Macrophages enhance cisplatin resistance in gastric cancer through the transfer of circTEX2.

Cisplatin-based chemotherapy is often used in advanced gastric cancer (GC) treatment, yet resistance to cisplatin may lead to treatment failure. Mechanisms underlying cisplatin resistance remain unclear. Recent evidence highlighted the role of macrophages in cancer chemoresistance. Macrophage-derived exosomes were shown to facilitate intercellular communication. Here, we investigated the cisplatin resistance mechanism based on macrophage-derived exosomes in gastric cancer. Cell growth and apoptosis detection experiments revealed that M2-polarized macrophages increased the resistance of GC cells to cisplatin. qRT-PCR, RNAase R assay, actinomycin D assay and cell nucleo-cytoplasmic separation experiments confirmed the existence of circTEX2 in macrophage cytoplasm, with a higher expression level in M2 macrophages than that in M1 macrophages. Further experiments showed that circTEX2 acted as microRNA sponges for miR-145 and regulated the expression of ATP Binding Cassette Subfamily C Member 1 (ABCC1). Inhibition of the circTEX2/miR-145/ABCC1 axis blocked the cisplatin resistance of gastric cancer induced by M2 macrophages, as evidenced by in vitro and in vivo experiments. In conclusion, our research suggests that the exosomal transfer of M2 macrophage-derived circTEX2 enhances cisplatin resistance in gastric cancer through miR-145/ABCC1. Additionally, communication between macrophages and cancer cells via exosomes may be a promising therapeutic target for the treatment of cisplatin-resistant gastric cancer.

GelMA/PEGDA microneedles patch loaded with HUVECs-derived exosomes and Tazarotene promote diabetic wound healing.

Clinical work and research on diabetic wound repair remain challenging globally. Although various conventional wound dressings have been continuously developed, the efficacy is unsatisfactory. The effect of drug delivery is limited by the depth of penetration. The sustained release of biomolecules from biological wound dressings is a promising treatment approach to wound healing. An assortment of cell-derived exosomes (exos) have been proved to be instrumental in tissue regeneration, and researchers are dedicated to developing biomolecules carriers with unique properties. Herein, we reported a methacrylate gelatin (GelMA) microneedles (MNs) patch to achieve transdermal and controlled release of exos and tazarotene. Our MNs patch comprising GelMA/PEGDA hydrogel has distinctive biological features that maintain the biological activity of exos and drugs in vitro. Additionally, its unique physical structure prevents it from being tightly attached to the skin of the wound, it promotes cell migration, angiogenesis by slowly releasing exos and tazarotene in the deep layer of the skin. The full-thickness cutaneous wound on a diabetic mouse model was carried out to demonstrate the therapeutic effects of GelMA/PEGDA@T + exos MNs patch. As a result, our GelMA/PEGDA@T + exos MNs patch presents a potentially valuable method for repairing diabetic wound in clinical applications.

Adsorption and mechanistic study of the invasive plant-derived biochar functionalized with CaAl-LDH for Eu(III) in water.

Herein, we developed the invasive plant-derived biochar (IPB) functionalized with CaAl-LDH at five mass ratios using a physical mixture method, assessed their adsorption perform for Eu(III), and explored the relative mechanisms. Results show that the IPB successfully loaded CaAl-LDH in five composites and their Eu(III) sorption affinities were strongly affected by solution pH, contact time, temperature, and the mass ratio of LDH and IPB. All the sorpiton process for Eu(III) occurred on the heterogeneous surface of five composites and the boundary layer diffusion limited the chemical sorption rate. Interestingly, the CaAl-LDH/IPB composite with high ratio of IPB had higher sorption capacity than the one with high ratio of LDH due to larger porosity of the former. Three mechanisms containing ion exchange between Al and Eu ions, surface complexation with carboxyl- and oxygen-containing functional groups, and precipitation were involved in the Eu(III) sorption, but the dominant sorption mechanism for each CaAl-LDH/IPB composite differed with different mass ratio of CaAl-LDH and IPB. In composite with more IPB (e.g., CaAl-LDH/IPB-13), both ion exchange and surface complexes dominated the sorption process and the intensity of Eu3+ was identified with the one of Eu2O3. Whereas in composites with high LDH, ion exchange dominated the sorption and the intensity of Eu3+ was obviously higher than the one of Eu2O3. This research will provide a new perspective for the application of the LDH/biochar materials.

