Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, ...M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.
•LncRNA RP11 family and M2-Like polarization of tumor-associated macrophages (TAMs) regulate the tumorigenesis.•RP11-361F15.2 expression is positively correlated with CPEB4 and negatively correlated with miR-30c-5p.•Overexpression of RP11-361F15.2 and CPEB4 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro.•RP11-361F15.2 promotes CPEB4-mediated migration, invasion and M2-Like polarization of TAMs through miR-30c-5p in OS.•RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.
Preemptive scheduling efficiently addresses the coexistence of enhanced Mobile Broad Band (eMBB) and Ultra-Reliable Low-Latency Communications (URLLC). While URLLC puncturing influences eMBB ...performance, further investigation is necessary to study the trade-offs between stability, delay, and efficiency. However, existing studies overlook the imbalance in eMBB/URLLC load distribution and personalized fluctuations in eMBB performance, leading to sub-optimal results. To tackle this, we propose an unmanned aerial vehicle (UAV) relay-assisted eMBB/URLLC multiplexing framework. Specifically, considering the utilization of UAVs for connecting separated next-generation Node Bs (gNBs) and the individual subject experience of services, we first formulate the multiplexing problem as an optimization problem. The objective is to maximize eMBB throughput and minimize personalized fluctuations in eMBB performance and UAV consumption, subject to URLLC constraints. Then, the challenging problem is decomposed into the eMBB problem and the URLLC problem. For the former, we further decompose it into three sub-problems and solve them using optimization methods. For the latter, we propose a deep reinforcement learning-based algorithm to obtain an optimal strategy for relaying and puncturing URLLC into eMBB intelligently. Simulation results demonstrate that our proposals outperform benchmark schemes regarding eMBB throughput, UAV consumption, eMBB performance fluctuation, URLLC satisfaction, and learning efficiency.
As a global trauma event, the Coronavirus disease (COVID-19) hugely impacts people's mental health and well-being. The purpose of our study is threefold: first, investigate the relationship between ...exposure to COVID-19 and life satisfaction among a large sample in China; second, test the mediating role of hyperarousal in the association between exposure to COVID-19 and life satisfaction; third, explore the moderating/mediating role of affective forecasting in the association between hyperarousal and life satisfaction.
The current study recruited 5546 participants to complete a set of self-report questionnaires online from April 22, 2020 to April 24, 2020. The moderated mediation and chain mediation model analyses were conducted using the SPSS software and PROCESS macro program.
Exposure to COVID-19 negatively predicted life satisfaction (Effect = −0.058, p < 0.001). This relationship was partially mediated by the hyperarousal level (Effect = −0.018, CI = −0.024, −0.013). The moderating role of forecasted positive affect (PA)/forecasted negative affect (NA) between hyperarousal and life satisfaction was significant (β = 0.058, CI = 0.035, 0.081; β = 0.037, CI = 0.014, 0.06). The chain mediating effect of hyperarousal and forecasted PA/forecasted NA on the relationship between exposure to COVID-19 and life satisfaction was also significant (Effect = −0.003, CI = −0.004, −0.002; Effect = −0.006, CI = −0.008, −0.004).
The cross-sectional design precludes causal inference.
Greater exposure to COVID-19 was associated with more severe hyperarousal symptoms, decreased life satisfaction. Forecasted PA and forecasted NA could moderate and mediate the negative impact of hyperarousal on life satisfaction. The moderating/mediating role of forecasted PA/NA implied that future interventions targeting at improving affective forecasting and reducing hyperarousal might be helpful to improve life satisfaction during the post-COVID-19 era.
•Exposure to COVID-19 predicted lower life satisfaction.•Hyperarousal mediated the associations between COVID-19 exposure and life satisfaction.•Forecasted PA and forecasted NA could moderate and mediate the negative impact of hyperarousal on life satisfaction.
Due to the rapidly growing volume of data on the Internet, the methods of efficiently and accurately processing massive text information have been the focus of research. In natural language ...processing theory, sentence embedding representation is an important method. This paper proposes a new sentence embedding learning model called BRFP (Factorization Process with Bidirectional Restraints) that fuses syntactic information, uses matrix decomposition to learn syntactic information, and fuses and calculates with word vectors to obtain the embedded representation of sentences. In the experimental chapter, text similarity experiments are conducted to verify the rationality and effectiveness of the model and analyzed experimental results on Chinese and English texts with the current mainstream learning methods, and potential improvement directions are summarized. The experimental results on Chinese and English datasets, including STS, AFQMC, and LCQMC, show that the model proposed in this paper outperforms the CNN method in terms of accuracy and F1 value by 7.6% and 4.8. The comparison experiment with the word vector weighted model shows that when the sentence length is longer, or the corresponding syntactic structure is complex, the model’s advantages in this paper are more prominent than TF-IDF and SIF methods. Compared with the TF-IDF method, the effect improved by 14.4%. Compared with the SIF method, it has a maximum advantage of 7.9%, and the overall improvement in each comparative experimental task is between 4 and 6 percentage points. In the neural network model comparison experiment, the model in this paper compared the CNN, RNN, LSTM, ST, QT, and InferSent models, and the effect significantly improved on the 14’OnWN, 14’Tweet-news, and 15’Ans.-forum datasets. For example, in the 14’OnWN dataset, the BRFP method has a 10.9% improvement over the ST method. The 14’Tweet-news dataset has a 22.9% advantage over the LSTM method, and the 15’Ans.-forum dataset has a 24.07% improvement over the RNN method. The article also demonstrates the generality of the model, proving that the model proposed in this paper is also a universal learning framework.
