Chemoresistance, whether intrinsic or acquired, is a major obstacle in the treatment of cancer. The resistance of cancer cells to chemotherapeutic drugs can result from various mechanisms. Over the ...last decade, it has been reported that 1ong noncoding RNAs (lncRNAs) can mediate carcinogenesis and drug resistance/sensitivity in cancer cells. This article reviews, in detail, recent studies regarding the roles of lncRNAs in mediating drug resistance.
Aqueous rechargeable zinc‐ion batteries (ZIBs) have attracted considerable attention as a promising candidate for low‐cost and high‐safety electrochemical energy storage. However, the advancement of ...ZIBs is strongly hindered by the sluggish ionic diffusion and structural instability of inorganic metal oxide cathode materials during the Zn2+ insertion/extraction. To address these issues, a new organic host material, poly(2,5‐dihydroxy‐1,4‐benzoquinonyl sulfide) (PDBS), has been designed and applied for zinc ion storage due to its elastic structural factors (tunable space and soft lattice). The aqueous Zn‐organic batteries based on the PDBS cathode show outstanding cycling stability and rate capability. The coordination moieties (O and S) display the strong electron donor character during the discharging process and can act as the coordination arms to host Zn2+. Also, under the electrochemical environment, the malleable polymer structure of PDBS permits the rotation and bending of polymer chains to facilitate the insertion/extraction of Zn2+, manifesting the superiority and uniqueness of organic electrode materials in the polyvalent cation storage. Finally, quasi‐solid‐state batteries based on aqueous gel electrolyte demonstrate highly stable capacity under different bending conditions.
A new organic polymer has been identified as a cathode material for efficient zinc ion storage due to its elastic structural factors. The coordination moieties (O and S) display strong electron donor character during the charging process and can act as the coordination arms to synergistically host Zn2+, manifesting the superiority and uniqueness of organic electrode materials in the multi‐valence cation storage.
Display omitted
Drug resistance is a major obstacle in the field of pre-clinical and clinical therapeutics. The development of novel technologies and targeted therapies have yielded new modalities to ...overcome drug resistance, but multidrug resistance (MDR) remains one of the major challenges in the treatment of cancer. The ubiquitin-proteasome system (UPS) has a central role in regulating the levels and activities of a multitude of proteins as well as regulation of cell cycle, gene expression, response to oxidative stress, cell survival, cell proliferation and apoptosis. Therefore, inhibition of the UPS could represent a novel strategy for the treatment and overcoming of drug resistance in chemoresistant malignancies. In 2003, bortezomib was approved by the FDA for the treatment of multiple myeloma (MM). However, due to its limitations, second generation proteasome inhibitors (PIs) like carfilzomib, ixazomib, oprozomib, delanzomib and marizomib were introduced which displayed clinical activity in bortezomib-resistant tumors. Past studies have demonstrated that proteasome inhibition potentiates the anti-cancer efficacy of other chemotherapeutic drugs by: i) decreasing the expression of anti-apoptotic proteins such as TNF-α and NF-kB, ii) increasing the levels of Noxa, a pro-apoptotic protein, iii) activating caspases and inducing apoptosis, iv) degrading the pro-survival protein, induced myeloid leukemia cell differentiation protein (MCL1), and v) inhibiting drug efflux transporters. In addition, the mechanism of action of the immunoproteasome inhibitors, ONX-0914 and LU-102, suggested their therapeutic role in the combination treatment with PIs. In the current review, we discuss various PIs and their underlying mechanisms in surmounting anti-tumor drug resistance when used in combination with conventional chemotherapeutic agents.
This paper is concerned with the problem of robust fault estimation and fault-tolerant control for a class of Takagi-Sugeno (T-S) fuzzy systems with time-varying state delay and actuator faults. ...Based on the ( k-1)th fault estimation information, a novel k-step fault-estimation observer is proposed to construct the kth fault error dynamics. The obtained fault estimates via k-step fault-estimation can practically better depict the size and shape of the faults. Then, based on the information of online k -step fault-estimation, a dynamic output feedback fault tolerant controller is designed to compensate the fault effects on the closed-loop fuzzy system. Furthermore, some less conservative delay dependent sufficient conditions for the existence of fault estimation observers and fault tolerant controllers are given in terms of solution to a set of linear matrix inequalities. Finally, simulation results of two numerical examples are presented to show the effectiveness and merits of the proposed methods.
Summary
The fault estimation for a class of nonlinear systems with Lipschitzian nonlinearities and faults is studied in this article. An integrated estimation observer that covers the robust ...estimation observer (REO) and adaptive estimation observer (AEO) is proposed to improve the accuracy of fault estimation. Compared with the traditional AEO, the designed observer does not involve the output derivatives and can be more suitable for practical applications. Furthermore, based on the designed observer, the coupling term emerging in the obtained error dynamics can be eliminated reasonably and less conservative stability conditions for the error dynamics can be obtained, whereas the case is hard to be achieved based on the existing intermediate estimator approach in the literature. Compared with the traditional REO and AEO, the fault can be estimated with a good accuracy by using the proposed integrated estimation observer. Numerical examples test the effectiveness and advantages of the proposed method.