Chemical characterization and evaluation of the antioxidants in Chaenomeles fruits by an improved HPLC-TOF/MS coupled to an on-line DPPH-HPLC method.

An improved method based on HPLC-TOF/MS was developed to catalog the antioxidants in five species of Chaenomeles (Mugua). Forty-four fractions from the Mugua extracts show appreciable levels of antioxidative activity in scavenging the stable free-radical 2,2-diphenyl-1-picrylhydrazyl and the hydroxyl radicals. Twelve major antioxidant's chemical structures are identified. Antioxidant activities differ between species, but intra-species level of antioxidants, regardless of their ripeness, are similar. C. sinensis has the highest antioxidant level. A rigorous quality control procedure was implemented to ensure accuracy of antioxidant quantification. This improved procedure can be used for rapid discovery of antioxidants in other plant extracts.

A comprehensive screening shows that ergothioneine is the most abundant antioxidant in the wild macrofungus Phylloporia ribis Ryvarden.

The polar and non-polar extracts from the authenticated wild mushroom Phylloporia ribis were separated by hydrophilic interaction liquid chromatography (HILIC) and by reverse phase (RP)-HPLC, respectively. A split valve separated the eluents into two fractions for free-radical scavenging analysis and for structural identification. Forty-six compounds showed scavenging activity of the stable-free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The structures of 8 antioxidants (inosine, caffeic acid, ergothioneine, p-hydroxybenzoic acid, adenosine, 3,4-dihydroxybenzaldehyde, apigenin, and naringenin) are characterized by Mass Spectrometer. Among them, ergothioneine was the most abundant (>65%) and most active antioxidant in P. ribis.

Online Detection of Driver Fatigue Using Steering Wheel Angles for Real Driving Conditions.

This paper presents a drowsiness on-line detection system for monitoring driver fatigue level under real driving conditions, based on the data of steering wheel angles (SWA) collected from sensors mounted on the steering lever. The proposed system firstly extracts approximate entropy (ApEn)featuresfromfixedslidingwindowsonreal-timesteeringwheelanglestimeseries. Afterthat, this system linearizes the ApEn features series through an adaptive piecewise linear fitting using a given deviation. Then, the detection system calculates the warping distance between the linear features series of the sample data. Finally, this system uses the warping distance to determine the drowsiness state of the driver according to a designed binary decision classifier. The experimental data were collected from 14.68 h driving under real road conditions, including two fatigue levels: "wake" and "drowsy". The results show that the proposed system is capable of working online with an average 78.01% accuracy, 29.35% false detections of the "awake" state, and 15.15% false detections of the "drowsy" state. The results also confirm that the proposed method based on SWA signal is valuable for applications in preventing traffic accidents caused by driver fatigue.

An Efficient Method for the Preparative Isolation and Purification of Flavonoid Glycosides and Caffeoylquinic Acid Derivatives from Leaves of Lonicera japonica Thunb. Using High Speed Counter-Current Chromatography (HSCCC) and Prep-HPLC Guided by DPPH-HPLC Experiments.

In this work, the n-butanol extract from leaves of Lonicera japonica Thunb. (L. japonica) was reacted with DPPH and subjected to a HPLC analysis for the guided screening antioxidants (DPPH-HPLC experiments). Then, nine antioxidants, including flavonoid glycosides and caffeoylquinic acid derivatives, were isolated and purified from leaves of L. japonica using high speed counter-current chromatography (HSCCC) and prep-HPLC. The n-butanol extract was firstly isolated by HSCCC using methyl tert-butyl ether/n-butanol/acetonitrile/water (0.5% acetic acid) (2:2:1:5, v/v), yielding five fractions F1, F2 (rhoifolin), F3 (luteoloside), F4 and F5 (collected from the column after the separation). The sub-fractions F1, F4 and F5 were successfully separated by prep-HPLC. Finally, nine compounds, including chlorogenic acid (1), lonicerin (2), rutin (3), rhoifolin (4), luteoloside (5), 3,4-Odicaffeoylquinic acid (6), hyperoside (7), 3,5-O-dicaffeoylquinic acid (8), and 4,5-O-dicaffeoylquinic acid (9) were obtained, respectively, with the purities over 94% as determined by HPLC. The structures were identified by electrospray ionization mass spectrometry (ESI-MS), 1H- and 13C-NMR. Antioxidant activities were tested, and the isolated compounds showed strong antioxidant activities.

