Search

Abstract Aim Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, with genetic susceptibility and pathological processes such as autoimmunity and autoinflammation, but its pathogenesis is unclear. We conducted a transcriptome-wide association study (TWAS) using expression interpolation from a large-scale genome-wide association study (GWAS) dataset to identify genes, biological pathways, and environmental chemicals associated with JIA. Methods We obtained published GWAS data on JIA for TWAS and used mRNA expression profiling to validate the genes identified by TWAS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A protein–protein interaction (PPI) network was generated, and central genes were obtained using Molecular Complex Detection (MCODE). Finally, chemical gene expression datasets were obtained from the Comparative Toxicogenomics database for chemical genome enrichment analysis. Results TWAS identified 1481 genes associated with JIA, and 154 differentially expressed genes were identified based on mRNA expression profiles. After comparing the results of TWAS and mRNA expression profiles, we obtained eight overlapping genes. GO and KEGG enrichment analyses of the genes identified by TWAS yielded 163 pathways, and PPI network analysis as well as MCODE resolution identified a total of eight clusters. Through chemical gene set enrichment analysis, 287 environmental chemicals associated with JIA were identified. Conclusion By integrating TWAS and mRNA expression profiles, genes, biological pathways, and environmental chemicals associated with JIA were identified. Our findings provide new insights into the pathogenesis of JIA, including candidate genetic and environmental factors contributing to its onset and progression.

Abstract To elevate the accuracy of diagnostic results, CNV-seq is usually performed simultaneously with karyotyping or QF-PCR. Although several studies have investigated the performance of the combined use of CNV-seq with karyotyping or QF-PCR, there have been no reports focusing on the comparison of these 2 diagnostic strategies. In our study, 2507 pregnant women were included to investigate these 2 strategies. The detection rates of foetal genetic abnormalities and turnaround time were compared between these 2 groups. Moreover, the detection rates of foetal genetic abnormalities in different indications were analyzed. Our results unveiled that the detection rates of numerical chromosomal abnormalities were nearly the same in these 2 groups. In addition to numerical chromosomal abnormalities, 39 balanced karyotypic changes and chromosome polymorphisms were detected via the combined use of karyotyping and CNV-seq. Further investigation revealed that the vast majority of these karyotypic changes were inherited from parents. Compared with the karyotyping group, the combination of QF-PCR and CNV-seq reduced the reporting time from 31.593 ± 4.944 days to 11.460 ± 4.894 days. Meanwhile, NIPT, maternal serum screening and ultrasound scan significantly improved the detection of foetal genetic abnormalities. In conclusion, our results revealed that parental karyotyping is a useful supplementary method for CNV-seq and systematic prenatal examinations improved the detection of foetal genetic defects.

AIM: To analyse the prevalence and risk factors of dry eye among children aged 7-14 years in myopia prevention and control clinic.METHODS:A total of 222 children aged 7-14 years in myopia prevention and control clinic from December 2021 to February 2022 were included. General data of included children were collected, assessing the prevalence of dry eye by the ocular surface disease index(OSDI)scale and Keratograph 5M, and analyzing risk factors for dry eye occurrence by Logistic regression model.RESULTS:The prevalence of dry eye in children in myopia prevention and control clinic was 27.9%. Logistic Regression analysis showed that, allergic conjunctivitis(OR=2.31, 95%CI=1.12-4.78, P=0.02), refractive error(OR=5.57, 95%CI=2.40-12.94, P2h per day(OR=2.74, 95%CI=1.11-6.78, P=0.03), time of playing games >2h per day(OR=2.33, 95%CI=1.12-4.84, P=0.02), outdoor activity time ≤2h per day(OR=4.28, 95%CI=2.02-9.07, P

Stock index is an indicator that describes the changes in the total price level of the stock market, and it is susceptible to many dynamic factors, with such characteristics as high dimension, uncertainty, non-linearity, time delay, complexity, etc., resulting in abnormal and missing values in stock index data, which will lead to instability or unreliability of the stock index tracking model. In order to solve these problems, we take the historical stock index as the input, model the internal dynamic changes of features, and learn the change rule. Firstly, we introduce an attention mechanism, that is, to assign different weights to the implicit state of the long short term memory network (LSTM) through mapping weights and learning parameters. We further propose a stock index data preprocessing model of the LSTM based on the attention mechanism. Secondly, the group method of data handling type neural networks (GMDH-NN) is a self-organizing data mining technology, which is especially suitable for modeling complex systems. So we choose a discrete form of Kolmogorov-Gabor ( $K-G$ ) polynomial of the first-order as the reference function of GMDH-NN to establish the general relationship between input and output variables. We further present a deep evolutionary GMDH polynomial neural network (DGMDH) to perform stock index tracking. Moreover, for a high-dimensional stock index dataset, the traditional external criterion can no longer meet the needs of reality, so we propose a tracking error external criterion (TEEC) for stock indices, which is based on the difference between allocation yield and target yield. The TEEC provides better information for selecting the optimal complex DGMDH model. Our experiments clearly show the effectiveness of our methodology.

A hybrid drive wind turbine equipped with a speed regulating differential mechanism can generate electricity at the grid frequency by an electrically excited synchronous generator without requiring fully or partially rated converters. This mechanism has extensively been studied in recent years. To enhance the transient operation performance and low-voltage ride-through capacity of the proposed hybrid drive wind turbine, we aim to synthesize an advanced control scheme for the flexible regulation of synchronous generator excitation based on fractional-order sliding mode theory. Moreover, an extended state observer is constructed to cooperate with the designed controller and jointly compensate for parametric uncertainties and external disturbances. A dedicated simulation model of a 1.5 MW hybrid drive wind turbine is established and verified through an experimental platform. The results show satisfactory model performance with the maximum and average speed errors of 1.67% and 1.05%, respectively. Moreover, comparative case studies are carried out considering parametric uncertainties and different wind conditions and grid faults, by which the superiority of the proposed controller for improving system on-grid operation performance is verified.

Topic modelling is important for tackling several data mining tasks in information retrieval. While seminal topic modelling techniques such as Latent Dirichlet Allocation (LDA) have been proposed, the ubiquity of social media and the brevity of its texts pose unique challenges for such traditional topic modelling techniques. Several extensions including auxiliary aggregation, self aggregation and direct learning have been proposed to mitigate these challenges, however some still remain. These include a lack of consistency in the topics generated and the decline in model performance in applications involving disparate document lengths. There is a recent paradigm shift towards neural topic models, which are not suited for resource-constrained environments. This paper revisits LDA-style techniques, taking a theoretical approach to analyse the relationship between word co-occurrence and topic models. Our analysis shows that by altering the word co-occurrences within the corpus, topic discovery can be enhanced. Thus we propose a novel data transformation approach dubbed DATM to improve the topic discovery within a corpus. A rigorous empirical evaluation shows that DATM is not only powerful, but it can also be used in conjunction with existing benchmark techniques to significantly improve their effectiveness and their consistency by up to 2 fold.