SARS-CoV-2 infection causes spike-dependent fusion of infected cells with ACE2 positive neighboring cells, generating multi-nuclear syncytia that are often associated with severe COVID. To better ...elucidate the mechanism of spike-induced syncytium formation, we combine chemical genetics with 4D confocal imaging to establish the cell surface heparan sulfate (HS) as a critical stimulator for spike-induced cell-cell fusion. We show that HS binds spike and promotes spike-induced ACE2 clustering, forming synapse-like cell-cell contacts that facilitate fusion pore formation between ACE2-expresing and spike-transfected human cells. Chemical or genetic inhibition of HS mitigates ACE2 clustering, and thus, syncytium formation, whereas in a cell-free system comprising purified HS and lipid-anchored ACE2, HS stimulates ACE2 clustering directly in the presence of spike. Furthermore, HS-stimulated syncytium formation and receptor clustering require a conserved ACE2 linker distal from the spike-binding site. Importantly, the cell fusion-boosting function of HS can be targeted by an investigational HS-binding drug, which reduces syncytium formation in vitro and viral infection in mice. Thus, HS, as a host factor exploited by SARS-CoV-2 to facilitate receptor clustering and a stimulator of infection-associated syncytium formation, may be a promising therapeutic target for severe COVID.
The key to practical applications of sodium (Na) metal batteries is to develop high-performance Na metal anode. However, the unstable electrode/electrolyte interface induced by the Na dendrite growth ...severely shortens the working life of Na metal anode. In this work, we have developed a facile method based on a replacement reaction to construct an Ag metal layer for Na metal electrodes. The presence of robust and sodiophilic Ag metal layer can guide the uniform plating and stripping of Na ions on the surface of Na metal anode and effectively suppress the Na dendrite growth. Benefiting from a stable electrode/electrolyte interface, the increase of interfacial resistance of the Ag-protected Na metal (Na@Ag) electrode is significantly lower than that of the bare Na electrode after repeated plating/stripping. As a result, the symmetric cell with two identical Na@Ag electrodes exhibits superior cycling stability with stable over-potentials for more than 1100 h at a current density of 1 mA cm−2 and good rate performance with an over-potential of 210 mV at a current density of 5 mA cm−2 compared to the symmetric cell with two identical bare Na electrodes. Moreover, the full cell with an NaTi2(PO4)3 (NTP) cathode and an Na@Ag anode maintains good cycling stability with a capacity retention of 93.8% after 600 cycles, while the Na||NTP full cell breaks down in the 243th cycle.
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•A facile replacement reaction method is used to achieve Ag metal coating.•The Ag metal layer guides the uniform plating and stripping of Na ions.•The Ag metal layer effectively suppresses the decomposition of electrolyte.•Na@Ag exhibits superior cycling stability to bare Na.
Natural killer (NK) cells exert an indispensable role in innate immune responses against cancer progression, however NK cell dysfunction has been rarely reported in hepatocellular carcinoma (HCC). ...This study sought to uncover the immunoregulatory mechanisms of tumor-infiltrating NK cells in HCC. A consensus NK cell-based signature (NKS) was constructed using integrative machine learning algorithms based on multi-omics data of HCC patients. HCC tumors had lower numbers of infiltrating NK cells than para-tumor normal liver tissues. Based on the NK cell-associated genes, the NKS was built for HCC prognostic prediction and clinical utilities. Drug targets and novel compounds were then identified for high-NKS groups. RAC1 was confirmed as the hub gene in the NKS genes. RAC1 was upregulated in HCC tumors and positively correlated with shorter survival time. RAC1 overexpression in NK-92 cells facilitated the cancer-killing capacity by the anticancer cytotoxic effectors and the upregulated NKG2D. The survival time of PDX-bearing mice was also prolonged upon NK-92RAC1 cells. Mechanistically, RAC1 interacted with STAT3 and facilitated its activation, thereby enabling its binding to the promoter region of NKG2D and functioning as a transcriptional regulator in NK-92 via molecular docking, Co-IP assay, CHIP and luciferase experiments. Collectively, our study describes a novel function of RAC1 in potentiating NK cell-mediated cytotoxicity against HCC, highlighting the clinical utilities of NKS score and RAC1high NK cell subset in HCC immunotherapy.
•A novel NK cell-based signature (NKS) for HCC prognosis prediction and potential therapeutic targets was established by machine learning algorithms based on multi-omics data.•RAC1high NK cell subset enhanced the cancer-killing capacity by activating STAT3 and upregulating NKG2D against HCC cells.•RAC1high NK cells effectively inhibited the aggressiveness of HCC cells in vitro and in vivo, especially in patient-derived xenograft (PDX) models.•RAC1high NK cells might be a promising therapeutic option for HCC patients, especially for those with high NKS scores.
