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Background: Checkpoint Inhibitor Pneumonitis (CIP) poses a grave risk as a life-threatening complication defined by emerging lung infiltrates in cancer patients undergoing immune checkpoint inhibitor treatment. This study aims to investigate the value of bronchoalveolar lavage (BAL) combined with metagenomic next-generation sequencing (mNGS) in the diagnosis and precision treatment of CIP for providing evidence-based medicine. Methods: This study enrolled a total of 93 patients with Checkpoint Inhibitor Pneumonitis (CIP) from a prospective clinical cohort (NCT06192303), including 35 cases of pure-type CIP (PT-CIP) and 58 cases of mixed-type CIP (MT-CIP). Logistic regression analysis was employed to identify independent risk factors for mixed-type CIP and to construct a corresponding nomogram predictive model for MT-CIP. A comprehensive microbiota atlas was further used to display the microbiota characteristics of patients with different types of CIP. Additionally, we assessed the value of BAL combined with mNGS in guiding CIP treatment by comparing the 7-day effectiveness of treatment, the intensity of antibiotic use during hospitalization, the total time to relief to grade I or below, and the proportion of resolution within three months. Findings: Univariate and multivariate logistic regression analyses indicated that the history of COPD, dyspnea, CRP, and ALC are independent risk factors for mixed-type CIP. The area under the ROC curve (AUROC) of the MT-CIP prediction model, which was constructed based on clinical indicators and BAL mNGS results, reached 0.895 (95% CI: 0.805 – 0.985, Sensitivity: 0.871, Specificity: 0.9). BALF microbiota analysis suggested the potential of porphyromonas as a characteristic genus in mixed-type CIP, showing a significant negative correlation with Absolute Eosinophil Count (AEC) in the blood. The BAL mNGS group exhibited significantly higher efficacy rates at 7 days of treatment (90.2% vs 69.0%, P

Abstract Glioblastoma multiforme (GBM) is the most therapeutically challenging primary brain tumor owing to the unique physiological structure of the blood–brain barrier. Lately, research on targeted therapy for gliomas has shifted focus toward the tumor microenvironment and local immune responses. Pyroptosis is a newly identified cellular demise characterized by the release of numerous inflammatory factors. While pyroptosis shows promise in impeding the occurrence and progression of GBM, the regulatory mechanisms governing this process in gliomas still require further investigation. The function of the Enhancer of zeste homolog 2 (EZH2) in pyroptosis remains unexplored. In this study, we discovered that 3-Deazaneplanocin A (DZNep), an inhibitor of EZH2, can induce pyroptosis in GBM in vitro experiments. Moreover, our investigation unveiled that the signal transducer and activator of transcription (STAT3) could serve as a downstream regulator influenced by EZH2, impacting pyroptosis in GBM. Following treatment with DZNep and the STAT3 inhibitor (SH-4–54), there was an elevation in the levels of pyroptosis-related factors, namely NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) and Gasdermin D (GSDMD). Moreover, simultaneous inhibition of both EZH2 and STAT3 led to the expression of inflammatory factors such as IL-1β and IL-18. In summary, we have identified that EZH2 regulates pyroptosis in GBM through STAT3, and pyroptosis could potentially be targeted for immunotherapy in GBM.

Abstract Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next‐generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26–2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67–4.50) and in a biobank meta‐analysis (OR, 1.16; 95% CI, 1.04–1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9‐edited HEK293T cell lines show that loss‐of‐function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/− mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein‐stimulated pancreatitis models, Sec16a+/− mice display heightened pancreatic inflammation and fibrosis compared to wild‐type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

BackgroundHigh altitude pulmonary edema (HAPE) is an idiopathic, noncardiogenic form of pulmonary edema that occurs at high altitudes. It is characterized by a severe clinical course and carries a significant mortality risk. Despite its clinical relevance, the molecular mechanisms underlying HAPE are not well understood.MethodsWe conducted whole-transcriptome RNA sequencing on blood samples from 6 pairs of HAPE patients and healthy controls to identify differentially expressed (DE) mRNAs, miRNAs, circRNAs, lncRNAs, along with alternative splicing (AS) events, gene fusions, and novel transcripts. To explore the regulatory dynamics, we constructed ceRNA networks and analyzed immune cell infiltration patterns, further annotating the biological functions of these transcripts. For empirical validation, we selected five circRNAs from the ceRNA network and conducted RT-qPCR on 50 paired samples. Additionally, we assessed the correlations between circRNA expression levels and clinical data to evaluate their diagnostic potential.ResultsWe observed 2,023 differentially expressed mRNAs (DEmRNAs), 84 DEmiRNAs, 200 DEcircRNAs, and 3,573 DElncRNAs. A total of 139 ‘A3SS’ events, 103 ‘A5SS’ events, 545 ‘MXE’ events, 14 ‘RI’ events, and 1,482 ‘SE’ events were identified in the AS events analysis between the two groups. Two ceRNA networks were constructed. T cells, follicular helper, and Macrophages M1 cells exhibited the strongest positive correlation (R=0.82), while naive B cells and memory B cells demonstrated the strongest negative correlation (R=-0.62). In total, the expression of three circRNAs was significantly different in a larger cohort. Hsa_circ_0058497, hsa_circ_0081006, and hsa_circ_0083220 demonstrated consistent with the RNA sequencing results. These three circRNAs strongly correlate with clinical indicators and exhibit potential as diagnostic biomarkers. Finally, we verified five genes (CXCR4, HSD17B2, ANGPTL4, TIMP3, N4BP3) that were differentially expressed in endothelial cells under normoxia and hypoxia through bioinformatics and RT-qPCR analyses.ConclusionThis study elucidates the differential expression of coding and non-coding RNAs (ncRNAs) in HAPE, identifies new transcripts and genes, and enhances our understanding of the transcriptional characteristics of HAPE. Moreover, it highlights the potential role of circRNAs in advancing the diagnosis and treatment of HAPE.

Objective The turnout friction current on-site testing and adjustment involve three major unfavorable aspects of complex processes and high risks, high professional requirements for maintenance personnel, and significant subjective component in determining numerical values, calling for enhancement of the intelligent operation and maintenance level of turnout based on various intelligent algorithms and technologies. Method The characteristics of the four stages of turnout friction current testing curve are analyzed, and an intelligent analysis system for turnout friction current is proposed. The functionality and working principle of the system are elucidated, and standard values and threshold ranges for friction current are established. Based on density clustering algorithm and breadth-first search algorithm, the system can automatically retrieve the turnout friction current value. Screenshots of the system debugging interface are presented to illustrate how the system provides operational suggestions for on-site maintenance personnel in obtaining turnout frictional current values. Result & Conclusion This intelligent system demonstrates excellent usability and achieves the predefined goals of saving maintenance time, reducing maintenance costs, and increasing maintenance efficiency.

