Adaptive Cruise System Based on Fuzzy MPC and Machine Learning State Observer.

Under the trend of vehicle intelligentization, many electrical control functions and control methods have been proposed to improve vehicle comfort and safety, among which the Adaptive Cruise Control (ACC) system is a typical example. However, the tracking performance, comfort and control robustness of the ACC system need more attention under uncertain environments and changing motion states. Therefore, this paper proposes a hierarchical control strategy, including a dynamic normal wheel load observer, a Fuzzy Model Predictive Controller and an integral-separate PID executive layer controller. Firstly, a deep learning-based dynamic normal wheel load observer is added to the perception layer of the conventional ACC system and the observer output is used as a prerequisite for brake torque allocation. Secondly, a Fuzzy Model Predictive Control (fuzzy-MPC) method is adopted in the ACC system controller design, which establishes performance indicators, including tracking performance and comfort, as objective functions, dynamically adjusts their weights and determines constraint conditions based on safety indicators to adapt to continuously changing driving scenarios. Finally, the executive controller adopts the integral-separate PID method to follow the vehicle's longitudinal motion commands, thus improving the system's response speed and execution accuracy. A rule-based ABS control method was also developed to further improve the driving safety of vehicles under different road conditions. The proposed strategy has been simulated and validated in different typical driving scenarios and the results show that the proposed method provides better tracking accuracy and stability than traditional techniques.

Diverse effector and regulatory functions of fibro/adipogenic progenitors during skeletal muscle fibrosis in muscular dystrophy.

Fibrosis is a prominent pathological feature of skeletal muscle in Duchenne muscular dystrophy (DMD). The commonly used disease mouse model, mdx 5cv , displays progressive fibrosis in the diaphragm but not limb muscles. We use single-cell RNA sequencing to determine the cellular expression of the genes involved in extracellular matrix (ECM) production and degradation in the mdx 5cv diaphragm and quadriceps. We find that fibro/adipogenic progenitors (FAPs) are not only the primary source of ECM but also the predominant cells that express important ECM regulatory genes, including Ccn2, Ltbp4, Mmp2, Mmp14, Timp1, Timp2, and Loxs. The effector and regulatory functions are exerted by diverse FAP clusters which are different between diaphragm and quadriceps, indicating their activation by different tissue microenvironments. FAPs are more abundant in diaphragm than in quadriceps. Our findings suggest that the development of anti-fibrotic therapy for DMD should target not only the ECM production but also the pro-fibrogenic regulatory functions of FAPs.

Racewalking on a treadmill alters gait characteristics without increasing risk of disqualification.

PURPOSE: Treadmill training is useful for racewalking training; however, it may affect gait characteristics and lead to non-legal techniques. The aim of this study was to determine the kinematic differences between treadmill and overground conditions during racewalking at different speeds. METHODS: Twenty-two elite racewalkers participated in this study. They racewalked under treadmill and overground conditions at high and medium speeds. A 12-camera motion analysis system was used to record the racewalking trials. RESULTS: Significant condition by speed interactions were detected in step frequency and pelvis rotation angle; step frequency decreased while pelvis rotation angle increased from overground to treadmill conditions at high speed. Compared to overground conditions, racewalkers decreased the ankle dorsiflexion angle at heel strike and increased hip flexion, shoulder hyperextension, and elbow flexion angles at heel strike and hip and shoulder extension angles at toe-off under treadmill conditions. Compared to medium speed, racewalkers decreased the contact time, hip flexion, and shoulder hyperextension at heel strike, and ankle plantarflexion and shoulder extension angles at toe-off, and increased flight time, step length, and elbow flexion angle at heel strike at high speed. CONCLUSION: Several kinematic differences during racewalking were detected between treadmill and overground conditions, with more differences detected at high speed, indicating that treadmill racewalking, especially at high speed, has different gait characteristics. However, no differences were detected in flight time and knee angle under treadmill conditions compared to overground conditions, indicating that racewalking on a treadmill does not increase the risk of disqualification.

