In this article, we propose a hybrid framework using visual and force sensing for human-robot co-carrying tasks. Visual sensing is utilized to obtain human motion and an observer is designed for ...estimating control input of human, which generates robot's desired motion toward human's intended motion. An adaptive impedance-based control strategy is proposed for trajectory tracking with neural networks used to compensate for uncertainties in robot's dynamics. Motion synchronization is achieved and this approach yields a stable and efficient interaction behavior between human and robot, decreases human control effort and avoids interference to human during the interaction. The proposed framework is validated by a co-carrying task in simulations and experiments.
Clinical hyperthermic intraperitoneal chemotherapy (HIPEC) is regarded as a potential treatment that can prolong survival of patients with peritoneal metastases after cytoreductive surgery. However, ...treated tumor cells are prone to becoming heat resistant to HIPEC therapy through high expression of heat shock proteins (HSPs). Here, a carrier-free bifunctional nanoinhibitor was developed for HIPEC therapy in the management of peritoneal metastases. Self-assembly of the nanoinhibitor was formed by mixing Mn ion and epigallocatechin gallate (EGCG) in a controllable manner. Such nanoinhibitor directly inhibited HSP90 and impaired the HSP90 chaperone cycle by reduced intracellular ATP level. Additionally, heat and Mn ion synergistically induced oxidative stress and expression of caspase 1, which activated GSDMD by proteolysis and caused pyroptosis in tumor cells, triggering immunogenic inflammatory cell death and induced maturation of dendritic cells through the release of tumor antigens. This strategy to inhibit heat resistance in HIPEC presented an unprecedented paradigm for converting "cold" tumors into "hot" ones, thus significantly eradicating disseminated tumors located deep in the abdominal cavity and stimulating immune response in peritoneal metastases of a mouse model. Collectively, the nanoinhibitor effectively induced pyroptosis of colon tumor cells under heat conditions by inhibiting heat stress resistance and increasing oxidative stress, which may provide a new strategy for treatment of colorectal peritoneal metastases.
Abstract
Background
The triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes. ...Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS.
Methods
A total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study. Patients were divided into tertiles according to their TyG index. The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke. The TyG index was calculated as the ln (fasting triglyceride level mg/dL × fasting glucose level mg/dL/2).
Results
The incidence of MACE increased with TyG index tertiles at a 3-year follow-up. The Kaplan–Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005). Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201–1.746; P < 0.001). The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001). Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019).
Conclusions
The TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS.
Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous ...characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1
tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/ .
FOXP3＋ regulatory T （Treg） cells are critical in maintaining immune tolerance and homeostasis of the immune system. The molecular mechanisms underlying the stability, plasticity and functional ...activity of Treg cells have been much studied in recent years. Here, we summarize these intriguing findings, and provide insight into their potential use or manipulation during Treg cell therapy for the treatment of autoimmune diseases, graft-versus-host disease （GVHD） and cancer.
Hypocretin/orexin neurons are distributed restrictively in the hypothalamus, a brain region known to orchestrate diverse functions including sleep, reward processing, food intake, thermogenesis, and ...mood. Since the hypocretins/orexins were discovered more than two decades ago, extensive studies have accumulated concrete evidence showing the pivotal role of hypocretin/orexin in diverse neural modulation. New method of viral-mediated tracing system offers the possibility to map the monosynaptic inputs and detailed anatomical connectivity of Hcrt neurons. With the development of powerful research techniques including optogenetics, fiber-photometry, cell-type/pathway specific manipulation and neuronal activity monitoring, as well as single-cell RNA sequencing, the details of how hypocretinergic system execute functional modulation of various behaviors are coming to light. In this review, we focus on the function of neural pathways from hypocretin neurons to target brain regions. Anatomical and functional inputs to hypocretin neurons are also discussed. We further briefly summarize the development of pharmaceutical compounds targeting hypocretin signaling.
