Integrative single-cell RNA sequencing and metabolomics decipher the imbalanced lipid-metabolism in maladaptive immune responses during sepsis

BackgroundTo identify differentially expressed lipid metabolism-related genes (DE-LMRGs) responsible for immune dysfunction in sepsis.MethodsThe lipid metabolism-related hub genes were screened using machine learning algorithms, and the immune cell infiltration of these hub genes were assessed by CIBERSORT and Single-sample GSEA. Next, the immune function of these hub genes at the single-cell level were validated by comparing multiregional immune landscapes between septic patients (SP) and healthy control (HC). Then, the support vector machine-recursive feature elimination (SVM-RFE) algorithm was conducted to compare the significantly altered metabolites critical to hub genes between SP and HC. Furthermore, the role of the key hub gene was verified in sepsis rats and LPS-induced cardiomyocytes, respectively.ResultsA total of 508 DE-LMRGs were identified between SP and HC, and 5 hub genes relevant to lipid metabolism (MAPK14, EPHX2, BMX, FCER1A, and PAFAH2) were screened. Then, we found an immunosuppressive microenvironment in sepsis. The role of hub genes in immune cells was further confirmed by the single-cell RNA landscape. Moreover, significantly altered metabolites were mainly enriched in lipid metabolism-related signaling pathways and were associated with MAPK14. Finally, inhibiting MAPK14 decreased the levels of inflammatory cytokines and improved the survival and myocardial injury of sepsis.ConclusionThe lipid metabolism-related hub genes may have great potential in prognosis prediction and precise treatment for sepsis patients

SYSTEM ANALYSIS OF THE FOUR-PRONG LEGGED ACCELEROMETER BASED ON TRAPEZOIDAL VARIABLE CROSS-SECTION BEAM

Combining the four-prong legged acceleration system dynamic response,stability and sensitivity of support stiffness,a trapezoidal beam with variable cross section was designed and optimized. The dynamic model of the accelerometer was established and a relationship was found between the system dynamic response parameters and the beam rigidity. The trapezoidal variable cross-section beam rigidity-size relation was deduced with a bending mathematical model. The size requirements were raised by strength. By analyzing the system stability and sensitivity of the accelerometer,the beam rigidity was obtained.Compared with uniform cross-section under the equal rigidity in the no-detection direction,the trapezoidal variable section beam reduces the stiffness in detection direction with the equal stress on the critical section,improves the system sensitivity and dynamic output characteristics. However,quality greatly reduces

Investigation of Vortex-Induced Vibration of Double-Deck Truss Girder with Aerodynamic Mitigation Measures

The long-span double-deck truss girder bridge has become a recommend structural form because of its good performance on traffic capacity. However, the vortex-induced vibration (VIV) characteristics for double-deck truss girders are more complicated and there is a lack of related research. In this research, wind tunnel tests were utilized to investigate the VIV characteristics of a large-span double-deck truss girder bridge. Meanwhile, the VIV suppression effect of the aerodynamic mitigation measures was measured. Furthermore, the VIV suppression mechanism was studied from the perspective of vortex shedding characteristics. The results indicated that the double-deck truss girder had a significant VIV when the wind attack angles were +3° and +5°. The aerodynamic mitigation measures had an influence on the VIV response of the double-deck truss girder. The upper chord fairing and lower chord inverted L-shaped deflector plate played a crucial role in suppressing VIV. Numerical analysis indicated that vortex shedding above the upper deck or in the wake region may dominate vertical VIV, while vortex shedding in the wake region of the lower deck may dominate torsional VIV. The upper chord fairing and lower chord inverted L-shaped deflector plate disrupted the original vortex shedding pattern in both regions, thereby suppressing VIV. This research can provide a foundation for bridge design and vibration suppression measures for large-span double-deck truss girder bridges

Shear analysis and static load test of a single-box and multicell composite girders with corrugated steel webs: a case study

The shear design of a corrugated steel web box girder is important for structural reliability. At presently, corrugated steel webs bear all shear forces, and the top and bottom plates of concrete bear no shear force. Each steel web has equal force. This design is conservative and uneconomical and may be unsafe sometimes. The shear ratio and transfer efficiency of each corrugated steel web are investigated in this study through numerical analysis. Then, the distribution of shear stress in corrugated steel webs is verified through a static load test. Results show that the shear is shared by the top and bottom concrete plates and corrugated steel webs. Shear ratio presents a close relation with boundary, loading, and section position. The influence of transverse diaphragm to the shear ratio is minimal and this influence demonstrates a certain only effect on the steel web located at the area of the transverse diaphragm.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Sevoflurane affects evoked electromyography monitoring in cerebral palsy

To explore the effect of sevoflurane inhalation anesthesia on evoked electromyography monitoring of spinal nerve root in children associated with cerebral palsy