A Dual Distribution Control Method for Multi-Power Components Energy Output of 4WD Electric Vehicles.

Energy management strategies are vitally important to give full play to the energy-saving of the four-wheel drive electric vehicle (4WD EV). The cooperative output of multi-power components is involved in the process of driving and braking energy recovery of 4WD EV. This paper proposes a novel energy management strategy of dual equivalent consumption minimization strategy (D-ECMS) to improve the economy of the vehicle. According to the different driving and braking states of the vehicle, D-ECMS can realize the proportional control of the energy cooperative output among the multi-power components. Under the premise of satisfying the dynamic performance of the vehicle, the operating points of the power components are distributed more in the high-efficiency range, and the economy and driving range of the vehicle are optimized. In order to achieve the effectiveness of D-ECMS, MATLAB/Simulink is used to realize the simulation of the vehicle. Compared with the rule-based strategy, the economy of D-ECMS increased by 4.35%.

Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis.

BACKGROUND AND AIMS: Renal fibrosis is the common outcome in all progressive forms of chronic kidney disease. Unfortunately, the pathogenesis of renal fibrosis remains largely unexplored, among which metabolic reprogramming plays an extremely crucial role in the evolution of renal fibrosis. Ceria nanoparticles (CeNP-PEG) with strong ROS scavenging and anti-inflammatory activities have been applied for mitochondrial oxidative stress and inflammatory diseases. The present study aims to determine whether CeNP-PEG has therapeutic value for renal fibrosis. METHODS: The unilateral ureteral obstructive fibrosis model was used to assess the therapeutic effects in vivo. Transforming growth factor beta1-induced epithelial-to-mesenchymal transition in HK-2 cells was used as the in vitro cell model. The seahorse bioscience X96 extracellular flux analyzer was used to measure the oxygen consumption rate and extracellular acidification rate. RESULTS: In the present study, CeNP-PEG treatment significantly ameliorated renal fibrosis by increased E-cadherin protein expression, and decreased α-SMA, Vimentin and Fibronectin expression both in vitro and in vivo. Additionally, CeNP-PEG significantly reduced the ROS formation and improved the levels of mitochondrial ATP. The seahorse analyzer assay demonstrated that the extracellular acidification rate markedly decreased, whereas the oxygen consumption rate markedly increased, in the presence of CeNP-PEG. Furthermore, the mitochondrial membrane potential markedly enhanced, hexokinase 1 and hexokinase 2 expression significantly decreased after treatment with CeNP-PEG. CONCLUSIONS: CeNP-PEG can block the dysregulated metabolic status and exert protective function on renal fibrosis. This may provide another therapeutic option for renal fibrosis.

A novel role of BK potassium channel activity in preventing the development of kidney fibrosis.

Kidney fibrosis is a common characteristic of chronic kidney disease and while the large conductance voltage and calcium-activated potassium channel (BK) is widely expressed in kidneys, its role in kidney fibrosis is unknown. To evaluate this, we found that BK protein expression was decreased in the fibrotic kidneys. Accompanying this was increased fibrotic marker protein expression of fibronectin, vimentin and α-smooth muscle actin and increased mRNA expressions of fibronectin, α-smooth muscle actin, collagen III and collagen I. These changes occurred in the unilateral ureteral obstruction and folic acid models of fibrosis and were more pronounced in BK knockout than in wild-type mice. Activation of BK activity by chemical NS1619 or BMS191011 channel openers attenuated kidney fibrosis in these two models while protecting kidney function in wild-type mice. BK deficiency up-regulated transforming growth factor-ß (TGF-ß)/transcription factor Smad2/3 signaling in the fibrotic kidney, whereas activation of BK activity inhibited this signaling pathway both in vivo and in vitro. BK channel activation increased the degradation of TGF-ß receptors induced by TGF-ß1 in vivo and in vitro. Furthermore, in cell lines HK-2, NRK49, and NRK-52E, BK channel activation by NS1619 led to increased caveolae formation and facilitated localization of TGF-ß receptors in the microdomains of lipid rafts. Thus, our data demonstrated that BK activation has an anti-fibrotic effect on kidney fibrosis by inhibiting the TGF-ß signaling pathway through accelerating TGF-ß receptor degradation via the caveolae route. Hence, our study provides innovative insight into BK as a potential therapeutic target for the treatment of kidney fibrosis.

