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Abstract The Capsule Network (CapsNet) has been shown to have significant advantages in improving the accuracy of bearing fault identification. Nevertheless, the CapsNet faces challenges in identifying the type of bearing fault under nonstationary and noisy conditions. These challenges arise from the distinctive nature of its dynamic routing algorithm and the use of fixed single-scale kernels. To address these challenges, a multi-scale spatial–temporal capsule network (MSCN) based on sequence encoding is proposed for bearing fault identification under nonstationary and noisy environments. A spatial–temporal sequence encoding module focuses on feature correlations at various times and positions. Dilated convolution-based multiscale capsule layer (MCaps) is designed to capture spatial–temporal features at different scales. MCaps establishes connections between various layers, enhancing the comprehension and interpretation of spatial–temporal features. Furthermore, the Bhattacharyya coefficient is introduced into the dynamic routing to compare the similarity between capsules. The validity of the model is verified through comparative experiments, and the results show that MSCN has significant advantages over traditional methods.

Abstract Background The diagnosis of adolescent Depressive Disorder (DD) lacks specific biomarkers, posing significant challenges. This study investigates the potential of Niacin Skin Flush Response (NSFR) as a biomarker for identifying and assessing the severity of adolescent Depressive Disorder, as well as distinguishing it from Behavioral and Emotional Disorders typically emerging in childhood and adolescence(BED). Methods In a case-control study involving 196 adolescents, including 128 Depressive Disorder, 32 Behavioral and Emotional Disorders, and 36 healthy controls (HCs), NSFR was assessed. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and anxious symptoms with the Generalized Anxiety Disorder 7-item scale (GAD-7). Pearson correlation analysis determined the relationships between NSFR and the severity of depression in DD patients. Receiver Operating Characteristic (ROC) was used to identify DD from BED integrating NSFR data with clinical symptom measures. Results The adolescent Depressive Disorder group exhibited a higher rate of severe blunted NSFR (21.4%) compared to BED (12.5%) and HC ( 8.3%). Adolescent Depressive Disorder with psychotic symptoms showed a significant increase in blunted NSFR (p = 0.016). NSFR had negative correlations with depressive (r = -0.240, p = 0.006) and anxious (r = -0.2, p = 0.023) symptoms in adolescent Depressive Disorder. Integrating NSFR with three clinical scales improved the differentiation between adolescent Depressive Disorder and BED (AUC increased from 0.694 to 0.712). Conclusion The NSFR demonstrates potential as an objective biomarker for adolescent Depressive Disorder, aiding in screening, assessing severity, and enhancing insights into its pathophysiology and diagnostic precision.

Irradiation-induced defects such as dislocation loops, cavities or solute clusters and chemical composition segregation of reactor pressure vessel (RPV) steel are the root causes of irradiation embrittlement. Combining two nucleation mechanisms, namely, the uniform nucleation and non-uniform nucleation of solute clusters (such as Cu-rich phase), a cluster kinetic simulation was established based on the reaction rate theory, and the co-evolution of matrix damage and Cu-rich phase in low-copper RPV steel was simulated under irradiation. And the average size and number density of defective clusters and solute clusters were established with irradiation dose. Compared with the average size and number density of dislocation loops observed by transmission electron microscopy (TEM) of proton irradiated RPV steel at 290°C, the verification results show that the cluster dynamics model considering both the nucleation mechanism of interstitial dislocation loops and vacancy clusters can well simulate the irradiation damage behavior of materials.

Co-based catalysts have shown great promise for propane dehydrogenation (PDH) reactions due to their merits of environmental friendliness and low cost. In this study, ordered mesoporous molecular sieve-supported CoOx species (CoOx/Al-SBA-15 catalyst) were prepared by one-step organometallic complexation. The catalysts show worm-like morphology with regular straight-through mesoporous pores and high external specific surface area. These typical features can substantially enhance the dispersion of CoOx species and mass transfer of reactants and products. Compared with the conventional impregnation method, the 10CSOC (10 wt.% Co/Al-SBA-15 prepared by the organometallic complexation method) sample presents a smaller CoOx size and higher Co2+/Co3+ ratio. When applied to PDH reaction, the 10CSOC delivers higher propane conversion and propylene selectivity. Under the optimal conditions (625 °C and 4500 h−1), 10CSOC achieves high propane conversion (43%) and propylene selectivity (83%). This is attributed to the smaller and better dispersion of CoOx nanoparticles, more suitable acid properties, and higher content of Co2+ species. This work paves the way for the rational design of high-performance catalysts for industrially important reactions.

