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Offshore drilling platforms are exposed to wind, waves, currents, and other unknown disturbances. Accurately estimating and rejecting these disturbances is the key to ensuring reliable station-keeping of the platforms. In this study, a novel dynamic positioning method using an improved equivalent-input-disturbance (EID) approach is proposed for offshore drilling platforms. An improved EID estimator is employed to estimate and suppress unknown disturbances, significantly enhancing the disturbance-rejection performance of the dynamic positioning system. The input channels are decoupled through linear transformation, and the parameter tuning process of the observer and controller is optimized, thus improving system performance. The bounded-input bounded-output stability of the closed-loop system is proved. This study provides insights into the design of dynamic positioning systems for offshore drilling platforms. • Effective disturbance compensation for offshore drilling platforms. • Input channel linear transformation improves disturbance-rejection performance. • Simplified parameter design using linear matrix inequalities. • Nonlinear state feedback and observer gains ensure the global stability of the system. [ABSTRACT FROM AUTHOR]

This paper presents an optimization design method for a two-dimensional (2D) modified repetitive control system (MRCS) with an anti-windup compensator. Using lifting technology, a 2D hybrid model of the MRCS considering actuator saturation is established to describe the control and learning of the repetitive control. A linear-matrix-inequality (LMI)-based sufficient condition is derived to ensure the stability of the MRCS. Two tuning parameters, the selection of which is critical to the system design, are used in the LMI to adjust the control and learning, and hence the reference-tracking performance. A new cost function, developed through time domain analysis, directly evaluates the control performance of the system without calculating control errors, thus reducing the optimization time. Based on this cost function, an adaptive multi-population particle swarm optimization algorithm is presented to select an optimal pair of tuning parameters in which multiple populations cooperatively search in non-intersecting search intervals. An anti-windup term is added between the low-pass filter and the time delay in the modified repetitive controller to mitigate the undesirable effect of actuator saturation on system performance and stability. Simulations and experiments on the speed control of a rotation control system demonstrate the validity of the approach. • Evaluate control performance only with the information of controller gains. • An optimization algorithm is used to optimize tuning parameters. • An anti-windup compensator mitigates the undesired influence of actuator saturation. • Separate design of repetitive control system and anti-windup compensator. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is the severe subtype of nonalcoholic fatty diseases (NAFLD) with few options for treatment. Patients with NASH exhibit partial responses to the current therapeutics and adverse effects. Identification of the binding proteins for the drugs is essential to understanding the mechanism and adverse effects of the drugs and fuels the discovery of potent and safe drugs. This paper aims to critically discuss recent advances in covalent and noncovalent approaches for identifying binding proteins that mediate NASH progression, along with an in-depth analysis of the mechanisms by which these targets regulate NASH. A literature search was conducted to identify the relevant studies in the database of PubMed and the American Chemical Society. The search covered articles published from January 1990 to July 2024, using the search terms with keywords such as NASH, benzophenone, diazirine, photo-affinity labeling, thermal protein profiling, CETSA, target identification. The covalent approaches utilize drugs modified with diazirine and benzophenone to covalently crosslink with the target proteins, which facilitates the purification and identification of target proteins. In addition, they map the binding sites in the target proteins. By contrast, noncovalent approaches identify the binding targets of unmodified drugs in the intact cell proteome. The advantages and limitations of both approaches have been compared, along with a comprehensive analysis of recent innovations that further enhance the efficiency and specificity. The analyses of the applicability of these approaches provide novel tools to delineate NASH pathogenesis and promote drug discovery. [Display omitted] • Photoaffinity labeling approaches identify the drug targets that regulate NASH. • Target identification delineates the adverse effects and toxicity of anti-NASH drugs. • Noncovalent approaches identify the in situ binding targets for small molecules. • Multidisciplinary advances greatly facilitate target identification to treat NASH. [ABSTRACT FROM AUTHOR]

• Prediction of the patient specific treatment planning Pareto front is feasible. • Prediction accuracy of Pareto fronts was below 2 Gy for 90% of cases. • Patient specific trade-offs could be estimated in seconds after completing delineations. To demonstrate the feasibility of predicting the patient-specific treatment planning Pareto front (PF) for prostate cancer patients based only on delineations of PTV, rectum and body. Our methodology consists of four steps. First, using Erasmus-iCycle, the Pareto fronts of 112 prostate cancer patients were constructed by generating per patient 42 Pareto optimal treatment plans with different priorities. Dose parameters associated to homogeneity, conformity and dose to rectum were extracted. Second, a 3D convex function representing the PF spanned by the 42 plans was fitted for each patient using three patient-specific parameters. Third, ten features were extracted from the, aforementioned, structures to train a linear-regressor prediction algorithm to predict these three patient-specific parameters. Fourth, the quality of the predictions was assessed by calculating the average and maximum distances of the predicted PF to the 42 plans for patients in the validation cohort. The prediction model was able to predict the clinically relevant PF within 2 Gy for 90% of the patients with a median average distance of 0.6 Gy. We demonstrate the feasibility of fast, accurate predictions of the patient-specific PF for prostate cancer patients based only on delineations of PTV, rectum and body. [ABSTRACT FROM AUTHOR]

