Methyltransferase-like 3 (METTL3) is a member of the m
A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes ...controlling m
A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33
myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).
Specimens of paraffin embedded tumour from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson's or Spearman's chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33
cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls.
We found that tumour tissues displayed increased levels of METTL3 and CD33
MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33
cells in tumour tissues (P = 0.011). We further found that the direct CD33
CD11b
HLA-DR
MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33
MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33
MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II-IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P = 0.010) and OS (HR = 5.140, P = 0.021), while CD33
MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).
Our findings suggest that CD33
MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33
MDSCs are independent prognostic factors in CC.
With the increase of spacecrafts, data relay satellite network (DRSN) plays an essential role in the space task transmission and processing through broad coverage and efficient information ...distribution of data relay satellites. However, the growing demand of space tasks and the limited number of satellite antenna lead to the conflicts between high-priority unpredictable tasks and common tasks with timely processing requirements, which further result in the decreasing scheduling efficiency of space tasks. In this paper, a dynamic scheduling scheme with task laxity (DSTL) is proposed to solve scheduling conflicts and enhance scheduling efficiency. Firstly, a task model in visible time window is analyzed according to the processing time limit of tasks and the intermittent connection nature of satellites under a constructed DRSN model. After that, the task laxity is defined by the deadline and execution time of tasks to judge the urgency of tasks, and the optimization problem is formulated to maximize the number of tasks and prioritize high priority tasks by calculating task laxity. Then, the DSTL scheme is designed via four stages, which are task preprocessing, task-resource matching, task-conflict assessment, task-resource updating. In DSTL, a task sorting method with task laxity is raised to arrange the priority of tasks; an urgent task scheduling algorithm (UTS) is put forward to prioritize unpredictable tasks; a task-conflict resolution algorithm (TCR) is brought up to assess conflicting tasks and reschedule them. Following that, an adaptive large neighborhood search algorithm combined with deadline-aware scheduling (ALNS-DAS) is presented to obtain the optimal scheduling scheme, which has the maximum number of completed tasks. The simulation results show that the DSTL can maximize the guarantee ratio of completed tasks and ensure timely processing with the increase of tasks demand.
Coating the nanoparticle surface with cancer cell recognizing ligands is expected to facilitate specific delivery of nanoparticles to diseased cells in vivo. While this targeting strategy is ...appealing, no nanoparticle-based active targeting formulation for solid tumor treatment had made it past phase III clinical trials. Here, we quantified the cancer cell-targeting efficiencies of Trastuzumab (Herceptin) and folic acid coated gold and silica nanoparticles in multiple mouse tumor models. Surprisingly, we showed that less than 14 out of 1 million (0.0014% injected dose) intravenously administrated nanoparticles were delivered to targeted cancer cells, and that only 2 out of 100 cancer cells interacted with the nanoparticles. The majority of the intratumoral nanoparticles were either trapped in the extracellular matrix or taken up by perivascular tumor associated macrophages. The low cancer cell targeting efficiency and significant uptake by noncancer cells suggest the need to re-evaluate the active targeting process and therapeutic mechanisms using quantitative methods. This will be important for developing strategies to deliver emerging therapeutics such as genome editing, nucleic acid therapy, and immunotherapy for cancer treatment using nanocarriers.
As a platform for data transmission, space data relay network (SDRN), which has high coverage and continuous communications, provides data relay services for the spacecrafts and satellites by ...allocating antenna resource. However, the diversity between emergency tasks and common tasks for antenna requirements may result in the conflicts of resource occupation. This leads to the loss of emergency information and the low scheduling efficiency. In this paper, a real-time dynamic scheduling (RTDS) scheme is proposed to ensure the transmission of emergency tasks and improve the scheduling efficiency by scheduling sequence adjustment and task management. Firstly, the relative SDRN system models are given and a dynamic scheduling mechanism is designed to deal with the disturbance factors during the scheduling process. Then, based on the dynamic scheduling mechanism, the RTDS scheme is implemented in three stages, which include initial scheduling, dynamic scheduling for emergency tasks, and final scheduling. The simulation results demonstrate that the proposed RTDS scheme can guarantee the timely transmission of emergency tasks and enhance the scheduling efficiency compared with the existing scheduling algorithms.
The satellite-terrestrial integrated networks (STINs) have gradually become a new class of effective ways to satisfy the requirements of a higher capacity and stronger connection in the future ...communications. In contrast with terrestrial networks, the fast periodic motion of satellites results in the dynamic time-varying features of STIN, which further leads to frequent changes in the connectivity of satellite-terrestrial links and the backhaul capacities of satellite networks. To balance the accessible capacity of STIN under the intermittent connectivity and dynamic backhaul capacity, an effective user association mechanism is needed. In this article, a dynamic user association (DUA) mechanism with task classification is proposed to meet the requirements of load balancing and the user task processing. First, a STIN model is constructed with low earth orbit satellites and the three types of base station, which are a macro base station, small cell base station, and low earth orbit based base station. After that, the optimization problem is formulated via jointly considering the task classification, the load condition of base stations, and the backhaul capacity of low earth orbit based base stations. Then, the DUA mechanism is proposed to find the most suitable base station serving each user. In DUA, a dynamic cell range extension algorithm is developed to adjust the load of STIN in terms of the resilient backhaul capacity, and a greedy-based user-centric user association with task classification algorithm is proposed to find the base station, which has the maximum rate and minimum load for each user and to meet the requirements of user task processing. The simulation results show that the proposed DUA can enhance the load balance and guarantee the task processing demand of STIN compared with the reference signal receiving power association and the max-sum rate association algorithms.