Abstract Background SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer. Methods This cohort study used multidimensional genomic data of 6726 sequencing samples from our cooperative and non-public GenePlus institute from April 1 through April 10, 2020. MSIsensor score, HRD score, RNAseq, mutational data, and corresponding clinical data were obtained from the TCGA and MSKCC cohort for seven solid tumor types. Results A total of 1021 genes underwent target panel sequencing reveal that SETD2 mutations were associated with a higher TMB. SETD2 deleterious mutation dysfunction affected ICI treatment prognosis independently of TMB-H (p

Abstract The aim of this study is to investigate the nutrients of Agrocybe cylindracea from different regions and discover the law of its nutritional value. In this study, 43 A. cylindracea samples were collected from 13 provinces in China. The differences in nutritional components of this A. cylindracea were explored. The main nutritional components, including protein, dietary fiber, amino acids, fat, ash, and moisture, were evaluated. Further factor and cluster analysis were applied to analyze these nutrients. The results showed A. cylindracea had high protein (14.09–27.24 g/100 g dw) and insoluble dietary fiber (25.27–34.17 g/100 g dw), but low soluble dietary fiber (0.49–3.19 g/100 g dw) and fat (1.69–3.45 g/100 g dw). Seventeen amino acids were detected from these mushrooms, of which glutamic (18.24–46.78 g/100 g dw) was the most abundant. Based on Eta analysis, factor analysis, and cluster analysis, it was found that the comprehensive nutritional value of A. cylindracea was related to the factors of both the geographical origin and maturity stage. In addition, geographical origin had a greater influence on the nutritional value of A. cylindracea than the maturity stage. This study will serve as a useful reference for the selection of the consumption and further processing directions of A. cylindracea.

Abstract Aspect level sentiment analysis aims at identifying sentiment polarity towards specific aspect terms in a given sentence. Most methods based on deep learning integrate Recurrent Neural Network (RNN) and its variants with the attention mechanism to model the influence of different context words on sentiment polarity. In recent research, Convolutional Neural Network (CNN) and gating mechanism are introduced to obtain complex semantic representation. However, existing methods have not realized the importance of sufficiently combining the sequence modeling ability of RNN with the high-dimensional feature extraction ability of CNN. Targeting this problem, we propose a novel solution named Interactive Attention-based Convolutional Bidirectional Gated Recurrent Unit (IAC-GRU). IAC-GRU not only incorporates the sequence feature extracted by Bi-GRU into CNN to accurately predict the sentiment polarity, but also models the target and the context words separately and learns mutual influence between them. Additionally, we also incorporate the position information and Part-of-Speech (POS) information as prior knowledge into the embedding layer. The experimental results on SemEval2014 datasets show the effectiveness of our proposed model.

Abstract Chromosomal copy number variants (CNVs) are an important cause of congenital malformations and mental retardation. This study reported a large Chinese pedigree (4-generation, 76 members) with mental retardation caused by chromosome microduplication/microdeletion. There were 10 affected individuals with intellectual disability (ID), developmental delay (DD), and language delay phenotypes. SNP array analysis was performed in the proband and eight patients and found all of them had a microduplication of chromosome 4p16.3p15.2 and a microdeletion of chromosome 8p23.3p23.2. The high-resolution karyotyping analysis of the proband had unbalanced karyotype [46, XY, der(8)t(4;8)(p15.2;p23.1)mat], his mother had balanced karyotype [46, XX, t(4;8) (p15.2;p23.1)], whereas his father had normal karyotype [46,XY]. Fluorescence in situ hybridization (FISH) analysis further confirmed that the proband’s mother had a balanced translocation between the short arm terminal segment of chromosome 4 and the short arm end segment of chromosome 8, ish t(4;8)(8p + ,4q + ;4p + ,8q +). In conclusion, all the patients inherited chromosomes 8 with 4p16.3p15.2 duplication and 8p23.3p23.2 deletion from their parental balanced translocation, which might be the cause of the prevalence of intellectual disability. Meanwhile, 8p23.3p23.2 deletion, rather than 4p16.3p15.2 duplication might cause a more severe clinical syndrome.