Let GRS$ _k(\boldsymbol{\alpha}, \boldsymbol{\upsilon}) $ be a $ k $-dimensional generalized Reed-Solomon (GRS) code over $ \mathbb{F}_q $ associated with $ \boldsymbol{\alpha} = (\alpha_1, \ldots, \alpha_n) $ and $ \boldsymbol{\upsilon} = (\upsilon_1, \ldots, \upsilon_n) $. In this paper, we determined the dimension of the Euclidean hull GRS$ _k(\boldsymbol{\alpha}, \boldsymbol{\upsilon})\; \cap $ GRS$ _k(\boldsymbol{\alpha}, \boldsymbol{\upsilon})^\bot $, which addresses an open problem posed in [Chen et al., IEEE-TIT, 2023]. We also presentd a new approach to generating all self-dual RS codes.

Approximately 20% of colorectal cancer (CRC) patients are first diagnosed with metastatic colorectal cancer (mCRC) because they develop symptoms at an advanced stage. Despite advancements in treatment, patients with metastatic disease still experience inferior survival rates. Our objective is to investigate the association between long noncoding RNAs (lncRNAs) and prognosis and to explore their role in mCRC. In this study, we find that elevated expression of PCAT6 is independently linked to unfavourable survival outcomes in The Cancer Genome Atlas (TCGA) data, and this finding is further confirmed in CRC samples obtained from Fudan University Shanghai Cancer Center. Cell lines and xenograft mouse models are used to examine the impact of PCAT6 on tumor metastasis. Knockdown of PCAT6 is observed to impede the metastatic phenotype of CRC, as evidenced by functional assays, demonstrating the suppression of epithelial-mesenchymal transition (EMT) and stemness. Our findings show the significance of PCAT6 in mCRC and its potential use as a prognostic biomarker.

The rapid advancement of Industry 4.0 and intelligent manufacturing has elevated the demands for fault diagnosis in servo motors. Traditional diagnostic methods, which rely heavily on handcrafted features and expert knowledge, struggle to achieve efficient fault identification in complex industrial environments, particularly when faced with real-time performance and accuracy limitations. This paper proposes a novel fault diagnosis approach integrating multi-scale convolutional neural networks (MSCNNs), long short-term memory networks (LSTM), and attention mechanisms to address these challenges. Furthermore, the proposed method is optimized for deployment on resource-constrained edge devices through knowledge distillation and model quantization. This approach significantly reduces the computational complexity of the model while maintaining high diagnostic accuracy, making it well suited for edge nodes in industrial IoT scenarios. Experimental results demonstrate that the method achieves efficient and accurate servo motor fault diagnosis on edge devices with excellent accuracy and inference speed.

Abstract Background Accurately distinguishing between pulmonary infection and colonization in patients with Acinetobacter baumannii is of utmost importance to optimize treatment and prevent antibiotic abuse or inadequate therapy. An efficient automated sorting tool could prompt individualized interventions and enhance overall patient outcomes. This study aims to develop a robust machine learning classification model using a combination of time-series chest radiographs and laboratory data to accurately classify pulmonary status caused by Acinetobacter baumannii. Methods We proposed nested logistic regression models based on different time-series data to automatically classify the pulmonary status of patients with Acinetobacter baumannii. Advanced features were extracted from the time-series data of hospitalized patients, encompassing dynamic pneumonia indicators observed on chest radiographs and laboratory indicator values recorded at three specific time points. Results Data of 152 patients with Acinetobacter baumannii cultured from sputum or alveolar lavage fluid were retrospectively analyzed. Our model with multiple time-series data demonstrated a higher performance of AUC (0.850, with a 95% confidence interval of [0.638–0.873]), an accuracy of 0.761, a sensitivity of 0.833. The model, which only incorporated a single time point feature, achieved an AUC of 0.741. The influential model variables included difference in the chest radiograph pneumonia score. Conclusion Dynamic assessment of time-series chest radiographs and laboratory data using machine learning allowed for accurate classification of colonization and infection with Acinetobacter baumannii. This demonstrates the potential to help clinicians provide individualized treatment through early detection.

Abstract Objective To explore the potential mechanism of Yougui Wan on deformed lumbar intervertebral disk structure in rats. Methods Thirty male Sprague–Dawley rats were randomly divided into 3 groups, with 10 rats in each group. The animals in the blank control group were healthy rats without specific treatment, and those in the model group and traditional Chinese medicine (TCM) group were used to establish the intervertebral disk degeneration (IDD) model by puncturing the annulus. Four weeks after modeling, rats in the TCM group were administered Yougui Wan by gavage for 2 consecutive weeks. Serum interleukin-6 (IL-10), macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNF-α) levels were measured by ELISA, and the protein expression levels of collagen II and Notch1 in intervertebral disk tissues were examined by Western blotting. Apoptosis was detected by the TUNEL method. Results Compared with those in the blank group, IL-10, MIF and TNF-α levels in the model group and TCM group were increased (P

The environmental risk of oil spill was comprehensively evaluated based on the risk source of hazardous chemicals, sea-related sensitive targets and ship traffic density. Firstly, from the perspective of spatial distribution and quantitative characteristics, the impact factors of marine environmental risk in Ningbo City were extracted, and the assessment methods and index system of marine environmental risk were established. Then the GIS spatial information platform was used to evaluate the spatial distribution of environmental risks in Ningbo coastal waters. The results show that Cixi City in northwest and Zhenhai potential environmental risk of oil spill is extremely high, to the sensitivity of oil spill is relatively high, that these areas as the key control object; Beilun and Fenghua area in southeast coastal area and Xiangshan island in the east China sea, its environmental risk is general risk, that these areas for general control object, the potential environmental risk belongs to the medium sensitivity; The east and southeast of Xiangshan County and the south of Ninghai County have very low potential environmental risk, and their sensitivity to oil spill is low. The evaluation results can provide a scientific basis and effective reference for Ningbo's marine environmental risk prevention and control, emergency response measures, and the utilization and allocation of sea space resources.

Background/Aim. High-grade glioma (HGG) is an interstitial cell-derived primary tumor of the nervous system. The current guidelines for the diagnosis and treatment of glioma recommend the maximum safe range of tumor resection for treatment methods. Adjuvant concurrent chemoradiotherapy is recommended after surgery, followed by six cycles of single-drug chemotherapy, temozolomide. Evaluation of the early efficacy of concurrent chemoradio-therapy after HGG surgery, especially for patients with a high risk of recurrence, is a crucial step in enhancing the treatment efficiency for patients diagnosed with HGG. In this study, we investigated the clinical utility of magnetic resonance (MR) spectroscopy (MRS) in assessing the early curing impact of concurrent chemoradiotherapy following HGG surgery. Methods. A total of 50 patients with incomplete resection or suspected residual postoperative HGG, treated in the radiotherapy department of our hospital between January 2016 and June 2021, were selected for routine concurrent chemoradiotherapy. Conventional MR imaging and MRS were performed one week prior to treatment and one month after treatment to assess changes in specific brain metabolites. All 50 patients were followed up for 6 to 12 months. Based on the follow-up results, the patients were divided into two groups: the tumor recurrence group and the tumor suppression group. One month after the end of the treatment, the differences in levels of brain metabolites between the two groups were analyzed using MRS. Results. The levels of N-acetylaspartate (NAA) and creatine (Cr) increased after radiotherapy, while choline (Cho) peak value, and Cho/Cr, NAA/Cr, and Cho/NAA ratios decreased compared to pre-treatment levels. There were statistically significant differences in the NAA peak value, and Cho/Cr, and Cho/NAA ratios in the tumor enhancement area before and after treatment (p < 0.05). There were also statistically significant differences in Cho/Cr ratio in the peritumoral edema area before and after treatment (p < 0.05). Conclusion. After concurrent chemoradiotherapy, MRS can be used to detect early metabolic changes in the tumor enhancement and peritumoral edema areas of HGG.