[Research on periodical changes and metabolism relations of active components in Lonicera japonica leaves].

The study is aimed to explore the metabolism rule of Lonicera japonica by investigating the primary and secondary metabolism process in different growth periods. HPLC and other methods were used to measure metabolism indexes of leaves collected in last ten days of every month. The results suggested that the maximum (78.59%) and minimum (60.83%) of water content were found in March and December. The content of total sugar reached a high level from December to February and the maximum (275.8 mg•g⁻¹) appeared in October, while it reduced significantly at other time. The change of chlorogenic acid, neochlorogenic acid, galuteolin, caffeic acid were basically consistent and the highest content of them synchronously appeared (42.79, 2.01, 7.13, 0.16 mg•g⁻¹) in March. The content of primary and secondary metabolite in L. japonica leaves reached a high level from March to May, and the main related elements with effective components were K, Mg, P, aspartate, threonine, proline, valine, cysteine, isoleucine and phenylalanine.

[Comparative Analysis of Different Strains of Lonicera japonica on Appearance and Internal Quality].

Objective: To provide the reference for germplasm identification and breeding of Lonicera japonica. Methods: Morphological taxonomy was used to observe, describe and preliminary classify different strains of Lonicera japonica. HPLC was used to determine the content of 5-caffeoylquinic acid,chlorogenic acid,cryptochlorogenic acid,luteolin,3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid in the buds and leaves; SPSS 17. 0 was used to analyze the data. Results: The differences between different strains of Lonicera japonica were on four aspects( leaf color, leaf shape,bud size and color). The buds of strain YTQL-01 and ITA-01 contained higher content of 5-caffeoylquinic acid, chlorogenic acid and 3,5-dicaffeoylquinic acid. There was no significant correlation between appearance and internal quality of different Lonicera japonica strains. Conclusions: Genetic diversity exists between different strains of Lonicera japonica according to appearance and internal quality.

[Biological Characteristics and Pollen Morphology of Different Chaenomeles Species in Flowering Stage].

OBJECTIVE: The biological characteristics and pollen morphology of different Chaenomeles species in the flowering stage were studied,in order to provide a theoretical basis to discriminate the germplasm resources and new cultivars selection. METHODS: Field research and scanning electron were used for the research of the biological characteristics and pollen morphology of Chaenomeles species. RESULTS: The differences were significant both in the size of petal and the quantity of stamen in different kinds of Chaenomeles species. The pollen of Chaenomeles speciosa and Chaenomeles japonica were perprolate, and the ratio of the length between poles and diameter of the equator was more than two. The ratio of Chaenomeles sinensis, Chaenomeles cathayensis and Chaenomeles thibeticae ranged from 1.87 to 1.93 and they were prolate. The characteristics,such as the length between poles of pollen grain,diameter of the equator, the ratio of the length between poles and diameter of the equator, surface ornamentation and tectum perforation, had close genetic relationship with Chaenomeles species. CONCLUSION: Biological characteristics and pollen morphology could be the value reference to identify different kinds of Chaenomeles species.

Combined use of transmyocardial laser revascularization and endothelial progenitor cells enhances neovascularization and regional contractility in a canine model of ischemic hearts.

