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This paper reports an experimental study on the forming mechanism and bearing behavior of single-lap composite riveted joints with different hole diameters (4.82 mm and 4.9 mm) and squeeze forces (15 KN, 18 KN, 20 KN, and 23 KN). Pressure riveting and tensile tests are conducted to composite riveted joints to obtain the joint interference, joint stiffness and bearing strength needed to quantitatively evaluate their deformation features and mechanical properties. Furthermore, microscopic studies on damaged areas using applying ultra-depth three-dimensional microscope to monitor damage evolution are conducted to comprehend the joint shear failure mechanism. Results show that the hole diameter and riveting force have a significant effect on the performance of the joint. The forming damage occurs mainly in the hole wall near the driven head and is dominated by fiber crushing and interfacial shear cracks. The radial expansion of the rivet shank is not uniform under the riveting force and the whole is drum shaped. But the hole expansion of the joint at 4.82 mm hole diameter is more uniform than 4.9 mm, which would lead to better joint stiffness and bearing strength. Moreover, high interference fit would cause the shear fracture of the rivet, while lower interference joints are dominated by compression-pull mixed failure. In general, the size of interference fit is an unneglectable factor in the composite riveted joints that should be thoroughly investigated.

This study explored how the neural efficiency and proficiency worked in athletes with different skill levels from the perspective of effective connectivity brain network in resting state. The deconvolved conditioned Granger causality (GC) analysis was applied to functional magnetic resonance imaging (fMRI) data of 35 elite athletes (EAs) and 42 student-athletes (SAs) of racket sports as well as 39 normal controls (NCs), to obtain the voxel-wised hemodynamic response function (HRF) parameters representing the functional segregation and effective connectivity representing the functional integration. The results showed decreased time-to-peak of HRF in the visual attention brain regions in the two athlete groups compared with NC and decreased response height in the advanced motor control brain regions in EA comparing to the nonelite groups, suggesting the neural efficiency represented by the regional HRF was different in early and advanced skill levels. GC analysis demonstrated that the GC values within the middle occipital gyrus had a linear trend from negative to positive, suggesting a stepwise "neural proficiency" of the effective connectivity from NC to SA then to EA. The GC values of the inter-lobe circuits in EA had the trend to regress to NC levels, in agreement with the neural efficiency of these circuits in EA. Further feature selection approach suggested the important role of the cerebral-brainstem GC circuit for discriminating EA. Our findings gave new insight into the complementary neural mechanisms in brain functional segregation and integration, which was associated with early and advanced skill levels in athletes of racket sports.

Background Patients with rheumatoid arthritis (RA) have increased mortality and morbidity due to cardiovascular disease (CVD). Distinguishing RA with CVD, RA with CVD risk factors and patients with RA only (pure RA), is still a challenge. The study aimed to develop a better model to predict the likelihood of CVD in RA. Methods Pure RA (n = 402), RA with CVD risk factors (n = 394), and RA with CVD (n = 201) were ultimately recruited into the study and their peripheral bloods were collected to measure the levels of routine examination indicators, vascular endothelial growth factor (VEGF) and immune cells. Univariate analysis, the least absolute shrinkage and selection operator (LASSO), the random forest (RF) and the logistic regression models (LR) were employed to screen characteristic variables between each two groups, and individualized nomograms were further established to more conveniently predict the likelihood of CVD in RA. Results Univariate analysis showed that the levels of WBC, BUN, creatinine, CK, LDH and VEGF were significantly elevated in RA with CVD, as well as serum TC, TG, LDL, ApoB100 and ApoE, while ApoA1 and HDL/CHOL were decreased. Furthermore, the ratio of Treg cells, exhibiting excellent separation performance, in RA with CVD was significantly lower than that in other groups, while the ratio of Th1/Th2/NK and Treg were significantly elevated. LASSO, RF and LR models were also used to find the risk factors for CVD in RA. Through the final selected indicators screened by three machine learning models and univariate analysis, a convenient nomogram was established for predicting CVD risk in RA. Conclusions Serum lipids, lipoproteins, and Treg cells have been identified as risk factors for CVD in patients with RA, and three nomograms combining various risk factors were constructed and were used for individualized prediction of CVD in patients with RA (pure RA and/or with CVD risk factors).

