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Learning graph embeddings for high-dimensional data is an important technology for dimensionality reduction. The learning process is expected to preserve the discriminative and geometric information of high-dimensional data in a new low-dimensional subspace via either manual or automatic graph construction. Although both manual and automatic graph constructions can capture the geometry and discrimination of data to a certain degree, they working alone cannot fully explore the underlying data structure. To learn and preserve more discriminative and geometric information of the high-dimensional data in the low-dimensional subspace as much as possible, we develop a novel Discriminative and Geometry-Preserving Adaptive Graph Embedding (DGPAGE). It systematically integrates manual and adaptive graph constructions in one unified graph embedding framework, which is able to effectively inject the essential information of data involved in predefined graphs into the learning of an adaptive graph, in order to achieve both adaptability and specificity of data. Learning the adaptive graph jointly with the optimized projections, DGPAGE can generate an embedded subspace that has better pattern discrimination for image classification. Results derived from extensive experiments on image data sets have shown that DGPAGE outperforms the state-of-the-art graph-based dimensionality reduction methods. The ablation studies show that it is beneficial to have an integrated framework, like DGPAGE, that brings together the advantages of manual/adaptive graph construction.

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.

Cement-retained restorations have the advantages of passive fit, less complexity of clinical and laboratory methods, cost, esthetics, and dimensional stability over screw-retained restorations, especially in multiple abutment implant-supported prostheses. A common and difficult technical problem with cement-retained implant prostheses is abutment screw loosening. Three-dimensional (3D) printing is a technology that has been rapidly developed and has become widely accepted in dentistry. The aim of this study was to establish a novel method of using 3D implant planning guide to locate the abutment screw in cement-retained implant prosthesis.Six standard gypsum complete denture models were used to locate the abutment screw. An implant analog (4.5 mm in diameter and 12 mm in length) was placed in the drilling hole (5 mm in diameter and 14 mm in depth). After scanning with a 3D scanner, the 3D printing software was used to design the abutment screw location guide, which was printed by a resin-based 3D printer.A total of 30 abutment screws were located and removed using the guide. The locating guide's actual diameter was 2.4 mm. The drilling point was accurate and precise, and no excessive loss of the abutment was noticed.The guide would help the dentist in locating the abutment screw access channel, resulting in a more precise and accurate drilling point. The guide for locating the abutment screw enhances the accuracy of screw channel access and reduces damage to the crown and abutment.

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).

Background Giant hepatic hemangiomas are rare and can cause serious complications that contribute to a high risk of perinatal mortality. The purpose of this article is to review the prenatal imaging features, treatment, pathology, and prognosis of an atypical fetal giant hepatic hemangioma and to discuss the differential diagnosis of fetal hepatic masses. Case presentation A gravida 9, para 0 woman at 32 gestational weeks came to our institution for prenatal ultrasound diagnosis. A complex, heterogeneous hepatic mass measuring 5.2 × 4.1 × 3.7 cm was discovered in the fetus using conventional two-dimensional ultrasound. The mass was solid and had both a high peak systolic velocity (PSV) of the feeding artery and intratumoral venous flow. Fetal magnetic resonance imaging (MRI) revealed a clear, hypointense T1-W and hyperintense T2-W solid hepatic mass. Prenatal diagnosis was very difficult due to the overlap of benign and malignant imaging features on prenatal ultrasound and MRI. Even postnatally, neither contrast-enhanced MRI nor contrast-enhanced computed tomography (CT) was useful in accurately diagnosing this hepatic mass. Due to persistently elevated Alpha-fetoprotein (AFP), a laparotomy was performed. Histopathological examination of the mass showed atypical features such as hepatic sinus dilation, hyperemia, and hepatic chordal hyperplasia. The patient was ultimately diagnosed with a giant hemangioma, and the prognosis was satisfactory. Conclusions When a hepatic vascular mass is found in a third trimester fetus a hemangioma should be considered as a possible diagnosis. However, prenatal diagnosis of fetal hepatic hemangiomas can be challenging due to atypical histopathological findings. Imaging and histopathological assays can provide useful information for the diagnosis and treatment of fetal hepatic masses.