Wind turbines that operate under cold climates sustain icing events. Ice accretion on the surfaces of wind turbine blades not only constitutes a severe threat to operation safety, but also reduces wind energy output. As a novel mechanical de-icing method, the ultrasonic de-icing technique has attracted high attention in both wind energy and aviation industry, due to its low energy consumption, light weight and low cost. According to the ultrasonic de-icing mechanism, a damage accumulation model was proposed to describe the ice detachment behavior under ultrasonic wave. This model that was constructed with damage mechanics provided an assessment method for the ultrasonic de-icing effect and predicted the time consumption of ice layer detachment. This method was numerically simulated with the finite element method. In addition, a set of experimental apparatus for ultrasonic de-icing method was designed. Following, a confirmatory experiment was carried out in laboratory environment. The parameters of the damage accumulation model were determined by the experimental data. The ice detachment behavior in the experiment was consistent with the prediction assessment proposed in this paper. Image 1034 • This work proposed a quantitative model in describing ice detaching behavior. • The de-icing process was predicted by this model with computer simulation. • The ice shedding process was verified in a de-icing experiment. [ABSTRACT FROM AUTHOR]

[Display omitted] Nonalcoholic fatty liver disease (NAFLD) is featured with excessive hepatic lipid accumulation and its global prevalence is soaring. Nonalcoholic steatohepatitis (NASH), the severe systemic inflammatory subtype of NAFLD, is tightly associated with metabolic comorbidities, and the hepatocytes manifest severe inflammation and ballooning. Currently the therapeutic options for treating NASH are limited. Potent small molecules specifically intervene with the signaling pathways that promote pathogenesis of NASH. Nevertheless they have obvious adverse effects and show long-term ineffectiveness in clinical trials. It poses the fundamental question to efficiently and safely inhibit the pathogenic processes. Targeted protein degradation (TPD) belongs to the direct degradation strategies and is a burgeoning strategy. It utilizes the small molecules to bind to the target proteins and recruit the endogenous proteasome, lysosome and autophagosome-mediated degradation machineries. They effectively and specifically degrade the target proteins. It has exhibited promising therapeutic effects in treatment of cancer, neurodegenerative diseases and other diseases in a catalytic manner at low doses. We critically discuss the principles of multiple direct degradation strategies, especially PROTAC and ATTEC. We extensively analyze their emerging application in degradation of excessive pathogenic proteins and lipid droplets, which promote the progression of NASH. Moreover, we discuss the opposite strategy that utilizes the small molecules to recruit deubiquinases to stabilize the NASH/MASH-suppressing proteins. Their advantages, limitations, as well as the solutions to address the limitations have been analyzed. In summary, the innovative direct degradation strategies provide new insights into design of next-generation therapeutics to combat NASH with optimal safety paradigm and efficiency. [ABSTRACT FROM AUTHOR]