Fault segmentation plays a critical role in assessing seismic hazards, particularly in tectonically complex regions. The Laji-Jishi Shan Fault Zone (LJSFZ), located on the northeastern margin of the Tibetan Plateau, is a key structure that accommodates regional tectonic stress. This study integrates geomorphic indices, cross-fault deformation rate profiles, and 3D crustal electrical structure data to analyze the varying levels of tectonic activity across different segments of the LJSFZ. We extracted 160 drainage basins along the strike of the LJSFZ from a 30 m resolution digital elevation model and calculated geomorphic indices, including the hypsometric integral (HI), stream length-gradient index (SL), and channel steepness index (ksn), to assess the variations in tectonic activity intensity along the strike of the LJSFZ. The basins were categorized based on river flow directions to capture potential differences across the fault zone. Our results show that the eastern basins of the LJSFZ exhibit the strongest tectonic activity, demonstrated by significantly higher SL and ksn values compared to other regions. A detailed segmentation analysis along the northern Laji Shan Fault and eastern Jishi Shan Fault identified distinct fault segments characterized by variations in SL and ksn indices. Segments with high SL values (>500) correspond to higher crustal uplift rates (~3 mm/year), while segments with lower SL values exhibit lower uplift rates (~2 mm/year), as confirmed by cross-fault deformation profiles derived from GNSS and InSAR data. This correlation demonstrates that geomorphic indices effectively reflect fault activity intensity. Additionally, 3D crustal electrical structure data further indicate that highly conductive mid- to lower-crustal materials originating from the interior of the Tibetan Plateau are obstructed at segment L3 of the LJSFZ. This obstruction leads to localized intense uplift and enhanced fault activity. These findings suggest that while the regional stress–strain pattern of the northeastern Tibetan Plateau is the primary driver of the segmented activity along the Laji-Jishi Shan belt, the direction of localized crustal flow is a critical factor influencing fault activity segmentation.

In recent years, artificial intelligence technology has seen increasingly widespread application in the field of intelligent manufacturing, particularly with deep learning offering novel methods for recognizing geometric shapes with specific features. In traditional CNC machining, computer-aided manufacturing (CAM) typically generates G-code for specific machine tools based on existing models. However, the tool paths for most CNC machines consist of a series of collinear motion commands (G01), which often result in discontinuities in the curvature of adjacent tool paths, leading to machining defects. To address these issues, this paper proposes a method for CNC system machining trajectory feature recognition and path optimization based on intelligent agents. This method employs intelligent agents to construct models and analyze the key geometric information in the G-code generated during CNC machining, and it uses the MCRL deep learning model incorporating linear attention mechanisms and multiple neural networks for recognition and classification. Path optimization is then carried out using mean filtering, Bézier curve fitting, and an improved novel adaptive coati optimization algorithm (NACOA) according to the degree of unsmoothness of the path. The effectiveness of the proposed method is validated through the optimization of process files for gear models, pentagram bosses, and maple leaf models. The research results indicate that the CNC system machining trajectory feature recognition and path optimization method based on intelligent agents can significantly enhance the smoothness of CNC machining paths and reduce machining defects, offering substantial application value.

Abstract Background Extracellular vesicles (EVs) from human umbilical cord mesenchymal stem cells (hUMSCs) are widely considered to be the best mediators for cell-free therapy. An understanding of their composition, especially RNA, is particularly important for the safe and precise application of EVs. Up to date, the knowledge of their RNA components is limited to NGS sequencing and cannot provide a comprehensive transcriptomic landscape, especially the long and full-length transcripts. Our study first focused on the transcriptomic profile of hUMSC-EVs based on nanopore sequencing. Methods In this study, different EV subtypes (exosomes and microvesicles) derived from hUMSCs were isolated and identified by density gradient centrifugation. Subsequently, the realistic long transcriptomic profile in different subtypes of hUMSC-EVs was systematically compared by nanopore sequencing and bioinformatic analysis. Results Abundant transcript variants were identified in EVs by nanopore sequencing, 69.34% of which transcripts were fragmented. A series of full-length and long transcripts was also observed and showed a significantly higher proportion of intact or near-complete transcripts in exosomes than that in microvesicles derived from hUMSCs. Although the composition of RNA biotypes transported by different EV subtypes was similar, the distribution of transcripts and genes revealed the inter-heterogeneity and intra-stability between exosomes and microvesicles. Further, 85 different expressed transcripts (56 genes) and 7 fusion genes were identified. Pathway enrichment analysis showed that upregulated-expressed genes in microvesicles were mainly enriched in multiple neurodegenerative diseases, while upregulated-expressed genes in exosomes were mainly enriched in neutrophil extracellular trap formation, suggesting different functional tendencies of EV subtypes. Conclusions This study provides a novel understanding of different types of hUMSC-EVs, which not only suggests different transcriptome sorting mechanisms between exosomes and microvesicles, but also shows that different EV subtypes from the same source have different physiological functions, suggesting distinct clinical application prospects.

Background: In the central nervous system, glioma is the most common malignant tumor, and patients have a poor prognosis. Identification of novel marker genes and establishment of prognostic models are important for early diagnosis and prognosis determination. Methods: Download glioma data from the CGGA and TCG databases. Application of bioinformatics to analyze the impact of CYBB on the clinicopathological characteristics, immunological features and prognosis of gliomas. Using single-cell sequencing data from 7 glioblastoma patients in the CGGA database, the role of CYBB in the tumor microenvironment was analyzed. In addition, a prognostic model was constructed based on CYBB high and low differentially expressed genes and mitochondrial genes. Results: The expression of CYBB is closely related to various clinical features, immune cell infiltration level, immune checkpoint and survival time of patients. A 10-gene prediction model was constructed based on the differentially expressed genes of low and high CYBB and mitochondria-related genes. Glioma patients with higher risk scores had significantly lower survival probabilities. Receiver operating characteristic curves and nomograms were plotted over time to show the predictive accuracy and predictive value of the 10-gene prognostic model. Conclusions: Our study shows that CYBB is strongly correlated with clinical characteristics features and prognosis of glioma patients, and can be used as a potential therapeutic target. Prognostic models based on CYBB and mitochondrial genes have good performance in predicting prognosis of glioma patients.

