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Abstract PTBP1 is an oncogene that regulates the splicing of precursor mRNA. However, the relationship between PTBP1 expression and gene methylation, cancer prognosis, and tumor microenvironment remains unclear. The expression profiles of PTBP1 across various cancers were derived from the TCGA, as well as the GTEx and CGGA databases. The CGGA mRNA_325, CGGA mRNA_301, and CGGA mRNA_693 datasets were utilized as validation cohorts. Immune cell infiltration scores were approximated using the TIMER 2.0 tool. Functional enrichment analysis for groups with high and low PTBP1 expression was conducted using Gene Set Enrichment Analysis (GSEA). Methylation data were predominantly sourced from the SMART and Mexpress databases. Linked-omics analysis was employed to perform functional enrichment analysis of genes related to PTBP1 methylation, as well as to conduct protein functional enrichment analysis. Single-cell transcriptome analysis and spatial transcriptome analysis were carried out using Seurat version 4.10. Compared to normal tissues, PTBP1 is significantly overexpressed and hypomethylated in various cancers. It is implicated in prognosis, immune cell infiltration, immune checkpoint expression, genomic variation, tumor neoantigen load, and tumor mutational burden across a spectrum of cancers, with particularly notable effects in low-grade gliomas. In the context of gliomas, PTBP1 expression correlates with WHO grade and IDH1 mutation status. PTBP1 expression and methylation play an important role in a variety of cancers. PTBP1 can be used as a marker of inflammation, progression and prognosis in gliomas.

Abstract With the development of digital technology, the proportion of time spent on digital informal learning in students’ daily lives is increasing. However, digital informal learning behaviors in sports field have not been fully justified and studied. This article aims to investigate the current situation and influencing factors of digital informal learning of sports knowledge (DIL-S) of Chinese undergraduates. As a cross-sectional study, 401 non-sports undergraduate students from six Chinese universities completed the DIL-S measurement questionnaire. The partial least squares structural equation modeling (PLS-SEM) was constructed to explore association among DIL-S, technology expectancy (TE) and digital competence (DC). Results show that (1) Male students’ cognitive learning (CL) was significantly better than that of females; Senior students’ metacognitive learning (MCL) was significantly better than that of junior students; Sports university students’ cognitive learning, metacognitive learning, and social and motivation learning (SML) were significantly better than that of non-sports university students. (2) Digital competence has a significant positive impact on technology expectancy and digital informal learning of sport knowledge, while technology expectancy has a significant negative impact on digital informal learning of sport knowledge. Based on the results, following conclusions can be made (1) Undergraduates have a strong competence to use digital technology and have a high interest in using digital technology to participate in learning. However, they have a low investment in digital informal learning of sports knowledge fields. (2) Males’ sports knowledge learning consciousness and actual performance are better than girls; Compared with freshmen, senior students have stronger monitoring and planning ability for personal sports knowledge learning; The behavior of digital informal learning of sports knowledge in sports university students is better than that of non-sports university students. (3) Digital competence and technological expectancy are key factors influencing digital informal learning of sport knowledge, with digital competence having the most significant impact. These findings underscore the need to enhance the promotion of digital informal learning among undergraduates and to develop assessments that improve their understanding and knowledge of sports.

The ability to maintain and manipulate sequential information in working memory, referred to as sequential working memory, plays a vital role in our daily life. While research has shown that methamphetamine abuse affects the neural substrates and the overall functioning of working memory, its specific impact on sequential working memory remains unclear. In this study, we asked 62 abstinent methamphetamine-dependent participants and 59 control participants to complete a digit ordering task in which they saw four digits one-by-one over time and subsequently rearranged them in ascending order. The four digits were presented either randomly in the experimental condition or in ascending order in the control condition. Results show that methamphetamine-dependent participants performed worse than the controls in the experimental condition in which sequential working memory was needed to complete the task, but not in the control condition in which only short-term memory was needed. This finding demonstrates that methamphetamine abuse impairs sequential working memory.

This study aimed to investigate ultrasound features of arteriovenous fistula stenosis and their relationship with primary patency after percutaneous transluminal angioplasty (post-intervention primary patency) and compare this classification with that using lesion location. Hemodialysis patients who underwent ultrasound-guided percutaneous transluminal angioplasty for arteriovenous fistula stenosis from July 2020 to December 2021 were retrospectively evaluated. Lesions (excluding inflow arteries) were categorized into five groups based on ultrasound features, and the clinical characteristics and risk factors affecting the post-intervention primary patency of the arteriovenous fistula were analyzed. Among 185 patients, 100 (54.05%), 36 (19.46%), 22 (11.89%), 11 (5.95%), and 16 (8.65%) were classified into the intima-dominant, non-intima-dominant, valve obstruction, vascular calcification, and mixed groups, respectively. The dialysis duration and arteriovenous fistula use time were the highest in the vascular calcification group at 86 (interquartile range: 49–140) and 77 (interquartile range: 49–110) months, respectively. Diabetes mellitus was most common in the intima-dominant group (42.0%). In Kaplan–Meier and univariate Cox analysis, type III lesion location (stenosis in the venous confluence site) was associated with the lower post-intervention primary patency. In the multivariate Cox analysis, percutaneous transluminal angioplasty times (the number of times patients were treated with percutaneous transluminal angioplasty for arteriovenous fistula stenosis dysfunction), vascular calcification, calcification at the lesion site requiring percutaneous transluminal angioplasty, and serum parathyroid hormone levels were independent risk factors for post-intervention primary patency. Ultrasound features showed that calcification of the arteriovenous fistula was detrimental to the post-intervention primary patency of arteriovenous fistula.

Abstract Introduction Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well‐established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words’ uniqueness in patients with PSP. Methods Twenty‐seven patients with PSP Richardson's syndrome (PSP‐RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio‐recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity. Results The PSP‐RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP‐RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP‐RS. The PSP‐RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words. Conclusions These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP‐RS.

Abstract Kidney diseases result from various causes, which can generally be divided into neoplastic and non-neoplastic diseases. Deep learning based on medical imaging is an established methodology for further data mining and an evolving field of expertise, which provides the possibility for precise management of kidney diseases. Recently, imaging-based deep learning has been widely applied to many clinical scenarios of kidney diseases including organ segmentation, lesion detection, differential diagnosis, surgical planning, and prognosis prediction, which can provide support for disease diagnosis and management. In this review, we will introduce the basic methodology of imaging-based deep learning and its recent clinical applications in neoplastic and non-neoplastic kidney diseases. Additionally, we further discuss its current challenges and future prospects and conclude that achieving data balance, addressing heterogeneity, and managing data size remain challenges for imaging-based deep learning. Meanwhile, the interpretability of algorithms, ethical risks, and barriers of bias assessment are also issues that require consideration in future development. We hope to provide urologists, nephrologists, and radiologists with clear ideas about imaging-based deep learning and reveal its great potential in clinical practice. Critical relevance statement The wide clinical applications of imaging-based deep learning in kidney diseases can help doctors to diagnose, treat, and manage patients with neoplastic or non-neoplastic renal diseases. Key points • Imaging-based deep learning is widely applied to neoplastic and non-neoplastic renal diseases. • Imaging-based deep learning improves the accuracy of the delineation, diagnosis, and evaluation of kidney diseases. • The small dataset, various lesion sizes, and so on are still challenges for deep learning. Graphical Abstract

Abstract Background Little is known about the impact of the COVID-19 pandemic on patients with Parkinson’s disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy. Methods This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management. Results A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P

Abstract Background This study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF). Methods This single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day. Results Twenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e’) improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P 40%.

