Prognostic roles of dysregulated METTL3 protein expression in cancers and potential anticancer value by inhibiting METTL3 function.

BACKGROUND: Many studies have demonstrated the relationship between METTL3 protein expression and clinical outcomes in various cancers and elucidated the mechanism by which METTL3 disrupts the behavior of cancer cells. Here, we attempted to define the prognostic value of METTL3 protein in patients with cancer via systematic analysis and explored the potential effect of inhibiting METTL3 using its specific inhibitor. METHODS: We searched PubMed, Embase, and the Web of Science databases for studies that elucidated the prognostic value of METTL3 protein expression in all cancer types and then calculated the pooled hazard ratios with 95% confidence intervals for the overall survival (OS) of all cancer types and subgroups. Data from The Cancer Genome Atlas dataset were used to study METTL3 mRNA expression in cancers. Further, the effects of a METTL3-specific inhibitor were studied in cancer cells via the colony formation assay, the cell proliferation assay, and apoptosis detection. RESULTS: Meta-analysis of the 33 cohorts in 32 studies (3666 patients in total) revealed that higher METTL3 protein expression indicated poor OS in the majority of cancers. Bioinformatics analysis of METTL3 mRNA expression and cancer prognosis did not show the extremely prominent prognostic value of METTL3 mRNA. Nevertheless, the METTL3-specific inhibitor attenuated cell proliferation and cell cloning formation and promoted apoptosis. CONCLUSIONS: METTL3 protein expression is associated with poor prognosis in most cancer types and could be a biomarker for OS. Further, METTL3 inhibition might be a potential treatment strategy for cancers.

[Retracted] MicroRNA­320a suppresses tumour cell proliferation and invasion of renal cancer cells by targeting FoxM1.

Subsequently to the publication of the above paper, the authors drew to the attention of the Editorial Office that they made a couple of errors in terms of the data assembly in Figs. 2 and 4 in their paper; specifically, the Transwell assay data shown for the 'miR-320a+/FoxM1+' panel in Fig. 5D on p. 1923 also appeared as the 'ACTN/NC' data panel in Fig. 4E on the same page (Fig. 4E contained the erroneously duplicated panel). In addition, data featured in Fig. 2D of the above paper were strikingly similar to data that appeared in Fig. 6e of the following paper, published subsequently to this article, written by different authors (although a Dr Shiyue Zhao worked in the molecular biology laboratory of Harbin Medical University from 2017 to 2018, and the research collaboration was conducted with Dr Chenlong Li's research group): Li C, Zheng H, Hou W, Bao H, Xiong J, Che W, Gu Y, Sun H and Liang P: Long non-coding RNA linc00645 promotes. TGF-ß-induced epithelial-mesenchymal transition by regulating miR-205-3p-ZEB1 axis in glioma. Cell Death Dis 10: 17, 2019. Finally, after having conducted an independent investigation of the data in this paper, the Editorial Office noted that one of the Petri dish images in Fig. 2C was also strikingly similar to data that appeared in Fig. 2H of the abovementioned article in the journal Cell Death & Disease. After having considered the authors' request for corrigendum, in view of the problems that were identified with the data, the Editor of Oncology Reports has decided that, owing to a lack of confidence in the presented data, the paper should instead be retracted from the journal. After having informed the authors of this decision, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused.  [Oncology Reports 40: 1917­1926, 2018; DOI: 10.3892/or.2018.6597].

Risk factors of different mortality periods in older patients with end-stage renal disease undergoing urgent-start peritoneal dialysis: a retrospective observational study.

