Shifting and state transformations-based adaptive tracking control for deferred full state-constrained uncertain nonlinear systems.

This paper concerns the tracking control problem of a class of uncertain nonlinear systems subject to deferred time-varying state constraints and external disturbances. The states of the system are free in the initial phase and are restricted by some time-varying constraints after a particular time. A class of novel shifting functions are defined, which make any initial states that beyond the constraint region move to the desired position (such as zero). Thereafter, a new state transformation is implemented for the shifted state, which transforms the state constraint problem into the boundedness of a new variable. Compared with the existing BLF method, this approach avoids feasibility test for virtual control variables. Adaptive backstepping control and dynamic surface control are used in system controller design and stability analysis, and the ideal tracking performance is achieved. Finally, simulation example and comparative studies are carried out to illustrate the effectiveness and outstanding characteristics of the proposed approach. Simulation results show that the proposed control scheme broadens the scope of application, shortens running time and improves control efficiency compared with the existing control strategies.

Adaptive fixed-time stabilization for a class of nonlinear uncertain systems.

Finite-time stability (FTS) has attained great interest in nonlinear control systems in recent two decades. Fixed-time stability (FxTS) is an improved version of FTS in consideration of its settling time independent of the initial values. In this article, the adaptive fixed-time stabilization issue is studied for a kind of nonlinear systems with nonlinear parametric uncertainties and uncertain control coefficients. Using the adaptive estimate and the adding one power integrator (AOPI) design tool, we propose a two-phase control strategy, which makes that the system states tend to the origin in fixed-time, and other signals are bounded on [0,+∞). We prove the main results by means of the recently developed fixed-time Lyapunov stability theory. Finally, we apply the proposed adaptive fixed-time stabilizing control strategy into the pendulum system, and the simulation results verify the efficacy of the presented method.

BODIPY-based near-infrared semiconducting polymer dot for selective yellow laser-excited cell imaging.

Semiconducting polymer dots (Pdots) with both narrow-band absorption and emission are desirable for multiplexed bioassay applications, but such Pdots with absorption peaks beyond 400 nm are difficult to achieve. Here we describe a donor-energy transfer unit-acceptor (D-ETU-A) design strategy to produce a BODIPY-based Pdot that exhibits simultaneously narrow absorption and emission bands. A green BODIPY (GBDP) unit was employed as the main building block of the polymer backbone, conferring a strong, narrow-band absorption around 551 nm. An NIR720 acceptor provides narrow-band NIR emission. The small Stokes shift of the GBDP donor allows introduction of a benzofurazan-based ETU, resulting in a ternary Pdot with a fluorescence quantum yield of 23.2%, the most efficient yellow-laser excitable Pdot. Due to the strong absorbance band centered at 551 nm and weak absorbance at 405 nm and 488 nm, the Pdot showed high single-particle brightness when excited by a 561 nm (yellow) laser, and selective yellow laser excitation when used to label MCF cells, with much greater brightness when excited at 561 nm than at 405 nm or 488 nm.

Identification of predictors for the comprehensive clinical risk and severity of coronary lesions of acute coronary syndrome.

Background: Acute coronary syndrome (ACS) is the most common cause of death in patients with coronary artery disease. The aim of the study was to identify the predictors of both comprehensive clinical risk and severity of coronary lesions by comprehensive use of GRACE and SYNTAX scores in patients with ACS. Methods: Clinical data of 225 ACS patients who underwent coronary angiography between 2015 and 2016 were collected. Multiple logistic regression analysis (stepwise) was used to identify the predictors. The predictive ability of predictors and the model were determined using receiver operating characteristics analyses. Results: Multivariable logistic regression analyses showed that high aspartate aminotransferase (AST) predicted the comprehensive clinical risk with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.011 (1.002-1.021). High total cholesterol (TC) and red blood cell distribution width (RDW) predicted the severity of coronary lesions with ORs and 95% CIs of 1.517 (1.148-2.004) and 1.556 (1.195-2.028), respectively. Low prealbumin predicted both severity of coronary lesions and comprehensive clinical risk of ACS patients with ORs and 95% CIs of 0.743 (0.672-0.821) and 0.836 (0.769-0.909), respectively. The model with a combination of prealbumin and AST had the highest predictive efficacy for comprehensive clinical risk, and the combination of prealbumin, TC, and RDW had the highest predictive efficacy for the severity of coronary lesions. The sensitivity and specificity, and the optimal cut-off values of these four indexes were determined. Conclusions: Four predictors for the comprehensive clinical risk and severity of coronary lesions of ACS were identified, which provided important information for the early diagnosis and appropriate treatment of ACS.