Abstract Purpose Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is differently impaired in patients with PSP versus PD. Method Twenty‐nine patients with PSP Richardson's syndrome (PSP‐RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well‐established neuropsychological tests, including digit span forward (DST‐F), digit span backward (DST‐B), and adaptive digit ordering tests (DOT‐A). The DST‐F required maintaining digit sequences, and the DST‐B and DOT‐A required maintaining and manipulating digit sequences. Finding The PSP‐RS group scored lower than the PD and HC groups in the DST‐B and DOT‐A but not in the DST‐F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP‐RS patients. Moreover, in PSP‐RS, the DST‐B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST‐B ordering cost (DST‐F score vs. DST‐B score). The PSP patients who took a greater dose of levodopa tended to have higher DST‐B ordering cost. There was no effect of levodopa on DST‐B or DOT‐A in PD. Conclusion These results suggested that the ability to manipulate sequence was already reduced in patients with PSP‐RS and was worse than in patients with PD.

Studies report that rapidly repeated sensory stimulation can evoke LTP-like improvement of neural response in the sensory cortex. Whether this neural response potentiation is similar to the classic LTP induced by presynaptic electrical stimulation remains unclear. This study examined the effects of repeated high-frequency (9 Hz) versus low-frequency (1 Hz) visual stimulation on visually-evoked field potentials (VEPs) and the membrane protein content of AMPA / NMDA receptors in the primary visual cortex (V1) of cats. The results showed that repeated high-frequency visual stimulation (HFS) caused a long-term improvement in peak-to-peak amplitude of V1-cortical VEPs in response to visual stimuli at HFS-stimulated orientation (SO: 90°) and non-stimulated orientation (NSO: 180°), but the effect exhibited variations depending on stimulus orientation: the amplitude increase of VEPs in response to visual stimuli at SO was larger, reached a maximum earlier and lasted longer than at NSO. By contrast, repeated low-frequency visual stimulation (LFS) had not significantly affected the amplitude of V1-cortical VEPs in response to visual stimuli at both SO and NSO. Furthermore, the membrane protein content of the key subunit GluA1 of AMPA receptors and main subunit NR1 of AMPA receptors in V1 cortex was significantly increased after HFS but not LFS when compared with that of control cats. Taken together, these results indicate that HFS can induce LTP-like improvement of VEPs and an increase in membrane protein of AMPA and NMDA receptors in the V1 cortex of cats, which is similar to but less specific to stimulus orientation than the classic LTP.

Purpose: To evaluate the feasibility of rib fracture detection in low-dose computed tomography (CT) images with a RetinaNet-based approach and to evaluate the potential of lowdose CT for rib fracture detection compared with regular-dose CT images. Materials and methods: The RetinaNet-based deep learning model was trained using 7300 scans with 50,410 rib fractures that were used as internal training datasets from four multicenter. The external test datasets consisted of both regular-dose and low-dose chest-abdomen CT images of rib fractures; the MICCAI 2020 RibFrac Challenge Dataset was used as the public dataset. Radiologists' interpretations were used as reference standards. The performance of the model in rib fracture detection was compared with the radiologists’ interpretation. Results: In total, 728 traumatic rib fractures of 100 patients [60 men (60 %); mean age, 53.45 ± 11.19 (standard deviation (SD)); range, 18–77 years] were assessed in the external datasets. In these patients, the regular-dose group had a mean CT dose index volume (CTDIvol) of 7.18 mGy (SD: 2.22) and a mean dose length product (DLP) of 305.38 mGy cm (SD: 95.31); the low-dose group had a mean CTDIvol of 2.79 mGy (SD: 1.11) and a mean DLP of 131.52 mGy cm (SD: 55.58). The sensitivity of the RetinaNet-based model and that of the radiologists was 0.859 and 0.721 in the low-dose CT images and 0.886 and 0.794 in the regular-dose CT images, respectively. Conclusions: These findings indicate that the RetinaNet-based model can detect rib fractures in low-dose CT images with a robust performance, indicating its feasibility in assisting radiologists with rib fracture diagnosis.

ObjectiveThis study aimed to investigate the association between the risk of suicidal behaviors and student-supervisor relationships and subjective family socioeconomic status (SFSS) in medical graduate students, and to propose preventive strategies to reduce the suicidal risk among medical graduate students.Materials and methodsA total of 1,310 validated questionnaires were collected from medical graduate students, which included demographic information, study programs, the Suicidal Behaviors Questionnaire-Revised (SBQ-R) questionnaire, the Leader-Member Exchange 7 (LMX-7) questionnaire, and SFSS by MacArthur Scale. Multiple regression analysis was employed to examine the associations between variables and adjust for confounders. A moderation analysis, containing simple slope analysis and Johnson-Neyman interval plots were used to analyze the moderating effect of the SFSS in the association of SBQ-R and LMX-7 scores.ResultsA total of 88 participants (6.7%) were at risk of suicidal behaviors. In the high-quality student-supervisor relationship group (LMX-7 score ≥ 25), SFSS was significantly higher than in the low- and moderate-quality relationship group (p=0.002). The median SBQ-R score and proportion of suicide risk was significantly lower (p

IntroductionJujube kernel is a low-cost and abundant fiber resource, but its application in food industry is little because of its lower soluble fiber content and poor physicochemical properties.MethodsIn the current study, jujube kernel fiber (JKF) was modified by three composite methods: superfine-grinding and mix enzymatic hydrolysis alone, and combined with acetylation or hydroxypropylation.Results and discussionAfter these modifications, the microstructure of JKF became more porous, and its soluble fiber and extractable polyphenol contents, surface area, water adsorption and expansion capacities, and cation exchange capacity were all significantly improved (p

Background: Ovarian cancer, as a highly malignant tumor, features the critical involvement of tumor-associated fibroblasts in the ovarian cancer tissue microenvironment. However, due to the apparent heterogeneity within fibroblast subpopulations, the specific functions of these subpopulations in the ovarian cancer tissue microenvironment remain insufficiently elucidated. Methods: In this study, we integrated single-cell sequencing data from 32 ovarian cancer samples derived from four distinct cohorts and 3226 bulk RNA-seq data from GEO and TCGA-OV cohorts. Utilizing computational frameworks such as Seurat, Monocle 2, Cellchat, and others, we analyzed the characteristics of the ovarian cancer tissue microenvironment, focusing particularly on fibroblast subpopulations and their differentiation trajectories. Employing the CIBERSORTX computational framework, we assessed various cellular components within the ovarian cancer tissue microenvironment and evaluated their associations with ovarian cancer prognosis. Additionally, we conducted Mendelian randomization analysis based on cis-eQTL to investigate causal relationships between gene expression and ovarian cancer. Results: Through integrative analysis, we identified 13 major cell types present in ovarian cancer tissues, including CD8+ T cells, malignant cells, and fibroblasts. Analysis of the tumor microenvironment (TME) cell proportions revealed a significant increase in the proportion of CD8+ T cells and CD4+ T cells in tumor tissues compared to normal tissues, while fibroblasts predominated in normal tissues. Further subgroup analysis of fibroblasts identified seven subgroups, with the MMP11+Fib subgroup showing the highest activity in the TGFβ signaling pathway. Single-cell analysis suggested that oxidative phosphorylation could be a key pathway driving fibroblast differentiation, and the ATRNL1+KCN + Fib subgroup exhibited chromosomal copy number variations. Prognostic analysis using a large sample size indicated that high infiltration of MMP11+ fibroblasts was associated with poor prognosis in ovarian cancer. SMR analysis identified 132 fibroblast differentiation-related genes, which were linked to pathways such as platinum drug resistance. Conclusions: In the context of ovarian cancer, fibroblasts expressing MMP11 emerge as the primary drivers of the TGF-beta signaling pathway. Their presence correlates with an increased risk of adverse ovarian prognoses. Additionally, the genetic regulation governing the differentiation of fibroblasts associated with ovarian cancer correlates with the emergence of drug resistance.