Background & Aims: Liver macrophage-mediated inflammation contributes to the pathogenesis of the nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Odd skipped-related 1 (Osr1) is a putative transcription factor previously reported to be involved in NASH progression; however, the underlying mechanisms remain unknown. The current study focused on the role of Osr1 in macrophage polarization and metabolism and its associated functions in the inflammation-induced pathogenesis of NASH. Methods: OSR1/Osr1 expression patterns were compared in normal and NASH patients and mouse livers. NASH was established and compared between hepatocyte-specific Osr1 knockout (Osr1ΔHep), macrophage-specific Osr1 knockout (Osr1ΔMφ), and wild-type (Osr1F) mice fed with 3 different chronic obesogenic diets and methionine choline-deficient diet. Using genetic and therapeutic strategies in vitro and in vivo, the downstream targets of Osr1 and the associated mechanisms in inflammation-induced NASH were established. Results: Osr1 was expressed in both hepatocytes and macrophages and exhibited different expression patterns in NASH. In NAFLD and NASH murine models, deleting Osr1 in myeloid cells (Osr1ΔMφ), but not hepatocytes, aggravated steatohepatitis with pronounced liver inflammation. Myeloid Osr1 deletion resulted in a polarization switch toward a pro-inflammatory phenotype associated with reduced oxidative phosphorylation activity. These inflamed Osr1ΔMφ macrophages promoted steatosis and inflammation in hepatocytes via cytokine secretion. We identified 2 downstream transcriptional targets of Osr1, c-Myc, and PPARγ and established the Osr1-PPARγ cascade in macrophage polarization and liver inflammation by genetic study and rosiglitazone treatment in vivo. We tested a promising intervention strategy targeting Osr1-PPARγ by AAV8L-delivered Osr1 expression or rosiglitazone that significantly repressed NAFLD/NASH progression in Osr1F and Osr1ΔMφ mice. Conclusions: Myeloid Osr1 mediates liver immune homeostasis and disrupting Osr1 aggravates the progression of NAFLD/NASH.

Abstract In recent years, a large number of studies have shown that the subcellular localization of long non-coding RNAs (lncRNAs) can bring crucial information to the recognition of lncRNAs function. Therefore, it is of great significance to establish a computational method to accurately predict the subcellular localization of lncRNA. Previous prediction models are based on low-level sequences information and are troubled by the few samples problem. In this study, we propose a new prediction model, GM-lncLoc, which is based on the initial information extracted from the lncRNA sequence, and also combines the graph structure information to extract high level features of lncRNA. In addition, the training mode of meta-learning is introduced to obtain meta-parameters by training a series of tasks. With the meta-parameters, the final parameters of other similar tasks can be learned quickly, so as to solve the problem of few samples in lncRNA subcellular localization. Compared with the previous methods, GM-lncLoc achieved the best results with an accuracy of 93.4 and 94.2% in the benchmark datasets of 5 and 4 subcellular compartments, respectively. Furthermore, the prediction performance of GM-lncLoc was also better on the independent dataset. It shows the effectiveness and great potential of our proposed method for lncRNA subcellular localization prediction. The datasets and source code are freely available at https://github.com/JunzheCai/GM-lncLoc .

Designing scaled electronic devices for neuromorphic applications remains a challenge. Here, Zhang et al. develop an artificial molecular synapse based on self-assembled peptide molecule monolayer whose conductance can be dynamically modulated and used for waveform recognition.

Abstract Background T cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer. Methods We previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule. ET019003 cells were tested in preclinical studies followed by a phase 1 clinical trial. Results ET019003 cells produced less cytokines but retained comparable antitumor potency than ET190L1-CAR-T cells in vivo and in vitro. In the first-in-human trial, eight patients with relapsed or refractory DLBCL were treated. CRS of grade 1 was observed in three (37.5%) patients; ICANS of grade 3 was noted in one (12.5%) patient. Elevation of serum cytokines after ET019003 infusion was almost modest. With a median follow-up of 34 (range 6–38) months, seven (87.5%) patients attained clinical responses and six (75%) achieved complete responses (CR). OS, PFS and DOR at 3 years were 75.0%, 62.5%, and 71.4%, respectively. Notably, patient 1 with primary CNS lymphoma did not experience CRS or ICANS and got an ongoing CR for over 3 years after infusion, with detectable ET019003 cells in CSF. ET019003 showed striking in vivo expansion and persisted in 50% of patients at 12 months. Three patients received a second infusion, one for consolidation therapy after CR and two for salvage therapy after disease progression, but no response was observed. ET019003 expansion was striking in the first infusion, but poor in the second infusion. Conclusions CD19-specific γ/δ TCR-T cells, ET019003, had a good safety profile and could induce rapid responses and durable CR in patients with relapsed or refractory DLBCL, even primary CNS lymphoma, presenting a novel and potent therapeutic option for these patients. Trial registration: NCT04014894.

Abstract Background Behavioral variant frontotemporal dementia (bvFTD) is predominantly considered a dysfunction in cortico-cortical transmission, with limited direct investigation of cortical-subcortical transmission. Thus, we aimed to characterize the metabolic connectivity between areas of the limbic cortico-striato-thalamic-cortical (CSTC) circuit in presymptomatic and symptomatic bvFTD patients. Methods Thirty-three bvFTD patients and 33 unrelated healthy controls were recruited for this study. Additionally, six asymptomatic carriers of the MAPT P301L mutation were compared with 12 non-carriers who were all from the same family of bvFTD. Each participant underwent neuropsychological assessment, genetic testing, and a hybrid PET/MRI scan. Seed-based metabolic connectivity based on [18F]-fluorodeoxyglucose PET between the main components within the limbic CSTC circuit was explored according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Results BvFTD patients exhibited reduced metabolic connectivity between the relays in the limbic CSTC circuit, which included the frontal region (ventromedial prefrontal cortex, orbitofrontal cortex, rectus gyrus, and anterior cingulate cortex), the limbic striatum, and thalamus compared to controls. In the bvFTD patients, the involvement of the limbic CSTC circuit was associated with the severity of behavior disruption, as measured by the frontal behavior inventory, the disinhibition subscale, and the apathy subscale. Notably, asymptomatic MAPT carriers had weakened frontostriatal connectivity but enhanced striatothalamus and thalamofrontal connectivity within the limbic CSTC circuit compared with noncarriers. Conclusion These findings suggested that aberrant metabolic connectivity within the limbic CSTC circuit is present in symptomatic and even asymptomatic stages of bvFTD. Thus, metabolic connectivity patterns could be used as a potential biomarker to detect the presymptomatic stage and track disease progression.