Integrins are heterodimers composed of non-covalently associated alpha and beta subunits that mediate the dynamic linkage between extracellular adhesion molecules and the intracellular actin cytoskeleton. Integrins are present in various tissues and organs and are involved in different physiological and pathological molecular responses in vivo. Wound healing is an important process in the recovery from traumatic diseases and consists of three overlapping phases: inflammation, proliferation, and remodeling. Integrin regulation acts throughout the wound healing process to promote wound healing. Prolonged inflammation may lead to failure of wound healing, such as wound chronicity. One of the main causes of chronic wound formation is bacterial colonization of the wound. In this review, we review the role of integrins in the regulation of wound healing processes such as angiogenesis and re-epithelialization, as well as the role of integrins in mediating bacterial infections during wound chronicity, and the challenges and prospects of integrins as therapeutic targets for infected wound healing.

Abstract The NFAT1-mediated IL6/JAK-STAT signaling pathway has been observed to contribute to malignant progression in glioma patients. To predict the overall survival (OS) rate of these patients, a prognostic model was developed based on this pathway. Two datasets, mRNAseq_325 and mRNAseq_693, were obtained from the China Glioma Genome Atlas (CGGA), excluding some patients with a lack of survival information, resulting in the inclusion of 684 glioma cases. The two groups were randomly divided into training and validation groups to analyze the differential expression of NFAT1 in pan-cancer and investigate the relationship between differential NFAT1 expression and glioma clinicopathological factors and Transcriptional subtypes. A prediction model based on the IL6/JAK/STAT signaling pathway was constructed using the LASSO-COX dimension reduction analysis to predict the OS of glioma patients. Pearson correlation analysis was utilized to identify gene sets associated with patient risk scores and to perform GO and KEGG analyses. NFAT1 is differentially expressed in a variety of cancers and is enriched in the more malignant potential glioma subtypes. It is an independent prognostic factor in glioma patients, and its expression is significantly positively correlated with the IL6/JAK/STAT signalling pathway in glioma patients. The final prediction model incorporating the seven candidate genes together with other prognostic factors showed strong predictive performance in both the training and validation groups. Risk scores of glioma patients were correlated with processes such as NF-κB and protein synthesis in glioma patients. This individualized prognostic model can be used to predict the OS rate of patients with glioma at 1, 2, 3, 5, and 10 years, providing a reference value for the treatment of glioma patients.

The emergence of anti-EGFR therapy has revolutionized the treatment of colorectal cancer (CRC). However, not all patients respond consistently well. Therefore, it is imperative to conduct further research to identify the molecular mechanisms underlying the development of cetuximab resistance in CRC. In this study, we find that the expressions of many metabolism-related genes are downregulated in cetuximab-resistant CRC cells compared to their sensitive counterparts. Specifically, acetyl-CoA acyltransferase 2 (ACAA2), a key enzyme in fatty acid metabolism, is downregulated during the development of cetuximab resistance. Silencing of ACAA2 promotes proliferation and increases cetuximab tolerance in CRC cells, while overexpression of ACAA2 exerts the opposite effect. RTK-Kras signaling might contribute to the downregulation of ACAA2 expression in CRC, and ACAA2 predicts CRC prognosis in patients with Kras mutations. Collectively, our data suggest that modulating ACAA2 expression contributes to secondary cetuximab resistance in Kras wild-type CRC patients. ACAA2 expression is related to Kras mutation and demonstrates a prognostic role in CRC patients with Kras mutation. Thus, ACAA2 is a potential target in CRC with Kras mutation.

Currently, platinum-containing regimens are the most commonly used regimens for advanced gastric cancer patients, and chemotherapy resistance is one of the main reasons for treatment failure. Thus, it is important to reveal the mechanism of oxaliplatin resistance and to seek effective intervention strategies to improve chemotherapy sensitivity, thereby improving the survival and prognosis of gastric cancer patients. To understand the molecular mechanisms of oxaliplatin resistance, we generate an oxaliplatin-resistant gastric cancer cell line and conduct assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) for both parental and oxaliplatin-resistant AGS cells. A total of 3232 genomic regions are identified to have higher accessibility in oxaliplatin-resistant cells, and DNA-binding motif analysis identifies JUNB as the core transcription factor in the regulatory network. JUNB is overexpressed in oxaliplatin-resistant gastric cancer cells, and its upregulation is associated with poor prognosis in gastric cancer patients, which is validated by our tissue microarray data. Moreover, chromatin immunoprecipitation sequencing (ChIP-seq) analysis reveals that JUNB binds to the transcriptional start site of key genes involved in the MAPK signaling pathway. Knockdown of JUNB inhibits the MAPK signaling pathway and restores sensitivity to oxaliplatin. Combined treatment with the ERK inhibitor piperlongumine or MEK inhibitor trametinib effectively overcomes oxaliplatin resistance. This study provides evidence that JUNB mediates oxaliplatin resistance in gastric cancer by activating the MAPK pathway. The combination of MAPK inhibitors with oxaliplatin overcomes resistance to oxaliplatin, providing a promising treatment opportunity for oxaliplatin-resistant gastric cancer patients.

Solid-state ionic thermoelectric generators have emerged as promising solutions for efficient harvesting of low-grade waste heat. However, the main challenge in achieving continuous power supply is the low efficiency of thermoelectric conversion. In this work, substantial achievements have been made in improving the thermoelectric conversion characteristics by introducing redox pairs on the electrode surfaces. This approach takes advantage of the synergistic effect of thermal diffusion and thermoelectric effects to maximize the conversion efficiency. To improve the thermoelectric storage and output power performance, Prussian blue was attached to a carbon woven fabric and used as an electrode. The incorporation of Prussian blue/carbon woven fabric electrodes results in an increase in current density output and an instantaneous power density of 3.7 mW/m2·K2. Furthermore, under a temperature gradient of 10 K, the output energy density for 2 h is 194 J/m2, and the Carnot relative efficiency is as high as 0.12% at a hot side temperature (TH) of 30 °C and a cold side temperature (TC) of 20 °C. Our findings validate the efficacy of integrating thermal diffusion and redox reactions in ionic thermoelectric generators, paving the way for the progress of thermocharged devices and their potential commercial applications.

The vibration signals of rolling bearings under variable speed conditions exhibit time-varying, nonstationary, and nonlinear characteristics, making it challenging to extract fault features. A fast path optimization-based multitime-frequency ridge extraction (FPOMRE) method is proposed in this paper to address the problem. First, the time-frequency representation of the fault signal is obtained through the adaptive short-time Fourier transform (STFT), and then the FPOMRE algorithm is used to extract additional ridges below the lowest time-frequency ridge multiple times. The frequency ratio of each ridge to the additional ridge, the average value of the ratio, and the variance of the ratio are calculated, respectively, and finally, the matching degree between the average ratio and the fault feature coefficient is compared with the diagnosis of the bearing fault. The simulation and experimental results show that the FPOMRE method can effectively diagnose the bearing fault under constant speed and variable speed conditions, and the extraction accuracy of time-frequency ridges under constant speed is higher than that under variable speed, and the extraction accuracy under high speed is higher than that under low speed. The relative error of extracting rotation frequency under constant speed and variable speed is 0.5% and 1.3%, respectively. In addition, comparing the FPOMRE with the maximum amplitude method (MAM), both FPOMRE and MAM can effectively extract the instantaneous shaft rotation frequency at a constant speed. However, under variable speed conditions, the ridge extracted by FPOMRE has a higher accuracy and lower average processing time than that extracted by MAM.