A Target-Triggered Emission Enhancement Strategy Based on a Y-Shaped DNA Fluorescent Nanoprobe with Aggregation-Induced Emission Characteristic for microRNA Imaging in Living Cells.

DNA self-assembled fluorescent nanoprobes have been developed for bio-imaging owing to their high resistance to enzyme degradation and great cellular uptake capacity. In this work, we designed a new Y-shaped DNA fluorescent nanoprobe (YFNP) with aggregation-induced emission (AIE) characteristic for microRNA imaging in living cells. With the modification of the AIE dye, the constructed YFNP had a relatively low background fluorescence. However, the YFNP could emit a strong fluorescence due to the generation of microRNA-triggered AIE effect in the presence of target microRNA. Based on the proposed target-triggered emission enhancement strategy, microRNA-21 was detected sensitively and specifically with a detection limit of 122.8 pM. The designed YFNP showed higher bio-stability and cell uptake than the single-stranded DNA fluorescent probe, which has been successfully applied for microRNA imaging in living cells. More importantly, the microRNA-triggered dendrimer structure could be formed after the recognition of target microRNA, achieving a reliable microRNA imaging with a high spatiotemporal resolution. We expect that the proposed YFNP will become a promising candidate for bio-sensing and bio-imaging.

Near-Infrared Optical Transducer for Dynamic Imaging of Cerebrospinal Fluid Glucose in Brain Tumor.

Aberrant cerebral glucose metabolism is related to many brain diseases, especially brain tumor. However, it remains challenging to measure the dynamic changes in cerebral glucose. Here, we developed a near-infrared (NIR) optical transducer to sensitively monitor the glucose variations in cerebrospinal fluid in vivo. The transducer consists of an oxygen-sensitive nanoparticle combined with glucose oxidase (GOx), yielding highly sensitive NIR phosphorescence in response to blood glucose change. We demonstrated long-term continuous glucose monitoring by using the NIR transducer. After subcutaneous implantation, the glucose transducer provides a strong luminescence signal that can continuously monitor blood glucose fluctuations for weeks. By using the NIR emission of the transducer, we further observed abnormal dynamic changes in cerebrospinal fluid glucose and quantitatively assessed cerebral glucose uptake rates in transgenic mice bearing brain tumors. This study provides a promising method for the diagnosis of various metabolic diseases with altered glucose metabolism.

FOXM1 is regulated by DEPDC1 to facilitate development and metastasis of oral squamous cell carcinoma.

The Disheveled, EGL-10, Pleckstrin domain containing 1 (DEPDC1) is a new oncogene that has recently been described. The mechanisms and functions of its expression are yet to be determined in oral squamous cell carcinoma (OSCC). In the present study, the impact of DEPDC1 on the growth and development of OSCC was investigated using animal models, cell lines and human tissue samples. Elevated DEPDC1 expression within cancer cell lines and human OSCC has been identified. Mechanistic examination showed that restored DEPDC1 expression in vivo and in vitro stimulated OSCC tumour development. In addition, FOXM1 interacts with DEPDC1 as indicated by co-immunoprecipitation and immunofluorescence testing. Functionally, DEPDC1 facilitated Wnt/ß-catenin signal transduction and ß-catenin protein nuclear expression. In summary, the DEPDC1, interacting with FOXM1 via Wnt/ß-catenin signaling, the closely regulated OSCC pathogenesis, suggesting that targeting the novel DEPDC1/FOXM1/ß-catenin complex is an essential OSCC therapeutic approach.

Kinetics and Mechanism of Ternesite Formation from Dicalcium Silicate and Calcium Sulfate Dihydrate.