Figure S4 shows that radiotherapy and immunotherapy can synergistically induce tumoral ferroptosis

A challenge in oncology is to rationally and effectively integrate immunotherapy with traditional modalities, including radiotherapy. Here, we demonstrate that radiotherapy induces tumor-cell ferroptosis. Ferroptosis agonists augment and ferroptosis antagonists limit radiotherapy efficacy in tumor models. Immunotherapy sensitizes tumors to radiotherapy by promoting tumor-cell ferroptosis. Mechanistically, IFNγ derived from immunotherapy-activated CD8+ T cells and radiotherapy-activated ATM independently, yet synergistically, suppresses SLC7A11, a unit of the glutamate–cystine antiporter xc−, resulting in reduced cystine uptake, enhanced tumor lipid oxidation and ferroptosis, and improved tumor control. Thus, ferroptosis is an unappreciated mechanism and focus for the development of effective combinatorial cancer therapy.Significance:This article describes ferroptosis as a previously unappreciated mechanism of action for radiotherapy. Further, it shows that ferroptosis is a novel point of synergy between immunotherapy and radiotherapy. Finally, it nominates SLC7A11, a critical regulator of ferroptosis, as a mechanistic determinant of synergy between radiotherapy and immunotherapy.This article is highlighted in the In This Issue feature, p. 1631

Table S1 shows the information on the antagonists and agonists used in this study

Background: PM2.5, the particles with diameters no larger than 2.5 micrometers, are important contributors to air pollution and have been related to diabetes and kidney injury. The present study aims to investigate whether PM2.5 aggravates kidney conditions in the context of diabetes. Methods: Db/db mice were used to model diabetes and treated with escalating doses of PM2.5 particles. The treatments were performed through intratracheal instillation. Kidney conditions were assessed using a battery of histopathological staining and laboratory tests. Results: PM2.5 treatment led to more severe phenotypes of kidney injury characterized by altered histology and overall deteriorated kidney functions. Many biological processes were implicated in the injury including progression of renal interstitial fibrosis, increased monocyte infiltration and an exhausted antioxidative defense system. Conclusions: PM2.5 induces an additional detrimental effects on kidney conditions in diabetic mice, calling for focuses on the diabetes patients living at highly PM2.5-polluted environments.

Depression after brain damage may impede the motivation and consequently influence the motor recovery after spinal cord injury (SCI); however, the neural mechanism underlying the psychological effects remains unclear. This study aimed to examine the casual connectivity changes of the emotion-motivation-motor circuit and the potential mediating effects of depression on motor recovery after SCI. Using the resting-state functional magnetic resonance imaging data of 35 SCI patients (24 good recoverers, GR and 11 poor recoverers, PR) and 32 healthy controls (HC), the results from the conditional Granger causality (GC) analysis demonstrated that the GR group exhibited sparser emotion-motivation-motor GC network compared with the HC and PR groups, though the in−/out-degrees of the emotion subnetwork and the motor subnetwork were relatively balanced in the HC and GR group. The PR group showed significantly inhibitory causal links from amygdala to supplementary motor area and from precentral gyrus to nucleus accumbens compared with GR group. Further mediation analysis revealed the indirect effect of the 2 causal connections on motor function recovery via depression severity. Our findings provide further evidence of abnormal causal connectivity in emotion-motivation-motor circuit in SCI patients and highlight the importance of emotion intervention for motor function recovery after SCI.