Abstract Background Colorectal cancer is considered as the second most common cancer worldwide. Studies have shown that m6A RNA methylation abnormalities play an important role in the pathogenesis of many human diseases, including cancer. The current study was designed to characterize the mutation of m6A related genes and explore their prognostic role in colorectal cancer. Methods RNA-seq data and somatic mutation data of TCGA-COAD and TCGA-READ were downloaded from UCSC xena for comprehensive analysis. M6A related genes were selected from previous literatures, including "Writer" protein (METTL3, METTL5, METTL14, METTL16, ZC3H13, RBM15, WTAP, KIAA1429), "Reader" protein YTHDF1, YTHDF2, YTHDF3, YTHDC1, YTHDC2, HNRNPC, IGF2BP1, IGF2BP2, IGF2BP3), and "Eraser" protein (FTO, ALKBH5). Kaplan–Meier diagrams were used to explore the correlation between m6A-related genes and colorectal cancer prognosis. The correlations between m6A-related genes and clinical parameters and immune-related indicators were explored by Spearman correlation analysis. And finally, the expression patterns of five key genes (RBMX, FMR1, IGF2BP1, LRPPRC and YTHDC2) were detected by qPCR in CRC specimens. Results In CRC, the expressions of m6A-related genes were significantly different between CRC and normal control except METTL14, YTHDF2, YTHDF3. Some of CRC patients (178 in 536) have a m6A-related genes mutation. ZC3H13 has highest mutation frequency of all m6A-related genes. M6A-related genes mainly enrich in regulation of mRNA metabolic process pathway. Patients with high expressions of FMR1, LRPPRC, METTL14, RBMX, YTHDC2, YTHDF2, YTHDF3 have poor prognosis in CRC. There was a significant correlation between the FMR1, LRPPRC, RBMX, YTHDC2, IGF2BP1 expression and the clinical characteristics of CRC. In addition, these genes are significantly associated with immune-related indicators. According to the expression patterns of FMR1, LRPPRC, RBMX, YTHDC2, and IGF2BP1, patients with CRC were clustered into two groups, and their survival was significantly different. By evaluating the tumor microenvironment in two clusters using ssGSEA, expressions of immune checkpoints and GSVA enrichment analysis, we observed that the immune and stem cell index of two cluster were much different. The qPCR results showed that RBMX expression was markedly elevated in cancerous tissues than in the normal colonic tissues. Conclusion Our study identified novel prognostic markers associated with immune of CRC cancer patients. Moreover, the potential mechanisms of prognostic markers in regulating the etiology of CRC cancer were investigated. These findings enrich our understanding of the relationships between m6a related genes and CRC, and may provide novel ideas in the therapy of CRC patients.

In this paper, arc oscillation is applied in the fabrication of 2319 aluminum alloy samples by cold metal transition wire arc additive manufacturing process (CMT-WAAM). The porosity, microstructure and mechanical properties of 2319 aluminum alloy under different arc oscillation patterns were discussed. The results showed that the stirring of arc oscillation can influence the molten pool shape and improve the fluidity, change the thermal distribution and the growth direction of columnar crystal. Arc oscillation has a obvious effect on reducing the grain size and proportion of pores. After using the spiral arc oscillation pattern and asymmetrical trapezoid arc oscillation pattern, the volume fraction of pores reduced from 2.64% to 1.09% and 1.22%, and the size of pores was mainly smaller than 40 μm, respectively. The tensile strength in vertical direction and plasticity were improved with arc oscillation, but its effect on the horizontal tensile strength was not noticeable. After solid solution-aging treatment, the tensile strength of the sample with spiral arc oscillation pattern increased to 277 MPa, with a cross-section reduction of 3.6%.

Abstract Background The Mg–Al-lactate layered double hydroxide nanosheet (LDH-NS) has shown great potential as an optimal nanocarrier for extensive use in plants. However, previous studies in plant sciences have not provided a clear description of the application for the LDH-NSs-based double-stranded RNA (dsRNA) delivery (LDH-dsRNA) system in different tissues of both model and non-model species. Results LDH-NSs were synthesized by using the co-precipitation method, while the dsRNAs targeting genes of interest were prepared in vitro using T7 RNA polymerase. The LDH-dsRNA bioconjugates with a neutral charge were produced by incubating with the mass ratio of LDH-NSs to dsRNA at 3:1, which were then introduced into intact plant cells using three different approaches, including injection, spray, and soak. The LDH-dsRNA delivery method was optimized by inhibiting the expression of the Arabidopsis thaliana ACTIN2 gene. As a result, soaking A. thaliana seedlings in a medium containing LDH-dsRNA for 30 min led to the silencing of 80% of the target genes. The stability and effectiveness of the LDH-dsRNA system were further confirmed by the high-efficiency knockdown of plant tissue-specific genes, including that encoding phytoene desaturase (PDS), WUSCHEL (WUS), WUSCHEL-related homeobox 5 (WOX5), and ROOT HAIR DEFECTIVE 6 (RHD6). In addition, the LDH-dsRNA system was employed in cassava, where it was found that the expression of the gene encoding nucleotide-binding site and leucine-rich repeat (NBS-LRR) was significantly reduced. As a result, the resistance of cassava leaves to pathogens was weakened. Noteworthy, the injection of LDH-dsRNA into leaves resulted in a significant downregulation of target genes in both stems and flowers, indicating the successful transport of LDH-dsRNA from leaves to other parts of plants. Conclusions LDH-NSs have proven to be a highly effective molecular tool for delivering dsRNA into intact plant cells, enabling accurate control of target gene expression.

Abstract Gastric cancer (GC) has been identified as the third deadly cancer in the world. Accumulating researches suggest a potential role of microorganisms in tumorigenesis. However, the composition of microbiota in GC tissues is not clear and it changes throughout the different stages of GC remain mostly elusive. Our study integrated RNA-Seq data of 727 samples derived from gastric tissues across four datasets and revealed its microbial composition. In order to remove the false positive results, core taxa were defined and characterized. Based on it, we analyzed the influence of biological factors on its composition. The pan-microbiome of gastric tissues was estimated to be over than 1400 genera. Seventeen core genera were identified. Among them, Helicobacter, Lysobacter were significantly enriched in normal tissues, while Pseudomonas was enriched in tumor tissues. Interestingly, Acinetobacter, Pasteurella, Streptomyces, Chlamydia, and Lysobacter, showed a significant increase trend during tumor development and formed strong intra/inter-correlations among them or with other genera. Furthermore, we found that tumor stage played an important role in altering the microbial composition of GC tissues. This study provides support for the in-depth study of tumor microbiome, and the specific microbiome excavated provides a possibility for the subsequent identification of potential biomarkers for GC.