Research on Mechanism of Vortex-Induced Vibration Railing Effect of Double-Deck Large-Span Suspension Bridge

Large-span suspension bridges are susceptible to wind loads. Therefore, a more precise analysis of their wind-induced vibration response is necessary to ensure the structure’s absolute safety. This investigation conducted wind tunnel tests for the construction and completion stages to reveal the vortex-induced vibration (VIV) phenomenon of a double-deck suspension bridge. The results showed that no VIV occurred during the construction stage. However, the inclusion of railings significantly deteriorated the aerodynamic performance of the suspension bridge, leading to significant VIV at +3° and +5° wind angles of attack. Additionally, reducing the railing ventilation rate can significantly suppress the VIV amplitude. A new analysis method based on computational fluid dynamics (CFD) simulation is proposed to investigate the VIV mechanism of the double-deck truss girder. Twenty-nine measurement points were used to explore the vortex that causes VIV. The numerical simulations found that the area above and aft of the upper deck dominated the vertical VIV, while the aft of the lower deck dominated the torsional VIV. Furthermore, the intensity of the vortex in these areas was significantly lower during the construction stage. Moreover, reducing the railing ventilation rate significantly suppresses the torsional VIV by reducing the intensity of the vortex in the region behind the lower deck

Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma

Abstract Background Patients who possess various histological subtypes of early‐stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early‐stage LUAD due to intratumour intricacy. Methods We included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single‐cell RNA sequencing (scRNA‐seq) was carried out on matched tumour and normal tissue. Three formalin‐fixed and paraffin‐embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP). Results Using DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA‐seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = –.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD‐L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region. Conclusions These findings illustrate that assessing patient histological subtypes at the single‐cell level is feasible. Additionally, tumour endothelial cells that express PD‐L1 in stage IA LUAD suppress immune‐responsive CD8+ T cells

Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma.

Publication status: PublishedBACKGROUND: Patients who possess various histological subtypes of early-stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early-stage LUAD due to intratumour intricacy. METHODS: We included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single-cell RNA sequencing (scRNA-seq) was carried out on matched tumour and normal tissue. Three formalin-fixed and paraffin-embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP). RESULTS: Using DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA-seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = -.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD-L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region. CONCLUSIONS: These findings illustrate that assessing patient histological subtypes at the single-cell level is feasible. Additionally, tumour endothelial cells that express PD-L1 in stage IA LUAD suppress immune-responsive CD8+ T cells

A large-scale clinical validation study using nCapp cloud plus terminal by frontline doctors for the rapid diagnosis of COVID-19 and COVID-19 pneumonia in China

Background: The outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic acute infectious disease, especially with the features of possible asymptomatic carriers and high contagiousness. Currently, it is difficult to quickly identify asymptomatic cases or COVID-19 patients with pneumonia due to limited access to reverse transcription-polymerase chain reaction (RT-PCR) nucleic acid tests and CT scans. Goal: This study aimed to develop a scientific and rigorous clinical diagnostic tool for the rapid prediction of COVID-19 cases based on a COVID-19 clinical case database in China, and to assist doctors to efficiently and precisely diagnose asymptomatic COVID-19 patients and cases who had a false-negative RT-PCR test result. Methods: With online consent, and the approval of the ethics committee of Zhongshan Hospital Fudan University (NCT04275947, B2020-032R) to ensure that patient privacy is protected, clinical information has been uploaded in real-time through the New Coronavirus Intelligent Auto-diagnostic Assistant Application of cloud plus terminal (nCapp) by doctors from different cities (Wuhan, Shanghai, Harbin, Dalian, Wuxi, Qingdao, Rizhao, and Bengbu) during the COVID-19 outbreak in China. By quality control and data anonymization on the platform, a total of 3,249 cases from COVID-19 high-risk groups were collected. The effects of different diagnostic factors were ranked based on the results from a single factor analysis, with 0.05 as the significance level for factor inclusion and 0.1 as the significance level for factor exclusion. Independent variables were selected by the step-forward multivariate logistic regression analysis to obtain the probability model. Findings: We applied the statistical method of a multivariate regression model to the training dataset (1,624 cases) and developed a prediction model for COVID-19 with 9 clinical indicators that are accessible. The area under the receiver operating characteristic (ROC) curve (AUC) for the model was 0.88 (95% CI: 0.86, 0.89) in the training dataset and 0.84 (95% CI: 0.82, 0.86) in the validation dataset (1,625 cases). Discussion: With the assistance of nCapp, a mobile-based diagnostic tool developed from a large database that we collected from COVID-19 high-risk groups in China, frontline doctors can rapidly identify asymptomatic patients and avoid misdiagnoses of cases with false-negative RT-PCR results