•We established a new P3D hydraulic fracture propagation model applicable to Sandstone reservoirs.•Compared with 2D models such as the PKN model, the new P3D model has an outstanding advantage, that ...is, the fracture height is changing.•The simulation results are highly consistent with the actual propagation of hydraulic fractures, which indicates the accuracy of the proposed model.
Due to the thin layers in sandstone reservoir, the fractures are likely to break through the target horizon and extend to the interlayer. Therefore, it is necessary to control the fracture height according to the penetrated height diameters. However, currently available 2D (PKN and KGD) and pseudo 3D (P3D) hydraulic fracturing models are unable to simulate the height of fractures penetrating through the sandstone reservoir. Address this issue, we coupling the wedge-shaped fracture model (pressure drop model in fractures), penetrating fracture propagation model, PKN model and Carter fluid loss model, we established a new P3D hydraulic fracture propagation model applicable to sandstone reservoir, and use new model simulate the effects of factors, e.g. injection ratio, filtration coefficient, stress difference between reservoir and its adjoining bed, fracture toughness of interlayer, Young’s modulus of interlayer and Poisson’s ratio of interlayer, on fracture propagation. A negative correlation is found between fracture height, fracture toughness of interlayer, stress difference between reservoir and its adjoining bed and filtration coefficient, while fracture length and width increase as these factors increase; fracture height is positively correlated with injection ratio, Young’s modulus and Poisson’s ratio of reservoir rock, while fracture length and width decrease with the increase of these factors. The simulation results are well consistent with the previous studies, which verifies the accuracy and superiority of the established model, this model can effectively simulate the propagation of hydraulic fractures in sandstone reservoir.
Patient-specific instrumentation (PSI) has the potential to improve the accuracy of implant positioning in total hip arthroplasty (THA). This prospective clinical study aimed to develop artificial ...intelligence to increase PSI production efficiency and assess accuracy, clinical outcomes, and learning curves.
A convolutional neural network was applied to automatically process computer tomography images. PSI size and position were designed to guide the acetabular preparation and femoral neck resection. Thirty patients who underwent PSI-assisted THAs were matched to thirty patients who underwent free-hand THAs, and the component positions, as well as radiographic and clinical outcomes were analyzed.
PSI-assisted THA was significantly more accurate than free-hand THA at achieving the target component position. The mean absolute errors of cup inclination (P = .004) and anteversion (P < .001) were significantly smaller in the PSI group with fewer outliers. Calcar length (P = .002) and neck length (P = .026) were also more accurate in the PSI group. The leg length discrepancy was significantly lower in the PSI group (P = .002). There were no significant differences in operation time, blood loss, leg length discrepancy, or cup position among the first, second, and last 10 cases.
PSI-assisted THA offered more accurate component positions and better radiographic outcomes than free-hand THA. There was no evidence of a learning curve. Our findings suggest that PSI is a convenient and practical option to help surgeons achieve accurate surgical outcomes.
Evidence for microbial mats has been reported repeatedly from marine Lower Triassic rocks, but scarcely mentioned in post-mass extinction terrestrial facies. Here, we report from the terrestrial ...Lower Triassic Liujiagou Formation in North China the presence of five kinds of microbially induced sedimentary structures (MISS) or sedimentary surface textures, including “old elephant skin” textures, wrinkle structures, palimpsest ripples, “Manchuriophycus” structures and sand cracks. Terrestrial microbial communities that produced these MISS adapted not only to periodically desiccated conditions, but also to the storm-dominated palaeoenvironments in the Liujiagou Formation. The Permian–Triassic mass extinction (PTME) in North China is marked by the die-off of plants, disappearance of coal beds, extinction of pareiasaurs among tetrapods, decreased bioturbation levels and a dramatic change of sedimentary systems through the Sunjiagou Formation. The Sunjiagou Formation recorded the turnover from an ever-wet to a progressively drier and hotter climate and it spans the PTME in North China. Following this mass extinction, MISS became much more common and widespread, suggesting that the mass extinction provided favourable biological and environmental conditions for the development of the MISS in terrestrial ecosystems, especially the decreased bioturbation intensity and grazing pressure associated with increased temperature and climatic drying. In the upper part of the Liujiagou Formation and overlying Heshanggou Formation, the disappearance of MISS coupled with increased bioturbation might indicate an improvement of terrestrial ecosystems and the beginning of the Triassic biotic recovery. However, as the investigation of MISS in space and time through the geological record is in its early stages, further geobiologic and geochemical studies, as well as high-precision isotopic dating from Permian–Triassic terrestrial successions, are needed to fully reveal the timing and pattern of the Early Triassic terrestrial ecosystem reconstruction.
•Five kinds of MISS were recognized from terrestrial Lower Triassic of North China.•The morphological and microscopic characteristics of MISS were described.•We present a more detailed analysis of terrestrial extinction in North China.•Microbial proliferation indicates the decreased bioturbation and environmental stress.
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