The kinetics and mechanism of ternesite formation (calcium sulfosilicate, Ca5(SiO4)2SO4, C5S2$) were investigated by studying the reaction between beta-dicalcium silicate (ß-C2S) and calcium sulfate dihydrate (CaSO4∙2H2O). Mineralogical composition development was monitored using X-ray diffraction (XRD) and backscattered scanning electron microscopy (BSEM) coupled to energy-dispersive X-ray spectroscopy (EDS). Ternesite can form in the 1100 to 1200 °C range by the solid-phase reaction of ß-C2S and CaSO4. The formation of ternesite is favored by increasing the sintering temperature or extending the sintering time. The solid-phase reaction is carried out by diffusion of CaSO4 to ß-C2S. The kinetics equation of ternesite is consistent with three-dimensional diffusion models (3-D model, D3 model or Jander model). The equation of the D3 model is 1 - 2α/3 - (1 - α)2/3 = kt. On the basis of the Arrhenius equation, the activation energy of ternesite is 239.8 kJ/mol.

Ultrabright Pdots with a Large Absorbance Cross Section and High Quantum Yield.

Semiconducting polymer dots (Pdots) are increasingly used in biomedical applications due to their extreme single-particle brightness, which results from their large absorption cross section (σ). However, the quantum yield (Φ) of Pdots is typically below 40% due to aggregation-induced self-quenching. One approach to reducing self-quenching is to use FRET between the donor (D) and acceptor (A) groups within a Pdot; however, Φ values of FRET-based Pdots remain low. Here, we demonstrate an approach to achieve ultrabright FRET-based Pdots with simultaneously high σ and Φ. The importance of self-quenching was revealed in a non-FRET Pdot: adding 30 mol % of a nonabsorbing polyphenyl to a poly(9,9-dioctylfluorene) (PFO) Pdot increased Φ from 13.4 to 71.2%, yielding an ultrabright blue-emitting Pdot. We optimized the brightness of FRET-based Pdots by exploring different D/A combinations and ratios with PFO and poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-phenylene)] (PFP) as donor polymers and poly[(9,9-dioctyl-2,7-divinylenefluorenylene)-alt-co-(1,4-phenylene)] (PFPV) and poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo-{2,1',3}-thiadiazole)] (PFBT) as acceptor polymers, with a fixed concentration of poly(styrene-co-maleic anhydride) as surfactant polymer. Ultrabright blue-emitting Pdots possessing high Φ (73.1%) and σ (σR = σabs/σall, 97.5%) were achieved using PFP/PFPV Pdots at a low acceptor content (A/[D + A], 2.5 mol %). PFP/PFPV Pdots were 1.8 times as bright as PFO/PFPV Pdots due to greater coverage of acceptor absorbance by donor emission─a factor often overlooked in D/A pair selection. Ultrabright green-emitting PFO Pdots (Φ = 76.0%, σR = 92.5%) were obtained by selecting an acceptor (PFBT) with greater spectral overlap with PFO. Ultrabright red-emitting Pdots (Φ = 64.2%, σR = 91.0%) were achieved by blending PFO, PFBT, and PFTBT to create a cascade FRET Pdot at a D:A1:A2 molar ratio of 61:5:1. These blue, green, and red Pdots are among the brightest Pdots reported. This approach of using a small, optimized amount of FRET acceptor polymer with a large donor-acceptor spectral overlap can be generalized to produce ultrabright Pdots with emissions that span the visible spectrum.

Long-Term In Vivo Glucose Monitoring by Polymer-Dot Transducer in an Injectable Hydrogel Implant.

Optical sensors have attracted a great deal of interest for glucose detection. However, their practical applications for continuous glucose monitoring are still constrained by operational reliability in subcutaneous tissues. Here, we show an implantable hydrogel platform embedded with luminescent polymer dots (Pdots) for sensitive and long-term glucose monitoring. We use Pdot transducer in a polyacrylamide hydrogel matrix to construct an implantable platform. The hydrogel-Pdot transducer showed bright luminescence with ratiometric response to glucose changes. The in vitro and in vivo sensitivities of the hydrogel implant were enhanced by varying the enzyme concentration and injection volume. After implantation, the hydrogel with Pdot transducer remained at the implanted site without migration for 1 month and can be removed from the subcutaneous tissue for further analysis. Our results indicate that the hydrogel-Pdot platform maintains the intrinsic sensing property with excellent stability during 1 month implantation, while fibrous capsule formation on the implant in some cases needs to be solved for long-term continuous glucose monitoring.

N6-Methyladenosine Methyltransferase METTL3 Promotes Angiogenesis and Atherosclerosis by Upregulating the JAK2/STAT3 Pathway via m6A Reader IGF2BP1.