To improve the service performances of nickel-based superalloys by controlling the type and proportion of precipitate phases, the resistances against harmful atoms (weakening effect caused by harmful atoms and capacity for hindering intrusion of harmful atoms) of the representative γ-matrix/γ′- or γ′′-precipitated phase heterogeneous interfaces (γ-Ni/γ′-Ni3Al, γ-Ni/γ′-Ni3Ti, and γ-Ni/γ′′-Ni3Nb interfaces) was investigated. The results show that, the harmful atoms (H, O, and S atoms) can be stable adsorbed on heterogeneous interfaces and weaken the interfacial bonding strength, resulting in the fracture position change from γ′- or γ′′ slab to interface during tensile deformation. Because of the minimum changes on interfacial bonding characteristics after the intrusion of harmful atoms, γ-Ni/γ′′-Ni3Nb heterogeneous interface (HIγ″−Ni3Nb) demonstrates the strongest resistance against weakening effect, presented as the smallest deterioration of interfacial ideal work of adhesion and tensile strength. Meanwhile, the energy barrier of harmful atoms diffusing along HIγ″−Ni3Nb is much larger than those along HIγ″−Ni3Al and HIγ″−Ni3Ti, leading to a smallest diffusion coefficient for harmful atoms diffusing along HIγ″−Ni3Nb. The result indicates HIγ″−Ni3Nb also shows the strongest capacity for hindering the intrusion of harmful atoms. This phenomenon is attributed to the strongest interaction between harmful atoms on saddle point and the neighboring atoms on HIγ″−Ni3Nb during the diffusion process. To summary, the Ni-based superalloys with γ′′-Ni3Nb as the main precipitated phase demonstrate the most promising properties in resistance against harmful atoms. This work not only contributes to the further improvement of Ni-based superalloys, but also provides the creative ideas for the research of other superalloys.

Abstract Objective This study aimed to assess the feasibility of software-aided selection of monoenergetic level for acute necrotising pancreatitis (ANP) depiction compared to other automatic image series generated using dual-energy computed tomography (CT). Methods The contrast-enhanced dual-source dual-energy CT images in the portal venous phase of 48 patients with ANP were retrospectively analysed. Contrast-to-noise ratio (CNR) of pancreatic parenchyma-to-necrosis, signal-to-noise ratio (SNR) of the pancreas, image noise, and score of subjective diagnosis were measured, calculated, and compared among the CT images of 100 kV, Sn140 kV, weighted-average 120 kV, and optimal single-energy level for CNR. Results CNR of pancreatic parenchyma-to-necrosis in the images of 100 kV, Sn140 kV, weighted-average 120 kV, and the optimal single-energy level for CNR was 5.18 ± 2.39, 3.13 ± 1.35, 5.69 ± 2.35, and 9.99 ± 5.86, respectively; SNR of the pancreas in each group was 6.31 ± 2.77, 4.27 ± 1.56, 7.21 ± 2.69, and 11.83 ± 6.30, respectively; image noise in each group was 18.78 ± 5.20, 17.79 ± 4.63, 13.28 ± 3.13, and 9.31 ± 2.96, respectively; and score of subjective diagnosis in each group was 3.56 ± 0.50, 3.00 ± 0.55, 3.48 ± 0.55, and 3.88 ± 0.33, respectively. The four measurements of the optimal single-energy level for CNR images were significantly different from those of images in the other three groups (P

Taking advantage of the invar effect of Fe–Ni alloy at low temperatures, a novel stress-relaxing approach based on forming Fe–Ni invar interlayer was proposed for joining carbon fiber reinforced carbon (C/C) composites in this paper. Mixed Fe + Ni62Ti38 (at %) powders were used as the filler materials. Microstructure, mechanical property, and formation mechanism of the bonded joints were investigated. The results indicate that, based on the eutectic reaction of (Fe,Ni)–C at the C/C/interlayer interface and the in-situ reaction of Ti–C in the interlayer, a (Fe,Ni)–C eutectic reaction layer was formed at the C/C side interface and the Fe–Ni invar effect interlayer reinforced by TiC particles was obtained. Owing to the low thermal expansion coefficient and good plasticity of the Fe–Ni alloy matrix at low temperatures, the high residual thermal stress of the joint was effectively reduced and the shear strength of the joint was improved. With the increase of Ni content in the Fe–Ni alloy matrix of the interlayer, the shear strength of the joint decreases gradually. When the composition of the Fe–Ni matrix was designed to be Fe–36Ni, i.e., the invar alloy with the lowest thermal expansion coefficient at 100 °C, the average shear strength of the bonded joint reached the highest value of 36 MPa. The fracture of the joint occurred in the (Fe,Ni)–C eutectic reaction layer close to the C/C composite.

The task of question matching/retrieval focuses on determining whether two questions are semantically equivalent. It has garnered significant attention in the field of natural language processing (NLP) due to its commercial value. While neural network models have made great strides and achieved human-level accuracy, they still face challenges when handling complex scenarios. In this paper, we delve into the utilization of different specializations encoded in different layers of large-scale pre-trained language models (PTMs). We propose a novel attention-based model called ERNIE-ATT that effectively integrates the diverse levels of semantics acquired by PTMs, thereby enhancing robustness. Experimental evaluations on two challenging datasets showcase the superior performance of our proposed model. It outperforms not only traditional models that do not use PTMs but also exhibits a significant improvement over strong PTM-based models. These findings demonstrate the effectiveness of our approach in enhancing the robustness of question matching/retrieval systems.

High-performance joining especially brazing has been highly expected in the manufacture or maintenance of single crystal blades. In this paper, a Ni-40Cr-10Ta (at.%) alloy was developed as filler material for single crystal superalloys. High-performance brazing of DD5 superalloy was achieved. The joints brazed at 1260 °C contained an isothermal solidification zone (ISZ) with “γ + γ′” structure and an athermal solidification zone (ASZ) composed of γ, γ', γ/γ′-eutectics, TaCr2 and TaC. Unlike the conventional filler materials with melting point depressants of B and Si, the Ni-Cr-Ta filler material was free of B and Si, and thus the resulting joints contained no B-rich and Si-rich compounds and eutectics with low melting points, which enhanced the brazed joint performance. The tensile strength at 980 ℃ of the heat-treated joints reached 654 MPa, which is 88.5 % that of the base metal.