BACKGROUND: The first six months of therapy represents a high-risk period for peritoneal dialysis (PD) failure. The risk of death in the first six months is higher for older patients treated with urgent-start PD (USPD). However, there are still gaps in research on mortality and risk factors for death in this particular group of patients. We aimed to investigate mortality rates and risk factors for death in older patients with end-stage renal disease (ESRD) receiving USPD within and after six months of therapy. METHODS: We retrospectively studied the clinical information of older adults aged ≥ 65 years with ESRD who received USPD between 2013 and 2019 in five Chinese hospitals. Patients were followed up to June 30, 2020. The mortality and risk factors for death in the first six months of USPD treatment and beyond were analyzed. RESULTS: Of the 379 elderly patients in the study, 130 died over the study period. During the follow-up period, the highest number (45, 34.6%) of deaths occurred within the first six months. Cardiovascular disease was the most common cause of death. The baseline New York Heart Association (NYHA) class III-IV cardiac function [hazard ratio (HR) = 2.457, 95% confidence interval (CI): 1.200-5.030, p = 0.014] and higher white blood cell (WBC) count (HR = 1.082, 95% CI: 1.021-1.147, p = 0.008) increased the mortality risk within six months of USPD. The baseline NYHA class III-IV cardiac function (HR = 1.945, 95% CI: 1.149-3.294, p = 0.013), lower WBC count (HR = 0.917, 95% CI: 0.845-0.996, p = 0.040), lower potassium levels (HR = 0.584, 95% CI: 0.429-0.796, p = 0.001), and higher calcium levels (HR = 2.160, 95% CI: 1.025-4.554, p = 0.043) increased the mortality risk after six months of USPD. CONCLUSION: Different risk factors correlated with mortality in older adults with ESRD within and after six months of undergoing USPD, including baseline NYHA class III-IV cardiac function, WBC count, potassium, and calcium levels.

Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma.

OBJECTIVE: Lung squamous cell carcinoma (LUSC) is associated with a low survival rate. Evidence suggests that bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play crucial roles in tumorigenesis and progression. However, a comprehensive analysis of their role in LUSC is lacking. Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC. METHODS: The "R/Limma" package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC, using data from TCGA, GTEx, and GEO databases. Concurrently, the "survminer" packages were employed to investigate their prognostic value and correlation with clinical features in LUSC. The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis (WGCNA). LASSO analysis was conducted to construct a prognostic risk model for LUSC. Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC. Furthermore, based on the tumor immune estimation resource database and tumor-immune system interaction database, the role of the core gene in the tumor microenvironment of LUSC was explored. RESULTS: GDF10 had a significant correlation only with the pathological T stage of LUSC, and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC. A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes (HRASLS, HIST1H2BH, FLRT3, CHEK2, and ALPL) for LUSC. GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression. CONCLUSION: GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

G protein-coupled estrogen receptor activates PI3K/AKT/mTOR signaling to suppress ferroptosis via SREBP1/SCD1-mediated lipogenesis.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. The sex differences in the occurrence and fatality rates of non-small cell lung cancer (NSCLC), along with its association with estrogen dependence, suggest that estrogen receptors (ERs) contribute to the development of NSCLC. However, the influence of G protein-coupled estrogen receptor (GPER1) on NSCLC remains to be determined. Escape from ferroptosis is one of the hallmarks of tumor discovered in recent years. In this context, the present study evaluated whether GPER1 promotes NSCLC progression by preventing ferroptosis, and the underlying mechanism through which GPER1 protects against ferroptosis was also explored. METHODS: The effects of GPER1 on the cytotoxicity of H2O2, the ferroptosis inducer RSL3, and Erastin were assessed using the CCK8 assay and plate cloning. Lipid peroxidation levels were measured based on the levels of MDA and BODIPY™581/591C11. GPER1 overexpression and knockdown were performed and G1 was used, and the expression of SCD1 and PI3K/AKT/mTOR signaling factors was measured. Immunofluorescence analysis and immunohistochemistry were performed on paired specimens to measure the correlation between the expression of GPER1 and SCD1 in NSCLC tissues. The effect of GPER1 on the cytotoxicity of cisplatin was measured in vitro using the CCK8 assay and in vivo using xenograft tumor models. RESULTS: GPER1 and G1 alleviated the cytotoxicity of H2O2, reduced sensitivity to RSL3, and impaired lipid peroxidation in NSCLC tissues. In addition, GPER1 and G1 promoted the protein and mRNA expression of SCD1 and the activation of PI3K/AKT/mTOR signaling. GPER1 and SCD1 expression were elevated and positively correlated in NSCLC tissues, and high GPER1 expression predicted a poor prognosis. GPER1 knockdown enhanced the antitumor activity of cisplatin in vitro and in vivo. CONCLUSION: GPER1 prevents ferroptosis in NSCLC by promoting the activation of PI3K/AKT/mTOR signaling, thereby inducing SCD1 expression. Therefore, treatments targeting GPER1 combined with cisplatin would exhibit better antitumor effects.

