In the upcoming decades, connected vehicles will join regular vehicles to appear on roads, and the characteristics of traffic flow will be changed accordingly. To model the heterogeneous traffic ...mixing regular and connected vehicles, a generic car-following framework is first proposed in this paper. A linear stability condition is theoretically derived, which indicates that the stability of the heterogeneous traffic is closely related to the penetration rate and the spatial distribution of connected vehicles. The generic car-following framework is applied by taking the Intelligent Driver Model as an example, and it is shown that connected vehicles can obviously enhance the stability of traffic flow and improve traffic efficiency in particular when traffic is in congestion. Moreover, a driver assistance strategy based on distributed feedback control is developed for connected vehicles, and the simulation results show that the proposed driver assistance strategy performs satisfactorily in stabilizing traffic as well as improving traffic efficiency.
With the rapid development of information technology, cloud computing is also gradually applied to business English teaching practice in higher vocational education. Cloud computing can build a broad ...training platform for students, extend students' English knowledge, and also meet the practical training needs of business English students, greatly improving the efficiency of business English teaching in vocational colleges. The effective connection between cloud computing and business English practice teaching meets the requirements of quality education, so higher vocational colleges should pay attention to it. This article analyzes the overview of cloud computing, explores the current status of business English teaching, and proposes strategies for cloud computing applications.
Syndecan-4 (SDC4) functions as a major endogenous membrane-associated receptor and widely regulates cytoskeleton, cell adhesion, and cell migration in human tumorigenesis and development, which ...represents a charming anti-cancer therapeutic target. Here, SDC4 was identified as a direct cellular target of small-molecule bufalin with anti-hepatocellular carcinoma (HCC) activity. Mechanism studies revealed that bufalin directly bond to SDC4 and selectively increased SDC4 interaction with substrate protein DEAD-box helicase 23 (DDX23) to induce HCC genomic instability. Meanwhile, pharmacological promotion of SDC4/DDX23 complex formation also inactivated matrix metalloproteinases (MMPs) and augmented p38/JNK MAPKs phosphorylation, which are highly associated with HCC proliferation and migration. Notably, specific knockdown of SDC4 or DDX23 markedly abolished bufalin-dependent inhibition of HCC proliferation and migration, indicating SDC4/DDX23 signaling axis is highly involved in the HCC process. Our results indicate that membrane-spanning proteoglycan SDC4 is a promising druggable target for HCC, and pharmacological regulation of SDC4/DDX23 signaling axis with small-molecule holds great potential to benefit HCC patients.
Diabetic nephropathy (DN) is the most frequent complication of diabetes and causes millions of deaths each year. Finding novel therapy to DN is urgent, which requires a good understanding of the ...pathogenesis. Aims are to investigate the molecular mechanisms of DN by focusing on ANRIL/miR-497/TXNIP axis.
Kidney tissues were collected from diagnosed DN patients. High glucose (HG) treatment of human renal tubular epithelial cell cells (HK-2) was used as the cell model of DN. qRT-PCR and Western blotting were performed to measure levels of ANRIL, miR-497, TXNIP, IL-1β, IL-18, caspase-1, and NLRP3. LDH leakage and cell viability were determined with commercial LDH activity kit and MTT assay. ELISA was employed to examine secreted IL-1β and IL-18 levels. Flow cytometry was used to examine caspase-1 activity. Dual luciferase assay was performed to validate interactions of ANRIL/miR-497 and miR-497/TXNIP.
ANRIL and TXNIP were elevated in DN kidney tissues and HG-treated HK-2 cells while miR-497 was reduced. ANRIL bound miR-497 while miR-497 directly targeted TXNIP. Knockdown of ANRIL suppressed HG-induced LDH leakage, TXNIP/NLRP3/caspase-1 activation, and increases of IL-1β and IL-18 secreted levels. miR-497 knockdown or TXNIP overexpression reversed the effects of ANRIL knockdown on LDH leakage and pyroptosis-related signaling. miR-497 mimics inhibited caspase-1-dependent pyroptosis while co-overexpression of TXNIP blocked its effects in HG-treated HK-2 cells.
ANRIL promotes pyroptosis and kidney injury in DN via acting as miR-497 sponge to disinhibit TXNIP expression. These results shed light on the mechanisms of DN and provide targets for therapy development.
Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the ...potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.