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

Figure S3 shows that radiotherapy and IFNgamma can synergistically downregulate SLC7A11 expression in tumor cells

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

Figure S2 shows that CD8+ T cells can promote radiotherapy induced ferroptosis via secreting IFNgamma

Figure S1 shows that radiotherapy can induce tumor cell ferroptosis

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.

Internal delamination damage in composite connection structures can occur in the process of the overloading of a high-speed bearing, with alternating force loads, high or low temperatures, and the humid or hot environment loads. Mechanical drilling and riveting are usually used at the delamination position and outside its envelope, to inhibit delamination expansion. However, delamination damage can change the structural stress state of the original structure. It is difficult to achieve a better inhibition effect using conventional drilling mechanisms and process methods with intact composite panels, and new damage forms can even be introduced into the drilling process due to unreasonable parameter settings. Therefore, this paper combined finite element simulation technology and experimental processing technology, to analyze the influence of different delamination dimensions and positions on processing quality. The results showed that the feed speed and rotating speed had significant effects on the axial force of composite laminates. In particular, in the case of a low speed and high feed, the axial force will increase significantly.

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.

Nemaline myopathy (NM) is a rare, hereditary heterogeneous myopathy. Fetal NM has a more severe disease course and a poorer prognosis and is usually lethal during the first few months of life. Hence, early prenatal diagnosis is especially important for clinical interventions and patient counseling. We report the case of a fetus with NM due to KLHL40 gene variation leading to arthrogryposis multiplex congenita (AMC). The ultrasonography and histopathology results revealed an enhanced echo intensity and decreased muscle thickness, which may be novel features providing early clues for the prenatal diagnosis of NM. Moreover, to our knowledge, this article is the first report to describe a case of NM associated with complex congenital heart disease (CHD).

Kidney functions, including electrolyte and water reabsorption and secretion, could be influenced by circulating hormones. The pituitary gland produces a variety of hormones and cytokines; however, the influence of these factors on the kidney has not been well explained and explored. To provide more in-depth information and insights to support the pituitary–kidney axis connection, we used mouse pituitary and kidney single-cell transcriptomics data from the GEO database for further analysis. Based on a ligand–receptor pair analysis, cell–cell interaction patterns between the pituitary and kidney cell types were described. Key ligand–receptor pairs, such as GH-GHR, PTN-SDC2, PTN-SDC4, and DLK1-NOTCH3, were relatively active in the pituitary–kidney axis. These ligand–receptor pairs mainly target proximal tubule cells, principal cells, the loop of Henle, intercalated cells, pericytes, mesangial cells, and fibroblasts, and these cells are related to physiological processes, such as substance reabsorption, angiogenesis, and tissue repair. Our results suggested that the pituitary gland might directly regulate kidney function by secreting multiple hormones or cytokines and indicated that the above ligand–receptor pairs might represent a new research focus for studies on kidney function or kidney disease.

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 ...

Plasmodium vivaxis the most widespread human malaria parasite. The spleen is one of the most significant immune organs in the course ofPlasmodiuminfection, and it contains splenic fibroblasts (SFs), which supports immunologic function by secreting type I collagen (collagen I).Plasmodiumproteins have rarely been found to be involved in collagen alterations in the spleen during infection. Here, we selected the proteinP. vivaxtryptophan-rich antigen 23 (PvTRAg23), which is expressed by the spleen-dependent genePv-fam-aand is a member of the PvTRAgs family of export proteins, suggesting that it might have an effect on SFs. The protein specifically reduced the level of collagen I in human splenic fibroblasts (HSFs) and bound to cells with vimentin as receptors. However, such collagen changes were not mediated by binding to vimentin, but rather activating the NF-κBp65 pathway to produce inflammatory cytokines. Collagen impaired synthesis accompanied by extracellular matrix-related changes occurred in the spleen of mice infected withP. yoelii17XNL. Overall, this study is the first one to report and verify the role ofPlasmodiumproteins on collagen in HSFin vitro. Results will contribute to further understanding of host spleen structural changes and immune responses afterPlasmodiuminfection.

