubiquitination of PPARγ caused by FBOX9 is essentially required for adipogenesis, while targeting PPARγ-FBXO9 interaction provides a new avenue for the therapy of adipogenesis-related metabolic disorder.

Honokiol acts as an AMPK complex agonist therapeutic in non-alcoholic fatty liver disease and metabolic syndrome.

BACKGROUND: Non-alcoholic fatty liver (NAFLD) and its related metabolic syndrome have become major threats to human health, but there is still a need for effective and safe drugs to treat these conditions. Here we aimed to identify potential drug candidates for NAFLD and the underlying molecular mechanisms. METHODS: A drug repositioning strategy was used to screen an FDA-approved drug library with approximately 3000 compounds in an in vitro hepatocyte model of lipid accumulation, with honokiol identified as an effective anti-NAFLD candidate. We systematically examined the therapeutic effect of honokiol in NAFLD and metabolic syndrome in multiple in vitro and in vivo models. Transcriptomic examination and biotin-streptavidin binding assays were used to explore the underlying molecular mechanisms, confirmed by rescue experiments. RESULTS: Honokiol significantly inhibited metabolic syndrome and NAFLD progression as evidenced by improved hepatic steatosis, liver fibrosis, adipose inflammation, and insulin resistance. Mechanistically, the beneficial effects of honokiol were largely through AMPK activation. Rather than acting on the classical upstream regulators of AMPK, honokiol directly bound to the AMPKγ1 subunit to robustly activate AMPK signaling. Mutation of honokiol-binding sites of AMPKγ1 largely abolished the protective capacity of honokiol against NAFLD. CONCLUSION: These findings clearly demonstrate the beneficial effects of honokiol in multiple models and reveal a previously unappreciated signaling mechanism of honokiol in NAFLD and metabolic syndrome. This study also provides new insights into metabolic disease treatment by targeting AMPKγ1 subunit-mediated signaling activation.

A high-throughput drug screening identifies luteolin as a therapeutic candidate for pathological cardiac hypertrophy and heart failure.

Background: Pathological cardiac hypertrophy is commonly resulted from sustained pressure overload and/or metabolic disorder and eventually leads to heart failure, lacking specific drugs in clinic. Here, we aimed to identify promising anti-hypertrophic drug(s) for heart failure and related metabolic disorders by using a luciferase reporter-based high-throughput screening. Methods: A screen of the FDA-approved compounds based on luciferase reporter was performed, with identified luteolin as a promising anti-hypertrophic drug. We systematically examined the therapeutic efficacy of luteolin on cardiac hypertrophy and heart failure in vitro and in vivo models. Transcriptome examination was performed to probe the molecular mechanisms of luteolin. Results: Among 2,570 compounds in the library, luteolin emerged as the most robust candidate against cardiomyocyte hypertrophy. Luteolin dose-dependently blocked phenylephrine-induced cardiomyocyte hypertrophy and showed extensive cardioprotective roles in cardiomyocytes as evidenced by transcriptomics. More importantly, gastric administration of luteolin effectively ameliorated pathological cardiac hypertrophy, fibrosis, metabolic disorder, and heart failure in mice. Cross analysis of large-scale transcriptomics and drug-target interacting investigations indicated that peroxisome proliferator activated receptor γ (PPARγ) was the direct target of luteolin in the setting of pathological cardiac hypertrophy and metabolic disorders. Luteolin can directly interact with PPARγ to inhibit its ubiquitination and subsequent proteasomal degradation. Furthermore, PPARγ inhibitor and PPARγ knockdown both prevented the protective effect of luteolin against phenylephrine-induced cardiomyocyte hypertrophy in vitro. Conclusion: Our data clearly supported that luteolin is a promising therapeutic compound for pathological cardiac hypertrophy and heart failure by directly targeting ubiquitin-proteasomal degradation of PPARγ and the related metabolic homeostasis.

Intelligent fault detection scheme for constant-speed wind turbines based on improved multiscale fuzzy entropy and adaptive chaotic Aquila optimization-based support vector machine.

