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Abstract Background Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood. Methods To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP). Results Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression. Conclusions Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.

Research shows that gamified learning experiences can effectively improve the outstanding issues of students in online learning, such as lack of continuous motivation and easy burnout, thereby improving the effectiveness of online learning. However, how to enhance the gamified learning experience in online learning, and what impact there is between the gamified learning experience and the effectiveness of online learning, remain to be further explored. This research article is based on the theory of gamified learning experience and uses structural equation modeling methodology to explore the relationship among the three dimensions of situation-based cognitive experience, collaboration-based social experience, and motivation-based subjectivity experience and the effectiveness of online learning. The results indicate that there is a significant positive correlation among the three dimensions, and all three dimensions have a significant positive impact on the online learning effectiveness. The subjective experience based on motivation has the greatest impact on the online learning effectiveness, and the other two dimensions have a significant positive impact on the online learning effectiveness. The impact on online learning effectiveness is similar. Finally, the article makes recommendations based on the research conclusions, expecting to provide a research foundation for enhancing the gamified learning experience and improving the effectiveness of online learning.

Abstract Background Severe pneumonia has consistently been associated with high mortality. We sought to identify risk factors for the mortality of severe pneumonia to assist in reducing mortality for medical treatment. Methods Electronic databases including PubMed, Web of Science, EMBASE, Cochrane Library, and Scopus were systematically searched till June 1, 2023. All human research were incorporated into the analysis, regardless of language, publication date, or geographical location. To pool the estimate, a mixed-effect model was used. The Newcastle–Ottawa Scale (NOS) was employed for assessing the quality of included studies that were included in the analysis. Results In total, 22 studies with a total of 3655 severe pneumonia patients and 1107 cases (30.29%) of death were included in the current meta-analysis. Significant associations were found between age [5.76 years, 95% confidence interval [CI] (3.43, 8.09), P

Abstract Background Extracorporeal membrane oxygenation (ECMO) is a cutting-edge life-support measure for patients with severe cardiac and pulmonary illnesses. Although there are several systematic reviews (SRs) about ECMO, it remains to be seen how quality they are and how efficacy and safe the information about ECMO they describe is in these SRs. Therefore, performing an overview of available SRs concerning ECMO is crucial. Methods We searched four electronic databases from inception to January 2023 to identify SRs with or without meta-analyses. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were used to assess the methodological quality, and evidence quality for SRs, respectively. A bubble plot was used to visually display clinical topics, literature size, number of SRs, evidence quality, and an overall estimate of efficacy. Results A total of 17 SRs met eligibility criteria, which were combined into 9 different clinical topics. The methodological quality of the included SRs in this mapping was “Critically low” to “Moderate”. One of the SRs was high-quality evidence, three on moderate, three on low, and two on very low-quality evidence. The most prevalent study used to evaluate ECMO technology was observational or cohort study with frequently small sample sizes. ECMO has been proven beneficial for severe ARDS and ALI due to the H1N1 influenza infection. For ARDS, ALF or ACLF, and cardiac arrest were concluded to be probably beneficial. For dependent ARDS, ARF, ARF due to the H1N1 influenza pandemic, and cardiac arrest of cardiac origin came to an inconclusive conclusion. There was no evidence for a harmful association between ECMO and the range of clinical topics. Conclusions There is limited available evidence for ECMO that large sample, multi-center, and multinational RCTs are needed. Most clinical topics are reported as beneficial or probably beneficial of SRs for ECMO. Evidence mapping is a valuable and reliable methodology to identify and present the existing evidence about therapeutic interventions.

Diarrheagenic Escherichia coli serotypes are associated with various clinical syndromes, yet the precise correlation between serotype and pathotype remains unclear. A major barrier to such studies is the reliance on antisera-based serotyping, which is culture-dependent, low-throughput, and cost-ineffective. We have established a highly multiplex PCR-based serotyping assay, termed the MeltArray E. coli serotyping (EST) assay, capable of identifying 163 O-antigen-encoding genes and 53 H-antigen-encoding genes of E. coli. The assay successfully identified serotypes directly from both simulated and real fecal samples, as demonstrated through spike-in validation experiments and a retrospective study. In a multi-province study involving 637 E. coli strains, it revealed that the five major diarrheagenic pathotypes have distinct serotype compositions. Notably, it differentiated 257 Shigella isolates into four major Shigella species, distinguishing them from enteroinvasive E. coli based on their distinct serotype profiles. The assay’s universality was further corroborated by in silico analysis of whole-genome sequences from the EnteroBase. We conclude that the MeltArray EST assay represents a paradigm-shifting tool for molecular serotyping of E. coli, with potential routine applications for comprehensive serotype analysis, disease diagnosis, and outbreak detection.