Atherosclerosis (AS) is a life-threatening vascular disease. RNA N6-methyladenosine (m6A) modification level is dysregulated in multiple pathophysiologic processes including AS. In this text, the roles and molecular mechanisms of m6A writer METTL3 in AS progression were explored in vitro and in vivo. In the present study, cell proliferative, migratory, and tube formation capacities were assessed through CCK-8, Transwell migration, and tube formation assays, respectively. RNA m6A level was examined through a commercial kit. RNA and protein levels of genes were measured through RT-qPCR and western blot assays, respectively. VEGF secretion level was tested through ELISA assay. JAK2 mRNA stability was detected through actinomycin D assay. The relationship of METTL3, IGF2BP1, and JAK2 was investigated through bioinformatics analysis, MeRIP, RIP, RNA pull-down, and luciferase reporter assays. An AS mouse model was established to examine the effect of METTL3 knockdown on AS development in vivo. The angiogenetic activity was examined through chick chorioallantoic membrane assay in vivo. The results showed that METTL3 was highly expressed in ox-LDL-induced dysregulated HUVECs. METTL3 knockdown inhibited cell proliferation, migration, tube formation, and VEGF expression/secretion in ox-LDL-treated HUVECs, hampered AS process in vivo, and prevented in vivo angiogenesis of developing embryos. METTL3 positively regulated JAK2 expression and JAK2/STAT3 pathway in an m6A dependent manner in HUVECs. IGF2BP1 positively regulated JAK2 expression through directly binding to an m6A site within JAK2 mRNA in HUVECs. METTL3 knockdown weakened the interaction of JAK2 and IGF2BP1. METTL3 exerted its functions through JAK2/STAT3 pathway. In conclusion, METTL3 knockdown prevented AS progression by inhibiting JAK2/STAT3 pathway via IGF2BP1.

Monitoring Metabolites Using an NAD(P)H-sensitive Polymer Dot and a Metabolite-Specific Enzyme.

We introduce an NAD(P)H-sensitive polymer dot (Pdot) biosensor for point-of-care monitoring of metabolites. The Pdot is combined with a metabolite-specific NAD(P)H-dependent enzyme that catalyzes the oxidation of the metabolite, generating NAD(P)H. Upon UV illumination, the NAD(P)H quenches the fluorescence emission of Pdot at 627 nm via electron transfer, and also fluoresces at 458 nm, resulting in a shift from red to blue emission at higher NAD(P)H concentrations. Metabolite concentration is quantified ratiometrically-based on the ratio of blue-to-red channel emission intensities, with a digital camera-with high sensitivity and specificity. We demonstrate phenylalanine biosensing in human plasma for a phenylketonuria screening test, quantifying several other disease-related metabolites (lactate, glucose, glutamate, and ß-hydroxybutyrate), and a paper-based assay with smartphore imaging for point-of-care use.

Fucoxanthin-rich fraction from Sargassum fusiformis alleviates particulate matter-induced inflammation in vitro and in vivo.

Particulate matter (PM) contributes to air pollution and primarily originates from unregulated industrial emissions and seasonal natural dust emissions. Fucoxanthin (Fx) is a marine natural pigment from brown macroalgae that has been shown to have various beneficial effects on health. However, the effects of Fx on PM-induced toxicities in cells and animals have not been assessed. In this study, we investigated the anti-inflammatory potential of the Fx-rich fraction (FxRF) of Sargassum fusiformis against PM-mediated inflammatory responses. The FxRF composition was analyzed by rapid-resolution liquid chromatography mass spectrometry. Fx and other main pigments were identified. FxRF attenuated the production of inflammatory components, including prostaglandin E2 (PGE2), cyclooxygenase-2, interleukin (IL)-1ß, and IL-6 from PM-exposed HaCaT keratinocytes. PM exposure also reduced the levels of nitric oxide (NO), tumor necrosis factor-α, inducible nitric oxide synthase (iNOS), and PGE2 in PM-exposed RAW264.7 macrophages. Additionally, the culture medium from PM-exposed HaCaT cells induced upregulation of NO, iNOS, PGE2, and pro-inflammatory cytokines in RAW264.7 macrophages. FxRF also significantly decreased the expression levels of factors involved in inflammatory responses, such as NO, reactive oxygen species, and cell death, in PM-exposed zebrafish embryos. These results demonstrated the potential protective effects of FxRF against PM-induced inflammation both in vitro and in a zebrafish model.

Metabolic study of ginsenoside Rg3 and glimepiride in type 2 diabetic rats by liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry.