Diabetic kidney disease (DKD) is a major health burden closely related to lipid metabolism disorders. Leptin has lipid-lowering efficacy, but the specific mechanism of its local effects on kidney is still unclear. This study aims to investigate the role of ectopic lipid deposition (ELD) in DKD and evaluate the lipid-lowering efficacy of leptin in the palmitic acid (PA)-induced renal tubular epithelial cells (NRK-52E). DKD model was established in Sprague-Dawley (SD) rats by giving single intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) after high-fat diet for 8 weeks. Then, the expression changes of lipid metabolism-related markers were observed. At week 12, the protein expression level of lipid-deposited marker adipose differentiation-related protein (ADRP) was significantly increased. Besides, the lipid synthesis marker sterol regulatory element-binding protein 1c (SREBP 1c) was highly expressed while the expression of insulin-induced gene 1 (Insig-1), a key molecular of inhibiting SREBP 1c, was decreased. Leptin and compound c were incubated with the PA-induced NRK-52E cells to investigate the lipid-lowering effects and whether this effect was mediated by the AMPK/Insig-1/SREBP 1c signaling pathways. mRNA and protein of ADRP and SREBP 1c were reduced after leptin treatment, while Insig-1 and phosphorylated AMP-activated protein kinase (AMPK) were increased. Conversely, inhibition of AMPK phosphorylation by compound c mostly eliminated lipid-lowering efficacy of leptin in PA-induced cells. Collectively, these results suggested that there was ELD of renal tubular epithelial cells in DKD rats. Leptin upregulated the expression level of Insig-1 by activating AMPK to attenuate ELD in PA-induced NRK-52E cells.

Polycomb group (PcG) proteins are crucial chromatin regulators during development. H2AK119ub1 (H2Aub) and H3K27me3 are catalyzed by Polycomb-repressive complex 1 and 2 (PRC1/2) respectively, and they largely overlap in the genome due to mutual recruitment of the two complexes. However, it is unclear whether PRC1/H2Aub and PRC2/H3K27me3 can also function independently. By developing an ultra-sensitive carrier-DNA-assisted chromatin immunoprecipitation sequencing method termed CATCH-Seq, we generated allelic H2Aub profiles in mouse gametes and early embryos. Our results revealed an unexpected genomewide decoupling of H2Aub and H3K27me3 in mouse preimplantation embryos, where H2Aub but not H3K27me3 was enriched at PcG targets while only H3K27me3 was deposited in the broad distal domains associated with DNA methylation-independent non-canonical imprinting. These observations suggest that H2Aub represses future bivalent genes during early embryogenesis without H3K27me3, but it is not required for the maintenance of non-canonical imprinting, which is mediated by maternal H3K27me3. Thus, our study reveals the distinct depositions and independent functions of H2Aub and H3K27me3 during early mammalian development.

The development of broadband and high-efficiency broadband microwave-absorbing materials is one of the keys to resisting electromagnetic radiation and electromagnetic interference. In this paper, we used zeolitic imidazolate framework-67 (ZIF-67) as the template to obtain Ni-doped ZIF-67 via Ni(NO3)2 etching followed by pyrolysis to prepare Co-Ni/C composites successfully. The morphology and microstructure of Co-Ni/C composites can be well-tuned by altering the Ni doping content. ZIF-67-derived Co-Ni/C porous materials exhibit extremely strong microwave absorption performance thanks to dielectric loss, magnetic loss, and the synergistic effect between different components. When the dosage of Ni(NO3)2 used reaches 0.32 g, the obtained composite possesses the optimal absorbing properties with a maximum reflection loss (RL) of −72.88 dB and an effective bandwidth (fe, representing RL ≤ −10 dB) of 7.04 GHz (9.76–16.8 GHz) corresponding to a thickness of 2.53 mm. The results of this work indicate that Co-Ni/C composites have potential application value in the field of microwave absorption.