METTL3 drives NSCLC metastasis by enhancing CYP19A1 translation and oestrogen synthesis.

BACKGROUND: METTL3 plays a significant role as a catalytic enzyme in mediating N6-methyladenosine (m6A) modification, and its importance in tumour progression has been extensively studied in recent years. However, the precise involvement of METTL3 in the regulation of translation in non-small cell lung cancer (NSCLC) remains unclear. RESULTS: Here we discovered by clinical investigation that METTL3 expression is correlated with NSCLC metastasis. Ablation of METTL3 in NSCLC cells inhibits invasion and metastasis in vitro and in vivo. Subsequently, through translatomics data mining and experimental validation, we demonstrated that METTL3 enhances the translation of aromatase (CYP19A1), a key enzyme in oestrogen synthesis, thereby promoting oestrogen production and mediating the invasion and metastasis of NSCLC. Mechanistically, METTL3 interacts with translation initiation factors and binds to CYP19A1 mRNA, thus enhancing the translation efficiency of CYP19A1 in an m6A-dependent manner. Pharmacological inhibition of METTL3 enzymatic activity or translation initiation factor eIF4E abolishes CYP19A1 protein synthesis. CONCLUSIONS: Our findings indicate the crucial role of METTL3-mediated translation regulation in NSCLC and reveal the significance of METTL3/eIF4E/CYP19A1 signaling as a promising therapeutic target for anti-metastatic strategies against NSCLC.

Immune characteristics analysis and construction of a four-gene prognostic signature for lung adenocarcinoma based on estrogen reactivity.

Lung adenocarcinoma (LUAD) is a common type of malignant tumor with poor prognosis and high mortality. In our previous studies, we found that estrogen is an important risk factor for LUAD, and different estrogen statuses can predict different prognoses. Therefore, in this study, we constructed a prognostic signature related to estrogen reactivity to determine the relationship between different estrogen reactivities and prognosis. We downloaded the LUAD dataset from The Cancer Genome Atlas (TCGA) database, calculated the estrogen reactivity of each sample, and divided them into a high-estrogen reactivity group and a low-estrogen reactivity group. The difference in overall survival between the groups was significant. We also analyzed the status of immune cell infiltration and immune checkpoint expression between the groups. We analyzed the differential gene expression between the groups and screened four key prognostic factors by the least absolute shrinkage and selection operator (LASSO) regression and univariable and multivariable Cox regression. Based on the four genes, a risk signature was established. To a certain extent, the receiver operating characteristic (ROC) curve showed the predictive ability of the risk signature, which was further verified using the GSE31210 dataset. We also determined the role of estrogen in LUAD using an orthotopic mouse model. Additionally, we developed a predictive nomogram combining the risk signature with other clinical characteristics. In conclusion, our four-gene prognostic signature based on estrogen reactivity had prognostic value and can provide new insights into the development of treatment strategies for LUAD.

Selective Laser Sintering Parameter Optimization of Prosopis Chilensis/Polyethersulfone Composite Fabricated by AFS-360 SLS.

The current available selective laser sintering (SLS) materials are often high in cost and limited in variety; the mechanical properties of wood-composite SLS parts are low quality, which restricts the development of SLS technology. This article aims to optimize the SLS processing parameters to enhance the mechanical properties of the Prosopis chilensis powder (PCP)/polyethersulfone (PES) composite (PCPC) part fabricated via SLS. The PCP and PES powder were proposed as the feedstock of the PCPC powder bed for SLS. First, the thermal decomposition and glass transition temperatures (Tg) of PCP and PES powder were estimated to reduce the produced PCPC parts from warping and deformation during SLS. An orthogonal experimental methodology with five factors and four levels was used to optimize the SLS parameters for the PCPC SLS test. The scanning speed, preheating temperature, and laser power are selected as the main affecting factors on this study. The influence of these factors on dimension accuracies, bending and tensile strengths, and surface roughness quality of the produced PCPC parts was studied. The PCPC particle distribution and microstructure were inspected via scanning electron microscopy. Furthermore, the synthesis weighted scoring methods were utilized to determine the optimal SLS processing parameters of the produced PCPC parts. The combined results of tests showed that the optimal SLS parameters were as follows: the scanning speed is 1.8 m/s, preheating temperature is 80°C, and the laser power is 12 W. Thus, the quality of PCPC SLS parts was significantly enhanced when the optimal parameters were utilized in the SLS process. This article provided the main reference values of SLS parameters of the PCPC. To further enhance the surface roughness quality and mechanical strengths, the postprocessing infiltration with wax was introduced; after wax infiltration, the surface roughness and mechanical strengths were significantly improved.