Timely and effective fault detection is essential to ensure the safe and reliable operation of wind turbines. However, due to the complex kinematic mechanisms and harsh working environments of wind turbine equipment, it is difficult to extract sensitive features and detect faults from acquired wind turbine signals. To address this challenge, a novel intelligent fault detection scheme for constant-speed wind turbines based on refined time-shifted multiscale fuzzy entropy (RTSMFE), supervised isometric mapping (SI), and adaptive chaotic Aquila optimization-based support vector machine (ACAOSVM) is proposed. In the first step, the RTSMFE method is used to fully extract features of the wind turbine system. The time-shifted coarse-grained construction technique and a refined computing technique are adopted in the RTSMFE method to enhance the capability of traditional multiscale fuzzy entropy for measuring the complexity of signals. Subsequently, an effective manifold learning approach, SI, is applied to obtain the important and low-dimensional feature set from the high-dimensional feature set. Finally, sensitive features are fed into the ACAOSVM classifier to identify faults. The proposed ACAO algorithm is used to optimize important parameters of the SVM, thereby improving its detection performance. Simulations and wind turbine experiments verified that the proposed RTSMFE outperforms existing entropy techniques in terms of complexity measurement and feature extraction. Furthermore, the proposed ACAOSVM classifier is superior to existing advanced classifiers for fault pattern recognition. Finally, the proposed intelligent fault detection scheme can more correctly and efficiently detect wind turbine single/hybrid faults than other recently published schemes.

The influence of target layout and target graphic type on searching performance based on eye-tracking technology.

With the development of various intelligent technologies, the application of interactive interfaces is becoming more and more widespread, and the related researches conducted for interactive interfaces are also increasing. The purpose of this study was to explore the influence of icon layout location, icon graphic type, and icon layout method on users' searching performance in interactive interfaces through eye-tracking technology. Participants were asked to perform search tasks for the search target (facet icon or linear icon) on each image. Thus, each trial consisted of a search task on a given image. In total, each participant had 36 trials to complete. Searching time, fixation duration, and fixation count were collected to evaluate the searching performance of participants. Results showed that when faced with familiar icons, whether the graphic type of icons was facet or linear did not affect the user's experience, but when other factors of the interaction interface changed, facet icons provided a more stable experience for users. And compared to the rectangular layout, the circular layout method provided a more stable experience for users when the location of icons in the interactive interface changed, but icons located in the top half of the interactive interface were easier to find than those located in the bottom half, regardless of whether the layout was circular or rectangular. These results could be used in the layout and icon design of the interactive interfaces to facilitate their optimization.

Identification of Two Insulin Receptors from the Swimming Crab Portunus trituberculatus: Molecular Characterization, Expression Analysis, and Interactions with Insulin-Like Androgenic Gland Hormone.

AbstractThe insulin-like androgenic gland hormone is a crucial sexual regulator that is involved in the masculine sexual differentiation of crustaceans. As an insulin-like peptide, the insulin-like androgenic gland hormone has been proposed to act through the insulin receptor-mediated pathway. The present study cloned and characterized two insulin receptors (PtIR1 and PtIR2) from the swimming crab Portunus trituberculatus hallmarked with a conserved intracellular tyrosine kinase catalytic domain and several other typical insulin receptor domains in their deduced amino acid sequences. Both insulin receptors were predominately expressed in the testis and the insulin-like androgenic gland hormone-producing organ androgenic gland. Their testicular expression during the annual cycle suggested that they may play critical roles in spermatogenesis. By using the protein colocalization analysis in HEK293 cells, interactions of PtIAG with the two PtIRs were further confirmed. In addition, the insulin receptor antagonist was found to attenuate the stimulatory effects of androgenic gland homogenate on the phosphorylated MAPK levels in testis explants, suggesting that the insulin receptor-dependent MAPK pathway may be essential for insulin-like androgenic gland hormone functions.