RATIONALE: Ginsenoside Rg3 and glimepiride have been applied to treat type 2 diabetes (T2DM) because of their good hypoglycemic effects. In this study, the effects of ginsenoside Rg3 acting synergistically with glimepiride were investigated in liver microsomes from rats with type 2 diabetes. METHODS: An in vitro incubation system with normal rat liver microsomes (RLM) and type 2 diabetic rat liver microsomes (TRLM) was developed. The system also included two experimental groups consisting of RLM and TRLM pretreated with ginsenoside Rg3 and glimepiride (named the RLMR and TRLMR groups, respectively). The metabolism in the different groups was analyzed by ultra-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry (UPLC/Q-Orbitrap MS). RESULTS: The results showed that the concentration of glimepiride increased in RLM and TRLM after treatment with ginsenoside Rg3. Five metabolites (M1-M5) of glimepiride were found, and they were named 3N-hydroxyglimepiride, hydroxyglimepiride, 1,2-epoxy ether-3-hydroxyglimepiride, 1N-hydroxyglimepiride and 1N,2C,S,O,O-epoxy ether-3-hydroxyglimepiride. The metabolite of ginsenoside Rg3 was ginsenoside Rh2. CONCLUSIONS: An in vitro incubation system with RLM and TRLM was developed. The system revealed pathways that produce glimepiride metabolites. Ginsenoside Rg3 may inhibit the activity of cytochrome P450 enzymes in vitro. The present study showed that ginsenoside Rg3 and glimepiride may be combined for the treatment of T2DM.

Reversible Ratiometric NADH Sensing Using Semiconducting Polymer Dots.

Reduced nicotinamide adenine dinucleotide (NADH) is a key coenzyme in living cells due to its role as an electron carrier in redox reactions, and its concentration is an important indicator of cell metabolic state. Abnormal NADH levels are associated with age-related metabolic diseases and neurodegenerative disorders, creating a demand for a simple, rapid analytical method for point-of-care NADH sensing. Here we develop a series of NADH-sensitive semiconducting polymer dots (Pdots) as nanoprobes for NADH measurement, and test their performance in vitro and in vivo. NADH sensing is based on electron transfer from semiconducting polymer chains in the Pdot to NADH upon UV excitation, quenching Pdot fluorescence emission. In polyfluorene-based Pdots, this mechanism resulted in an on-off NADH sensor; in DPA-CNPPV Pdots, UV excitation resulted in NADH-sensitive emission at two wavelengths, enabling ratiometric detection. Ratiometric NADH detection using DPA-CNPPV Pdots exhibits high sensitivity (3.1 µM limit of detection), excellent selectivity versus other analytes, reversibility, and a fast response (less than 5 s). We demonstrate applications of the ratiometric NADH-sensing Pdots including smartphone-based NADH imaging for point-of-care use.

Low Molecular Weight Oligosaccharide from Panax ginseng C.A. Meyer against UV-Mediated Apoptosis and Inhibits Tyrosinase Activity In Vitro and In Vivo.

To find new anti-UV and whitening agents, 21 fractions isolated from three preparations of ginseng (white, red, and black ginseng) were screened, and their antioxidant effects on AAPH- or H2O2-induced damage were investigated. Furthermore, the protective effect against UV-mediated apoptosis and the tyrosinase inhibitory activity of the targeted fractions were evaluated in vitro and in a zebrafish model. Among all fractions, F10 from white ginseng was selected as having the strongest anti-UV and antimelanogenesis activities. This fraction exhibited excellent inhibitory effects on the pigmentation of zebrafish, which may be due to its potential tyrosinase inhibitory activity. Additionally, the chemical composition of F10 was evaluated by UPLC-MS and NMR instruments. The results indicated that F10 had a carbohydrate content of more than 76%, and the weight-average molecular weight was approximately 239 Da. Disaccharide sucrose was the main active compound in F10. These results suggest that F10 could be used as an ingredient for whitening cosmetics and regarded as an anti-UV filter in the future.

Improving the Accuracy of Pdot-Based Continuous Glucose Monitoring by Using External Ratiometric Calibration.