Study of Biomass Composite Workpiece Support Structure Based on Selective Laser Sintering Technology.

When using selective laser sintering to print parts with thin-walled structures, the thermal action of the laser can cause thermal stresses that lead to plastic deformation, resulting in large warpage and dimensional deviations. To address this issue, this study proposes a bottom support method for selective laser sintering. The impact of lattice-type, concentric-type, and cross-type support structures with varying filling densities and thicknesses on the suppression of warpage and dimensional errors was investigated. The optimal process parameters for each support structure were then determined through optimization. The findings of this study demonstrated a reduction in Z-axis dimensional errors of the workpiece following the addition of supports. The reduction amounted to 33.809%, 86.160%, and 66.214%, respectively, compared to the original workpiece. Moreover, the corresponding warpage was reduced by 35.673%, 46.189%, and 46.059% for each respective case, showcasing an improvement in the printing precision. Therefore, the bottom support effectively reduces dimensional and shape errors in thin-walled parts printed by selective laser sintering. Specifically, the results obtained indicated that the concentric type of support is more effective in reducing dimensional errors and enhancing the shape accuracy of the printed workpiece. Conversely, the cross type of support demonstrated superior capabilities in minimizing the consumption of printing materials while still delivering satisfactory results. Thus, this study holds promise for contributing to the advancement of thin-walled part quality using selective laser sintering technology. This research can contribute to achieving greater accuracy in the fabrication of parts through 3D printing.

ERß promoted invadopodia formation-mediated non-small cell lung cancer metastasis via the ICAM1/p-Src/p-Cortactin signaling pathway.

In a previous study, our research group observed that estrogen promotes the metastasis of non-small cell lung cancer (NSCLC) through the estrogen receptor ß (ERß). Invadopodia are key structures involved in tumor metastasis. However, it is unclear whether ERß is involved in the promotion of NSCLC metastasis through invadopodia. In our study, we used scanning electron microscopy to observe the formation of invadopodia following the overexpression of ERß and treatment with E2. In vitro experiments using multiple NSCLC cell lines demonstrated that ERß can increase the formation of invadopodia and cell invasion. Mechanistic studies revealed that ERß can upregulate the expression of ICAM1 by directly binding to estrogen-responsive elements (EREs) located on the ICAM1 promoter, which in turn can enhance the phosphorylation of Src/cortactin. We also confirmed these findings in vivo using an orthotopic lung transplantation mouse model, which validated the results obtained from the in vitro experiments. Finally, we examined the expressions of ERß and ICAM1 using immunohistochemistry in both NSCLC tissue and paired metastatic lymph nodes. The results confirmed that ERß promotes the formation of invadopodia in NSCLC cells through the ICAM1/p-Src/p-Cortactin signaling pathway.

Stearoyl-CoA Desaturases1 Accelerates Non-Small Cell Lung Cancer Metastasis by Promoting Aromatase Expression to Improve Estrogen Synthesis.

Metastases contribute to the low survival rate of non-small cell lung cancer (NSCLC) patients. Targeting lipid metabolism for anticancer therapies is attractive. Accumulative evidence shows that stearoyl-CoA desaturases1 (SCD1), a key enzyme in lipid metabolism, enables tumor metastasis and the underlying mechanism remains unknown. In this study, immunohistochemical staining of 96 clinical specimens showed that the expression of SCD1 was increased in tumor tissues (p < 0.001). SCD1 knockdown reduced the migration and invasion of HCC827 and PC9 cells in transwell and wound healing assays. Aromatase (CYP19A1) knockdown eliminated cell migration and invasion caused by SCD1 overexpression. Western blotting assays demonstrated that CYP19A1, along with ß-catenin protein levels, was reduced in SCD1 knocked-down cells, and estrogen concentration was reduced (p < 0.05) in cell culture medium measured by enzyme-linked immunosorbent assay. SCD1 overexpression preserving ß-catenin protein stability was evaluated by coimmunoprecipitation and Western blotting. The SCD1 inhibitor A939572, and a potential SCD1 inhibitor, grape seed extract (GSE), significantly inhibited cell migration and invasion by blocking SCD1 and its downstream ß-catenin, CYP19A1 expression, and estrogen concentration. In vivo tumor formation assay and a tail vein metastasis model indicated that knockdown of SCD1 blocked tumor growth and metastasis. In conclusion, SCD1 could accelerate metastasis by maintaining the protein stability of ß-catenin and then promoting CYP19A1 transcription to improve estrogen synthesis. SCD1 is expected to be a promised therapeutic target, and its novel inhibitor, GSE, has great therapeutic potential in NSCLC.