In this work, aiming at finding a novel, potent, and selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor with good pharmacokinetic profiles for the treatment of diabetes, we focus on modifying the sugar moiety of SGLT2 inhibitors, which dominates the binding with glucose binding site of hSGLT, via removing the C-6 hydroxy group to adjust the physicochemical properties and target-recognition manners of SGLT2 inhibitors. In addition, tofogliflozin containing a special O -spiroketal C -arylglucoside scaffold, displayed good efficacy and bioavailability both in animals and in humans. Therefore, a series of 6-deoxy O -spiroketal C -arylglucosides as novel SGLT2 inhibitors were designed, synthesized, and evaluated in this work. The structure-activity relationship (SAR) research on this novel series and a comprehensive in vitro and in vivo biological evaluation afforded compound 39 with high in vitro hSGLT2 inhibitory activity (IC 50 = 4.5 nM), good pharmacokinetic profiles, and more remarkable efficacy in C57BL/6J mice and Sprague-Dawley rats than marketed drug tofogliflozin. Image 1 • Novel 6-deoxy O -spiroketal C -arylglucosides as SGLT2 inhibitors were designed, synthesized, and evaluated. • The structure-activity relationship (SAR) of this novel series of 31 compounds was demonstrated. • Compound 39 demonstrated higher potency of inhibiting hSGLT2 than dapagliflozin (IC 50 = 4.5 nM vs 8.3 nM). • Compound 39 displayed greater efficacy than tofogliflozin on urinary glucose excretion and oral glucose tolerance in mice. • The half-life of compound 39 in mice was longer than tofogliflozin after oral administration (5.95 h vs 2.57 h). [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of protocatechuic acid (PCA) on the growth performance, meat quality, and intestinal health of Chinese yellow-feathered broilers. Growing broilers were fed the basal diet or diets supplemented with 300 or 600 mg/kg PCA, or 200 mg/kg enramycin for 52 D. We found that addition of 300 mg/kg PCA significantly increased body weight, live weight, and carcass weight and decreased the feed to gain ratio of broilers; PCA improved meat quality through reducing shear force, and increasing a* (relative redness) and decreasing b* (relative yellowness) at 24 h after slaughter. The activities of alkaline phosphatase and diamine oxidase in plasma were significantly decreased by administration of 300 mg/kg PCA; PCA also significantly increased total antioxidant capability and decreased malondialdehyde content and activity of xanthine oxidase in liver. Meanwhile, it enhanced activities of total superoxide dismutase, glutathione s-transferase, and glutathione peroxidase in the jejunal mucosa. Interleukin-10 and transforming growth factor-β were significantly increased in jejunal mucosa and plasma of 300 mg/kg PCA diet group, whereas interluekin-2 and interferon-γ dropped dramatically. Moreover, relative expression of apoptosis-related genes decreased in liver, whereas that of intestinal barrier-related and immunity-related genes increased in jejunum. Furthermore, 300 mg/kg PCA treatment significantly changed α-diversity and structure of the cecal microflora in broilers, with increasing relative abundance of Firmicutes and Actinobacteria while reducing Bacteroidetes and Proteobacteria. These results indicated that PCA improved the feed efficiency, growth performance, meat quality of broilers, and antioxidant capacity. It also enhanced intestinal immune function and improved the structure of intestinal flora to favor improved intestinal health in Chinese yellow-feathered broilers. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • E. coli O157:H7 biofilm affinity peptide SGVYKVAYDWQH was obtained by biopanning. • Designed affinity surfactant peptide SGVYKVAYDWQHKKK formed micelle effectively. • Biofilm removal efficiency reached 75% at 125 mg/L affinity surfactant peptide. • Designed peptide adsorbed on biofilm before removing and surrounding the bacteria. • Different constituents of biofilm associated with binding and removal efficiency. Abstract Conventional chemical surfactants attach on blots randomly, accompanied with health and environmental issues. To address this, a surfactant peptide was designed to mimic chemical surfactants with an affinity binding peptide as a hydrophobic tail for the cleanup of biofilm contaminations. The micelle forming and structural changes of the peptide in aqueous solution were systematically investigated. More importantly, the biofilm removal efficiency toward Escherichia coli O157:H7 biofilm reached 75% in neutral aqueous solutions at the concentration of 125 mg/L (critical micelle concentration 91 mg/L), a significant improvement in comparison to conventional surfactants and random surfactant peptide. The dynamic removal process reported by confocal laser scanning microscope (CLSM) also displayed the different constituents of biofilm blots, which associated with surfactant peptide binding efficiency. Hopefully, this surfactant strategy will eventually provide new scopes in the design of surface active biological agents. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Hyperthermic treatment up-regulates miR-31a-5p expression and induced CC-2511 cells injury. • MiR-31a-5p inhibition alleviates hyperthermia-induced CC-2511 cells injury by regulating IL-25. • HSP70 regulates miR-31a-5p and proliferation of CC-2511 cells under hyperthermic stress. • IL-25 aggravates hyperthermia-induced CC-2511 cells injury by mediation of Wnt/β-catenin signal pathway. Abstract Background Hypertrophic scar is a skin disorder, which occurs following damage to deep dermis by burns. MicroRNAs (miRNAs) are involved in various skin disorders, including hypertrophic scar. The present study evaluated the effects of miR-31a-5p on human dermal fibroblast cells (CC-2511 cells) under hyperthermic stress. Methods CC-2511 cells were incubated at high temperature conditions (41 °C–43 °C for 1–3 h). The expression levels of miR-31a-5p, interleukin (IL)-25, and the productions of other pro-inflammatory mediators in CC-2511 cells under hyperthermic stress were examined by using qRT-PCR and ELISA assay. Luciferase reporter assay was used to identify the relationship between miR-31a-5p and IL-25. Effects of heat shock protein 70 (HSP70) on miR-31a-5p and cell viability were then examined under hyperthermic stress. Furthermore, the effects of IL-25 on pro-inflammatory mediators, cell proliferation and Wnt/β-catenin pathway were finally studied. Results Hyperthermic treatment increased miR-31a-5p expression, enhanced IL-1β, IL-6, IL-8 and TNF-α productions, as well as decreased proliferation and induced apoptosis in CC-2511 cells. MiR-31a-5p suppression decreased IL-25 expression, inhibited IL-1β, IL-6, IL-8, and TNF-α secretions, and decreased proliferation in CC-2511 cells under hyperthermic stress. Additionally, miR-31a-5p expression was increased by HSP70, and HSP70 knockdown promoted cell viability in CC-2511 cells under hyperthermic stress. Further, we observed that IL-25 promoted the expression of inflammatory mediators and regulated cell survival by activating Wnt/β-catenin signal pathway in CC-2511 cells. Conclusions These results demonstrated that miR-31a-5p inhibition could decrease inflammation and improve cell survival of CC-2511 cells under hyperthermic stress via regulation Wnt/β-catenin signal pathway. [ABSTRACT FROM AUTHOR]