Continuous glucose monitoring (CGM) allows type I and II diabetes patients to track changes in their glucose levels, allowing detection of impending hypoglycemia or hyperglycemia. Polymer dots (Pdots) are candidates for use in implanted CGM systems due to their exceptional brightness, photostability, sensitivity, and biocompatibility. However, Pdot glucose transducers are oxygen-dependent, and changes in tissue oxygen levels affect their measurement accuracy. Here, we describe an external ratiometric calibration method that corrects for changes in tissue oxygen levels to improve measurement accuracy. This method uses the ratio of oxygen concentrations inside and outside the Pdot glucose transducer as an indicator of glucose concentration to correct for signal deviations caused by tissue oxygen fluctuations. A second oxygen-sensitive Pdot that is not conjugated with glucose oxidase is used to measure the oxygen concentration outside the Pdot glucose transducer. We describe the theoretical basis for this approach and demonstrate its effectiveness experimentally in a subcutaneous mouse implant model. This external ratiometric system achieves higher accuracy glucose measurements than previous Pdot-based CGM systems and comparable accuracy to current commercial CGM systems, demonstrating the utility of the external ratiometric calibration strategy.

Enhancing the Long-Term Stability of a Polymer Dot Glucose Transducer by Using an Enzymatic Cascade Reaction System.

Impaired glucose metabolism in diabetes causes severe acute and long-term complications, making real-time detection of blood glucose indispensable for diabetic patients. Existing continuous glucose monitoring systems are unsuitable for long-term clinical glycemic management due to poor long-term stability. Polymer dot (Pdot) glucose transducers are implantable optical nanosensors that exhibit excellent brightness, sensitivity, selectivity, and biocompatibility. Here, it is shown that hydrogen peroxide-a product of glucose oxidation in Pdot glucose sensors-degrades sensor performance via photobleaching, reduces glucose oxidase activity, and generates cytotoxicity. By adding catalase to a glucose oxidase-based Pdot sensor to create an enzymatic cascade, the hydrogen peroxide product of glucose oxidation is rapidly decomposed by catalase, preventing its accumulation and improving the sensor's photostability, enzymatic activity, and biocompatibility. Thus, a next-generation Pdot glucose transducer with a multienzyme reaction system (Pdot-GOx/CAT) that provides excellent sensing characteristics as well as greater detection system stability is presented. Pdot glucose transducers that incorporate this enzymatic cascade to eliminate hydrogen peroxide will possess greater long-term stability for improved continuous glucose monitoring in diabetic patients.

Diagnostic and therapeutic role of microRNAs in oral cancer (Review).

Oral cancer is one of the leading types of cancer and remains the most common cause of cancer­related mortality in Asia. The pathogenesis of oral cancer is complicated and, due to lack of accurate diagnostic methods and efficient treatment strategies, oral cancer is responsible for a large number of deaths. Therefore, there is an urgent need for developing novel diagnostic tools and targeted therapies. MicroRNAs (miRNAs) represent a class of small non­coding RNAs that are key elements and play critical regulatory roles in the pathological processes of various diseases. miRNAs are widely distributed in body fluids and are specifically expressed in different cancers, and they may represent effective biomarkers that may be used for early detection of oral cancer. In addition, miRNAs are involved in oral cancer development, progression and prognosis by targeting a broad range of mRNAs that may be of therapeutic value for oral cancer. The aim of the present review was to summarize the role of miRNAs as new diagnostic tools and potential therapeutic targets in oral cancer, and investigate the underlying molecular mechanisms.

State transformation-based adaptive tracking control for a class of nonlinear systems with time-varying state constraints.

It is meaningful to study the control problems of nonlinear systems with uncertain parameters and external disturbances, especially for those subject to state constraints. In this paper, a state transformation approach is proposed to address time-varying asymmetric state constraints. By this state transformation, the state constrained problem is transformed into the boundedness problem of the transformed function. When the initial states are in the constrained region, the state constraints can be guaranteed as long as the boundedness of the transformed functions are guaranteed. Compared with the barrier Lyapunov function (BLF) approach, it successfully removes the feasibility test from virtual controllers, and thus broadens its application scope. In addition, for the parametric uncertainties and external disturbances exist in the system simultaneously, the tuning function and the adaptive laws for the upper bounds of disturbances are designed to help realize the control performance of the system. Consequently, a novel tuning function based adaptive backstepping control scheme is given. The designed controller ensures the error signals converge to a small neighbourhood of zero and the asymmetric time-varying constraints on system states are maintained for all the time. Finally, simulation results are given to illustrate the efficacy of the presented control scheme.