Catalysis Preparation of Biodiesel from Waste Schisandra chinensis Seed Oil with the Ionic Liquid Immobilized in a Magnetic Catalyst: Fe3O4@SiO2@[C4mim]HSO4.

The purpose of this study was to synthesize a magnetic material that could be easily separated by a magnetic field and combined the catalytic function of an acid/base ionic liquid with silicon for biodiesel preparation. A kind of magnetic catalyst-immobilized ionic liquid was synthesized by a three-step method. The synthesis conditions in each step were optimized by single-factor analysis. Under the optimum conditions, 206.83 mg of ionic liquid (>43.63%) was immobilized on SiO2 (per gram). Heating under reflux was applied to extract Schisandra chinensis seed oil with an average yield of 10.9%. According to the biodiesel yields, Fe3O4@SiO2@[C4mim]HSO4 was the most efficient catalyst in the methyl esterification reaction. Under the optimum reaction conditions, seed oil (10.0 g) was mixed with methanol (70 mL) under continuous mechanical stirring for 3 h, and the yield of biodiesel was 0.557 g/g (the catalyst efficiency was about 89.2%). Also, the thermal value was increased from 32.14 kJ/g (seed oil) to 38.28 kJ/g (biodiesel). The catalytic efficiency of Fe3O4@SiO2@[C4mim]HSO4 was 87.6% of the first being used after four reuse cycles, and 71.4% of the first being used after six reuse cycles in the methylation reaction. The yields and physical and chemical properties of biodiesel were determined.

The influx/efflux mechanisms of d-peptide ligand of nAChRs across the blood-brain barrier and its therapeutic value in treating glioma.

A d-peptide ligand of the nicotine acetylcholine receptors (nAChRs), termed DCDX, enables drug delivery to the brain when incorporated into liposomes and has shown promise as a nanocarrier for treating brain diseases. However, few reports have described the mechanisms whereby DCDX-modified liposomes traverse the blood-brain barrier (BBB). Here, we studied the molecular mechanisms enabling DCDX (and its associated liposomes) to cross an in vitro BBB using a simulated cerebral endothelium monolayer formed by brain capillary endothelial cells (bEnd.3 cells). We also examined the mechanisms whereby DCDX-modified liposomes cross the BBB in vivo using the brain efflux-index method. Transport of DCDX and its modified liposomes was dominantly mediated via the lipid raft/caveolae endocytic pathway. Both the endoplasmic reticulum (ER) and Golgi complex participated in delivering DCDX-modified liposomes to the plasma membrane (PM). DCDX-modified liposomes also participated in the endosome/lysosome pathway (with high-efficiency BBB crossing observed in vitro), while competing for the ER/Golgi/PM pathway. In addition, nAChR α7 did not promote the transportation of DCDX-modified liposomes in vivo or in vitro, as assessed with α7-knockout mice and by performing α-bungarotoxin (α-Bgt) binding-competition experiments. P-glycoprotein (P-gp) was identified as the main efflux transporter across the BBB, in vivo and in vitro. Using a xenograft nude mouse model of human glioblastoma multiforme, blocking the efflux function of P-gp with verapamil enhanced the therapeutic efficiency of DCDX-modified liposomes that were formulated with doxorubicin against glioblastoma. The findings of this study reveal novel mechanisms underlying crossing of the BBB by DCDX-modified liposomes, suggesting that DCDX-modified liposomes can potentially serve as a powerful therapeutic tool for treating glioma.