Our previous study suggested that hypomethylation of perforin promoter of CD4 + T cells might be involved in the pathogenesis of autoimmune emphysema of rats. Whether transfer of this kind of cells hypomethylated in vitro into naive immunocompetent rats also results in emphysema is unknown yet. To test the hypothesis above, thirty Sprague Dawley (SD) rats were randomly divided into three groups: a model group (n = 10), a normal control group (n = 10) and a sham operation group (n = 10). In the model group, spleen-derived CD4 + T cells of normal rats were treated with 5-azacytidine (5-Aza), complete Freund’s adjuvant and Phosphate Buffered Saline (PBS), then transferred into naive immunocompetent rats. The normal control group was injected with CD4 + T lymphocytes from spleens of normal rats and the same amount of adjuvant and PBS as above. In sham operation group, normal rats were injected intraperitoneally with complete Freund’s adjuvant and PBS. Histopathological evaluations (mean linear Intercept (MLI) and mean alveolar numbers (MAN)), anti-endothelial cell antibodies (AECA) in serum and bronchoalveolar lavage fluid (BALF), lung vascular endothelial growth factor (VEGF)), the apoptotic index (AI) of alveolar septal cells and the methylation levels of perforin promoter of CD4 + T cells were investigated. The levels of the methylation above and MAN were lower in the model group than in the control and the sham operation group, while the AECA in serum and BALF, VEGF, MLI and the AI were greater (all p

Seismic data interpolation, especially irregularly sampled data interpolation, is a critical task for seismic processing and subsequent interpretation. Recently, with the development of machine learning and deep learning, convolutional neural networks (CNNs) are applied for interpolating irregularly sampled seismic data. CNN based approaches can address the apparent defects of traditional interpolation methods, such as the low computational efficiency and the difficulty on parameters selection. However, current CNN based methods only consider the temporal and spatial features of irregularly sampled seismic data, which fail to consider the frequency features of seismic data, i.e., the multi-scale features. To overcome these drawbacks, we propose a wavelet-based convolutional block attention deep learning (W-CBADL) network for irregularly sampled seismic data reconstruction. We firstly introduce the discrete wavelet transform (DWT) and the inverse wavelet transform (IWT) to the commonly used U-Net by considering the multi-scale features of irregularly sampled seismic data. Moreover, we propose to adopt the convolutional block attention module (CBAM) to precisely restore sampled seismic traces, which could apply the attention to both channel and spatial dimensions. Finally, we adopt the proposed W-CBADL model to synthetic and pre-stack field data to evaluate its validity and effectiveness. The results demonstrate that the proposed W-CBADL model could reconstruct irregularly sampled seismic data more effectively and more efficiently than the state-of-the-art contrastive CNN based models.

Abstract Background Colorectal cancer (CRC), a commonly diagnosed cancer often develops slowly from benign polyps called adenoma to carcinoma. Altered gut microbiota is implicated in colorectal carcinogenesis. It is warranted to find non-invasive progressive microbiota biomarkers that can reflect the dynamic changes of the disease. This study aimed to identify and evaluate potential progressive fecal microbiota gene markers for diagnosing advanced adenoma (AA) and CRC. Results Metagenome-wide association was performed on fecal samples from different cohorts of 871 subjects (247 CRC, 234 AA, and 390 controls). We characterized the gut microbiome, identified microbiota markers, and further constructed a colorectal neoplasms classifier in 99 CRC, 94 AA, and 62 controls, and validated the results in 185 CRC, 140 AA, and 291 controls from 3 independent cohorts. 21 species and 277 gene markers were identified whose abundance was significantly increased or decreased from normal to AA and CRC. The progressive gene markers were distributed in metabolic pathways including amino acid and sulfur metabolism. A diagnosis model consisting of four effect indexes was constructed based on the markers, the sensitivities of the Adenoma Effect Index 1 for AA, Adenoma Effect Index 2 for high-grade dysplasia (HGD) adenoma were 71.3% and 76.5%, the specificities were 90.5% and 90.3%, respectively. CRC Effect Index 1 for all stages of CRC and CRC Effect Index 2 for stage III–IV CRC to predict CRC yielded an area under the curve (AUC) of 0.839 (95% CI 0.804–0.873) and 0.857 (95% CI 0.793–0.921), respectively. Combining with fecal immunochemical test (FIT) significantly improved the sensitivity of CRC Effect Index 1 and CRC Effect Index 2 to 96.7% and 100%. Conclusions This study reports the successful diagnosis model establishment and cross-region validation for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene markers. The results suggested that the novel diagnosis model can significantly improve the diagnostic performance for advanced adenoma.

Abstract Background Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease caused by mutations in the Serine-Threonine Kinase 11 (STK11) gene. This study aimed to diagnose a Chinese pedigree with PJS and to expand the spectrum of STK11 variants. Methods We performed an inductive analysis of clinical features, gastrointestinal endoscopy, radiologic imaging, and pathological findings in a Chinese family with PJS. Whole-exome sequencing (WES), Sanger sequencing, and STK11 protein 3D structure prediction were performed for establishing a molecular diagnosis. Results The proband, her mother, and grandfather presented with pigmentation spots on lips, oral mucosa, and fingers. Her mother and grandfather also had pigmentation spots on face and feet, while her brother had pigmentation spots only on the lower lip. On endoscopy, polyps were discovered in the proband, her mother, and grandfather. A novel heterozygous mutation (c.521A > C) in exon 4 of STK11 was identified in all four patients, leading to a change from histidine to proline in amino acid 174. The variable site p.H174 was highly conserved in different species on multiple sequence alignment analysis. Conclusions We diagnosed a Chinese pedigree with PJS based on clinical features, gastrointestinal endoscopy, and genetic testing results. Our results expanded the spectrum of STK11 variants, which will be helpful for genetic counseling.

Abstract Background F. nucleatum, as an important periodontal pathogen, is not only closely associated with the development of periodontitis, but also implicated in systemic diseases. Macrophages may act as an important mediator in the pathogenic process of F. nucleatum infection. As non-coding RNAs (ncRNAs) have attracted extensive attention as important epigenetic regulatory mechanisms recently, we focus on the competing endogenous RNA (ceRNA) regulatory networks to elucidate the pathogenesis of F. nucleatum-associated diseases. Results We screen abnormally expressed mRNAs, miRNAs, lncRNAs and circRNAs in macrophages after F. nucleatum infection via the whole transcriptome sequencing technology, including 375 mRNAs, 5 miRNAs, 64 lncRNAs, and 180 circRNAs. The accuracy of RNA-seq and microRNA-seq result was further verified by qRT-PCR analysis. GO and KEGG analysis show that the differentially expressed genes were mainly involved in MAPK pathway, Toll-like receptor pathway, NF-κB pathway and apoptosis. KEGG disease analysis reveals that they were closely involved in immune system diseases, cardiovascular disease, cancers, inflammatory bowel disease (IBD) et al. We constructed the underlying lncRNA/circRNA-miRNA-mRNA networks to understand their interaction based on the correlation analysis between the differentially expressed RNAs, and then screen the core non-coding RNAs. In which, AKT2 is controlled by hsa_circ_0078617, hsa_circ_0069227, hsa_circ_0084089, lncRNA NUP210, lncRNA ABCB9, lncRNA DIXDC1, lncRNA ATXN1 and lncRNA XLOC_237387 through miR-150-5p; hsa_circ_0001165, hsa_circ_0008460, hsa_circ_0001118, lncRNA XLOC_237387 and lncRNA ATXN1 were identified as the ceRNAs of hsa-miR-146a-3p and thereby indirectly modulating the expression of MITF. Conclusions Our data identified promising candidate ncRNAs responsible for regulating immune response in the F. nucleatum-associated diseases, offering new insights regarding the pathogenic mechanism of this pathogen.