Radiation is one of the standard therapies for pediatric high-grade glioma (pHGG), of which the prognosis remains poor. To gain an in-depth understanding of biological consequences beyond the classic DNA damage, we treated 9 patient-derived orthotopic xenograft (PDOX) models, including one with DNA mismatch repair (MMR) deficiency, with fractionated radiations (2 Gy/day x 5 days). Extension of survival time was noted in 5 PDOX models (P < 0.05) accompanied by γH2AX positivity in >95 % tumor cells in tumor core and >85 % in the invasive foci as well as ∼30 % apoptotic and mitotic catastrophic cell death. The model with DNA MMR (IC-1406HGG) was the most responsive to radiation with a reduction of Ki-67(+) cells. Altered metabolism, including mitochondria number elevation, COX IV activation and reactive oxygen species accumulation, were detected together with the enrichment of CD133+ tumor cells. The latter was caused by the entry of quiescent G0 cells into cell cycle and the activation of self-renewal (SOX2 and BMI1) and epithelial mesenchymal transition (fibronectin) genes. These novel insights about the cellular and molecular mechanisms of fractionated radiation in vivo should support the development of new radio-sensitizing therapies.

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

The sand-bearing natural gas causes severe erosion to the components of wellhead desanders，thereby reducing production efficiency and posing safety hazards.Aiming at the serious erosion problem of key parts in desanders，the study focused on the erosion resistance of erosion resistance materials such as 42CrMo，45 steel，2Cr13，20CrMnTi，and H13 (4Cr5MoSiV1) from perspectives of erosion angle and heat treatment effects.Firstly，an erosion test platform was established to conduct erosion simulation tests.Secondly，the micro-morphology of the target materials after erosion was observed using scanning electron microscope (SEM)，and the erosion wear mechanisms were discussed.Results showed that for erosion angles between 30° and 90°，the erosion rate decreased as the angle increased.It was also found that not all materials showed improved erosion resistance following heat treatment.The erosion resistance of 2Cr13 in the quenched and tempered state was the best.The wear mode of 2Cr13，45 steel in quenched and tempered state and H13 steel in factory state during oblique impact was mainly cutting，while the wear mode during vertical impact was abrasive impact，which caused plastic deformation and detachment of the target materials.This experiment provided a reference for selecting corrosion-resistant components in desanders.

As the protective component, steel plate had attracted extensive attention because of frequently threats of explosive loads. In this paper, the evolution of microstructure and the mechanism of damage in the quasi-cracking area of steel plate subjected to explosive load were discussed and the relationships between micro defects and dynamic mechanical response were revealed. After the explosion experiment, five observation points were selected equidistant from the quasi-cracking area of the section of the steel plate along the thickness direction, and the characteristics of micro defects at the observation points were analyzed by optical microscope (OM), scanning electron microscope (SEM) and electron back-scattered diffraction (EBSD). The observation result shows that many slip bands (SBs) appeared, and the grain orientation changed obviously in the steel plate, the two were the main damage types of micro defects. In addition, cracks, peeling pits, grooves and other lager micro defects were appeared in the lower area of the plate. The stress parameters of the observation points were obtained through an effective numerical model. The mechanism of damage generation and crack propagation in the quasi-cracking area were clarified by comparing the specific impulse of each observation point with the corresponding micro defects. The result shows that the generation and expansion of micro defects are related to the stress area (i.e. the upper compression area, the neutral plane area, and the lower tension area). The micro defects gather and expand at the grain boundary, and will become macroscopic damage under the continuous action of tensile stress. Besides, the micro defects at the midpoint of the section of the steel plate in the direction away from the explosion center (i.e. the horizontal direction) were also studied. It was found that the specific impulse at these positions were much smaller than that in the thickness direction, the micro defects were only SBs and a few micro cracks, and the those decreased with the increase of the distance from the explosion center.