Abstract Objective To investigate the relationship between absolute neutrophils count (ANC) in different periods of treatment and the outcomes of patients and assess effect of longitudinal neutrophils variation during radiotherapy (RT) on prognosis in patients with nasopharyngeal carcinoma (NPC). Methods A total of 1753 patients with newly diagnosed NPC were retrospectively analyzed. Complete blood counts of patients were obtained before treatment, before, during, and end of RT. The survival rate was calculated by Kaplan‐Meier method and the result was compared by the log‐rank test. The univariate and multivariate COX regression analyses were performed to investigate the association between the variation of ANC and survival for patients in different periods. Results Higher ANC pretreatment (>4 × 109/L) and pre‐RT (>7 × 109/L) were correlated with poor OS (89.7% vs 85.6%, P = .009; 88.3% vs 77.3%, P = .002, respectively). An increase >5 × 109/L of ANC during RT was associated with adverse OS (87.9% vs 73.6%, P = .042). The multivariate Cox regression analysis showed that high ANC of pre‐RT (>7 × 109/L) and a high increase (>5 × 109/L) of ANC during RT were independent prognostic factors of patients with NPC (P = .002, .044, respectively). Conclusion Our results demonstrated that ANC was an independent prognostic factor for survival in patients with NPC who received RT. Neutrophils may promote tumor resistance to radiotherapy in NPC. Level of Evidence 2a.

Agave species are widely planted for fiber production. However, the molecular basis of agave fiber development has not been well understood. In this study, we performed a transcriptomic analysis in A. amaniensi, a well-known variety with high-quality fiber production. Approximately 43.87 million clean reads were obtained using Illumina sequencing. The de novo assembly produced 66,746 unigrams, 54% of which were annotated in a public database. In the Nr database, 21,490 unigenes of A. amaniensis were shown to be most closely related to Asparagus officinalis. Nine expansin A orthologs with full coding regions were obtained, which were named EXP1a, EXP1b, EXP2, EXP3, EXP4a, EXP4b, EXP11, EXP12, and EXP13. The maximum likelihood phylogenetic tree revealed the species-specific expansion of expansin genes in Arabidopsis, rice and agave. The expression analysis suggested the negative correlation between the expression of expansin genes and the leaf growth rate, except AhEXP11. Moreover, expansin genes were differentially affected by abiotic and biotic stresses. Notably, AhEXP2 expression level was highly upgraded after the infection of Phytophthora nicotiana. Nutrient deficiency also influent expansin genes expression. Together, our research will benefit future studies related to fiber development, disease resistance and nutrient usage in agave.

XYY-CP1106, a candidate compound synthesized from a hybrid of hydroxypyridinone and coumarin, has been shown to be remarkably effective in treating Alzheimer’s disease. A simple, rapid and accurate high-performance liquid chromatography coupled with the triple quadrupole mass spectrometer (LC-MS/MS) method was established in this study to elucidate the pharmacokinetics of XYY-CP1106 after oral and intravenous administration in rats. XYY-CP1106 was shown to be rapidly absorbed into the blood (Tmax, 0.57–0.93 h) and then eliminated slowly (T1/2, 8.26–10.06 h). Oral bioavailability of XYY-CP1106 was (10.70 ± 1.72)%. XYY-CP1106 could pass through the blood–brain barrier with a high content of (500.52 ± 260.12) ng/g at 2 h in brain tissue. The excretion results showed that XYY-CP1106 was mainly excreted through feces, with an average total excretion rate of (31.14 ± 0.05)% in 72 h. In conclusion, the absorption, distribution and excretion of XYY-CP1106 in rats provided a theoretical basis for subsequent preclinical studies.

Abstract Hearing loss is one of the most common birth disorders in humans, with an estimated prevalence of 1–3 in every 1000 newborns. This study investigates the molecular etiology of a hearing loss cohort using a stepwise strategy to effectively diagnose patients and address the challenges posed by the genetic heterogeneity and variable mutation spectrum of hearing loss. In order to target known pathogenic variants, multiplex PCR plus next-generation sequencing was applied in the first step; patients which did not receive a diagnosis from this were further referred for exome sequencing. A total of 92 unrelated patients with nonsyndromic hearing loss were enrolled in the study. In total, 64% (59/92) of the patients were molecularly diagnosed, 44 of them in the first step by multiplex PCR plus sequencing. Exome sequencing resulted in eleven diagnoses (23%, 11/48) and four probable diagnoses (8%, 4/48) among the 48 patients who were not diagnosed in the first step. The rate of secondary findings from exome sequencing in our cohort was 3% (2/58). This research presents a molecular diagnosis spectrum of 92 non-syndromic hearing loss patients and demonstrates the benefits of using a stepwise diagnostic approach in the genetic testing of nonsyndromic hearing loss.

