MMP11 is associated with the immune response and immune microenvironment in EGFR-mutant lung adenocarcinoma

BackgroundHigh expression of matrix metalloproteinase-11 (MMP11) is associated with various tumors and immune microenvironments. Conversely, poor response to immunotherapy in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LUAD) patients is closely related to the characteristics of immune microenvironment.MethodsThe Cancer Genome Atlas (TCGA)-LUAD database and our gathered clinical LUAD samples were used to examine the relationship between MMP11 expression and EGFR mutation. Then the correlation between MMP11 and immune response and the difference of immune cell infiltration in different groups were analyzed. Compared the differences in the immune microenvironment between the MMP11-positive and MMP11-negative expression groups using immunohistochemistry (IHC) and multiplex immunohistochemistry.ResultsThe expression of MMP11 in samples with exon 19 deletions, exon 21 L858R or de novo exon 20 T790M mutations was higher than wild type, but there was no difference between the samples with uncommon mutation and the wild-type. The high MMP11 expression group had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score. Pathways associated with enrichment in the extracellular matrix (ECM) were the main biological functions of differential genes between the high and low MMP11 groups. The IHC score of MMP11 in the EGFR-mutant group was higher than in the EGFR-wild group. In TCGA-LUAD, the high MMP11 group had a lower proportion of T cell CD8+ and NK cells activated. In the clinical samples, the infiltration levels of T cell CD8+ and NK cells in the tumor parenchyma of EGFR-mutant LUAD was lower in the MMP11-positive than in the MMP11-negative group. The expression levels of tumor cell PD-L1 were higher in the MMP11-positive expression group than in the MMP11-negative expression group, and the proportion of PD1+CD8+ T cells infiltrated was reduced in the MMP11-positive group compared to the MMP11-negative group.ConclusionsHigh expression of MMP11 was associated with EGFR mutations. Patients with EGFR-mutant LUAD with high expression of MMP11 responded poorly to immunotherapy, and the percentage of T cell CD8+ and NK cells in immune cell infiltration was lower in MMP11. Consequently, MMP11 is related to the immunological microenvironment of EGFR-mutant lung adenocarcinoma, which may be a predictor of possible immunotherapeutic response

Investigation of the prevalence and clinical implications of ERBB2 exon 16 skipping mutations in Chinese pan-cancer patients

BackgroundAlthough rare, ERBB2 exon 16 skipping mutations (ERBB2ΔEx16) have been implicated in resistance to anti-HER2 and anti-EGFR targeted agents. Our study investigated the prevalence and clinical significance of ERBB2ΔEx16 in Chinese pan-cancer patients.MethodsWe retrospectively screened 40996 patients, spanning 19 cancer types, who had available genomic profiles acquired with DNA-based next-generation sequencing (NGS). We characterized the clinical and molecular features of the ERBB2ΔEx16-positive patients. Furthermore, we also analyzed a pan-cancer dataset from the Cancer Genome Atlas (TCGA; n=8705).ResultsA total of 22 patients were detected with ERBB2ΔEx16, resulting in an overall prevalence rate of 0.054% (22/40996). Of them, 16 patients had lung cancer (LC; 0.05%, 16/30890), five patients had gastric cancer (GC; 0.35%, 5/1448), and one patient had ovarian cancer (0.12%, 1/826). Among the 16 LC patients, ERBB2ΔEx16 was detected in four treatment-naïve EGFR/ALK-negative patients and 12 EGFR-positive patients after the onset of resistance to EGFR tyrosine kinase inhibitors (TKIs). The treatment-naïve patients harbored no LC-associated oncogenic drivers except ERBB2 amplification, suggesting a potential oncogenic role for ERBB2ΔEx16. Consistently, ERBB2ΔEx16+ patients from TCGA data also carried no known drivers despite various concurrent alterations. In the 12 EGFR TKI-resistant LC patients, relative variant frequencies for ERBB2ΔEx16 were lower than in untreated patients, suggesting ERBB2ΔEx16 as secondary alterations following TKI treatment and thereby implicating ERBB2ΔEx16 in mediating therapeutic resistance.ConclusionsOur study identified an overall ERBB2ΔEx16 prevalence rate of 0.054% and provided insights into the clinical implications of ERBB2ΔEx16 in Chinese pan-cancer patients

Reliability Evaluation of Multiple DCFP System subject to Shifting Threshold

This paper focuses on system reliability analysis with dependent competing failure process due to soft failure and hard failure. Some new probabilistic methods based on cumulative shock model and nonlinear Wiener process under different shifting thresholds situation are obtained. Considering that nonlinearity exists extensively in practice, the continuous soft failure process is governed by random effected nonlinear Wiener process. Firstly, reliability evaluation models for hard failure and soft failure are obtained under the cumulative shock, respectively. Furthermore, some system reliability models under different shifting thresholds situation are studied, in which failure threshold will decrease after a certain number of shocks. A real numerical example about fatigue crack growth dataset is carried out to demonstrate the proposed procedure. Numerical results indicate that both random shocks and shifting threshold have significant effect on system reliability. Finally, some sensitivity analysis are also been given

Multiscale characterization of the UV aging resistance and mechanism of light stabilizer-modified asphalt