Abstract Background Unhealthy behaviors of coronary heart disease (CHD) patients are closely related to the occurrence of major heart events, which increases the readmission rate and brings a heavy economic burden to families and society. Therefore, it is necessary for health care workers to take active preventive and therapeutic measures to keep or establish healthy behaviors of patients. Positive psychological intervention has been proved to be effective, but it has not been reported in the field of CHD in China. The purpose of this study is to explore the effects of positive event recording based on positive psychology on the healthy behaviors, readmission rate, and anxiety of patients with CHD, in order to provide new ideas for the development of secondary prevention strategies for CHD. Methods This is a prospective, single-center, randomized controlled trial (RCT). The subjects will be enrolled from the Department of Cardiology, the First Affiliated Hospital of Soochow University. There are 80 cases in total; according to the random number table, the subjects are randomly divided into the intervention group (n = 40) and the control group (n = 40). The patients in the intervention group will receive the intervention of recording positive events once a week for 3 months, while the patients in the control group receive conventional nursing. The primary outcomes will include healthy behaviors, readmission rate, and anxiety, and the secondary outcomes will include psychological capital, subjective well-being, and corresponding clinical laboratory indicators. The protocol was approved by the Medical Ethics Committee of Soochow University (approval no. SUDA20200604H01) and is performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. All participants provide written informed consent. Discussion This study will verify whether positive event recording based on positive psychology can make patients maintain healthy behaviors, reduce readmission rate, and improve anxiety after PCI. Then, this study will provide new ideas and references for the development of secondary prevention strategies for patients with CHD. Trial registration Chinese Clinical Trials Registry 2000034538. Registered on 10 July 2020.

Comprehensive annotating of cell types in spatially resolved transcriptomics to understand biological processes at the single cell level remains challenging. Here the authors introduce Spatial-ID, a supervision-based cell typing method, that combines the existing knowledge of reference single-cell RNA-seq data and the spatial information of spatially resolved transcriptomics data.

Abstract Sodium metal has been regarded as the potential alternative for metal batteries owing to its advantages of high theoretical capacity and abundant reserves. Nevertheless, propagation of Na dendrites can boost the interfacial instability of Na metal, retarding its practical implementation. Thus, the Na–Ga alloy layer is designed and fabricated by in situ rolling of metal Ga on the surface of Na metal. This alloy layer possesses good sodiophilicity, which can effectively protect Na metal and favor the uniform Na+ deposition, obtaining the inhibition of Na dendrites growth. Consequently, the symmetric cells assembled by the alloy‐layer protected Na metal electrodes (NGAL‐Na||NGAL‐Na) have a long lifetime (468 h) even under a high plating/stripping capacity of 6 mAh cm−2 in carbonate electrolyte. The full battery of NGAL‐Na||Na3V2(PO4)3 is able to sustain an excellent rate capability of 100 mAh g−1 after 500 cycles at 10 C under ambient temperature. This work provides a new route to prevent metal anodes from severe dendrite growth, and paves the way toward safer and stable‐performing metal‐based rechargeable batteries.

Characterisation of macrophages from human carotid artery plaques and in vitro assays reveal that macrophages regulate vascular smooth muscle cell function during atherosclerosis progression through the IL-1β/STAT3 axis.

Background Prediction of delivery is important for assessing due dates, providing adequate prenatal care, and suggesting appropriate interventions in preterm and post-term pregnancies. Recent metabolomic findings suggested that the temporal abundance information of metabolome can be used to predict delivery timing with high accuracy in a cohort of healthy women. However, a targeted and quantitative assay is required to further validate the clinical performance and utility of this group of metabolomic candidates in delivery prediction with a larger and independent cohort.Method LC-MS/MS quantitative assays were applied to determine the plasma concentrations of four steroid metabolites, including oestriol-16-glucuronide (E3-16-Gluc), 17-alpha-hydroxyprogesterone (17-OHP), tetrahydrodeoxycorticosterone (THDOC), and androstane-3,17-diol (A-3,17-Diol) in asymptomatic women of singleton pregnancies (≥30th gestational weeks). Subsequent statistical analysis was conducted to assess the performance of the above candidates in delivery prediction.Result Using LC-MS/MS, four steroids were separated and quantified in 5.5 min. The coefficients of variation (CVs) of the four analytes at the lower limit of quantification ranged from 7.9% to 14.6%, with the R2 values greater than 0.990 in the calibration curves. Of the 585 recruited pregnant women who ended up with spontaneous delivery, 17.1% and 82.9% of the subjects delivered within and after 7 days since plasma collection, respectively. In the receiver operator curve analysis, the gestational age-adjusted area under the curve of the combined measurements of E3-16-Gluc and 17-OHP was 0.69 (95% CI: 0.60–0.76), with the sensitivity of 87.0% (95% CI: 78.8%–92.9%) and specificity of 60.2% (95% CI: 55.7%–64.6%). Moreover, the positive and the negative predictive values were 28.3%–34.0% and 93.1%–97.4% respectively for this combined panel.Conclusion We performed analytical and clinical validation of a quantitation LC-MS/MS panel for the four steroids in the plasma of pregnant women. The steroid metabolites panel of E3-16-Gluc and 17-OHP was potentially useful for predicting delivery within one week in asymptomatic women of singleton pregnancies. Key messagesA quantitative LC-MS/MS assay for determining the plasma levels of 17-OHP, THDOC, A-3,17-Diol and E3-16-Gluc was developed and validated, in order to evaluate their predictive performance in asymptomatic delivery of singleton pregnancy. The levels of E3-16-Gluc and 17-OHP were found to be significantly elevated at the time of sampling in women that delivered within one week and their combinational testing may be potentially useful in delivery prediction.

Dynamic changes of the paired heavy and light chain B cell receptor (BCR) repertoire provide an essential insight into understanding the humoral immune response post-SARS-CoV-2 infection and vaccination. However, differences between the endogenous paired BCR repertoire kinetics in SARS-CoV-2 infection and previously recovered/naïve subjects treated with the inactivated vaccine remain largely unknown. We performed single-cell V(D)J sequencing of B cells from six healthy donors with three shots of inactivated SARS-CoV-2 vaccine (BBIBP-CorV), five people who received the BBIBP-CorV vaccine after having recovered from COVID-19, five unvaccinated COVID-19 recovered patients and then integrated with public data of B cells from four SARS-CoV-2-infected subjects. We discovered that BCR variable (V) genes were more prominently used in the SARS-CoV-2 exposed groups (both in the group with active infection and in the group that had recovered) than in the vaccinated groups. The VH gene that expanded the most after SARS-CoV-2 infection was IGHV3-33, while IGHV3-23 in the vaccinated groups. SARS-CoV-2-infected group enhanced more BCR clonal expansion and somatic hypermutation than the vaccinated healthy group. A small proportion of public clonotypes were shared between the SARS-CoV-2 infected, vaccinated healthy, and recovered groups. Moreover, several public antibodies had been identified against SARS-CoV-2 spike protein. We comprehensively characterize the paired heavy and light chain BCR repertoire from SARS-CoV-2 infection to vaccination, providing further guidance for the development of the next-generation precision vaccine.