This study aimed to compare MRI quality between conventional fast spin echo T2 weighted imaging (FSE T2WI) with periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) FSE T2WI for patients with various porcelain fused to metal (PFM) crown and analyze the value of PROPELLER technique in reducing metal artifacts. Conventional FSE T2WI and PROPELLER FSE T2WI sequences for axial imaging of head were applied in participants with different PFM crowns: cobalt-chromium (Co–Cr) alloy, pure titanium (Ti), gold–palladium (Au–Pd) alloy. Two radiologists evaluated overall image quality of section in PFM using a 5-point scale qualitatively and measured the maximum artifact area and artifact signal-to-noise ratio (SNR) quantitatively. Fifty-nine participants were evaluated. The metal crown with the least artifacts and the optimum image quality shown in conventional FSE T2WI and PROPELLER FSE T2WI were in Au–Pd alloy, Ti, and Co–Cr alloy order. PROPELLER FSE T2WI was superior to conventional FSE T2WI in improving image quality and reducing artifact area for Co-Cr alloy (17.0 ± 0.2% smaller artifact area, p p = 0.005), but had similar performance compared to FSE T2WI for Au–Pd alloy. The SNRs of the tongue and masseter muscle were significantly higher on PROPELLER FSE T2WI compared with conventional FSE T2WI (tongue: 29.76 ± 8.45 vs. 21.54 ± 9.31, p = 0.007; masseter muscle: 19.11 ± 8.24 vs. 15.26 ± 6.08, p = 0.016). Therefore, the different PFM crown generate varying degrees of metal artifacts in MRI, and the PROPELLER can effectively reduce metal artifacts especially in the PFM crown of Co-Cr alloy.

Objective To explore the effect of low serum phosphorus and parathyroid hormone (PTH) levels on protein-energy wasting (PEW) in patients on maintenance hemodialysis (MHD) and provide a new method of nutritional monitoring and intervention in patients on MHD. Methods Four hundred end-stage renal disease (ESRD) patients on MHD for at least 3 months were selected from 17 dialysis units. Logistic regression analysis was used to analyze the relationship between serum phosphorus and PTH levels and PEW risk. Receiver operating characteristic (ROC) analysis was used to compare the predictive value of these two indices for PEW. We used the survival curve to analyze the effects of low serum phosphorus and PTH levels on mortality. Results In the unadjusted model, The PEW risk in group Q1 was 16.4 times higher than that in group Q4. Compared with group Q4 of PTH, the PEW risk in groups Q1 and Q2 of PTH was 2.817 times higher and 2.087 times higher, respectively, after adjusting. However, serum phosphorus and PTH levels were associated with PEW risk. PEW risk in the serum phosphorus Q1 group was 7.305 times higher than that in the Q4 group, and PEW risk in the PTH Q1 group was 2.75 times higher than that in the Q4 group. ROC analysis showed that the areas under the curve of serum phosphorus and PTH predicting PEW in MHD patients were 0.862 and 0.695, respectively, while the cut-off values of ROC curve were 1.36 mmol/L and 212.5 ng/L, respectively. The survival rate was significantly lower in patients with serum phosphorus ≤ 1.36 mmol/L of ≤ 212.5 ng/L. Conclusion Low serum phosphorus and PTH levels increased the incidence of PEW and death and seriously affected the prognosis of patients on hemodialysis. Therefore, The nutritional status of patients on MHD can be monitored and evaluated by integrating serum phosphorus, PTH, albumin, and body mass index.

Pleiotropic transcription regulator RNA polymerase II (Pol II)–associated factor 1 (PAF1) governs multiple transcriptional steps and the deposition of several epigenetic marks. However, it remains unclear how ultimate transcriptional outcome is determined by PAF1 and whether it relates to PAF1-controlled epigenetic marks. We use rapid degradation systems and reveal direct PAF1 functions in governing pausing partially by recruiting Integrator-PP2A (INTAC), in addition to ensuring elongation. Following acute PAF1 degradation, most destabilized polymerase undergoes effective release, which presumably relies on skewed balance between INTAC and P-TEFb, resulting in hyperphosphorylated substrates including SPT5. Impaired Pol II progression during elongation, along with altered pause release frequency, determines the final transcriptional outputs. Moreover, PAF1 degradation causes a cumulative decline in histone modifications. These epigenetic alterations in chromatin likely further influence the production of transcripts from PAF1 target genes.

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.