Abstract Bladder cancer, one of the most prevalent malignant cancers, has high rate of recurrence and metastasis. Owing to genomic instability and high-level heterogeneity of bladder cancer, chemotherapy and immunotherapy drugs sensitivity and lack of prognostic markers, the prognosis of bladder cancer is unclear. Necroptosis is a programmed modality of necrotic cell death in a caspase-independent form. Despite the fact that necroptosis plays a critical role in tumor growth, cancer metastasis, and cancer patient prognosis, necroptosis-related gene sets have rarely been studied in bladder cancer. As a result, the development of new necroptosis-related prognostic indicators for bladder cancer patients is critical. Herein, we assessed the necroptosis landscape of bladder cancer patients from The Cancer Genome Atlas database and classified them into two unique necroptosis-related patterns, using the consensus clustering. Then, using five prognosis-related genes, we constructed a prognostic model (risk score), which contained 5 genes (ANXA1, DOK7, FKBP10, MAP1B and SPOCD1). And a nomogram model was also developed to offer the clinic with a more useful prognostic indicator. We found that risk score was significantly associated with clinicopathological characteristics, TIME, and tumor mutation burden in patients with bladder cancer. Moreover, risk score was a valid guide for immunotherapy, chemotherapy, and targeted drugs. In our study, DOK7 was chosen to further verify our prognosis model, and functional assays indicated that knockdown the expression of DOK7 could prompt bladder cancer proliferation and migration. Our work demonstrated the potential role of prognostic model based on necroptosis genes in the prognosis, immune landscape and response efficacy of immunotherapy of bladder cancer.

An optimized method for the determination of benzopyrene in vegetable oil by molecular imprinting solid phase extraction with ultra-high performance liquid chromatography was established. During the experiment, through the investigation of different solid-phase extraction purification efficiency, optimal detection wavelength, mobile phase system and chromatographic column use, the results showed that the molecularly imprinted solid phase extraction purification column was more suitable for pretreatment extraction and purification of vegetable oil. The optimal detection the excitation wavelength and the emission wavelength were 365 nm and 410 nm, respectively. Under these conditions, the benzopyrene chromatographic peak had high response value and signal-to-noise ratio. Under the mobile phase system of 90% acetonitrile-10% water, the target peak had a good separation effect. Using 150 mm short columns can effectively improve work efficiency. Benzopyrene had a good linear relationship in the concentration range of 0.3~20 µg/L, and the correlation coefficient was greater than 0.999 9. The detection limit and quantitative limit of benzopyrene determination method were 0.1 µg/kg and 0.3 µg/kg, respectively. The average recoveries of three added concentrations were 87.6%~95.9%, and the relative standard deviations were 1.08%~2.16%. In the actual sample detection, the detection rate of benzopyrene, the exceeding rate and the qualified rate were 39.0%, 2.4%, and was 97.6%, respectively. This optimization method is sensitive, convenient, rapid and accurate, and can be used for batch detection of benzopyrene in vegetable oil and analysis of pollution monitoring.

This study proposes a new deep neural network to solve the multi-band image synchronous fusion problem (MBF-Net). Unlike other deep learning-based methods, our network architecture design combines the ideas of model-driven and data-driven methods, so it is more interpretable. First, a new multi-band image synchronous fusion model is proposed. The source image in the data fidelity terms and the prior regularization are implicitly represented by the deep learning network and jointly learned from the training data. The proposed model is then solved using a half quadratic splitting (HQS) algorithm and unfolded into a deep fusion network. In addition, a new saliency loss function is proposed to retain thermal radiation information to enhance the fusion effect. Finally, the experimental results on the TNO dataset demonstrated the effectiveness of the proposed MBF-Net.

Objectives The prognosis for adults with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. Blinatumomab is a CD3/CD19-directed BiTE® (bispecific T-cell engager) molecule approved globally for the treatment of BCP-ALL in adults and children. This multicenter open-label single-arm China registrational study evaluated the safety, efficacy, and pharmacokinetics of blinatumomab in Chinese adults with Philadelphia chromosome-negative (Ph−) R/R BCP-ALL (NCT03476239).Methods Patients aged ≥ 18 years were treated with up to 5 cycles of blinatumomab. The primary objective was to evaluate the hematological response rate (complete remission/complete remission with partial hematological recovery [CR/CRh]) within 2 cycles of blinatumomab.Results At the interim analysis (April 12, 2019), 90 patients (median age 31.5 years [range: 18-74]; 53.3% female; 77.8% with bone marrow blasts ≥ 50% at study entry) were enrolled at 23 study centers in China and had received blinatumomab. As of data cutoff, 43 patients (47.8%) continued the study. The CR/CRh rate within 2 cycles of blinatumomab was 45.6% (41/90 [CR, 37; CRh, 4]; 95% CI: 35.0–56.4). Median overall survival was 9.2 months (95% CI: 6.5–11.7); median relapse-free survival was 4.3 months (95% CI: 3.2–9.4). Mean serum concentration at steady-state and systemic clearance of blinatumomab in Chinese patients were within the range reported in adults from global clinical trials. No new safety risks were identified in Chinese patients.Conclusions The efficacy and safety of blinatumomab in these heavily pre-treated Chinese patients with Ph− R/R BCP-ALL is comparable to that for patients within global clinical trials.

1D organic metal halide hybrids (OMHHs) exhibit strongly anisotropic optical properties, highly efficient light emission, and large Stokes shift, holding promise for novel photodetection and lighting applications. However, the fundamental mechanisms governing their unique optical properties and in particular the impacts of surface effects are not understood. Herein, 1D C4N2H14PbBr4 by polarization‐dependent time‐averaged and time‐resolved photoluminescence (TRPL) spectroscopy, as a function of photoexcitation energy, is investigated. Surprisingly, it is found that the emission under photoexcitation polarized parallel to the 1D metal halide chains can be either stronger or weaker than that under perpendicular polarization, depending on the excitation energy. The excitation‐energy‐dependent anisotropic emission is attributed to fast surface recombination, supported by first‐principles calculations of optical absorption in this material. The fast surface recombination is directly confirmed by TRPL measurements, when the excitation is polarized parallel to the chains. The comprehensive studies provide a more complete picture for a deeper understanding of the optical anisotropy in 1D OMHHs.

Gliomas, the most prevalent primary tumors in the central nervous system, are marked by their immunosuppressive properties and consequent poor patient prognosis. Current evidence emphasizes the pivotal role of the tumor microenvironment in the progression of gliomas, largely attributed to tumor-associated macrophages (brain-resident microglia and bone marrow-derived macrophages) that create a tumor microenvironment conducive to the growth and invasion of tumor cells. Yet, distinguishing between these two cell subgroups remains a challenge. Thus, our review starts by analyzing the heterogeneity between these two cell subsets, then places emphasis on elucidating the complex interactions between microglia and glioma cells. Finally, we conclude with a summary of current attempts at immunotherapy that target microglia. However, given that independent research on microglia is still in its initial stages and has many shortcomings at the present time, we express our related concerns and hope that further research will be carried out to address these issues in the future.