Melioidosis is an infectious disease caused by Burkholderia pseudomallei (Bp), a gram-negative bacillus. Sepsis is the most prevalent type of melioidosis. Due to factors such as lack of precision and slow presentation of bacterial culture tests, the misdiagnosis rate could exceed 100 per cent. Therefore, more reliable, and adaptable diagnostic methods are urgently needed. Weighted gene co-expression network analysis (WGCNA) was employed to screen the featured modules specially expressed in sepsis patients caused by Bp. Two representative co-expression modules were selected to perform gene ontology(GO) and KEGG analysis using ClusterProfiler package based on R language. We found that antigen processing and presentation of exogenous peptide antigen via MHC class I pathway, cytosol to ER transport and cell killing related pathways enriched in darkmagenta module which significantly correlated with the sepsis caused by Bp. Eventually, a diagnostic 6-mRNA signature consisting of ASPHD2, LAP3, SEPT4, FAM26F, WARS and LGALS3BP was identified, which could discern the sepsis caused by Bp compared with other organisms. This will provide a new insight in screening markers for early detection of sepsis caused by Bp, and the interaction between pathogens and hosts. This should shed light on the early detection of Bp-caused infectious diseases.

The inversion of gas hydrate saturation is a critical procedure in the evaluation of hydrate reservoirs. In this paper, a theoretical model for a borehole acoustic wavefield excited by multipole sources is established for the first time. On this basis, the attenuation of the dipole flexural waves is obtained, and in combination with the results of sensitivity analysis, an approach for inverting natural gas hydrates using the attenuation characteristics of the dipole flexural wave is proposed. The results of the sensitivity analysis demonstrate that the attenuation of the dipole flexural wave is sensitive to gas hydrate saturation. Numerical results derived from synthetic logging data are provided to illustrate the viability of the inversion of gas hydrate saturation. Even when significant noise is introduced into the receiver signal arrays, the inversion method remains stable and accurately assesses gas hydrate saturation. The correctness and effectiveness of the proposed approach are substantiated through the processing of numerical simulation data. This work provides a potent processing approach for evaluating reservoir hydrate saturation utilizing acoustic well-logging information.

With the rapid growth of the photovoltaic industry, fire incidents in photovoltaic systems are becoming increasingly concerning as they pose a serious threat to their normal operation. Research findings indicate that direct current (DC) fault arcs are the primary cause of these fires. DC arcs are characterized by high temperature, intense heat, and short duration, and they lack zero crossing or periodicity features. Detecting DC fault arcs in intricate photovoltaic systems is challenging. Hence, researching DC fault arcs in photovoltaic systems is of crucial significance. This paper discusses the application of mathematical morphology for detecting DC fault arcs. The system utilizes a multi-stage mathematical morphology filter, and experimental results have shown its effective extraction of fault arc features. Subsequently, we propose a method for detecting DC fault arcs in photovoltaic systems using a cyclic neural network, which is well-suited for time series processing tasks. By combining multiple features extracted from experiments, we trained the neural network and achieved high accuracy. This experiment demonstrates that our recurrent neural network (RNN) based scheme for DC fault arc recognition has significant reference value and implications for future research. The ROC curve on the test set approaches 1 from the initial state, and the accuracy on the test set remains at 98.24%, indicating the strong robustness of the proposed model.

In order to solve such as difficulties in backfilling narrow foundation trenches in engineering, it was proposed to use alkali-activated slag cement (AASC) instead of traditional Portland cement to solidify silt and form AASC fluidized solidified soil. The effect of the content of AASC and the curing period on fluidized solidified soil has been studied by unconfined compression strength test, SEM and EDS. Moreover, the root cause for the improvement of the strength by the microstructure was explored. The results showed that: The fluidity increased first and then decreased with the increase of the content of AASC; 40% was the optimal content; in the same curing period, the unconfined compression strength increased with the increase of the content; 40% was the optimal content; the soil with different contents could reach the most of the 28d strength on Day 7; AASC generated a lot of low-Ca/Si C-S-H gel that consolidated soil particles into a denser structure. These results provide a theoretical basis for the application of AASC in fluidized solidified soil engineering.

As an important barrier between the cytoplasm and the microenvironment of the cell, the cell membrane is essential for the maintenance of normal cellular physiological activities. An abnormal cell membrane is a crucial symbol of body dysfunction and the occurrence of variant diseases; therefore, the visualization and monitoring of biomolecules associated with cell membranes and disease markers are of utmost importance in revealing the biological functions of cell membranes. Due to their biocompatibility, programmability, and modifiability, DNA nanomaterials have become increasingly popular in cell fluorescence imaging in recent years. In addition, DNA nanomaterials can be combined with the cell membrane in a specific manner to enable the real-time imaging of signal molecules on the cell membrane, allowing for the real-time monitoring of disease occurrence and progression. This article examines the recent application of DNA nanomaterials for fluorescence imaging on cell membranes. First, we present the conditions for imaging DNA nanomaterials in the cell membrane microenvironment, such as the ATP, pH, etc. Second, we summarize the imaging applications of cell membrane receptors and other molecules. Finally, some difficulties and challenges associated with DNA nanomaterials in the imaging of cell membranes are presented.

In August 2022, Pakistan experienced an unprecedented precipitation event that caused significant damage. Analysis of the observations reveals that this extreme rainfall is primarily driven by anomalous atmospheric zonal advection, resulting in an anomalous water vapor concentration in Pakistan. The climatological meridional advection also contributes to this flooding. Anomalous easterly winds and low-level vertical convection combine to be critical factors contributing to the moisture concentration over the country. Further investigation identifies the air-sea interaction over the tropical Indian Ocean and abnormal warming over the Arabian Sea are crucial factors influencing this extreme flooding event. The concurrent occurrence of a negative Indian Ocean Dipole event and the warming sea surface temperature anomalies in the northern Arabian Sea intensifies the easterly winds over Pakistan, helping to transfer the anomalous water vapor from the remote region into Pakistan, ultimately contributing to the extreme flooding in 2022.

Annex VI of the International Convention for the Prevention of Pollution from Ships (MARPOL Convention), adopted in October 2008, was dedicated to addressing environmental issues caused by ships, especially in ports, inland waterways, and some sea areas with concentrated routes and high navigational density. This study utilizes a regional-level ship dataset to assess the influences of emission-control areas (ECAs) on the ecological shipbuilding industry by fitting the policy utility through the synthetic control method and testing robustness via the difference-in-differences method. The outcomes of this study show that the cumulative new orders for eco-designed ships in China, The Netherlands, Republic of Korea, the UK, and the USA increased by 3401, 81, 234, 549, and −1435, respectively, after the implementation of ECAs. Compared to the implementation of ECAs, the increases were about 32%, 20%, 41%, 66%, and −83%, respectively.