With discretized particle velocity space, a multiscale unified gas-kinetic scheme for entire Knudsen number flows is constructed based on the BGK model. The current scheme couples closely the update ...of macroscopic conservative variables with the update of microscopic gas distribution function within a time step. In comparison with many existing kinetic schemes for the Boltzmann equation, the current method has no difficulty to get accurate Navier–Stokes (NS) solutions in the continuum flow regime with a time step being much larger than the particle collision time. At the same time, the rarefied flow solution, even in the free molecule limit, can be captured accurately. The unified scheme is an extension of the gas-kinetic BGK-NS scheme from the continuum flow to the rarefied regime with the discretization of particle velocity space. The success of the method is due to the un-splitting treatment of the particle transport and collision in the evaluation of local solution of the gas distribution function. For these methods which use operator splitting technique to solve the transport and collision separately, it is usually required that the time step is less than the particle collision time. This constraint basically makes these methods useless in the continuum flow regime, especially in the high Reynolds number flow simulations. Theoretically, once the physical process of particle transport and collision is modeled statistically by the kinetic Boltzmann equation, the transport and collision become continuous operators in space and time, and their numerical discretization should be done consistently. Due to its multiscale nature of the unified scheme, in the update of macroscopic flow variables, the corresponding heat flux can be modified according to any realistic Prandtl number. Subsequently, this modification effects the equilibrium state in the next time level and the update of microscopic distribution function. Therefore, instead of modifying the collision term of the BGK model, such as ES-BGK and BGK–Shakhov, the unified scheme can achieve the same goal on the numerical level directly. Many numerical tests will be used to validate the unified method.
Alzheimer's disease (AD) is the most common cause of disability in individuals aged >65 years worldwide. AD is characterized by the abnormal deposition of amyloid β (Aβ) peptide, and intracellular ...accumulation of neurofibrillary tangles of hyperphosphorylated τ protein and dementia. The neurotoxic oligomer Aβ peptide, which is the neuropathological diagnostic criterion of the disease, together with τ protein, are mediators of the neurodegeneration that is among the main causative factors. However, these phenomena are mainly initiated and enhanced by oxidative stress, a process referring to an imbalance between antioxidants and oxidants in favour of oxidants. This imbalance can occur as a result of increased free radicals or a decrease in antioxidant defense, free radicals being a species that contains one or more unpaired electrons in its outer shell. The major source of potent free radicals is the reduction of molecular oxygen in water, that initially yields the superoxide radical, which produces hydrogen peroxide by the addition of an electron. The reduction of hydrogen peroxide produces highly reactive hydroxyl radicals, termed reactive oxygen species (ROS) that can react with lipids, proteins, nucleic acids, and other molecules and may also alter their structures and functions. Thus, tissues and organs, particularly the brain, a vulnerable organ, are affected by ROS due to its composition. The brain is largely composed of easily oxidizable lipids while featuring a high oxygen consumption rate. The current review examined the role of oxidative stress in AD.
Summary
In this paper, the problem of fault estimation based on intermediate variable‐based adaptive observer for a class of nonlinear systems with Lipschitzian nonlinearities and faults is studied. ...An adaptive observer based on lower triangular matrix transformation is proposed, which comprise the output derivatives information so as to enhance the accuracy and speed of fault estimation effectually. The designed observer can be simplified to the lower triangular estimation observer, and is superior to the comprehensive estimation observer in the related literature. In addition, a more general error dynamics is derived based on the improved adaptive estimation observer, which makes it less conservative to obtain stability conditions. The uniformly ultimately bounded stability conditions of the estimated error dynamics are given by linear matrix inequalities (LMIs). Numerical examples are given to illustrate the effectiveness and merits of the proposed method.
In the past decade, the emergence of chimeric antigen receptor (CAR) T-cell therapy has led to a cellular immunotherapy revolution against various cancers. Although CAR-T cell therapies have ...demonstrated remarkable efficacy for patients with certain B cell driven hematological malignancies, further studies are required to broaden the use of CAR-T cell therapy against other hematological malignancies. Moreover, treatment failure still occurs for a significant proportion of patients. CAR antigen loss on cancer cells is one of the most common reasons for cancer relapse. Additionally, immune evasion can arise due to the hostile immunosuppressive tumor microenvironment and the impaired CAR-T cells
persistence. Other than direct antitumor activity, the adverse effects associated with CAR-T cell therapy are another major concern during treatment. As a newly emerged treatment approach, numerous novel preclinical studies have proposed different strategies to enhance the efficacy and attenuate CAR-T cell associated toxicity in recent years. The major obstacles that impede promising outcomes for patients with hematological malignancies during CAR-T cell therapy have been reviewed herein, along with recent advancements being made to surmount them.
Small RNAs（s RNAs） play essential roles in plants upon biotic stress. Plants utilize RNA silencing machinery to facilitate pathogen-associated molecular pattern-triggered immunity and ...effector-triggered immunity to defend against pathogen attack or to facilitate defense against insect herbivores. Pathogens, on the other hand, are also able to generate effectors and s RNAs to counter the host immune response. The arms race between plants and pathogens/insect herbivores has triggered the evolution of s RNAs,RNA silencing machinery and pathogen effectors. A great number of studies have been performed to investigate the roles of s RNAs in plant defense, bringing in the opportunity to utilize s RNAs in plant protection. Transgenic plants with pathogen-derived resistance ability or transgenerational defense have been generated, which show promising potential as solutions for pathogen/insect herbivore problems in the field. Here we summarize the recent progress on the function of s RNAs in response to biotic stress, mainly in plant-pathogen/insect herbivore interaction,and the application of s RNAs in disease and insect herbivore control.
PDF