To clarify the effect and mechanism of hindered amine light stabilizer (HALS) on the UV aging behavior of asphalt binder, T622-HALS was selected as the modifier for UV aging resistance of asphalt. The physicochemical properties and microstructure of T622 light stabilizer were comprehensively analyzed. The light stabilizer-modified asphalt was prepared and placed in the UV radiation chamber for UV aging treatment. Scanning electron microscope and atomic force microscope were used to analyze the microscopic morphology evolution of light stabilizer-modified asphalt induced by UV radiation. The thermal properties and functional group composition changes in light stabilizer-modified asphalt during UV aging were studied by using the thermogravimetric and infrared spectroscopy combined testing system. The decay laws of the physical and rheological performances of light stabilizer-modified asphalt were studied during UV aging process, and the effect of light stabilizer on the UV aging behavior of asphalt binder was clarified. The research results indicated that HALSs could alleviate the microcracks and roughness change on the surface of asphalt and reduce the content of functional groups such as carbonyl and sulfoxide in asphalt. Furthermore, HALS could reduce the value difference of physical and rheological properties of asphalt before and after UV aging, significantly improving the UV aging resistance of asphalt binder

Non-limit passive soil pressure on rigid retaining walls

This paper aims to reveal the depth distribution law of non-limit passive soil pressure on rigid retaining wall that rotates about the top of the wall (rotation around the top (RT) model). Based on Coulomb theory, the disturbance degree theory, as well as the spring-element model, by setting the rotation angle of the wall as the disturbance parameter, we establish both a depth distribution function for sand and a nonlinear depth distribution calculation method for the non-limit passive soil pressure on a rigid retaining wall under the RT model, which is then compared with experiment. The results suggest that under the RT model: the non-limit soil pressure has a nonlinear distribution; the backfill disturbance degree and the lateral soil pressure increase with an increase in the wall rotation angle; and, the points where the resultant lateral soil pressure acts on the retaining wall are less than 2/3 of the height of the wall. The soil pressure predicted by the theoretical calculation put forward in this paper are quite similar to those obtained by the model experiment, which verifies the theoretical value, and the engineering guidance provided by the calculations are of significance. Keywords: RT model, Rigid wall, Non-limit passive soil pressure, Spring element, Genetic algorith

Z-Scheme CuOx/Ag/TiO2 Heterojunction as Promising Photoinduced Anticorrosion and Antifouling Integrated Coating in Seawater

In the marine environment, steel materials usually encounter serious problems with chemical or electrochemical corrosion and fouling by proteins, bacteria, and other marine organisms. In this work, a green bifunctional Z-scheme CuOx/Ag/P25 heterostructure coating material was designed to achieve the coordination of corrosion prevention and antifouling by matching the redox potential of the reactive oxygen species and the corrosion potential of 304SS. When CuOx/Ag/P25 heterostructure was coupled with the protected metal, the open circuit potential under illumination negatively shifted about 240 mV (vs. Ag/AgCl) and the photoinduced current density reached 16.6 μA cm−2. At the same time, more reactive oxygen species were produced by the Z-shape structure, and then the photocatalytic sterilization effect was stronger. Combined with the chemical sterilization of Ag and the oxide of Cu, the bacterial survival rate of CuOx/Ag/P25 was low (0.006%) compared with the blank sample. This design provides a strategy for developing green dual-functional coating materials with photoelectrochemical anticorrosion and antifouling properties

Serum exosomal microRNA-370-3p and microRNA-196a-5p are potential biomarkers for the diagnosis and prognosis of hepatocellular carcinoma

Introduction. Evidence has shown that some microRNAs (miRNAs) play a role in tumorigenesis of hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the diagnostic and prognostic values of serum exosomal miR-370-3p and miR-196a-5p in patients with HCC.Material and methods. Serum exosomes in 90 HCC patients were extracted and identified. Serum exosomal miR-370-3p and miR-196a-5p expression in HCC patients were detected. The diagnostic value of miR-370-3p and miR-196a- 5p, relationship between miR-370-3p and miR-196a-5p expression and clinicopathological features and prognosis of patients with HCC were analyzed. Relationship between miR-370-3p and miR-196a-5p expression and liver function indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in HCC patients were analyzed. The effects of miR-370-3p and miR-196a-5p on Huh-7 HCC cells’ proliferation, invasion and migration were determined.Results. Lower expression of miR-370-3p and higher expression of miR-196a-5p were found in serum exosomes of HCC patients. Serum exosomal miR-370-3p and miR-196a-5p were associated with tumor size, tumor grade and TNM stage as well as prognosis and liver function indices of HCC patients. Overexpressed miR-370-3p or silenced miR-196a-5p suppressed proliferation, invasion and migration of Huh-7 HCC cells.Conclusions. We suggest that miR-370-3p/miR-196a-5p in serum exosomes of HCC patients could be potential biomarkers for the diagnosis and prognosis of HCC

Preliminary results of Calcium atom analysis by the wind-temperature-metal-constituents LiDAR at Mohe middle-upper atmosphere for the Phase II of Chinese Meridian Project

The Phase II of Chinese Meridian Project atmosphere wind-temperature-metal-constituents LiDAR at Mohe (122°E, 53°N) station uses a resonance fluorescence scattering mechanism to detect the metal layer composition in the upper atmosphere at 80-120 km , and subsequently uses these metal components as tracers to study various complex chemical and kinetic processes in the middle and upper atmosphere. The time resolution of this LiDAR is 1.1 min and the spatial resolution is 30 m. With high spatial and temporal resolution, we obtained a high signal to noise ratio for Ca number density. Further, we analyzed the evolution of Ca number density with time and height in January 2023. We observed that the peak value of background and sporadic Ca number densities reached approximately 33.55 cm−3 and 53.64 cm−3, respectively. In comparison with that in Yanqing (116.0°E, 40.5°N) station, the Ca number density in Mohe station was higher. Moreover, while examining the Ca observation studies conducted at foreign stations, we found that the Ca number density in Mohe was close to that of Kuhlungsborn station (54°N, 12°E; Germany) and was higher than that of Observatoire de Haute Provence station (44°N, 6E; France). Additionally, during January 12–14, 2023, we observed calcium meteor trails, consistently appearing near the peak of the metal layer spectrum