Currently, data auditing is an important means to check the integrity of the data stored on the cloud. Existing data auditing schemes have done a lot of work in terms of functionality, implementation, and security. As we can see, all of these schemes are based on the auditing framework proposed by Ateniese et al., which uses random sampling to probabilistically check whether the data is integrity or not. But multiple repeated sampling may lead to an intersection between the challenge sets selected each time, reducing the probability of detection, and the time for detecting corrupted blocks will be indefinite. If the corrupted data is not found for a long time, the data remedial measures will become invalid, resulting in permanent data loss. To address the above problem, we designed an efficient sampling verification algorithm. Based on this algorithm, the auditing scheme is further optimized, and a dynamic auditing function has been developed for the scheme to facilitate data owners to update data. Through the security analysis, our scheme is soundness. The experiment shows that our sampling verification can detect corrupted blocks faster than other auditing schemes.

Abstract Background The relationships between polymorphisms in interleukin-10 (IL-10) gene and the risk of viral hepatitis remain inconclusive. Therefore, the authors conducted so far the very first meta-analysis to robustly assess the relationships between polymorphisms in IL-10 gene and the risk of viral hepatitis by integrating the results of previous works. Methods Medline, Embase, Wanfang, VIP and CNKI were searched throughly for eligible studies, and 76 genetic association studies were finally included in this meta-analysis. Results We noticed that rs1800871 (− 819 C/T), rs1800872 (− 592 C/A) and rs1800896 (− 1082 G/A) polymorphisms were all significantly associated with the risk of viral hepatitis in Asians, whereas only rs1800896 (− 1082 G/A) polymorphism was significantly associated with the risk of viral hepatitis in Caucasians. In further analyses by disease subtypes, we noticed that the three investigated polymorphisms were all significantly associated with the risk of both HBV and HCV. Conclusions This meta-analysis demonstrates that rs1800871 (− 819 C/T), rs1800872 (− 592 C/A) and rs1800896 (− 1082 G/A) polymorphisms may influence the risk of viral hepatitis in Asians, while only rs1800896 (− 1082 G/A) polymorphism may influence the risk of viral hepatitis in Caucasians. In further analyses by disease subtypes, we noticed that the three investigated polymorphisms may influence the risk of both HBV and HCV.

Liver fibrosis is an outcome of chronic hepatic injury, which can eventually result in cirrhosis, liver failure, and even liver cancer. The activation of hepatic stellate cell (HSC) is a prominent driver of liver fibrosis. Recently, it has been found that the crosstalk between HSCs and immune cells, including hepatic macrophages, plays an important role in the initiation and development of liver fibrosis. As a vital vehicle of intercellular communication, exosomes transfer specific cargos into HSCs from macrophages. Here, we show that exosomes derived from lipopolysaccharide (LPS)-treated macrophages has higher expression level of miR-500. And overexpression or inhibition of miR-500 in macrophage exosomes could promote or suppress HSC proliferation and activation. Treatment of exosomes with miR-500 overexpression can accelerate liver fibrosis in CCl4-induced liver fibrosis mouse model. miR-500 promotes HSC activation and liver fibrosis via suppressing MFN2. Moreover, miR-500 in serum exosomes could be a biomarker for liver fibrosis. Taken together, exosomal miR-500 derived from LPS-activated macrophages promotes HSC proliferation and activation by targeting MFN2 in liver fibrosis.