Abstract Post-acute pancreatitis diabetes mellitus (PPDM-A) is the main component of pancreatic exocrine diabetes mellitus. Timely diagnosis of PPDM-A improves patient outcomes and the mitigation of burdens and costs. We aimed to determine risk factors prospectively and predictors of PPDM-A in China, focusing on giving personalized treatment recommendations. Here, we identify and evaluate the best set of predictors of PPDM-A prospectively using retrospective data from 820 patients with acute pancreatitis at four centers by machine learning approaches. We used the L1 regularized logistic regression model to diagnose early PPDM-A via nine clinical variables identified as the best predictors. The model performed well, obtaining the best AUC = 0.819 and F1 = 0.357 in the test set. We interpreted and personalized the model through nomograms and Shapley values. Our model can accurately predict the occurrence of PPDM-A based on just nine clinical pieces of information and allows for early intervention in potential PPDM-A patients through personalized analysis. Future retrospective and prospective studies with multicentre, large sample populations are needed to assess the actual clinical value of the model.

Abstract As the second-largest neurodegenerative disease in the world, Parkinson’s disease (PD) has brought a severe economic and medical burden to our society. Growing evidence in recent years suggests that the gut microbiome may influence PD, but the exact pathogenesis of PD remains unclear. In addition, the current diagnosis of PD could be inaccurate and expensive. In this study, the largest meta-analysis currently of the gut microbiome in PD was analyzed, including 2269 samples by 16S rRNA gene and 236 samples by shotgun metagenomics, aiming to reveal the connection between PD and gut microbiome and establish a model to predict PD. The results showed that the relative abundances of potential pro-inflammatory bacteria, genes and pathways were significantly increased in PD, while potential anti-inflammatory bacteria, genes and pathways were significantly decreased. These changes may lead to a decrease in potential anti-inflammatory substances (short-chain fatty acids) and an increase in potential pro-inflammatory substances (lipopolysaccharides, hydrogen sulfide and glutamate). Notably, the results of 16S rRNA gene and shotgun metagenomic analysis have consistently identified five decreased genera (Roseburia, Faecalibacterium, Blautia, Lachnospira, and Prevotella) and five increased genera (Streptococcus, Bifidobacterium, Lactobacillus, Akkermansia, and Desulfovibrio) in PD. Furthermore, random forest models performed well for PD prediction based on 11 genera (accuracy > 80%) or 6 genes (accuracy > 90%) related to inflammation. Finally, a possible mechanism was presented to explain the pathogenesis of inflammation leading to PD. Our results provided further insights into the prediction and treatment of PD based on inflammation.

IntroductionNatural menopause is an inevitable biological process with significant implications for women's health. However, the molecular mechanisms underlying menopause are not well understood. This study aimed to investigate the molecular and cellular changes occurring in the ovary before and after perimenopause.MethodsSingle-cell sequencing data from the GTEx V8 cohort (30-39: 14 individuals; 40-49: 37 individuals; 50-59: 61 individuals) and transcriptome sequencing data from ovarian tissue were analyzed. Seurat was used for single-cell sequencing data analysis, while harmony was employed for data integration. Cell differentiation trajectories were inferred using CytoTrace. CIBERSORTX assessed cell infiltration scores in ovarian tissue. WGCNA evaluated co-expression network characteristics in pre- and post-perimenopausal ovarian tissue. Functional enrichment analysis of co-expression modules was conducted using ClusterprofileR and Metascape. DESeq2 performed differential expression analysis. Master regulator analysis and signaling pathway activity analysis were carried out using MsViper and Progeny, respectively. Machine learning models were constructed using Orange3.ResultsWe identified the differentiation trajectory of follicular cells in the ovary as ARID5B+ Granulosa -> JUN+ Granulosa -> KRT18+ Granulosa -> MT-CO2+ Granulosa -> GSTA1+ Granulosa -> HMGB1+ Granulosa. Genes driving Granulosa differentiation, including RBP1, TMSB10, SERPINE2, and TMSB4X, were enriched in ATP-dependent activity regulation pathways. Genes involved in maintaining the Granulosa state, such as DCN, ARID5B, EIF1, and HSP90AB1, were enriched in the response to unfolded protein and chaperone-mediated protein complex assembly pathways. Increased contents of terminally differentiated HMGB1+ Granulosa and GSTA1+ Granulosa were observed in the ovaries of individuals aged 50-69. Signaling pathway activity analysis indicated a gradual decrease in TGFb and MAPK pathway activity with menopause progression, while p53 pathway activity increased. Master regulator analysis revealed significant activation of transcription factors FOXR1, OTX2, MYBL2, HNF1A, and FOXN4 in the 30-39 age group, and GLI1, SMAD1, SMAD7, APP, and EGR1 in the 40-49 age group. Additionally, a diagnostic model based on 16 transcription factors (Logistic Regression L2) achieved reliable performance in determining ovarian status before and after perimenopause.ConclusionThis study provides insights into the molecular and cellular mechanisms underlying natural menopause in the ovary. The findings contribute to our understanding of perimenopausal changes and offer a foundation for health management strategies for women during this transition.

By means of alteration of the transmitted linear frequency modulation (LFM) signal waveform parameters, such as pulse width or chirp rate, initial phase, pulse repetition interval (PRI), and chirp rate polarity at every position of synthetic apertures, the pseudo-random agility technology of interpulse waveform parameters in airborne Synthetic Aperture Radar (SAR) actively increases the complexity and uncertainty of radar waveforms. This technology confuses jamming interception receivers, thus improving its anti-interference ability for active coherent jamming, which is one of the main research interests of airborne SAR technology. But the pseudo-random agility technology for interpulse waveform parameters faces certain challenges of large computation and complex system design, which need to be further studied and solved. To address these issues, a processing scheme of high-resolution SAR image formation which is appropriate for agile interpulse waveform parameters is proposed in this paper. This method can deal with multiple agile parameters, not only single ones as in most existing literature. Its computation load is nearly comparable to that of traditional SAR image formation with constant waveform parameters. The high-resolution SAR imaging results obtained by processing SAR raw data with agile interpulse waveform parameters demonstrate the effectiveness of the proposed method. In addition, real SAR images with resolutions of 0.5 m and 0.15 m, which are rarely found in the public literature, are shown under the circumstance of randomly changing the transmitted wideband LFM signal pulse parameters one by one.