Structure and function of USP5: Insight into physiological and pathophysiological roles.

Deubiquitinase (DUB)-mediated cleavage of ubiquitin chains from substrate proteins plays a crucial role in various cellular processes, such as DNA repair and protein stabilization and localization. DUBs can be classified into five families based on their sequence and structural homology, and the majority belong to the ubiquitin-specific proteinase (USP) family. As one of the USPs, ubiquitin-specific proteinase 5 (USP5) is unique in that it can specifically recognize unanchored (not conjugated to target proteins) polyubiquitin and is essential for maintaining homeostasis of the monoubiquitin pool. USP5 has also been implicated in a wide variety of cellular events. In the present review, we focus on USP5 and provide a comprehensive overview of the current knowledge regarding its structure, physiological roles in multiple cellular events, and pathophysiological roles in relevant diseases, especially cancer. Signaling pathways and emerging pharmacological profiles of USP5 are also introduced, which fully embody the therapeutic potential of USP5 for human diseases ranging from cancer to neurological diseases.

BK ablation attenuates osteoblast bone formation via integrin pathway.

Impaired bone formation is one of the major causes of low bone mass and skeletal fragility that occurs in osteoporosis. However, the mechanisms underlying the defects in bone formation are not well understood. Here, we report that big conductance calcium-activated potassium channels (BKs) are required for bone formation and osteoblast function both in vivo and in vitro. By 15 weeks of age, BK knockout (BKO) mice exhibited a decline in bone mineral density and trabecular bone volume of the tibiae and lumbar vertebrae, which were associated with impaired bone formation and osteoblast activity. Mechanistically, BK ablation in bone and bone marrow mesenchymal stem cells (BMSCs) of BKO mice inhibited integrin signaling. Furthermore, the binding of α subunit of BK with integrin ß1 protein in osteoblasts was confirmed, and FAK-ERK1/2 signaling was proved to be involved by genetic modification of KCNMA1 (which encodes the α subunit of BK) in ROS17/2.8 osteoblast cells. These findings indicated that BK regulates bone formation by promoting osteoblast differentiation via integrin pathway, which provided novel insight into ion transporter crosstalk with the extracellular matrix in osteoblast regulation and revealed a new potential strategy for intervention in correcting bone formation defects.

Mechanism of Regulation of Big-Conductance Ca2+-Activated K+ Channels by mTOR Complex 2 in Podocytes.

Podocytes, dynamic polarized cells wrapped around glomerular capillaries, are an essential component of the glomerular filtration barrier. BK channels consist of one of the slit diaphragm (SD) proteins in podocytes, interact with the actin cytoskeleton, and play vital roles in glomerular filtration. Mechanistic target of rapamycin (mTOR) complexes regulate expression of SD proteins, as well as cytoskeleton structure, in podocytes. However, whether mTOR complexes regulate podocyte BK channels is still unclear. Here, we investigated the mechanism of mTOR complex regulation of BK channels via real-time PCR, western blot, immunofluorescence, and patch clamping. Inhibiting mTORC1 with rapamycin or downregulating Raptor had no significant effect on BK channel mRNA and protein levels and bioactivity. However, the dual inhibitor of mTORC1 and mTORC2 AZD8055 and short hairpin RNA targeting Rictor downregulated BK channel mRNA and protein levels and bioactivity. In addition, MK2206, GF109203X, and GSK650394, which are inhibitors of Akt, PKCα, and SGK1, respectively, were employed to test the downstream signaling pathway of mTORC2. MK2206 and GF109203X had no effect on BK channel protein levels. MK2206 caused an obvious decrease in the current density of the BK channels. Moreover, GSK650394 downregulated the BK channel protein and mRNA levels. These results indicate mTORC2 not only regulates the distribution of BK channels through Akt, but also modulates BK channel protein expression via SGK1 in podocytes.