Transient receptor potential vanillic acid 1 (TRPV1) is an ion channel activated by heat and inflammatory factors involved in the development of various types of pain. The P2X7 receptor is in the P2X family and is associated with pain mediated by satellite glial cells. There might be some connection between the P2X7 receptor and TRPV1 in neuropathic pain in diabetic rats. A type 2 diabetic neuropathic pain rat model was induced using high glucose and high-fat diet for 4 weeks and low-dose streptozocin (35 mg/kg) intraperitoneal injection to destroy islet B cells. Male Sprague Dawley rats were administrated by intrathecal injection of P2X7 shRNA and p38 inhibitor, and we recorded abnormal mechanical and thermal pain and nociceptive hyperalgesia. One week later, the dorsal root ganglia from the L4-L6 segment of the spinal cord were harvested for subsequent experiments. We measured pro-inflammatory cytokines, examined the relationship between TRPV1 on neurons and P2X7 receptor on satellite glial cells by measuring protein and transcription levels of P2X7 receptor and TRPV1, and measured protein expression in the PKCε/P38 MAPK/NF-κB signaling pathway after intrathecal injection. P2X7 shRNA and p38 inhibitor relieved hyperalgesia in diabetic neuropathic pain rats and modulated inflammatory factors in vivo. P2X7 shRNA and P38 inhibitors significantly reduced TRPV1 expression by downregulating the PKCε/P38 MAPK/NF-κB signaling pathway and inflammatory factors in dorsal root ganglia. Intrathecal injection of P2X7 shRNA alleviates nociceptive reactions in rats with diabetic neuropathic pain involving TRPV1 via PKCε/P38 MAPK/NF-κB signaling pathway.

Abstract Background Congenital hearing loss affects approximately 1–2 infants out of every 1000, with 50% of the cases resulting from genetic factors. Targeted gene panels have been widely used for genetic diagnosis of hearing loss. This study aims to reveal new diagnoses via reanalyzing historical data of a multigene panel, and exam the reasons for new diagnoses. Methods A total of 210 samples were enlisted, including clinical reports and sequencing data of patients with congenital/prelingual hearing loss who were referred to clinical genetic testing from October 2014 to June 2017. All variants listed on the original clinical reports were reinterpreted according to the standards and guidelines recommended by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). Expanded analysis of raw data were performed in undiagnosed cases. Results Re-analysis resulted in nine new diagnoses, improving the overall diagnostic rate from 39 to 43%. New diagnoses were attributed to newly published clinical evidence in the literature, adoption of new interpretation guidelines and expanded analysis range. Conclusion This work demonstrates benefits of reanalysis of targeted gene panel data, indicating that periodical reanalysis should be performed in clinical practice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Currently in clinic, people use hematoxylin and eosin stain (H&E stain) and immunohistochemistry methods to identify the generation and genre of cancers for human pathological samples. Since these methods are inaccurate and time consuming, developing a rapid and accurate method to detect cancer is urgently demanded. In our study, binding peptides for lung cancer cell line A549 were identified using bacteria surface display method. With those binding peptides for A549 cells on the surface, the fluorescent bacteria (Escherichia coli with stably expressed green fluorescent protein) were served as specific detecting reagents for the diagnosis of cancers. The binding activity of peptide-fluorescent bacteria complex was confirmed by detached cancer cells, attached cancer cells and mice tumor xenograft samples. A unique fixation method was developed for peptide-bacteria complex in order to make this complex more feasible for the clinic use. This peptide-fluorescent bacteria complex has great potential to become a new diagnostic tool for clinical application.

Electrocardiogram (ECG) signals contain a great deal of essential information which can be utilized by physicians for the diagnosis of heart diseases. Unfortunately, ECG signals are inevitably corrupted by noise which will severely affect the accuracy of cardiovascular disease diagnosis. Existing ECG signal denoising methods based on wavelet shrinkage, empirical mode decomposition and nonlocal means (NLM) cannot provide sufficient noise reduction or well-detailed preservation, especially with high noise corruption. To address this problem, we have proposed a hybrid ECG signal denoising scheme by combining extreme-point symmetric mode decomposition (ESMD) with NLM. In the proposed method, the noisy ECG signals will first be decomposed into several intrinsic mode functions (IMFs) and adaptive global mean using ESMD. Then, the first several IMFs will be filtered by the NLM method according to the frequency of IMFs while the QRS complex detected from these IMFs as the dominant feature of the ECG signal and the remaining IMFs will be left unprocessed. The denoised IMFs and unprocessed IMFs are combined to produce the final denoised ECG signals. Experiments on both simulated ECG signals and real ECG signals from the MIT-BIH database demonstrate that the proposed method can suppress noise in ECG signals effectively while preserving the details very well, and it outperforms several state-of-the-art ECG signal denoising methods in terms of signal-to-noise ratio (SNR), root mean squared error (RMSE), percent root mean square difference (PRD) and mean opinion score (MOS) error index.