Improved Sintering Quality and Mechanical Properties of Peanut Husk Powder/Polyether Sulfone Composite for Selective Laser Sintering.

Current wood-plastic materials available for selective laser sintering (SLS) are limited and often suffer from low-quality and mechanical strength. In this study, a new composite of peanut husk powder (PHP)/polyether sulfone (PES) was developed for SLS additive manufacturing (AM). To use the biomass waste materials in AM technology, such as furniture and wood flooring, this composite based on agricultural waste is environmentally friendly, energy efficient, and low in production cost. SLS parts made from PHPC had good mechanical strength and excellent dimensional precision (DP). The thermal decomposition temperature of composite powder components and the glass transition temperatures of PES and various PHPC were determined first to prevent the PHPC parts from warping during sintering. Furthermore, the formability of PHPC powders in various mixing ratios was examined through single-layer sintering; and the density, mechanical strength, surface roughness, and DP of the sintered parts were measured. Particle distribution and microstructure of the powders and the SLS parts (both before and after breakage in mechanical tests) were inspected using scanning electron microscopy. According to the combined results, a ratio of PHP/PES = 10/90 (w/w) resulted in the best forming quality and mechanical strength compared with other ratios and pure PES. The measured density, impact strength, tensile strength, and bending strength for this PHPC are 1.1825 g/cm3, 2.12 kJ/cm2, 6.076 MPa, and 14.1 MPa, respectively. After wax infiltration, these parameters were further improved to 2.0625 g/cm3, 2.96 kJ/cm2, 7.476 MPa, and 15.7 MPa, respectively.

A five-gene expression signature of centromeric proteins with prognostic value in lung adenocarcinoma.

Background: Centromere proteins (CENPs) form a large protein family. Sixteen proteins in this family are positioned at the centromere throughout the cell cycle. The overexpression of CENPs is common in many cancers and predicts a poor prognosis. However, a comprehensive analysis of CENPs expression has not been conducted, and their clinical significance in lung adenocarcinoma (LUAD) is unclear. Methods: We investigated the expression differences of the CENP family in LUAD using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) cohorts. Kaplan-Meier curve survival analysis was performed to assess their independent prognostic values. We then tested 5 clinical LUAD specimens by quantitative real time polymerase chain reaction (qRT-PCR). The risk model was constructed with least absolute shrinkage and selection operator (LASSO). Cox regression analyses were carried out to determine independent prognostic indicators. Weighted gene coexpression network analysis (WGCNA) was employed to define the coexpression networks. Results: The messenger RNA (mRNA) expression of 15 differential CENP proteins was higher in LUAD than in normal lung tissues. Among them, 10 CENP proteins had significant prognostic value. The risk model comprising CENPF, CENPU, CENPM, CENPH, and CENPW showed a significant correlation [hazard ratio (HR) 1.75, 95% confidence interval (CI): 1.3-2.35; P=2e-04]. However, the prognostic accuracy was not strong [1-year survival: area under curve (AUC) 0.63; 3-year survival: AUC 0.62; 5-year survival: AUC 0.6]. The qRT-PCR results showed that the 5 CENPs were upregulated in LUAD tissues compared to in normal lung tissues. A total of 441 hub genes coexpressed with the 5 CENPs were identified. Conclusions: CENPF, CENPU, CENPM, CENPH, and CENPW have prognostic values and may be potential targets for LUAD treatment.

Critical Roles of METTL3 in Translation Regulation of Cancer.