Abstract Background Jujube resources are abundant in China, and Shanxi Province in particular is one of the places where they originated. The most famous 6 geographical indication (GI) jujube species in Shanxi are often masqueraded by nonoriginal jujube species, which seriously undermines the brand image. However, the current national quality standards, which have simple indicators, cannot completely trace the botanical and geographical origin of GI jujubes. Compared with small biomolecules and genes, polysaccharides possess a complicated structure and are sensitive to their geographical location and botanical origin, and these characteristics are important for botanical and geographical traceability. Therefore, we selected the 6 most famous GI jujube species in Shanxi Province, measured and analyzed their crude polysaccharide characterizations, and then selected efficient tracing indicators. Results The crude polysaccharides from 6 GI jujube species of Shanxi Province were tested with several parameters, including their purity (the content of polysaccharides), uronic acid content, Mw distribution, monosaccharide composition, functional groups and bonds. In the assays that measured purity and uronic acid content, the purity varied within a very narrow band (96–99%) and presented no negative or positive correlation with uronic acid content. In the experiment that measured the Mw distribution by HPGPC, five peaks (RT1, RT2, RT3, RT4, RT5) were almost observed in 6 jujube species, and the RT3 content (240–250 Da), which showed a significant correlation to the content of RT4 and RT5, exhibited significant differences among 6 jujube species (RSD = 1.28 > 1.00). The monosaccharide composition indicated that the polysaccharides from 6 jujube species were rich in glucose (55–75%), arabinose (10–15%) and galactose acid (10–20%), with small amounts of rhamnose, glucosamine hydrochloride, galactose, xylose, and mannose (less than 5%). The FT-IR spectrum showed that crude polysaccharides from six jujube species shared similar functional groups and chemical bonds. Conclusions The results above indicated that in the 6 GI jujube species, both homogeneity and differences were observed in the Mw distribution of crude polysaccharides. First, five peaks (RT1, RT2, RT3, RT4, RT5), which represent the Mw of 186,646–285,262 Da (RT1), 4634–17,296 Da (RT2), 240–250 Da (RT3), 98–103 Da (RT4) and 57–64 Da (RT5), respectively, could be detected in all 6 jujube species. Second, the RT3 contents exhibited significant differences among the 6 jujube species (RSD = 1.28 > 1.00) and showed a significant correlation with RT4 and RT5. Therefore, the Mw distribution may be treated as a potential distinguishing indicator among the 6 jujube species. Graphical Abstract

Abstract Background Rapid mutation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is sweeping the world and delaying the full reopening of society. Acceleration of the vaccination process may be the key element in winning the race against this virus. We examine factors associated with personal considerations of and accessibility to the corona virus disease 2019 (COVID-19) vaccination in metropolises of China. Methods This multi-center, cross-sectional research was conducted using online questionnaires from April 1 to June 1, 2021, in community health service centers of Shanghai, Chengdu and Fuzhou. 9,047 vaccinated participants were included and data for 8,990 individuals were eligible for analysis. Chi-square test was conducted to find potential predictors, which were included in the logistic regressions. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the influence of region, socio-economic status (SES), and attitudes on vaccination process. Results In consideration phase, participants in Fuzhou (OR:2.26, 95%CI: 1.90 to 2.68) and Chengdu (OR: 2.48, 95%CI: 2.17 to 2.83) were more likely than those in Shanghai to consider longer than one month. These odds increased for participants with master or above degree (reference: illiteracy and primary school), higher monthly household income (reference:

This paper proposes a soft switching mode for electric vertical takeoff and landing (eVTOL) compound-wing unmanned aerial vehicles (UAVs) to achieve a smooth transition between modes. The proposed mode pre-compensates the lift loss with the rotary wing during the deceleration stage before UAV landing. The control law adopted in this paper consists of implicit nonlinear dynamic inversion (NDI) and incremental nonlinear dynamic inversion (INDI). The outer loop (attitude angle loop) control law is based on implicit NDI, while the inner loop (attitude angle rate loop) controller is based on INDI. An extended state observer (ESO) is employed to estimate the angular acceleration. This paper innovates by proposing a soft switching strategy that improves the robustness, safety, and smoothness of the transition for the compound-wing UAV, and applying advanced control law to mode transition design. For the future application of eVTOL aircraft in UAM scenarios, this paper evaluates the smoothness of transition and passenger comfort using normal overload as a physical quantity. The Monte Carlo (MC) simulation results demonstrate that the proposed mode can reduce the peak normal overload by about 89%.

How top-down influence affects behavioral detection of visual signals and neuronal response sensitivity in the primary visual cortex (V1) remains poorly understood. This study examined both behavioral performance in stimulus orientation identification and neuronal response sensitivity to stimulus orientations in the V1 of cat before and after top-down influence of area 7 (A7) was modulated by non-invasive transcranial direct current stimulation (tDCS). Our results showed that cathode (c) but not sham (s) tDCS in A7 significantly increased the behavioral threshold in identifying stimulus orientation difference, which effect recovered after the tDCS effect vanished. Consistently, c-tDCS but not s-tDCS in A7 significantly decreased the response selectivity bias of V1 neurons for stimulus orientations, which effect could recover after withdrawal of the tDCS effect. Further analysis showed that c-tDCS induced reduction of V1 neurons in response selectivity was not resulted from alterations of neuronal preferred orientation, nor of spontaneous activity. Instead, c-tDCS in A7 significantly lowered the visually-evoked response, especially the maximum response of V1 neurons, which caused a decrease in response selectivity and signal-to-noise ratio. By contrast, s-tDCS exerted no significant effect on the responses of V1 neurons. These results indicate that top-down influence of A7 may enhance behavioral identification of stimulus orientations by increasing neuronal visually-evoked response and response selectivity in the V1.

The well-established semantic fluency test measures the ability to produce a sequence of spoken words from a particular category within a limited period of time. Like patients with Parkinson’s disease (PD), patients with progressive supranuclear palsy (PSP) tend to produce fewer correct words than age-matched healthy adults. This study further examined the difference between patients with PSP and PD in their semantic fluency performance using a graph theory-based approach. Twenty-nine patients with PSP Richardson’s syndrome (PSP-RS), thirty-eight patients with PD, and fifty-one healthy controls (HC) were recruited. All participants completed a standard semantic fluency test (animals). Their verbal responses were recorded, transcripted, and transformed into directed speech graphs. The speech graphs of the PSP-RS group showed higher density, shorter diameter, and shorter average shortest path than those of the PD and HC groups. It indicates that the PSP-RS group produced smaller and denser speech graphs than the PD and HC groups. In the PSP-RS group, moreover, the average shortest paths of the speech graphs correlated with the severity of motor symptoms. This study shows the potential of the graph theory-based approach in distinguishing the semantic fluency performance of nondemented patients with PSP-RS and PD.

The robust and reliable joining of carbon/carbon (C/C) composites and metals has important application value in the aerospace field. However, the low interface bonding strength when joining the two dissimilar materials remains a persistent problem and leads to low joint strength. In this work, a novel interface strengthened brazing process has been developed for joining a C/C composite and a nickel-based superalloy (GH3044). Before joining, high-strength molybdenum (Mo) fibers are planted on the surface of the C/C composite, then the fiber-treated C/C composite is brazed to the GH3044 superalloy using a BNi-2 filler. The results show that a sound joint with robust Mo fibers crossing the interface between the C/C substrate and the brazing layer is obtained. Owing to the pinning effect of the Mo fibers, the joining interface area is increased and cracking is effectively prevented. As a result, the bonded joint exhibits excellent mechanical properties. The maximum shear strength of the joint was measured to be 60 MPa, which is 2.14-times that of the joint without fiber-planting. The maximum three-point bending strength of the joint was measured at 31 MPa, which is 2.58-times that of the joint without fiber-planting.