Underwater Wireless Optical Communication (UWOC) has the advantages of large capacity, high speed and etc. However, it suffers from limited communication range and data rate in practice due to the complex underwater environment and the limited bandwidth of optical devices. Multiple-Input Multiple-Output (MIMO) technology has received considerable attention since it converts spatial single-stream data into multiple-stream data for parallel transmission. Therefore it can extend the UWOC range and alleviate the performance degradation caused by underwater absorption, scattering, and turbulence. In this paper, focusing on the MIMO technology in UWOC systems, we analyzed the channel modeling, research progress, experimental setups and prototypes, and the development and future trend of MIMO-UWOC technology.

Male sterility plays an important role in the utilization of heterosis in rice. The establishment of male sterile lines in rice is one of the key technologies in hybrid rice production systems. The currently widely used male sterile line breeding systems mainly include: three-line hybrid rice based on cytoplasmic male sterility, two-line hybrid rice based on environmental sensitive gene male sterility, and third-generation hybrid rice based on nuclear gene male sterility Seed production system. This study reviewed the types and mechanisms of male sterility in rice, and looked forward to the development direction of hybrid rice.

Objective: This study focuses on the effects of twin-screw extrusion on the functional properties and structure of pea protein. Methods: The color change of pea protein extrudates were analyzed by automatic colorimeter, the water holding capacity and emulsifying characteristics of pea protein were analyzed by chemical analysis. The microstructure of pea protein and its extrudates were observed by scanning electron microscope, and the secondary structure of the extrudates were analyzed by Fourier transform infrared spectroscopy. Results: After extrusion treatment, no significant difference was found in the color of pea protein, indicating that the pea protein had a better product color and the water holding capacity was significantly reduced （P＜0.05）, with the emulsibility and emulsification stability significantly increased （P＜0.05）. Scanning electron microscope showed that the microstructure changed obviously, resulting in protein aggregates with compact structure. The infrared spectrum showed that no new characteristic peaks appeared after extrusion treatment, but the secondary structure conversion occurred; β-sheet and α-helix structure transformed into β-turn and random coil structure, and the structural stability increased. Conclusion: After extrusion treatment, the pea protein retained its original product color, emulsification characteristics were significantly improved, the structure was dense and stability was enhanced.

Abstract Background Uniparental disomy (UPD) is a condition in which both chromosomes are inherited from the same parent, except for imprinting disorders. Uniparental isodisomy (UPiD) may result in a homozygous variant contributing to an autosomal recessive disorder in the offspring of a heterozygous carrier. Junctional epidermolysis bullosa intermediate (JEB intermediate) is an autosomal recessive inherited disease that is associated with a series of gene variants, including those of COL17A1. Case presentation We report the first case of complete paternal UPiD of chromosome 10 harbouring a novel homozygous variant in COL17A1: c.1880(exon23)delG (p.G627Afs*56). This variant led to the clinical phenotype of junctional epidermolysis bullosa intermediate in a 5-year-old child. Trio-whole exome sequencing (Trio-WES) and in silico data analysis were used for variant identification, Sanger sequencing was performed for variant validation, and pathological examination was performed as the gold standard for phenotype confirmation. Conclusions We recommend the use of WES as a first-tier test for the diagnosis of epidermolysis bullosa, especially for paediatric patients. Moreover, UPD events should be detected and analysed routinely through WES data in the future.

Background: The impact of COVID-19 on public health has mandated an ‘all hands on deck’ scientific response. The current clinical study and basic research on COVID-19 are mainly based on existing publications or our knowledge of coronavirus. However, efficiently retrieval of accurate, relevant knowledge on COVID-19 can pose significant challenges for researchers. Methods: To improve quality in accessing important literature findings, we developed a novel natural language processing (NLP) method to automatically recognize the associations among potential targeted host organ systems, associated clinical manifestations, and pathways. We further validated these associations through clinician experts' evaluations and prioritize candidate drug targets through bioinformatics network analysis. Results: We found that the angiotensin-converting enzyme 2 (ACE2), a receptor that SARS-CoV-2 required for cell entry, is associated with cardiovascular and endocrine organ system and diseases. Furthermore, we found SARS-CoV-2 is associated with some important pathways such as IL-6, TNF-alpha, and IL-1 beta-induced dyslipidemia, which are related to inflammation, lipogenesis, and oxidative stress mechanisms, suggesting potential drug candidates. Conclusion: We prioritized the list of therapeutic targets involved in antiviral and immune modulating drugs for experimental validation, rendering it valuable during public health crises marked by stresses on clinical and research capacity. Our automatic intelligence pipeline also contributes to other novel and emerging disease management and treatments in the future.

This chapter highlights the significance of three-dimensional ecological architecture as a crucial direction for the development of green architecture in China. The design concept is centered around four main principles: green, energy-saving, user-friendly, and ecological circulation. This case analysis demonstrates the effectiveness of incorporating ecological elements and sustainable design strategies into building structures, resulting in reduced energy consumption, improved indoor environmental quality, and enhanced biodiversity. The chapter explores the development trends and insights derived from one case study, providing valuable references for China future advancement of green architecture.

The juice outflow of chilled meat during storage, which would not only accelerate the growth of microorganisms, shorten the shelf life, but also reduce its appearance quality in modified atmosphere packaged. Based on this, this article used electrospinning technology to embed different concentrations (0%, 5%, 10%, 15%, 20%) of eugenol to prepare antibacterial nanofiber water absorbent mats. The fresh-keeping effect of air-laid paper pads and antibacterial nanofiber absorbent mats was verified under 4 ℃ modified atmosphere packaging conditions, and compared with the blank group. The research results showed that the pH value, thiobarbituric acid value, TVB-N value, total number of colonies, cooking loss rate, juice loss rate of the samples increased with the extension of storage time. Trend, but the increase of the antibacterial nanofiber absorbent mats group was significantly smaller than that of the blank group and the air-laid paper pads group (P

Abstract Background Pulmonary arteriovenous malformations (PAVMs) are rare but cause various manifestations. Although the diameter of feeding arteries has been linked to treatment decisions, relationships among the characteristics of PAVMs, clinical symptoms, and treatment effect remain unclear. The present study was performed to investigate how collective characteristics of PAVMs relate to clinical symptoms and to provide proper treatment recommendations for patients with PAVMs. Methods We retrospectively analysed 838,447 patients’ radiographic data and medical records from January 2018 to December 2020. Patients were included if a PAVM was radiographically detected for the first time in our hospital. Ordered multivariable logistic regression and hierarchical multiple regression were performed to analyse the relationships between characteristics of PAVMs and various clinical symptoms. We investigated the management of PAVMs in four tertiary university hospitals. Results Detection rate of PAVMs was 0.025% (207/838,447), and 37.6% of patients (78/207) also had hereditary haemorrhagic telangiectasia. Eight patients were diagnosed with bilateral diffuse PAVMs. Two hundred thirty-six lesions were detected in 199 patients, and the mean diameter of the feeding artery was 4.13 ± 1.92 mm. Most PAVMs were the simple type and located in the peripheral pulmonary area. In total, 34.3% of patients (71/207) were symptom-free; remaining patients showed various manifestations, and respiratory symptoms were most common (dyspnoea on exertion, 47.8%). The diameter of the feeding artery and the type and the number of PAVMs were correlated with hypoxaemia (P