A ΣΔ Closed-Loop Interface for a MEMS Accelerometer with Digital Built-In Self-Test Function.

Sigma-delta (ΣΔ) closed-loop operation is the best candidate for realizing the interface circuit of MEMS accelerometers. However, stability and reliability problems are still the main obstacles hindering its further development for high-end applications. In situ self-testing and calibration is an alternative way to solve these problems in the current process condition, and thus, has received a lot of attention in recent years. However, circuit methods for self-testing of ΣΔ closed-loop accelerometers are rarely reported. In this paper, we propose a fifth-order ΣΔ closed-loop interface for a capacitive MEMS accelerometer. The nonlinearity problem of the system is detailed discussed, the source of it is analyzed, and the solutions are given. Furthermore, a built-in self-test (BIST) unit is integrated on-chip for in situ self-testing of the loop distortion. In BIST mode, a digital electrostatic excitation is generated by an on-chip digital resonator, which is also ΣΔ modulated. By single-bit ΣΔ-modulation, the noise and linearity of excitation is effectively improved, and a higher detection level for distortion is easily achieved, as opposed to the physical excitation generated by the motion of laboratory equipment.

Non-invasive detection of the early phase of kidney injury by photoacoustic/computed tomography imaging.

The early diagnosis of kidney diseases, which can remarkably impair the quality of life and are costly, has encountered great difficulties. Therefore, the development of methods for early diagnosis has great clinical significance. In this study, we used an emerging technique of photoacoustic (PA) imaging, which has relatively high spatial resolution and good imaging depth. Two kinds of PA gold nanoparticle (GNP)-based bioprobes were developed based on their superior photo detectability, size controllability and biocompatibility. The kidney injury mouse model was developed by unilateral ureteral obstruction for 96 h and the release of obstruction model). Giving 3.5 and 5.5 nm bioprobes by tail vein injection, we found that the 5.5 nm probe could be detected in the bladder in the model group, but not in the control group. These results were confirmed by computed tomography imaging. Furthermore, the model group did not show changes in the blood biochemical indices (BUN and Scr) and histologic examination. The 5.5 nm GNPs were found to be the critical point for early diagnosis of kidney injury. This new method was faster and more sensitive and accurate for the detection of renal injury, compared with conventional methods, and can be used for the development of a PA GNP-based bioprobe for diagnosing renal injury.

Berberine protects acute liver failure in mice through inhibiting inflammation and mitochondria-dependent apoptosis.

Acute liver failure (ALF) is characterized by sudden large area of inflammation and extensive hepatocyte apoptosis. This study identified the natural product berberine as a potential agent for acute liver failure(ALF). First, in vitro, BBR pre-incubation (5, 10 and 20µM) alleviated L02 hepatocytes injury induced by D-GalN (5mM)/TNF-α (100ng/ml). Second, in vivo, BBR pre-treatment attenuated D-Galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver failure, as evidenced by the reduction of mortality, the alleviation of liver pathological changes and the inhibition of alanine aminotransferase (ALT)/aspartate aminotransferase (AST). Our results further illustrated that BBR inhibited the nuclear translocation of NF-κB p65 and subsequently suppressed the expressions of inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at both mRNA and protein levels in ALF. Moreover, western blotting demonstrated that BBR effectively inhibited apoptosis via reducing cytochrome c release, Bax/Bcl-2 ratio and caspase-3/-9 cleavage in vitro and in vivo. In conclusion, our findings suggest that BBR serves as a potential agent for preventing or treating human ALF by inhibiting inflammation and mitochondria-dependent apoptosis.

Homogenization-assisted cavitation hybrid rotation extraction and macroporous resin enrichment of dihydroquercetin from Larix gmelinii.