Diabetic nephropathy (DN) is the leading cause of death and the greatest risk to the lives of people with advanced diabetes. Yet, the molecular mechanisms underlying its development and progression remain unknown. In this research, we studied the primary pathways driving DN using transcriptome sequencing and immune repertoire analysis. Firstly, we found that the diversity and abundance of the immune repertoire in late DN were significantly increased, while there was no significant change in early DN. Furthermore, B cell-mediated antibody responses may be the leading cause of DN progression. By analyzing master regulators, we found the key DN-driving transcription factors. In the late stage of DN, immune cells, fibroblasts, and epithelial cells were abundant, but other stromal cells were few. Early DN kidneys had a higher tissue stemness score than normal and advanced DN kidneys. We showed that DN progression involves proximal tubular metabolic reprogramming and stemness restoration using Monocle3. Through WGCNA, we found that co-expression modules that regulate DN progression and immune repertoire diversity mainly regulate immune-related signaling pathways. In addition, we also found that early DN had apparent activation of immune-related signaling pathways mainly enriched in immune cells. Finally, we found that activation of fibroblasts is typical of early DN. These results provide a research basis for further exploring the molecular biology and cellular mechanisms of the occurrence and development of DN and provide a theoretical basis for the prevention and treatment of DN.

Full-densely activated sintered W(Fe) was prepared by spark plasma sintering technique. The effects of Fe content (0 ∼ 1.0%(wt.%)) on relative density, microstructure and mechanical properties were discussed. The mechanisms of solution strengthening effect and grain boundary strengthening effect of Fe addition were revealed by calculating dislocation energy and vacancy formation energy. The results indicated that the relative density and the grain size were the Exponential function and the Boltzmann function of Fe contents, respectively. Full-dense W(Fe) could be obtained with ≥ 0.75 %Fe added. The W(Fe) microstructure consisted completely of solid solution. The microhardness was monotonically increased due to the increase of relative density with Fe content increased, while the flexural strength and fracture toughness showed a nonmonotonic trend depending on the interaction of relative density and grain size. Specifically, the mechanical properties were all increased accompanied by the appearance of the typical transgranular fracture and a novel “micro-area transgranular fracture” with Fe content increased from 0.75% to 1.0%. The increases in mechanical properties were attributed to the combined action of the solution strengthening effect and grain boundary strengthening effect. The decreases of the dislocation energy and vacancy formation energy led to the increases of the deformation resistance and grain bonding strength, respectively, which resulted in the strengthening and toughening effects.

Head and neck cancer is a highly heterogeneous malignant tumor. Numerous studies have shown that the immune microenvironment of head and neck cancer has a significant impact on its occurrence and development, as well as its prognosis. However, there have been fewer studies related to the accurate immunophenotyping of head and neck cancer. In this study, we used gene expression profile information and clinical information from the TCGA-HNSC cohort (502 samples) and the GSE655858 cohort (270 samples) to identify and independently validate three immune subtypes (Cluster1–Cluster3) with different immune-related molecular profiles and clinical outcomes. Cluster2, which is mainly dominated by B-lymphocyte infiltration, was found to have the best prognosis. In addition, a support vector machine (SVM)-based classifier was constructed, which could accurately classify HNSC based on 19 genes. Furthermore, the results of the prognostic analysis showed activation of antibody-secreting B-lymphocyte function, which showed a good prognostic effect in all three immune subtypes of HNSC. Finally, the immune evolutionary landscape of HNSC was constructed in an attempt to explain the evolutionary pattern of the immune subtypes of HNSC. In summary, we provide a conceptual framework for understanding the tumor immune microenvironment in HNSC and demonstrate the importance of immune infiltration of B lymphocytes in HNSC. Further research is needed to assess the importance of these immunophenotypes in combination drug therapy and to provide a basis for screening appropriate patients for immunotherapy.

Abstract How top-down influence affects neuronal activity and information encoding in the primary visual cortex (V1) remains elusive. This study examined changes of neuronal excitability and contrast sensitivity in cat V1 cortex after top-down influence of area 7 (A7) was modulated by transcranial direct current stimulation (tDCS). The neuronal excitability in V1 cortex was evaluated by visually evoked field potentials (VEPs), and contrast sensitivity (CS) was assessed by the inverse of threshold contrast of neurons in response to visual stimuli at different performance accuracy. We found that the amplitude of VEPs in V1 cortex lowered after top-down influence suppression with cathode-tDCS in A7, whereas VEPs in V1 did not change after sham-tDCS in A7 and nonvisual cortical area 5 (A5) or cathode-tDCS in A5 and lesioned A7. Moreover, the mean CS of V1 neurons decreased after cathode-tDCS but not sham-tDCS in A7, which could recover after tDCS effect vanished. Comparisons of neuronal contrast-response functions showed that cathode-tDCS increased the stimulus contrast required to generate the half-maximum response, with a weakly-correlated reduction in maximum response but not baseline response. Therefore, top-down influence of A7 enhanced neuronal excitability in V1 cortex and improved neuronal contrast sensitivity by both contrast gain and response gain.

Background: Keloid is a disease caused by abnormal proliferation of skin fibres, the causative mechanism of which remains unclear.Method: In this study, endothelial cells of keloids were studied using scRNAseq combined with bulk-RNAseq data from keloids. The master regulators driving keloid development were identified by transcription factor enrichment analysis. The pattern of changes in vascular endothelial cells during keloid development was explored by inferring endothelial cell differentiation trajectories. Deconvolution of bulkRNAseq by CIBERSORTX verified the pattern of keloidogenesis. Immunohistochemistry for verification of the lesion process in keloid endothelial cells.Results: The endothelial cells of keloids consist of four main cell populations (MMP1+ Endo0, FOS + JUN + Endo1, IL6+CSF3+Endo2, CXCL12 + Endo3). Endo3 is an endothelial progenitor cell, Endo1 is an endothelial cell in the resting state, Endo2 is an endothelial cell in the activated state and Endo0 is an endothelial cell in the terminally differentiated state. Activation of the NFΚB signaling pathway is a typical feature of Endo2 and represents the early skin state of keloids.Conclusion: We have identified patterns of vascular endothelial cell lesions during keloidogenesis and development, and have found that activation of the NFΚB signaling pathway is an essential feature of keloid formation. These findings are expected to contribute to the understanding of the pathogenesis of keloids and to the development of new targeted therapeutic agents for the lesional characteristics of vascular endothelial cells.

Cognitive impairment is a common non-motor symptom in Parkinson's disease (PD), with executive dysfunction being an initial manifestation. We aimed to investigate whether and how longitudinal changes in the prefrontal perfusion correlate with mild cognitive impairment (MCI) in patients with PD. We recruited 49 patients with PD with normal cognition and 37 matched healthy control subjects (HCs). Patients with PD completed arterial spin labeling MRI (ASL–MRI) scans and a comprehensive battery of neuropsychological assessments at baseline (V0) and 2-year follow-up (V1). HCs completed similar ASL–MRI scans and neuropsychological assessments at baseline. At V1, 10 patients with PD progressed to MCI (converters) and 39 patients remained cognitively normal (non-converters). We examined differences in the cerebral blood flow (CBF) derived from ASL–MRI and neuropsychological measures (a) between patients with PD and HCs at V0 (effect of the disease), (b) between V1 and V0 in patients with PD (effect of the disease progression), and (c) between converters and non-converters (effect of the MCI progression) using t-tests or ANOVAs with false discovery rate correction. We further analyzed the relationship between longitudinal CBF and neuropsychological changes using multivariate regression models with false discovery rate correction, focusing on executive functions. At V0, no group difference was found in prefrontal CBF between patients with PD and HCs, although patients with PD showed worse performances on executive function. At V1, patients with PD showed significantly reduced CBF in multiple prefrontal regions, including the bilateral lateral orbitofrontal, medial orbitofrontal, middle frontal, inferior frontal, superior frontal, caudal anterior cingulate, and rostral anterior cingulate. More importantly, converters showed a more significant CBF reduction in the left lateral orbitofrontal cortex than non-converters. From V0 to V1, the prolonged completion time of Trail Making Test-B (TMT-B) negatively correlated with longitudinal CBF reduction in the right caudal anterior cingulate cortex. The decreased accuracy of the Stroop Color-Word Test positively correlated with longitudinal CBF reduction in the left medial orbitofrontal cortex. In addition, at V1, the completion time of TMT-B negatively correlated with CBF in the left caudal anterior cingulate cortex. Our findings suggest that longitudinal CBF reduction in the prefrontal cortex might impact cognitive functions (especially executive functions) at the early stages of PD.