BackgroundPremature ovarian insufficiency (POI) is one of the most common causes of female infertility and the etiology is highly heterogeneous. Most cases are idiopathic and the pathogenesis remains unclear. Previous studies proved that the immune system plays a crucial role in POI. However, the precise role of immune system remains unclear. This study aimed to analyze the characteristics of peripheral blood mononuclear cells (PBMC) from patients with POI by single-cell RNA sequencing (scRNA-seq) and to explore the potential involvement of immune response in idiopathic POI.MethodsPBMC was collected from three normal subjects and three patients with POI. PBMC was subjected to scRNA-seq to identify cell clusters and differently expressed genes (DEGs). Enrichment analysis and cell-cell communication analysis were performed to explore the most active biological function in the immune cells of patients with POI.ResultsIn total, 22 cell clusters and 10 cell types were identified in the two groups. Compared with normal subjects, the percentage of classical monocytes and NK cells was decreased, the abundance of plasma B cells was increased, and CD4/CD8 ratio was significantly higher in POI. Furthermore, upregulation of IGKC, IFITM1, CD69, JUND and downregulation of LYZ, GNLY, VCAN, and S100A9 were identified, which were enriched in NK cell-mediated cytotoxicity, antigen processing and presentation, and IL-17 signaling pathway. Among them, IGHM and LYZ were respectively the most significantly upregulated and downregulated genes among all cell clusters of POI. The strength of cell-cell communication differed between the healthy subjects and patients with POI, and multiple signaling pathways were assessed. The TNF pathway was found to be unique in POI with classical monocytes being the major target and source of TNF signaling.ConclusionsDysfunction of cellular immunity is related to idiopathic POI. Monocytes, NK cells, and B cells, and their enriched differential genes may play a role in the development of idiopathic POI. These findings provide novel mechanistic insight for understanding the pathogenesis of POI.

The application field of longitudinally welded pipe is expanding day by day, and its quality requirements are increasing.The inner burr removal device, as a key equipment to improve the quality of the inner surface of the longitudinally welded pipe, has gradually attracted the attention of manufacturers.Taking the high frequency longitudinally welded pipe with constant bottom surface as the research object, an inner burr removal device was proposed based on the cantilever arbor to improve the burr scraping quality of the welded pipe.According to the working principle and functional requirements of the inner burr removal device, the structure of the inner burr removal device was designed and the three-dimensional model was established; According to the actual production conditions, using the ANSYS software, the finite element model of the inner burr removal device under different extreme working conditions was established and simulation analysis was performed to ensure the rationality of the structural design.The inner burr removal device, which integrates lifting, rotating, knife lifting and other auxiliary movements, also has the function of online breaking the inner burr, avoiding falling off inner burrs to block the welded pipe, enriching the functions of the inner burr removal device and laying a foundation for product development.

IntroductionRNA editing, a wide-acknowledged post-transcriptional mechanism, has been reported to be involved in the occurrence and development of cancer, especially the abnormal alteration of adenosine to inosine. However, fewer studies focus on pancreaticcancer. Therefore, we aimed to explore the possible linkages between altered RNA editing events and the development of PDAC.MethodWe characterized the global A-to-I RNA editing spectrum from RNA and matched whole-genome sequencing data of 41 primary PDAC and adjacent normal tissues. The following analyses were performed: different editing level and RNA expression analysis,pathway analysis, motif analysis, RNA secondary structure analysis, alternative splicing events analysis, and survival analysis.The RNA editing of single-cell RNA public sequencing data was also characterized.ResultA large number of adaptive RNA editing events with significant differences in editing levels were identified, which are mainly regulated by ADAR1. Moreover, RNA editing in tumors has a higher editing level and more abundant editing sites in general. 140genes were screened out since they were identified with significantly different RNA editing events and were significantly different in expression level between tumor and matched normal samples. Further analysis showed a preference that in the tumor-specific group, they are mainly enriched in cancer-related signal pathways, while in the normal tissue-specific group, they are mainly enriched in pancreatic secretion. At the same time, we also found positively selected differentially edited sites in a series of cancer immune genes, including EGF, IGF1R, and PIK3CD. RNA editing might participate in pathogenisis of PDAC through regulating the alternative splicing and RNA secondary structure of important genesto further regulate gene expression and protein synthesis, including RAB27B and CERS4. Furthermore, single cell sequencing results showed that type2 ductal cells contributed the most to RNA editing events in tumors.ConclusionRNA editing is an epigenetic mechanism involved in the occurrence and development of pancreatic cancer, which has the potential to diagnose of PDAC and is closely related to the prognosis.

Summary: The magnetic-flux-dependent dispersions of sub-bands in topologically protected surface states of a topological insulator nanowire manifest as Aharonov–Bohm oscillations (ABOs) observed in conductance measurements, reflecting the Berry’s phase of π because of the spin-helical surface states. Here, we used thermoelectric measurements to probe a variation in the density of states at the Fermi level of the surface state of a topological insulator nanowire (Sb-doped Bi2Se3) under external magnetic fields and an applied gate voltage. The ABOs observed in the magnetothermovoltage showed 180° out-of-phase oscillations depending on the gate voltage values, which can be used to tune the Fermi wave number and the density of states at the Fermi level. The temperature dependence of the ABO amplitudes showed that the phase coherence was kept to T = 15 K. We suggest that thermoelectric measurements could be applied for investigating the electronic structure at the Fermi level in various quantum materials.

Given the unprecedented and profound impact on the traditional sports industry and its economic driving force brought by the "Internet +", the purpose of this study is to explore the driving relationship between the sports industry and local economic development and deconstruct the dynamic regulation mechanism of "Internet +" on the economic spillover of the sports industry. Empirical data collected from China's 11 inter-provincial panel data from 2015-2019 were analyzed through the fixed-effects and threshold models. The study finds that the economic spillover of the sports industry has significantly promoted regional economic development, and the regulation effect of the Internet has complex non-linear characteristics. Only when Internet development exceeds a specific threshold can it develop a benign complementary mechanism with the sports industry. The impact of "Internet +" on the threshold regulation of the sports industry economic spillover has spatial and temporal differentiation characteristics in the three dimensions of Internet hardware level, Internet penetration rate, and Internet application value. The results of this study extend the current study, indicating that it is a practical choice for local governments to develop the economy through the sports industry. Provinces and cities should enhance the Internet penetration rate, expand Internet business applications, and upgrade Internet development to a specific point to maximize the drive of positive spillover. Regional heterogeneity requires differential regulation strategies and more concentration on the middle and western regions.