Because of the intensified electrochemical activities, mixed metal oxides as a representative for pseudocapacitive materials play a key role for high performance supercapacitor electrodes. Nevertheless, low ion and electron transfer rate and poor cycling performance in the electrode practically restrict further promotion of their electrochemical performance. In order to offset the defect, a novel copper (Cu) foam-supported nickel molybdate nanosheet decorated carbon nanotube wrapped copper oxide nanowire array (NiMoO4 NSs-CNTs-CuO NWAs/Cu foam) flexible electrode is constructed. The as-prepared electrode demonstrates a unique core-shell holey nanostructure with a large active surface area, which can provide a large number of active sites for redox reactions. Besides, the CNTs networks supply improved conductivity, which can hasten electron transport. Through this simple and efficient design method, the spatial distribution of each component in the flexible electrode is more orderly, short and fast electron transport path with low intrinsic resistance. As a result, the NiMoO4 NSs-CNTs-CuO NWAs/Cu foam as an adhesiveless supercapacitor electrode material exhibits excellent energy storage performance with high specific areal capacitance of 23.40 F cm−2 at a current density of 2 mA cm−2, which outperforms most of the flexible electrodes reported recently. The assembled asymmetric supercapacitor demonstrates an energy density up to 96.40 mW h cm-3 and a power density up to 0.4 W cm-3 under a working voltage window of 1.7 V. In addition, outstanding flexibility of up to 100° bend and good cycling stability with the capacitance retention of 82.53 % after 10,000 cycles can be obtained.

Background The pathogenesis of neck pain in the brain, which is the fourth most common cause of disability, remains unclear. Furthermore, little is known about the characteristics of dynamic local functional brain activity in cervical pain. Objective The present study aimed to investigate the changes of local brain activity caused by chronic neck pain and the factors leading to neck pain. Methods Using the amplitude of low-frequency fluctuations (ALFF) method combined with sliding window approach, we compared local brain activity that was measured by the functional magnetic resonance imaging (fMRI) of 107 patients with chronic neck pain (CNP) with that of 57 healthy control participants. Five pathogenic factors were selected for correlation analysis. Results The group comparison results of dynamic amplitude of low-frequency fluctuation (dALFF) variability showed that patients with CNP exhibited decreased dALFF variability in the left inferior temporal gyrus, the middle temporal gyrus, the angular gyrus, the inferior parietal marginal angular gyrus, and the middle occipital gyrus. The abnormal dALFF variability of the left inferior temporal gyrus was negatively correlated with the average daily working hours of patients with neck pain. Conclusions The findings indicated that the brain regions of patients with CNP responsible for audition, vision, memory, and emotion were subjected to temporal variability of abnormal regional brain activity. Moreover, the dALFF variability in the left inferior temporal gyrus might be a risk factor for neck pain. This study revealed the brain dysfunction of patients with CNP from the perspective of dynamic local brain activity, and highlighted the important role of dALFF variability in understanding the neural mechanism of CNP.

The directed brain functional network construction gives us the new insights into the relationships between brain regions from the causality point of view. The Granger causality analysis is one of the powerful methods to model the directed network. The complex brain network is also hierarchically constructed, which is particularly suited to facilitate segregated functions and the global integration of the segregated functions. Therefore, it is of great interest to explore new approach to model the hierarchical architecture of the directed network. In the present study, we proposed a new approach, namely, stepwise multivariate Granger causality (SMGC), considering both the directed and hierarchical features of brain functional network to explore the stepwise causal relationship in the network. The simulation study demonstrated that the diverse and complex hierarchical organization could be embedded in the apparently simple directed network. The proposed SMGC method could capture the multiple hierarchy of the directed network. When applying to the real functional magnetic resonance imaging (fMRI) datasets, the core triple resting-state networks in human brain showed within-network directed connections in the first-level directed network and rich and diverse between-network pathways in the second-level hierarchical network. The default mode network (DMN) had a prominent role in the resting-state acting as both the causal source and the important relay station. Further exploratory research on the adaption of directed hierarchical network in athletes suggested the enhanced bidirectional communication between the DMN and the central executive network (CEN) and the enhanced directed connections from the salience network (SN) to the CEN in the athlete group. The SMGC approach is capable of capturing the hierarchical architecture of the brain directed functional network, which refreshes the new stepwise causal relationship in the directed network. This might shed light on the potential application for exploring the altered hierarchical organization of brain directed network in neuropsychiatric disorders.