BackgroundThe decline in the quantity and quality of oocytes due to ovarian ageing in women is now a significant threat to reproductive health today as the concept of delayed fertility becomes widespread. However, the molecular mechanisms of natural ovarian ageing have not been fully elucidated.MethodHere, we used transcriptomic data from 180 normal ovarian tissues from GTEx V8 to analyze the expression profile of ovarian tissues from women with age segments of 20-29 (22 individuals), 30-39 (14 individuals), 40-49 (37 individuals), 50-59 (61 individuals), 60-69 (42 individuals), and 70-79 (4 individuals), respectively. XCELL was used to assess the infiltration score of 64 cell types of the ovary. WGCNA was used to characterize the co-expression network during the natural aging of the ovary. ClusterprofileR was used for functional enrichment analysis of co-expression modules. MsViper was used for master regulator analysis.ResultsThe infiltration score of endothelial cells and activated antigen-presenting cells during natural ovarian ageing increased significantly at ages 30-39, 40-49, and then decreased, whereas CD4+ Tcm increased with age. WGCNA identified six co-expression modules from ovarian tissue transcriptomic data species. The red module was significantly and positively correlated with senescence and CD4+ Tcm, and the turquoise module was significantly and positively correlated with Endothelial Cells. We further explored ovarian tissue for women aged 20-29 and 30-39 years. The GSEA results showed that the Chemokine signaling pathway was significantly activated in the 30-39-year-old group, while Oocyte meiosis was significantly inhibited. Finally, the results of msviper found that transcription factors such as KDM1A, PRDM5, ZNF726, PPARG, FOXJ2, and GLI2 were mainly activated in the 20-29 years group, while VAV1, RUNX3, ZC3H12D, MYCL, and IRF5 were mainly activated in the 30-39 years group and that these transcription factor activities were diagnostic of natural ovarian ageing (AUC: 0.65-0.71).ConclusionNatural ageing of the ovary is significantly correlated with immune cell infiltration and activation of inflammation-related signaling pathways, with inflammation levels reaching a maximum during early ovarian ageing (30-39, 40-49) and then gradually decreasing after that. These studies provide a research basis for exploring the mechanisms of natural ovarian ageing.

In this study, to obtain a stress-relieved and high-temperature resistant joint of Cf/SiC composite and stainless steel at relatively lower brazing temperature, reaction composite-diffusion brazing with the mixed powders of Cu–15Ti alloy and C particles as filler material was used to join Cf/SiC composite and nickel-plated stainless steel. Results show that C particles reacted with Cu–Ti alloy filler with low melting point not only formed a composite joining layer which can relieve residual stress in the joints, but also formed a heat resistant (Cu)ss matrix due to the consumption of the melting point depressant element Ti. Meanwhile, the nickel plating diffused melting raising element Ni into the joining layer formed a (Cu,Ni)ss matrix with higher heat resistance, further improving the heat resistance of the joining layer, so the filler isothermally solidified in a short time during the brazing process. In addition, the nickel plating also prevented the formation of the brittle compound TiFe that may cause crack at the interface of joining layer/stainless steel. As a result, a stress-relieved joint with high-temperature resistance was obtained at relatively lower brazing temperature, and the maximum shear strength of the joint reached 233.4 ± 21.3 MPa, which is 51.3% higher than that brazed with Cu–15Ti alloy alone.

Large-slenderness-ratio (LSR) aircraft exhibit more severe lateral–directional coupling compared with other aircraft, which poses a significant challenge to their flight safety, especially during high-speed maneuvers. Reliable attitude decoupling control is, therefore, essential for LSR aircraft. In this study, a novel control framework that combines incremental nonlinear dynamic inversion (INDI) and extended state observer (ESO) is proposed for supersonic roll maneuver control of LSR aircraft. The ESO is used to estimate the angular acceleration on the basis of an onboard mathematical model. The acceleration estimator based on ESO achieves superior noise reduction compared with the complementary filter (CF) and reduces the onboard model requirement without significantly sacrificing estimation accuracy. Monte Carlo (MC) simulations and frequency–domain analysis demonstrate the effectiveness and robustness of the proposed controller. The sensitivity of parameter uncertainties is also investigated, revealing that the natural frequency of the actuator is the most critical parameter affecting robustness. Finally, flight tests validate the effectiveness of the proposed control structure.

ObjectiveTo discuss the characteristics of psychological assistance hotline calls and operators' coping strategies of before and after the COVID-19 outbreak， in order to further improve the assistance ability of the psychological crisis hotline.MethodsA retrospective study was conducted on the demographics characteristics， call problems， coping strategies， and call time trends recorded by Changchun psychological assistance hotline information registration platform before the epidemic in Changchun City （January 20， 2019-April 20， 2019） and during the epidemic period （January 20， 2020-April 20， 2020）.ResultsThe differences between gender， age， marital status， location， and occupation type before and during the epidemic were statistically significant （χ2=11.205， 234.240， 152.083， 265.458， 353.385， P

Diabetes of the exocrine pancreas (DEP), also commonly described as pancreatogenic diabetes mellitus, is a type of diabetes secondary to abnormalities in pancreatic or exocrine secretion of the pancreas. However, its pathogenesis is not yet known. The aim of this article was to explore the biomarkers of DEP and their potential molecular mechanisms. Based on GSE76896 dataset, which was acquired from Gene Expression Omnibus (GEO), we identified 373 genes by weighted gene co-expression network analysis (WGCNA) and differential expression analysis. In addition, protein–protein interaction (PPI) network analysis and cytoHubba were used to screen potential hub genes. Five hub genes were determined, comprising Toll-like receptor 4 (TLR4), ITGAM, ITGB2, PTPRC, and CSF1R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways suggested macrophage activation and Toll-like receptor signaling pathway as important pathophysiological features of DEP. CIBERSORT suggested that TLR4 may regulate the immune pathway via macrophages. Next, we validated the expression and receiver operating characteristic curve (ROC) of the hub genes using the GSE164416 dataset. In addition, we used miRNet to predict the target miRNAs of hub genes and intersected them with common miRNAs in diabetes from the Human MicroRNA Disease Database (HMDD), which was used to propose a possible mechanistic model for DEP. The miRNA–mRNA network showed that has-miR-155-5p/has-miR-27a-3p/has-miR-21-5p-TLR4 might lead to TLR4 signaling pathway activation in DEP. In conclusion, we identified five hub genes, namely, TLR4, ITGAM, ITGB2, PTPRC, and CSF1R, as biomarkers to aid in the diagnosis of DEP and conducted an in-depth study of the pathogenesis of DEP at the genetic level.