The purpose of this study was to determine the combined effect of transmyocardial laser revascularization (TMLR) and the implantation of endothelial progenitor cells (EPCs) on cardiac function of ischemic hearts in canines. The left anterior descending artery (LAD) was occluded to establish the canine model of acute myocardial infarct (AMI). Four weeks later, the animals were randomly divided into four groups: TMLR group, in which transmyocardial laser-induced channels were established at the ischemic region; EPCs+TMLR group, in which EPCs were locally transplanted into laser-induced channels at the ischemic region; EPCs group, in which the EPCs were injected into the ischemic region; control group, in which the AMI animals received neither TMLR nor EPCs. The peripheral blood (50 mL) was sampled in all groups. Mononuclear cells from the peripheral blood were separated and cultured to obtain spindle-shaped attaching (AT) cells in vitro. AT cells were labeled with 1, 1'-dioctadecyl-1 to 3,3, 3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) before injecting into the laser-induced channels or ischemic region. Four weeks after the first operation, TMLR was performed in the TMLR group and EPCs+TMLR group, and at the same time, the EPCs originating from the AT cells were mixed with calcium alginate (CA). Then the EPCs-CA composites were implanted into myocardial channels induced by laser in the EPCs+TMLR group, and into the myocardial infarct area in the EPCs group. All dogs underwent echocardiography at second month after LAD occlusion. Finally the samples of myocardium around the LAD were subjected to histochemical and immunohistologic examinations. The results showed there was no significant difference in the diameter of left atrium and ventricle before treatment among all groups (P>0.05). Eight weeks after modeling, the regional contractility in the LAD territory in the EPCs+TMLR group was increased as compared with control group and TMLR group, but there was no significant difference between control group and TMLR group. Neoangiogenesis was observed in the EPCs+TMLR group, and the fibrosis was seen in the TMLR group. There was no significant difference in neoangiogenesis around the channels induced by laser among EPCs+TMLR, EPCs and TMLR groups. It was concluded that TMLR combined with EPCs could improve the regional and global cardiac function in AMI, and augment neovascularizaiton in channels of ischemic myocardium induced by laser.

Learn Zero-Constraint-Violation Safe Policy in Model-Free Constrained Reinforcement Learning.

We focus on learning the zero-constraint-violation safe policy in model-free reinforcement learning (RL). Existing model-free RL studies mostly use the posterior penalty to penalize dangerous actions, which means they must experience the danger to learn from the danger. Therefore, they cannot learn a zero-violation safe policy even after convergence. To handle this problem, we leverage the safety-oriented energy functions to learn zero-constraint-violation safe policies and propose the safe set actor-critic (SSAC) algorithm. The energy function is designed to increase rapidly for potentially dangerous actions, locating the safe set on the action space. Therefore, we can identify the dangerous actions prior to taking them and achieve zero-constraint violation. Our major contributions are twofold. First, we use the data-driven methods to learn the energy function, which releases the requirement of known dynamics. Second, we formulate a constrained RL problem to solve the zero-violation policies. We prove that our Lagrangian-based constrained RL solutions converge to the constrained optimal zero-violation policies theoretically. The proposed algorithm is evaluated on the complex simulation environments and a hardware-in-loop (HIL) experiment with a real autonomous vehicle controller. Experimental results suggest that the converged policies in all environments achieve zero-constraint violation and comparable performance with model-based baseline.

The role of miR-18a in gastric cancer angiogenesis.

BACKGROUND/AIMS: To investigate the effect of miR-18a on angiogenesis in gastric cancer. METHODOLOGY: We generated stable cell lines overexpressing miR-18a in SGC-7901 cells. Cell proliferation was assessed by the MTT assay. The effects of miR-18a overexpression on tumor growth and angiogenesis were assessed. Because of the key role of mammalian target of rapamycin (mTOR) signaling in gastric cancer progression, we also tested whether miR-18a overexpression affected the mTOR pathway. RESULTS: Ectopic expression of miR-18a significantly diminished cell proliferation in SGC-7901 cells (p<0.01). miR-18a overexpression significantly retarded SGC-7901 xenograft growth by 71.8% in vivo, and caused a marked reduction in tumor angiogenesis assessed by CD31-stained microvessel count. Western blot analysis of the xenografts showed that miR-18a overexpression substantially reduced the phosphorylation of two mTOR substrates, S6K1 and 4E-BPl, indicative of art inactivation of the mTOR pathway. Accompanying with the mTOR inactivation, the angiogenic factors, hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, were significantly downregulated. CONCLUSIONS: These data highlighted an important role for miR-18a in controlling gastric cancer growth and angiogenesis, therefore offering a possible therapeutic strategy against this malignancy.

[Dynamic changes of enzyme activities and active component contents in Lonicera japonica during different blossoming stages].