In this paper, we focus on the text classification task, which is a most import task in the area of Natural Language Processing (NLP). We propose an innovative convolutional neural network (CNN) model to perform temporal feature aggregation (TFA) effectively, which has a highly representative capacity to extract sequential features from vectorized numerical embeddings. First, we feed embedded vectors into a bi-directional LSTM (Bi-LSTM) model to capture the contextual information of each word. Afterwards, we propose to use the state-of-the-art deep-learning models as key components of the architecture, i.e., the Xception model and the WaveNet model, to extract temporal features from deep convolutional layers concurrently. To facilitate an effective feature fusion, we concatenate the outputs of two component models before forwarding to a drop-out layer to alleviate over-fitting and subsequently a fully-connected dense layer to perform the final classification of input texts. Experiments demonstrate that the proposed method achieves performance comparable to the state-of-the-art models while at a significantly lower computational complexity. Our approach obtains the cross-validation score of 95.83% for the Quora Insincere Question Classification (QIQC) dataset, and the cross-validation score of 83.10% for the Spooky Author Identification (SAI) dataset, respectively, which are among the best published results. The proposed method can be readily generalized to signal processing tasks, e.g., environmental sound classification (ESC) and machine fault analysis (MFA).

Heat-resistant supercapacitors with excellent mechanical strength are highly required for flexible and wearable electronics in our daily life. Here, high-performance and heat-resistant solid-state ...

Targeting the p53-MDM2 pathway to reactivate tumor p53 is a chemotherapeutic approach. However, the involvement of this pathway in CD8+ T cell-mediated antitumor immunity is unknown. Here, we report that mice with MDM2 deficiency in T cells exhibit accelerated tumor progression and a decrease in tumor-infiltrating CD8+ T cell survival and function. Mechanistically, MDM2 competes with c-Cbl for STAT5 binding, reduces c-Cbl-mediated STAT5 degradation and enhances STAT5 stability in tumor-infiltrating CD8+ T cells. Targeting the p53-MDM2 interaction with a pharmacological agent, APG-115, augmented MDM2 in T cells, thereby stabilizing STAT5, boosting T cell immunity and synergizing with cancer immunotherapy. Unexpectedly, these effects of APG-115 were dependent on p53 and MDM2 in T cells. Clinically, MDM2 abundance correlated with T cell function and interferon-γ signature in patients with cancer. Thus, the p53-MDM2 pathway controls T cell immunity, and targeting this pathway may treat patients with cancer regardless of tumor p53 status.

This work briefly investigates the coexistence of continuous attractors in the neural networks with Rectified Linear Unit (RELU) transfer function. Memory is stored as a manifold of stable states, or a continuous attractor. Continuous attractors are some low-dimensional manifolds embedded in a high-dimensional state space. One neural network may possess more than one continuous attractors. More importantly, we found that these multiple continuous attractors may have different dimensional, some are 2-D plane attractors and others are 1-D line attractors. It is also an enlightenment to study the continuous attractors of high dimensional models.

There has been limited research that examined the association between gratitude and acculturation stress and the mediation and moderation mechanisms of the link. This current study discussed whether affect balance and resilience mediate the relationship between gratitude and acculturation stress and whether social support moderates the mediation effects. We used the data selected from 266 international students from One Belt & One Road countries in China to test the theoretical model. The participants completed the measures of gratitude, acculturation stress, affect balance, resilience, and social support. The findings indicated that gratitude was negatively related to acculturation stress. Moreover, affect balance and resilience mediated the relationship between gratitude and acculturation stress. The findings further indicated that perceived social support moderates the association between gratitude and affect balance. The limitations and implications for future studies are discussed in the end.