...we combined the opinions of frontline epidemic control experts and reviewed the evidence in relevant literature. Two members of the evidence assessment team performed independent computer searches ...of English databases (PubMed, Ovid, Embase), Chinese databases (Chinese Biological Medical Literature database, China National Knowledge Infrastructure, Chinese Medical Journal Database), and relevant online website bulletins on COVID-19 (the World Health Organization, Elsevier, the Lancet, the New England Journal of Medicine, and the Journal of the American Medical Association, 2019 Novel Coronavirus Resource (2019nCoVR), and the Chinese Medical Journal Network). The search terms included the English terms and their Chinese equivalents: “novel coronavirus pneumonia,” “NCP,” “severe acute respiratory syndrome,” “SARS,” “Middle East Respiratory Syndrome,” “MERS,” “influenza,” “psychological therapy,” “guideline,” “statement,” “recommendation,” “randomized controlled trial,” and other rehabilitation-related English search terms and their Chinese equivalents included “respiratory rehabilitation,” “pulmonary rehabilitation,” “physiotherapy,” “physical therapy,” and “occupational therapy.” 11 Recommendations Intervention timing for respiratory rehabilitation in moderately ill patients Due to the limited understanding of the pathophysiological mechanisms of COVID-19, current clinical observations found that around 3% to 5% of moderately ill patients develop severe or even critical disease after 7 to 14 days of infection. ...the exercise intensity should not be too high as its objective is to maintain the existing physical status.
Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared to natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from natural resources, ...especially daily food, implies a promising direction for exploring treatment strategies for human diseases. Here, we report a CQDs-based biocompatible nanozyme prepared from chlorogenic acid (ChA), a major bioactive natural product from coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation of GPX4-catalyzed lipid repair systems. In vivo, ChA CQDs dramatically suppressed the tumor growth in HepG2-tumor-bearing mice with negligible side toxicity. Particularly, in hepatoma H22-bearing mice, ChA CQDs recruited massive tumor-infiltrating immune cells including T cells, NK cells, and macrophages, thereby converting “cold” to “hot” tumors for activating systemic antitumor immune responses. Taken together, our study suggests that natural product-derived CQDs from coffee can serve as biologically safe nanozymes for anticancer therapeutics and may aid the development of nanotechnology-based immunotherapeutic.
Understanding the direct interaction of nanostructures per se with biological systems is important for biomedical applications. However, whether nanostructures regulate biological systems by ...targeting specific cellular proteins remains largely unknown. In the present work, self‐assembling nanomicelles are constructed using small‐molecule oleanolic acid (OA) as a molecular template. Unexpectedly, without modifications by functional ligands, OA nanomicelles significantly activate cellular proteasome function by directly binding to 20S proteasome subunit alpha 6 (PSMA6). Mechanism study reveals that OA nanomicelles interact with PSMA6 to dynamically modulate its N‐terminal domain conformation change, thereby controlling the entry of proteins into 20S proteasome. Subsequently, OA nanomicelles accelerate the degradation of several crucial proteins, thus potently driving cancer cell pyroptosis. For translational medicine, OA nanomicelles exhibit a significant anticancer potential in tumor‐bearing mouse models and stimulate immune cell infiltration. Collectively, this proof‐of‐concept study advances the mechanical understanding of nanostructure‐guided biological effects via their inherent capacity to activate proteasome.
Self‐assembling nanomicelles constructed by small‐molecule oleanolic acid (OA) significantly activate cellular proteasome function by directly binding to 20S proteasome subunit alpha 6 (PSMA6). Mechanistically, OA nanomicelles interact with PSMA6 to dynamically modulate its N‐terminal domain conformation change, thereby controlling the entry of proteins into 20S proteasome, thus accelerating the degradation of several crucial proteins and driving cancer cell pyroptosis.
Magnetoelectric materials with a large magnetoelectric response, a low operating magnetic (or electric) field, and a room‐temperature (or higher) operating temperature are of key importance for ...practical applications. However, such materials are extremely rare because a large magnetoelectric response often requires strong coupling between spins and electric dipoles. Herein, an example of a magnetoelectric composite is prepared by using a room‐temperature multiaxial molecular–ionic ferroelectric, tetramethylammonium tetrachlorogallate(III) (1). Investigation of the magnetoelectric effect of the magnetoelectric laminate composite indicates that its room‐temperature magnetoelectric voltage coefficient (αME) is as high as 186 mV cm−1 Oe−1 at HDC = 275 Oe and at the HAC frequency of ≈39 kHz, providing a valid approach for the preparation of magnetoelectric materials and adding a new member to the magnetoelectric material family.
A magnetoelectric composite is prepared by using a room‐temperature multiaxial molecular–ionic tetramethylammonium tetrachlorogallate(III) ferroelectric. The room‐temperature magnetoelectric voltage coefficient is up to 186 mV cm−1 Oe−1 at HDC = 275 Oe and the HAC frequency is ≈39 kHz. This work demonstrates that multiaxial molecular–ionic ferroelectrics are new excellent candidates for the preparation of magnetoelectric composites.