This paper presents a monocular biological microscope with colorful 3D reconstruction and an extended depth of field using an electrically tunable lens. It is based on a 4f optical system with an electrically tunable lens at the confocal plane. Rapid and extensive depth scanning while maintaining consistent magnification without mechanical movement is achieved. We propose an improved Laplacian operator that considers pixels in diagonal directions to provide enhanced fusion effects and obtain more details of the object. Accurate 3D reconstruction is achieved using the shape-from-focus method by tuning the focal power of the electrically tunable lens. We validate the proposed method by performing experiments on biological samples. The 3D reconstructed images obtained from the biological samples match the actual shrimp larvae and bee antenna samples. Two standard gauge blocks are used to evaluate the 3D reconstruction performance of the proposed method. The experimental results show that the extended depth of fields are 120 µm, 240 µm, and 1440 µm for shrimp larvae, bee tentacle samples, and gauge blocks, respectively. The maximum absolute errors are −39.9 μm and −30.6 μm for the first and second gauge blocks, which indicates 3D reconstruction deviations are 0.78% and 1.52%, respectively. Since the procedure does not require any custom hardware, it can be used to transform a biological microscope into one that effectively extends the depth of field and achieves highly accurate 3D reconstruction results, as long as the requirements are met. Such a microscope presents a broad range of applications, such as biological detection and microbiological diagnosis, where colorful 3D reconstruction and an extended depth of field are critical.

In this study, coal fly ash was functionalized, using a simple one-step process (loading with Al3+ and sulfonation), to yield a solid acid catalyst (S/Al-CFA) with strong acid sites. The catalyst was then used to produce furfural from xylose in a biphasic system (H2O(NaCl)/tetrahydrofuran). The furfural yield reached 82% at 180 °C–60 min with catalyst/xylose ratio of 0.2:1.0 (w/w). With the reaction completed, all of the components could be effectively separated, and the furfural was 97.6% pure. The cycle and regeneration of the catalyst were evaluated, and the catalyst deactivation mechanism was investigated.

Due to the depletion of fossil fuels, the demand for renewable energy has increased, thus stimulating the development of novel materials for energy conversion devices such as fuel cells. In this work, nickel nanoparticles loaded on reduced graphene oxide (Ni/rGO) with small size and good dispersibility were successfully prepared by controlling the pyrolysis temperature of the precursor at 450 °C, assisted by a microwave-assisted hydrothermal method, and exhibited enhanced electrocatalytic activity towards oxygen reduction reaction (ORR). Additionally, the electron enrichment on Ni NPs was due to charge transfer from the rGO support to metal nickel, as evidenced by both experimental and theoretical studies. Metal–support interactions between nickel and the rGO support also facilitated charge transfer, contributing to the enhanced ORR performance of the composite material. DFT calculations revealed that the first step (from O2 to HOO*) was the rate-determining step with an RDS energy barrier lower than that of the Pt(111), indicating favorable ORR kinetics. The HOO* intermediates can be transferred onto rGO by the solid-phase spillover effect, which reduces the chemical adsorption on the nickel surface, thereby allowing continuous regeneration of active nickel sites. The HO2− intermediates generated on the surface of rGO by 2e− reduction can also efficiently diffuse towards the nearby Ni surface or the interface of Ni/rGO, where they can be further rapidly reduced to OH−. This mechanism acts as the pseudo-four-electron path on the RRDE. Furthermore, Ni/rGO-450 demonstrated superior stability, methanol tolerance, and durability compared to a 20 wt% Pt/C catalyst, making it a cost-effective alternative to conventional noble metal ORR catalysts for fuel cells or metal–air batteries.

As one of the major water supply systems for inland rivers, especially in arid and semi-arid regions, snow cover strongly affects hydrological cycles. In this study, remote sensing datasets combined with in-situ observation data from a route survey of snow cover were used to investigate the changes in snow cover parameters on the Chinese Altai Mountains from 2000 to 2022, and the responses of snow cover to climate and hydrology were also discussed. The annual snow cover frequency (SCF), snow cover area, snow depth (SD), and snow density were 45.03%, 2.27 × 104 km2, 23.4 cm, and ~0.21 g·cm−3, respectively. The snow water equivalent ranged from 0.58 km3 to 1.49 km3, with an average of 1.12 km3. Higher and lower SCF were mainly distributed at high elevations and on both sides of the Irtysh river. The maximum and minimum snow cover parameters occurred in the Burqin River Basin and the Lhaster River Basin. In years with high SCF, abnormal westerly airflow was favorable for water vapor transport to the Chinese Altai Mountains, resulting in strong snowfall, and vice versa in years with low SCF. There were significant seasonal differences in the impact of temperature and precipitation on regional SCF changes. The snowmelt runoff ratios were 11.2%, 25.30%, 8.04%, 30.22%, and 11.56% in the Irtysh, Kayit, Haba, Kelan, and Burqin River Basins. Snow meltwater has made a significant contribution to the hydrology of the Chinese Altai Mountains.

Both an offender’s home area and their daily activity area can impact the spatial distribution of crime. However, existing studies are generally limited to the influence of the offender’s home area and its immediate surrounding areas, while ignoring other activity spaces. Recent studies have reported that the routine activities of an offender are similar to those of the residents living in the same vicinity. Based on this finding, our study proposed a flow-based method to measure how offenders are distributed in space according to the spatial mobility of the residents. The study area consists of 2643 communities in ZG City in southeast China; resident flows between every two communities were calculated based on mobile phone data. Offenders’ activity locations were inferred from the mobility flows of residents living in the same community. The estimated count of offenders in each community included both the offenders living there and offenders visiting there. Negative binomial regression models were constructed to test the explanatory power of this estimated offender count. Results showed that the flow-based offender count outperformed the home-based offender count. It also outperformed a spatial-lagged count that considers offenders from the immediate neighboring communities. This approach improved the estimation of the spatial distribution of offenders, which is helpful for crime analysis and police practice.

An unstable influenza genome leads to the virus resistance to antiviral drugs that target viral proteins. Thus, identification of host factors essential for virus replication may pave the way to develop novel antiviral therapies. In this study, we investigated the roles of the poly(ADP-ribose) polymerase enzyme, tankyrase1 (TNKS1) and the endogenous small noncoding RNA, miR-9-1 in influenza A virus (IAV) infection. Increased expression of TNKS1 was observed in IAV-infected human lung epithelial cells and mouse lungs. TNKS1 knock-down by RNA interference repressed influenza viral replication. A screen using TNKS1 3’-untranslation region (3’-UTR) reporter assays and predicted microRNAs identified that miR-9-1 targeted TNKS1. Overexpression of miR-9-1 reduced influenza viral replication in lung epithelial cells as measured by viral mRNA and protein levels as well as virus production. miR-9-1 induced type I interferon production and enhanced the phosphorylation of STAT1 in cell culture. The ectopic expression of miR-9-1 in the lungs of mice by using an adenoviral viral vector enhanced type I interferon response, inhibited viral replication and reduced susceptibility to IAV infection. Our results indicate that miR-9-1 is an antiinfluenza microRNA that targeting TNKS1 and enhanced cellular antiviral state.