SignificanceAgricultural machinery serves as the fundamental support for implementing advanced agricultural production concepts. The key challenge for the future development of smart agriculture lies in how to enhance the design, manufacturing, operation, and maintenance of these machines to fully leverage their capabilities. To address this, the concept of the digital twin has emerged as an innovative approach that integrates various information technologies and facilitates the integration of virtual and real-world interactions. By providing a deeper understanding of agricultural machinery and its operational processes, the digital twin offers solutions to the complexity encountered throughout the entire lifecycle, from design to recycling. Consequently, it contributes to an all-encompassing enhancement of the quality of agricultural machinery operations, enabling them to better meet the demands of agricultural production. Nevertheless, despite its significant potential, the adoption of the digital twin for agricultural machinery is still at an early stage, lacking the necessary theoretical guidance and methodological frameworks to inform its practical implementation.ProgressDrawing upon the successful experiences of the author's team in the digital twin for agricultural machinery, this paper presents an overview of the research progress made in digital twin. It covers three main areas: The digital twin in a general sense, the digital twin in agriculture, and the digital twin for agricultural machinery. The digital twin is conceptualized as an abstract notion that combines model-based system engineering and cyber-physical systems, facilitating the integration of virtual and real-world environments. This paper elucidates the relevant concepts and implications of digital twin in the context of agricultural machinery. It points out that the digital twin for agricultural machinery aims to leverage advanced information technology to create virtual models that accurately describe agricultural machinery and its operational processes. These virtual models act as a carrier, driven by data, to facilitate interaction and integration between physical agricultural machinery and their digital counterparts, consequently yielding enhanced value. Additionally, it proposes a comprehensive framework comprising five key components: Physical entities, virtual models, data and connectivity, system services, and business applications. Each component's functions operational mechanism, and organizational structure are elucidated. The development of the digital twin for agricultural machinery is still in its conceptual phase, and it will require substantial time and effort to gradually enhance its capabilities. In order to advance further research and application of the digital twin in this domain, this paper integrates relevant theories and practical experiences to propose an implementation plan for the digital twin for agricultural machinery. The macroscopic development process encompasses three stages: Theoretical exploration, practical application, and summarization. The specific implementation process entails four key steps: Intelligent upgrading of agricultural machinery, establishment of information exchange channels, construction of virtual models, and development of digital twin business applications. The implementation of digital twin for agricultural machinery comprises four stages: Pre-research, planning, implementation, and evaluation. The digital twin serves as a crucial link and bridge between agricultural machinery and the smart agriculture. It not only facilitates the design and manufacturing of agricultural machinery, aligning them with the realities of agricultural production and supporting the advancement of advanced manufacturing capabilities, but also enhances the operation, maintenance, and management of agricultural production to better meet practical requirements. This, in turn, expedites the practical implementation of smart agriculture. To fully showcase the value of the digital twin for agricultural machinery, this paper addresses the existing challenges in the design, manufacturing, operation, and management of agricultural machinery. It expounds the methods by which the digital twin can address these challenges and provides a technical roadmap for empowering the design, manufacturing, operation, and management of agricultural machinery through the use of the digital twin. In tackling the critical issue of leveraging the digital twin to enhance the operational quality of agricultural machinery, this paper presents two research cases focusing on high-powered tractors and large combine harvesters. These cases validate the feasibility of the digital twin in improving the quality of plowing operations for high-powered tractors and the quality of grain harvesting for large combine harvesters.Conclusions and ProspectsThis paper serves as a reference for the development of research on digital twin for agricultural machinery, laying a theoretical foundation for empowering smart agriculture and intelligent equipment with the digital twin. The digital twin provides a new approach for the transformation and upgrade of agricultural machinery, offering a new path for enhancing the level of agricultural mechanization and presenting new ideas for realizing smart agriculture. However, existing digital twin for agricultural machinery is still in its early stages, and there are a series of issues that need to be explored. It is necessary to involve more professionals from relevant fields to advance the research in this area.