Cavitation hybrid rotation, which was and is still looked upon as an unavoidable nuisance in the flow systems, for extraction processing intensification of active chemical compounds from natural products. In this study, a homogenization-assisted cavitation hybrid rotation extraction method was applied to extract dihydroquercetin (DHQ) from larch (Larix gmelinii) wood root. The extraction parameters were optimized in single factor experiments with the DHQ extraction yields as the response values. The optimum conditions were as follows: number of extractions, three; ethanol volume fraction for the extraction, 60%; liquid-solid ratio for homogenization, 10mL/g; homogenization time, 8min; liquid-solid ratio for cavitation extraction, 9mL/g, and cavitation extraction time, 35min. Under these conditions, the DHQ content in extract was 4.50±0.02mg/g, and the extraction efficiency was higher than those of traditional techniques. Cavitation can be effectively used to improve the extraction rate by increasing the mass transfer rates and possible rupture of cell wall due to formation of microcavities leading to higher product yields with reduced processing time and solvent consumption. After the extraction process, macroporous resin column chromatography was used to concentrate and purify the DHQ. Three resins were selected from fifteen macroporous resins for further investigation of their performance. Among these resins, AB-8 resin exhibited relatively better adsorption capacities and desorption ratios for DHQ. The ethanol volume fraction of the solutions for sample loading and desorption, and flow rates for loading and desorption were optimized for the macroporous resin column chromatography.

Homogenate-assisted Vacuum-powered Bubble Extraction of Moso Bamboo Flavonoids for On-line Scavenging Free Radical Capacity Analysis.

A homogenate-assisted vacuum-powered bubble extraction (HVBE) method using ethanol was applied for extraction of flavonoids from Phyllostachys pubescens (P. pubescens) leaves. The mechanisms of homogenate-assisted extraction and vacuum-powered bubble generation were discussed in detail. Furthermore, a method for the rapid determination of flavonoids by HPLC was established. HVBE followed by HPLC was successfully applied for the extraction and quantification of four flavonoids in P. pubescens, including orientin, isoorientin, vitexin, and isovitexin. This method provides a fast and effective means for the preparation and determination of plant active components. Moreover, the on-line antioxidant capacity, including scavenging positive ion and negative ion free radical capacity of different fractions from the bamboo flavonoid extract was evaluated. Results showed that the scavenging DPPH˙ free radical capacity of vitexin and isovitexin was larger than that of isoorientin and orientin. On the contrary, the scavenging ABTS⁺˙free radical capacity of isoorientin and orientin was larger than that of vitexin and isovitexin.

Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress.

Non-alcoholic fatty liver disease (NAFLD) has reached an epidemic level globally, which is recognized to form non-alcoholic steatohepatitis (NASH) by the "two-hit" model, including oxidative stress and inflammation. AMP-activated protein kinase (AMPK) has long been regarded as a key regulator of energy metabolism, which is recognized as a critical target for NAFLD treatment. Here we introduce a natural product, demethyleneberberine (DMB), which potentially ameliorated NAFLD by activating AMPK pathways. Our study showed that the intraperitoneal injection of DMB (20 or 40 mg/kg body weight) decreased hepatic lipid accumulation in methionine and choline deficient (MCD) high-fat diet feeding mice and db/db mice. The further investigation demonstrated that DMB activated AMPK by increasing its phosphorylation in vitro and in vivo. Accompanied with AMPK activation, the expression of lipogenic genes were significantly reduced while genes responsible for the fatty acid ß-oxidation were restored in DMB-treated NAFLD mice. In addition, the remarkable oxidative damage and inflammation induced by NAFLD were both attenuated by DMB treatment, which is reflected by decreased lipid oxidative product, malonaldehyde (MDA) and inflammatory factors, tumor necrosis factor α (TNFα) and interleukin 1ß (IL-1ß). Based on all above, DMB could serve as a novel AMPK activator for treating NAFLD and preventing the pathologic progression from NAFLD to NASH by inhibiting the oxidative stress and inflammation.