BackgroundConfidence and appropriate care approach toward dementia among nursing staff (nurses and care assistants) are crucial manifestations of competency to deal with the complexity of dementia care in long-term care facilities (LTCFs). The purpose of this study was to investigate the confidence in dementia care and care approach among nursing staff in LTCFs in mainland China.MethodsA cross-sectional study design was utilized in LTCFs in Shandong Province, mainland China. A convenient sample included of 317 nursing staff drawn from 15 LTCFs. Survey questions included (a) demographics, (b) dementia knowledge, (c) dementia care confidence, and (d) approach to care for people with dementia. Data were analyzed with descriptive statistics. Factors associated with confidence and care approach for people with dementia were examined using Pearson’s correlation and multivariate regression analyses.ResultsDementia care confidence was generally moderate. Factors affecting confidence to care for people with dementia included educational level, months of caring dementia patients, and dementia knowledge. Most nursing staff did not use a person-centered care approach which was significantly associated with their age, dementia-learning experience, and knowledge and confidence toward caring for people with dementia.ConclusionA positive correlation was identified between confidence to care for people with dementia and nursing staff care approach. Clinical recommendations are provided to further develop education strategies tailored for nursing staff to meet the growing demand for dementia care services.

PurposeTo assess the usefulness of amide proton transfer-weighted (APTw) imaging in the differentiation of parotid gland tumors.Materials and methodsPatients with parotid gland tumors who underwent APTw imaging were retrospectively enrolled and divided into groups according to pathology. Two radiologists evaluated the APTw image quality independently, and APTw images with quality score ≥3 were enrolled. The maximum and average values of APTw imaging for tumor lesions (APTmax and APTmean) were measured. The differences in APTmax and APTmean were compared between malignant tumors (MTs) and benign tumors (BTs), as well as between MTs and pleomorphic adenomas (PAs) and between MTs and Warthin tumors (WTs). Independent-samples t-test, Kruskal–Wallis H test, and receiver operating characteristic (ROC) curve analyses were used for statistical analysis.ResultsSeventy-three patients were included for image quality evaluation. In this study, 32/73 and 29/73 parotid tumors were scored as 4 and 3, respectively. After excluding lesions with quality score ≤2 (12/73), the APTmean and APTmax of MTs were 4.15% ± 1.33% and 7.43% ± 1.61%, higher than those of BTs 2.74% ± 1.04% and 5.25% ± 1.54%, respectively (p < 0.05). The areas under the ROC curve (AUCs) of the APTmean and APTmax for differentiation between MTs and BTs were 0.819 and 0.821, respectively. MTs indicated significantly higher APTmean and APTmax values than those of PAs (p < 0.05) and WTs (p < 0.05). The AUCs of the APTmean and APTmax for differentiation between MTs and PAs were 0.830 and 0.815 and between MTs and WTs were 0.847 and 0.920, respectively.ConclusionMost APTw images for parotid tumors had acceptable image quality for APTw value evaluation. Both APTmax and APTmean can be used to differentiate MTs from BTs and to differentiate MTs from subtype parotid gland tumors.

ABSTRACT Hubei mosquito virus 2 (HMV2) is a novel mosquito virus that was first identified in 2016 in Hubei Province, China. Until now, HMV2 has been shown to be endemic in some areas of China and Japan, but its biological characteristics, epidemiology, and pathogenicity are not yet known. This report describes the detection of HMV2 in mosquitoes that were collected in Shandong Province in 2019 and presents the first isolation and molecular characterization of the virus. In this study, a total of 2,813 mosquitoes were collected and then divided into 57 pools, according to location and species. qRT-PCR and nested PCR were performed to confirm the presence of HMV2, and its genomic features, phylogenetic relationships, growth characteristics, and potential pathogenicity were further analyzed. The results showed that HMV2 was detected in 28 of the 57 mosquito pools and that the minimum infection rate (MIR) for HMV2 was 1.00% (28/2,813). A HMV2 strain and 14 viral partial sequences were obtained from the HMV2-positive pools, including one complete genome sequence. A phylogenetic analysis revealed that HMV2 from Shandong Province shared over 90% identity with other reported isolates and was closely related to the Culex inatomii luteo-like virus. IMPORTANCE Our study provided important epidemiological evidence for the epidemic of HMV2 in Shandong Province. Here, we report the first isolation and molecular characteristics of this virus and enrich our knowledge of the distribution of HMV2 in China.

Abstract Background Copy number variation sequencing (CNV‐seq) could detect most chromosomal abnormalities except polyploidy, and quantitative fluorescence polymerase chain reaction (QF‐PCR) is a supplementary method to CNV‐seq in triploid detection. This study aimed to evaluate the feasibility of sequential application of CNV‐seq and QF‐PCR in genetic analysis of miscarriage and stillbirth. Methods A total of 261 fetal specimens were analyzed by CNV‐seq, and QF‐PCR was only further performed for samples with normal female karyotype identified by CNV‐seq. Cost and turnaround time (TAT) was analyzed for sequential detection strategy. Subgroup analysis and logistic regression were carried out to evaluate the relationship between clinical characteristics (maternal age, gestational age, and number of pregnancy losses) and the occurrence of chromosomal abnormalities. Results Abnormal results were obtained in 120 of 261 (45.98%) cases. Aneuploidy was the most common abnormality (37.55%), followed by triploidy (4.98%) and pathogenic copy number variations (pCNVs) (3.45%). CNV‐seq could detect the triploidy with male karyotype, and QF‐PCR could further identify the remaining triploidy with female karyotype. In this study, we found more male triploidies than female triploidies. With the same ability in chromosomal abnormalities detection, the cost of sequential strategy decreased by 17.35% compared with combined strategy. In subgroup analysis, significant difference was found in the frequency of total chromosomal abnormalities between early abortion group and late abortion group. Results of logistic regression showed a trend that pregnant women with advanced age, first‐time abortion, and abortion earlier than 12 weeks were more likely to detect chromosomal aberrations in their products of conception. Conclusion Sequential application of CNV‐seq and QF‐PCR is an economic and practical strategy to identify chromosomal abnormalities in fetal tissue.

Summary: Meiotic crossovers are required for the faithful segregation of homologous chromosomes and to promote genetic diversity. However, it is unclear how crossover formation is regulated, especially on the XY chromosomes, which show a homolog only at the tiny pseudoautosomal region. Here, we show that ATF7IP2 is a meiosis-specific ortholog of ATF7IP and a partner of SETDB1. In the absence of ATF7IP2, autosomes show increased axis length and more crossovers; however, many XY chromosomes lose the obligatory crossover, although the overall XY axis length is also increased. Additionally, meiotic DNA double-strand break formation/repair may also be affected by altered histone modifications. Ultimately, spermatogenesis is blocked, and male mice are infertile. These findings suggest that ATF7IP2 constraints autosomal axis length and crossovers on autosomes; meanwhile, it also modulates XY chromosomes to establish meiotic sex chromosome inactivation for cell-cycle progression and to ensure XY crossover formation during spermatogenesis.