This article is part of the special issue on Neuropeptides.
•Hypocretin system plays a key role in sleep initiation and maintenance through modulation of multiple downstream arousal-promoting brain nuclei.•Hypocretin system modulates reward-processing and addiction through brain nuclei those are highly relevant to arousal modulation.•Development of hypocretin receptor antagonists (for insomnia and hyperarousal states) and agonists (for narcolepsy/cataplexy) provides new tools for sleep pharmacology.
Curcumin is a principal curcuminoid of turmeric (
), which is commonly used as a spice in cooking and a yellow pigment in the food processing industry. Recent studies have demonstrated that curcumin ...has a variety of biological activities and pharmacological performances, providing protection and promotion of human health. In addition to presenting an overview of the gut metabolism of curcumin, this paper reviews the current research progress on its versatile bioactivity, such as antioxidant, anti-inflammatory, and immune-regulatory activities, and also intensively discusses its health benefits, including the protective or preventive effects on cancers and diabetes, as well as the liver, nervous system, and cardiovascular systems, highlighting the potential molecular mechanisms. Besides, the beneficial effects of curcumin on human are further stated based on clinical trials. Considering that there is still a debate on the beneficial effects of curcumin, we also discuss related challenges and prospects. Overall, curcumin is a promising ingredient of novel functional foods, with protective efficacy in preventing certain diseases. We hope this comprehensive and updated review will be helpful for promoting human-based studies to facilitate its use in human health and diseases in the future.
The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven ...translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.
Providing ubiquitous connectivity to diverse device types is the key challenge for 5G and beyond 5G (B5G). Unmanned aerial vehicles (UAVs) are expected to be an important component of the upcoming ...wireless networks that can potentially facilitate wireless broadcast and support high rate transmissions. Compared to the communications with fixed infrastructure, UAV has salient attributes, such as flexible deployment, strong line-of-sight connection links, and additional design degrees of freedom with the controlled mobility. In this paper, a comprehensive survey on UAV communication toward 5G/B5G wireless networks is presented. We first briefly introduce essential background and the space-air-ground integrated networks, as well as discuss related research challenges faced by the emerging integrated network architecture. We then provide an exhaustive review of various 5G techniques based on UAV platforms, which we categorize by different domains, including physical layer, network layer, and joint communication, computing, and caching. In addition, a great number of open research problems are outlined and identified as possible future research directions.
Mud acid is regularly applied to recover or increase permeability of sandstone reservoir. However, due to its rapid reacting rate and heterogeneous displacement, the stimulation effect of ...conventional mud acid is relatively limited in sandstone formations. For mud acid, it is important to choose proper chemical additives to retard reaction rate and make it distributed homogenereously in formation. To overcome these shortcomings of mud acid, a new proprietary mud acid system has been developed for sandstone formations stimulation. The new system is composed of 2.0% multichemical solutions (MCS) +6.5%HCl+1.5% HF, and the combined solution contains nonionic surfactant, clay stabilizer, and dispersant which were specifically formulated. Core flooding experiments were conducted with the high effective mud acid; meanwhile, XRD and SEM analysis were performed before/after the core flooding tests. Retarded tests were also conducted for the new mud acid reacting with sandstone samples. Treatments with ten pores volume of the new high effective mud acid system were found to increase permeability of sandstone core approximately three times of its initial permeability. From the results of SEM and XRD analysis, most of clays were dissolved, and permeability was increased after core flooding by this new mud acid solution. On the basis of acidizing theory, the reaction retarded mechanism was explained about the new composite mud acid. Other properties of the new composite mud acid were also discussed. In comparison of conventional mud acid, the new composite mud acid can retard acidizing reaction rate and distribute evenly in formation; therefore, it can extend acidizing penetration and stimulate sandstone formation thoroughly. The new composite mud acid is more compatible and desirable than conventional mud acid, and it will be applied extensively for sandstone matrix stimulation.
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