OBJECTIVE: This paper aimed to study the dynamic changes of enzyme activities and active component contents in Lonicera japonica during different blossoming stages. METHOD: The enzyme activities of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), peroxidase (POD) and the contents of total phenol, total flavonoids, chlorogenic acid, anthocyanins in L. japonica during different blossoming stages were determined. RESULT: The contents of total phenolics, total flavonoids, anthocyanins decreased from the Sanqing stage to Jinhua stage while the content of chlorogenic acid increased slightly in white period, and then decreased gradually. The activities of three enzymes decreased gradually from Sanqing stage, and got to a minimum value in Yinhua stage, then increased slightly until the Jinhua stage. CONCLUSION: The enzyme activities of PPO and POD correlated the content of phenolic substances positively before the Jinhua stage in L. japonica. In the period of maturity, the POD activity was strengthened due to the induction of respiration and became the key enzyme to control active component content during the mature stage.

Robust Approximate Dynamic Programming for Nonlinear Systems With Both Model Error and External Disturbance.

Model error and external disturbance have been separately addressed by optimizing the definite H∞ performance in standard linear H∞ control problems. However, the concurrent handling of both introduces uncertainty and nonconvexity into the H∞ performance, posing a huge challenge for solving nonlinear problems. This article introduces an additional cost function in the augmented Hamilton-Jacobi-Isaacs (HJI) equation of zero-sum games to simultaneously manage the model error and external disturbance in nonlinear robust performance problems. For satisfying the Hamilton-Jacobi inequality in nonlinear robust control theory under all considered model errors, the relationship between the additional cost function and model uncertainty is revealed. A critic online learning algorithm, applying Lyapunov stabilizing terms and historical states to reinforce training stability and achieve persistent learning, is proposed to approximate the solution of the augmented HJI equation. By constructing a joint Lyapunov candidate about the critic weight and system state, both stability and convergence are proved by the second method of Lyapunov. Theoretical results also show that introducing historical data reduces the ultimate bounds of system state and critic error. Three numerical examples are conducted to demonstrate the effectiveness of the proposed method.

CircSOD2 polarizes macrophages towards the M1 phenotype to alleviate cisplatin resistance in gastric cancer cells by targeting the miR-1296/STAT1 axis.

Cisplatin is the first-line drug for gastric cancer (GC). Cisplatin resistance is the most important cause of poor prognosis for GC. Increasing evidence has identified the important role of macrophage polarization in chemoresistance. CircRNAs are newly discovered non-coding RNAs, characterized by covalently closed loops with high stability. Previous studies have reported a significant difference between circRNA profiles expressed in classically activated M1 macrophages, and those expressed in alternatively activated M2 macrophages. However, the underlying mechanism behind the regulation of GC cisplatin resistance by macrophages remains unclear. In our study, we observed the aberrant high expression of circSOD2 in M1 macrophages derived from THP-1. These expression patterns were confirmed in macrophages from patients with GC. Detection of the M1 and M2 markers confirmed that overexpression of circSOD2 enhances M1 polarization. The viability of cisplatin-treated GC cells was significantly reduced in the presence of macrophages overexpressing circSOD2, and cisplatin-induced apoptosis increased dramatically. In vivo experiments showed that macrophages expressing circSOD2 enhanced the effect of cisplatin. Moreover, we demonstrated that circSOD2 acts as a microRNA sponge for miR-1296 and regulates the expression of its target gene STAT1 (signal transducer and activator of transcription 1). CircSOD2 exerts its function through the miR-1296/STAT1 axis. Inhibition of circSOD2/miR-1296/STAT1 may therefore reduce M1 polarization. Overexpression of circSOD2 promotes the polarization of M1 macrophages and enhances the effect of cisplatin in GC. CircSOD2 is a novel positive regulator of M1 macrophages and may serve as a potential target for GC chemotherapy.

Microneedle Patches with Antimicrobial and Immunomodulating Properties for Infected Wound Healing.

Treatment of infected wounds remains a challenge owing to antibiotic resistance; thus, developing smart biomaterials for the healing of infected wounds is urgently needed. In this study, a microneedle (MN) patch system with antimicrobial and immunomodulatory properties is developed to promote and accelerate infected wound healing. In the MN patch (termed PFG/M MNs), a nanoparticle with polydopamine (PDA)-loaded iron oxide is grafted with glucose oxidase (GOx) and hyaluronic acid (HA) and then integrated into the tips, and amine-modified mesoporous silica nanoparticles (AP-MSNs) are incorporated into the bases. Results show that PFG/M MNs eradicate bacterial infections and modulate the immune microenvironment, combining the advantages of chemodynamic therapy, photothermal therapy, and M2 macrophage polarization from Fe/PDA@GOx@HA in the tips as well as anti-inflammatory effect of AP-MSNs from the MN bases. Thus, the PFG/M MN system is a promising clinical candidate for promoting infected wound healing.