ObjectiveEarly detection and diagnosis of hepatocellular carcinoma (HCC) is essential for prognosis; however, the imaging hallmarks for tumor detection and diagnosis has remained the same for years despite the use of many new immerging imaging methods. This study aimed to evaluate the detection performance of hepatic nodules in high risk patients using either hepatobiliary specific contrast (HBSC) agent or extracellular contrast agent (ECA), and further to compare the diagnostic performances for hepatocellular carcinoma (HCC) using different diagnostic criteria with the histopathological results as reference standard.MethodsThis prospective study included 247 nodules in 222 patients (mean age, 53.32 ± 10.84 years; range, 22–79 years). The detection performance and imaging features of each nodule were evaluated in all MR sequences by three experienced abdominal radiologists. The detection performance of each nodule on all MR sequences were compared and further the diagnostic performance of various diagnostic criteria were evaluated.ResultsFor those patients who underwent ECA-MRI, the conventional imaging hallmark of “AP + PVP and/or DP” was recommended, as 60.19% diagnostic sensitivity, 80.95% specificity and 100% lesion detection rate. Additionally, for those patients who underwent HBSC-MRI, the diagnostic criteria of “DWI + HBP” was recommended. This diagnostic criteria demonstrated, both in all tumor size and for nodules ≤2 cm, higher sensitivity (93.07 and 90.16%, all p 0.05, respectively) than that of the European Association for the Study of the Liver (EASL) criteria.ConclusionsDifferent abbreviated MR protocols were recommended for patients using either ECA or HBSC. These provided imaging settings demonstrated high lesion detection rate and diagnostic performance for HCC.

Background: To prospectively establish and validate new diagnostic criterion (DC) for liver-specific contrast agents and further compared the diagnostic sensitivity and specificity with conventional DC. Methods: Institutional Review Board approved and written informed consent were obtained for this prospective study. Two board-certified reviewers established the reference standard as hepatocellular carcinoma (HCC), non-HCC lesions by using marks on all cross-sectional MR images. Another 2 abdominal radiologists independently performed the marked lesion observations using 5 different DCs, including DC-1: arterial phase hyperenhancement (APHE) and portal venous phase washout; DC-2: APHE and hepatobiliary phase (HBP) hypointensity; DC-3: APHE and diffusion-weighted imaging (DWI) hyperintensity; DC-4: HBP hypointensity and DWI hyperintensity; DC-5: HBP hypointensity, DWI hyperintensity and excluded these markedly T2 hyperintensity. Diagnostic performance of sensitivity, specificity, and accuracy for each imaging DC was calculated, per-lesion diagnostic sensitivity and specificity of imaging criteria were compared by using McNemars test. Results: A total of 215 patients were included (mean age 53.82 ± 11.24 years; range 24–82 years) with 265 hepatic nodules (175 HCCs and 90 non-HCCs). The DC-4 (93.71%; 164/175) and DC-5 (92.57%; 162/175) yielded the highest diagnostic sensitivity and was better than DC-1 (72.57%; 127/175), DC-2 (82.86%; 145/175), and DC-3 (82.29%; 144/175) (all p < 0.001). The specificity of DC-1 (94.44%; 85/90) was significantly higher than that with DC-2 (83.33%; 75/90), DC-3 (84.44%; 76/90), DC-4 (74.44%; 67/90), and DC-5 (82.22%; 74/90) (all p < 0.05). Additionally, the DC-4 and DC-5 achieved the highest area under curve value of 0.841 (95% CI 0.783–0.899) and 0.874 (95% CI 0.822–0.925). Conclusions: The combined use of HBP hypointensity and DWI hyperintensity as a new DC for HCC enables a high diagnostic sensitivity and comparable specificity.

Abstract Background Neurosurgery represents one of the most challenging and delicate of any surgical procedure. Skull base tumors in particular oftentimes present as a very technically difficult procedures in the setting of neurosurgical teaching. Virtual reality technology is one of the most promising surgical planning tools. It can perform fast three-dimensional (3D) reconstruction of computed tomography (CT), magnetic resonance imaging (MRI) and other imaging data sets under conditions of virtual reality (VR). Surgical simulation can more intuitively understand the anatomical relationship of the surgical area in significantly greater detail. Methods Thirty clinical undergraduates from the class of 2016 were randomly divided into two groups: the traditional teaching group and the virtual reality teaching group. After the study concluded, the teaching effectiveness was evaluated by combining basic theoretical knowledge, case analysis and questionnaire survey methods. Results Comparative analysis between both groups showed the response effect of the virtual reality teaching group was better than that of the traditional teaching group (P 0.05).The results of theoretical knowledge assessment between both groups showed that the scores of basic theory, location, adjacent structure, clinical manifestation, diagnosis and analysis, surgical methods and total scores in the VR group exceeded those in the traditional teaching group (P

A long-running debate concerns whether dopamine or noradrenaline deficiency drives response disinhibition in Parkinson’s disease (PD). This study aimed to investigate whether damage to the locus coeruleus (LC) or substantia nigra (SN) might impact inhibitory functions of the fronto-subthalamic hyperdirect or fronto-striatal indirect pathway. Patients with PD (n = 29, 13 women) and matched healthy controls (n = 29, 15 women) participated in this cross-sectional study. LC and SN integrity was assessed using neuromelanin-sensitive MRI. Response inhibition was measured using fMRI with a stop-signal task. In healthy controls, LC (but not SN) integrity correlated with the stopping-related activity of the right inferior frontal gyrus (IFG) and right subthalamic nucleus (STN), which further correlated with stop-signal reaction time (SSRT). PD patients showed reduced LC integrity, longer SSRT, and lower stopping-related activity over the right IFG, pre-supplementary motor area, and right caudate nucleus than healthy controls. In PD patients, the relationship between SSRT and the fronto-subthalamic pathway was preserved. However, LC integrity no longer correlated with the stopping-related right IFG or right STN activity. No contribution of SN integrity was found during stopping. In conclusion, LC (but not SN) might modulate inhibitory functions of the right IFG-STN pathway. Damage to the LC might impact the right IFG-STN pathway during stopping, leading to response disinhibition in PD.

Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic memory, working memory, and executive function. Semantic disfluency is a common problem in Parkinson’s disease (PD) and Alzheimer’s disease (AD). We demonstrated a graph theoretical analysis of semantic fluency in patients with PD (N=86), patients with AD (N=40), and healthy controls (HC, N=88). All participants completed a standard animal fluency test. Their verbal responses were recorded, transcripted, and transformed into directed speech graphs. Patients with PD generated fewer correct words than HC and more correct words than patients with AD. Patients with PD showed higher density, shorter diameter, and shorter average shortest path length than HC, but lower density, longer diameter, and longer average shortest path length than patients with AD. It suggests that patients with PD produced relatively smaller and denser speech graphs. Moreover, in PD, the densities of speech graphs correlated with the severity of non-motor symptoms, but not the severity of motor symptoms. The graph theoretical analysis revealed new features of semantic disfluency in patients with PD.