In protein‐rich environments such as the blood, the formation of a protein corona on receptor‐targeting nanoparticles prevents target recognition. As a result, the ability of targeted nanoparticles ...to selectively bind to diseased cells is drastically inhibited. Backfilling the surface of a targeted nanoparticle with polyethylene glycol (PEG) molecules is demonstrated to reduce the formation of the protein corona and re‐establishes specific binding. The length of the backfilled PEG molecules must be less than the length of the ligand linker; otherwise, PEG interferes with the binding of the targeting ligand to its corresponding cellular receptor.
The long and short of it: The adsorption of serum proteins (colored knots) onto targeted nanoparticles (orange circles) can lead to nonspecific cell binding (solid red arrows). Polyethylene glycol (PEG; grey curves) can be used to prevent this; however, long PEG chains can disrupt specific target binding. Shorter PEG chains prevent nonspecific binding without interfering with target recognition (solid green arrow).
The phenomenon of female preponderance in depression has been well-reported, which has been challenged by higher rates of suicide and addictive behaviors in males, and a longer life-span in females. ...We thus propose an alternative hypothesis “Gender differences in self-reporting symptom of depression,” suggesting mild-moderate depression tends to be reported more often by females, and severe depression and suicide tend to be reported more often by males. Potential mechanisms that account for this difference may include three aspects: covariation between estrogen levels and the incidence peak of female depression, gender differences in coping style (e.g., comparative emotional inexpressiveness and non-help-seeking in males), and gender differences in symptom phenotypes (e.g., atypical symptoms in male depression). Our newly presented hypothesis implied the overlooked under-diagnosis and under-treatment of depression in males. For effective diagnoses and timely treatment of male depression, it is critical to incorporate symptoms of depression in males into the relevant diagnostic criteria, encourage males to express negative emotions, and increase awareness of suicidal behavior in males.
Resilience is important for people to maintain mental health after negative life-events. However, its longitudinal psychological and social predictors are poorly revealed. Based on the ecological ...system theory model, the current study aimed to determine the longitudinal temporal mechanism underlying the development of early-adulthood resilience using long-term (early-life trauma and personality), medium-term and short-term (life-events, social support, and depression) psychosocial predictors. A total of 505 university students were recruited at baseline (T1), 433 of whom took part in a three-year longitudinal investigation (T2). The results showed that at T1 and T2, the resilience scores of individuals were identically high (72.98 and 73.21, respectively). Pearson correlation analysis showed that early-adulthood resilience was negatively correlated with early-life trauma, psychoticism and neuroticism, depression, ad life-events, and positively correlated with extraversion, social-support, and resilience. Regression and structural equation models showed that extraversion had a direct positive effect on T1 resilience through the mediation of T1 life-events, depression, and social-support, while childhood emotional neglect (EN) had indirect negative effect and extraversion had direct positive effect on T2 resilience through the mediation of T1 resilience, and T2 depression and social-support. In conclusion, this study is among the first to reveal the longitudinal temporal process of the development of early-adulthood resilience using remote and adjacent psychosocial predictors. The findings confirm that childhood EN and extraversion have a remote impact on early-adulthood resilience through recent and current depression and social-support. Our results imply that early-life trauma does not hinder the development of early-adulthood resilience in a linear trend.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In Satellite Internet of Things (SIoT), satellite constellation design is used to satisfy more communication demands with fewer satellites by optimizing satellite orbits in specific areas. However, ...the diversity of user demands and satellite resource poses a great challenge in evaluating the Quality of Experience (QoE) of the satellite constellation. In this article, a QoE-aware satellite constellation design scheme is proposed to enhance the user satisfaction by constructing QoE factors. First, an SIoT network model is established with low-Earth-orbit (LEO) satellites and ground Internet of Things (IoT) devices, and the problem is formulated to calculate the QoE for different areas after analyzing the dynamic network topology. Then, the QoE factors are defined to assess QoE by taking into account the coverage performance, communication fluency, regional demand capacity, and profitability. Following that, an intelligent optimization algorithm named multilayer tabu search (MLTS) is designed to obtain reasonable satellite orbits with the best QoE, which provides orbit parameters for satellite constellation configuration. The simulation results demonstrate that the designed satellite constellation can effectively improve the users QoE by optimizing the various QoE factors.
Abstract Objective Depression is a commonly occurring mental disorder, and investigations have been carried out into attentional bias in this condition. The aim of the present study was to ...investigate the interference inhibition for emotional words in depressed individuals in the emotional Stroop task. Methods Control participants, who had never suffered depression (NC), depressed patients, who were currently in remission (RMD) and participants diagnosed with a current major depressive disorder (MDD) were recruited using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Hamilton Rating Scale for Depression (HRSD) and Diagnostic and Statistical Manual for Mental Disorders (DSM)-IV as tools. Seventeen participants in each group completed an emotional Stroop task, and the event-related potential (ERP) was recorded during this cognitive task. Results With regard to the behavioural data, MDD participants had higher interference effects for negative words compared with the other two groups and those of positive stimuli. With regard to the ERP data, the MDD participants showed a smaller N1 amplitude for negative words and a smaller P1 amplitude for positive words in bilateral hemispheres compared with the other groups. Both the MDD and RMD participants showed enhanced negativity (N450) over the parietal regions of the brain for negative words compared with NC groups. Conclusions MDD participants pay less attention to positive stimuli; they are characterised by deficient behavioural and neurophysiological indices of attentional inhibition for negative material. RMD participants are characterised by attentional inhibitory dysfunction of negative material only in terms of neurophysiological responses, a finding not entirely consistent with our previous study. Significance This is probably the first study to explore the cerebral mechanism of current and remitted depression using the emotional Stroop task. RMD participants were also examined to explore whether attentional bias of emotional stimuli was a stable cognitive vulnerability factor that might be associated with the recurrence of depression. This study and would shed light on the cognitive bias of depression for emotional stimuli.
PDF