Visual Volatile-Compound Fingerprint Based on Headspace Gas Chromatography-Ion Mobility Spectrometry Combined with Chemometrics Analysis and Exploration in the Authentic Identification of Lonicerae japonicae flos.

Headspace gas chromatography-ion mobility spectrometric (HS-GC-IMS) fingerprint of volatile organic compounds (VOCs) in Lonicerae japonicae flos (LJF, Jinyinhua in Chinese) was developed. This method, combined with chemometrics analysis, was explored in the identification of authentic LJF. Seventy VOCs were identified from LJF, including aldehydes, ketones, esters, etc. The developed volatile-compound fingerprint based on HS-GC-IMS coupled with PCA analysis can successfully discriminate LJF from its adulterant: Lonicerae japonicae(LJ, called Shanyinhua in China) and can equally discriminate the LJF samples from different geographical origins of China. Total of four (compound 120, compound 184, 2-heptanone and 2-heptanone#2) and nine VOCs (styrene, compound 41, 3z-hexenol, methylpyrazine, hexanal#2, compound 78, compound 110, compound 124 and compound 180) were exploited, which might serve as the chemical markers for the difference of LJF, LJ and LJF from different regions of China. The result showed that the fingerprint based on HS-GC-IMS combined with PCA exhibited distinct advantages, such as rapid, intuitive and powerful selectivity, which demonstrated great application potential in the authentic identification of LJF.

Optimization Landscape of Policy Gradient Methods for Discrete-Time Static Output Feedback.

In recent times, significant advancements have been made in delving into the optimization landscape of policy gradient methods for achieving optimal control in linear time-invariant (LTI) systems. Compared with state-feedback control, output-feedback control is more prevalent since the underlying state of the system may not be fully observed in many practical settings. This article analyzes the optimization landscape inherent to policy gradient methods when applied to static output feedback (SOF) control in discrete-time LTI systems subject to quadratic cost. We begin by establishing crucial properties of the SOF cost, encompassing coercivity, L -smoothness, and M -Lipschitz continuous Hessian. Despite the absence of convexity, we leverage these properties to derive novel findings regarding convergence (and nearly dimension-free rate) to stationary points for three policy gradient methods, including the vanilla policy gradient method, the natural policy gradient method, and the Gauss-Newton method. Moreover, we provide proof that the vanilla policy gradient method exhibits linear convergence toward local minima when initialized near such minima. This article concludes by presenting numerical examples that validate our theoretical findings. These results not only characterize the performance of gradient descent for optimizing the SOF problem but also provide insights into the effectiveness of general policy gradient methods within the realm of reinforcement learning.

Integrated Decision and Control: Toward Interpretable and Computationally Efficient Driving Intelligence.

Decision and control are core functionalities of high-level automated vehicles. Current mainstream methods, such as functional decomposition and end-to-end reinforcement learning (RL), suffer high time complexity or poor interpretability and adaptability on real-world autonomous driving tasks. In this article, we present an interpretable and computationally efficient framework called integrated decision and control (IDC) for automated vehicles, which decomposes the driving task into static path planning and dynamic optimal tracking that are structured hierarchically. First, the static path planning generates several candidate paths only considering static traffic elements. Then, the dynamic optimal tracking is designed to track the optimal path while considering the dynamic obstacles. To that end, we formulate a constrained optimal control problem (OCP) for each candidate path, optimize them separately, and follow the one with the best tracking performance. To unload the heavy online computation, we propose a model-based RL algorithm that can be served as an approximate-constrained OCP solver. Specifically, the OCPs for all paths are considered together to construct a single complete RL problem and then solved offline in the form of value and policy networks for real-time online path selecting and tracking, respectively. We verify our framework in both simulations and the real world. Results show that compared with baseline methods, IDC has an order of magnitude higher online computing efficiency, as well as better driving performance, including traffic efficiency and safety. In addition, it yields great interpretability and adaptability among different driving scenarios and tasks.