Summary: Background: Epileptiform activity is associated with worse patient outcomes, including increased risk of disability and death. However, the effect of epileptiform activity on neurological outcome is confounded by the feedback between treatment with antiseizure medications and epileptiform activity burden. We aimed to quantify the heterogeneous effects of epileptiform activity with an interpretability-centred approach. Methods: We did a retrospective, cross-sectional study of patients in the intensive care unit who were admitted to Massachusetts General Hospital (Boston, MA, USA). Participants were aged 18 years or older and had electrographic epileptiform activity identified by a clinical neurophysiologist or epileptologist. The outcome was the dichotomised modified Rankin Scale (mRS) at discharge and the exposure was epileptiform activity burden defined as mean or maximum proportion of time spent with epileptiform activity in 6 h windows in the first 24 h of electroencephalography. We estimated the change in discharge mRS if everyone in the dataset had experienced a specific epileptiform activity burden and were untreated. We combined pharmacological modelling with an interpretable matching method to account for confounding and epileptiform activity–antiseizure medication feedback. The quality of the matched groups was validated by the neurologists. Findings: Between Dec 1, 2011, and Oct 14, 2017, 1514 patients were admitted to Massachusetts General Hospital intensive care unit, 995 (66%) of whom were included in the analysis. Compared with patients with a maximum epileptiform activity of 0 to less than 25%, patients with a maximum epileptiform activity burden of 75% or more when untreated had a mean 22·27% (SD 0·92) increased chance of a poor outcome (severe disability or death). Moderate but long-lasting epileptiform activity (mean epileptiform activity burden 2% to

Alzheimer’s disease (AD), one of the leading diseases of the nervous system, is accompanied by symptoms such as loss of memory, thinking and language skills. Both mild cognitive impairment (MCI) and very mild cognitive impairment (VMCI) are the transitional pathological stages between normal aging and AD. While the changes in whole-brain structural and functional information have been extensively investigated in AD, The impaired structure–function coupling remains unknown. The current study employed the OASIS-3 dataset, which includes 53 MCI, 90 VMCI, and 100 Age-, gender-, and education-matched normal controls (NC). Several structural and functional parameters, such as the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and The ALFF/VBM ratio, were used To estimate The whole-brain neuroimaging changes In MCI, VMCI, and NC. As disease symptoms became more severe, these regions, distributed in the frontal-inf-orb, putamen, and paracentral lobule in the white matter (WM), exhibited progressively increasing ALFF (ALFFNC

Sodium metal, benefiting from its high theoretical capacity and natural abundance, is regarded as a promising anode for sodium‐metal batteries (SMBs). Unfortunately, the uncontrollable sodium dendrites formation caused from the sluggish ion‐transport kinetics and fragile solid electrolyte interphase (SEI) interlayer induces a low Coulombic efficiency and poor cycling stability. Constructing an artificial SEI interlayer with high ionic conductivity, stability, and mechanical toughness is an effective strategy for Na‐metal anode, yet it still presents major challenge for high current density and long cycling life. Herein, an artificial SEI interlayer composed of Na–Sn alloy, Sn, and Na2Te (denoted as NST) is designed via in‐situ conversion/alloying reaction of tin telluride (SnTe) with Na. Such artificial interlayer possesses rapid Na+‐transport kinetics and high Young's modulus (5.3 GPa), benefitting to even Na plating/stripping and suppressing Na dendrite growth. Owing to these merits, the symmetrical Na/NST cell presents an ultralong cycle life span over 1390 h with a small voltage hysteresis at 1 mA cm−2 with 1 mAh cm−2. And the Na3V2(PO4)3 (NVP)||Na/NST full cell exhibits a prolonged life of 1000 cycles with a high‐capacity retention of 88% at 5C. Herein, a promising strategy is provided to construct a high‐performance artificial interlayer for SMBs.

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one of the most significant biological events in cancer progression. Cancer cells generally represent a higher oxidant level, which suggests a dual therapeutic strategy by regulating redox status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, pro-oxidant therapy exhibits a great anti-cancer capability, attributing to a higher oxidant accumulation within cancer cells, whereas antioxidant therapy to restore redox homeostasis has been claimed to fail in several clinical practices. Targeting the redox vulnerability of cancer cells by pro-oxidants capable of generating excessive reactive oxygen species (ROS) has surfaced as an important anti-cancer strategy. However, multiple adverse effects caused by the indiscriminate attacks of uncontrolled drug-induced OS on normal tissues and the drug-tolerant capacity of some certain cancer cells greatly limit their further applications. Herein, we review several representative oxidative anti-cancer drugs and summarize their side effects on normal tissues and organs, emphasizing that seeking a balance between pro-oxidant therapy and oxidative damage is of great value in exploiting next-generation OS-based anti-cancer chemotherapeutics.

Hyperlipidemia is a common metabolic disorder, which can lead to obesity, hypertension, diabetes, atherosclerosis and other diseases. Studies have shown that polysaccharides absorbed by the intestinal tract can regulate blood lipids and facilitate the growth of intestinal flora. This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia.

Abstract Near‐infrared (NIR) fluorescence imaging poses significant superiority over traditional medical imaging for tumor resection, thus having attracted widely attention. However, for tiny tumor residues, it requires relative high sensitivity to determine. Here, based on persistent luminescence nanoparticles (PLNPs), an ultrasensitive nanoprobe with extraordinary tumor imaging result is developed to guide surgical removal. Persistent luminescence (PersL) is quenched in normal tissue by the outer layer of MnO2, and is recovered due to the degradation of MnO2 in tumor microenvironment, significantly improving the sensitivity of tumor imaging. Combined with the absence of background fluorescence in imaging of PLNPs, ultrahigh sensitivity is achieved. In orthotopic breast cancer model, the intraoperative tumor‐to‐normal tissue (T/NT) signal ratio of the nanoprobe is 58.8, about 9 times that of downconversion nanoparticles. The T/NT ratio of residual tumor (

Coherent technology has been employed in long-haul transmission systems in the past decade, with growing demand for capacity at ever-lower costs per bit. High-performance coherent modulators with high data rates, wide bandwidth, small footprint, and low power operation are highly desired. Toward this end, we propose a folded thin-film lithium niobate (TFLN) dual-polarization in-phase quadrature modulator featuring a low half-wave voltage of 1 V and a compact footprint of 4 × 8 mm2. To suppress RF wavefront distortion and optimize high-frequency electro-optic performance, we utilize air-bridge structures in the U-turns of the traveling-wave electrodes. As a demonstration of the long-haul transmission capacities with our device, we present driverless 703 Gb/s/λ line-rate transmissions, with a subcarrier modulation scheme, over a 1120 km single-mode fiber link. Here, for the first time, to our knowledge, our device allows for attojoule-per-bit level electrical energy consumption over transmission distances above 1000 km. The device opens opportunities for much lower-cost and capacity-intensive coherent systems that consume ultra-low power, support high data rate, and work in small spaces.