Aberrant translation, a characteristic feature of cancer, is regulated by the complex and sophisticated RNA binding proteins (RBPs) in the canonical translation machinery. N6-methyladenosine (m6A) modifications are the most abundant internal modifications in mRNAs mediated by methyltransferase-like 3 (METTL3). METTL3 is commonly aberrantly expressed in different tumors and affects the mRNA translation of many oncogenes or dysregulated tumor suppressor genes in a variety of ways. In this review, we discuss the critical roles of METTL3 in translation regulation and how METTL3 and m6A reader proteins in collaboration with RBPs within the canonical translation machinery promote aberrant translation in tumorigenesis, providing an overview of recent efforts aiming to 'translate' these results to the clinic.

IHAOAVOA: An improved hybrid aquila optimizer and African vultures optimization algorithm for global optimization problems.

Aquila Optimizer (AO) and African Vultures Optimization Algorithm (AVOA) are two newly developed meta-heuristic algorithms that simulate several intelligent hunting behaviors of Aquila and African vulture in nature, respectively. AO has powerful global exploration capability, whereas its local exploitation phase is not stable enough. On the other hand, AVOA possesses promising exploitation capability but insufficient exploration mechanisms. Based on the characteristics of both algorithms, in this paper, we propose an improved hybrid AO and AVOA optimizer called IHAOAVOA to overcome the deficiencies in the single algorithm and provide higher-quality solutions for solving global optimization problems. First, the exploration phase of AO and the exploitation phase of AVOA are combined to retain the valuable search competence of each. Then, a new composite opposition-based learning (COBL) is designed to increase the population diversity and help the hybrid algorithm escape from the local optima. In addition, to more effectively guide the search process and balance the exploration and exploitation, the fitness-distance balance (FDB) selection strategy is introduced to modify the core position update formula. The performance of the proposed IHAOAVOA is comprehensively investigated and analyzed by comparing against the basic AO, AVOA, and six state-of-the-art algorithms on 23 classical benchmark functions and the IEEE CEC2019 test suite. Experimental results demonstrate that IHAOAVOA achieves superior solution accuracy, convergence speed, and local optima avoidance than other comparison methods on most test functions. Furthermore, the practicality of IHAOAVOA is highlighted by solving five engineering design problems. Our findings reveal that the proposed technique is also highly competitive and promising when addressing real-world optimization tasks. The source code of the IHAOAVOA is publicly available at https://doi.org/10.24433/CO.2373662.v1.

Dynamic Compressive Mechanical Behavior and Microstructure Evolution of Rolled Fe-28Mn-10Al-1.2C Low-Density Steel.

In this study, the quasi-static and dynamic compressive mechanical behavior of a rolled Fe-28Mn-10Al-1.2C steel (low-density) was investigated. X-ray diffraction, optical microscopy, electron backscattered diffraction and transmission electron microscopy were conducted to characterize the microstructure evolution. The results displayed that the steel has remarkable strain rate sensitivity and strong strain hardenability under high strain rate compression. Most specifically, the deformation behavior was changed with the increase in the strain rate. A feasible mathematical analysis for the calculation of stacking fault energies and the critical resolve shear stresses for twinning was employed and discussed the nucleation of the twinning. The microband-induced plasticity and twinning-induced plasticity controlled the deformation under high strain rate compression and provided a strong strain hardening effect. The higher mechanical response can increase the broad use of low-density steel in automobile applications.

Impact Resistant Structure Design and Optimization Inspired by Turtle Carapace.

The turtle carapace has a high level of protection, due to its unique biological structure, and there is great potential to use the turtle carapace structure to improve the impact resistance of composite materials using bionic theory. In this paper, the chemical elements of the turtle carapace structure, as well as its mechanical properties, were investigated by studying the composition of the compounds in each part. In addition, the bionic sandwich structure, composed of the plate, core, and backplate, was designed using modeling software based on the microstructure of the keratin scutes, spongy bone, and the spine of the turtle carapace. Additionally, finite element analysis and drop-weight experiments were utilized to validate the impact-resistant performance of the bionic structures. The numerical results show that all of the bionic structures had improved impact resistance to varying degrees when compared with the control group. The experimental results show that the split plate, the core with changing pore gradients, and the backplate with stiffener all have a considerable effect on the impact-resistance performance of overall composite structures. This preliminary study provides theoretical support for composite material optimization.

The Prognostic Value of Bone Morphogenetic Proteins and Their Receptors in Lung Adenocarcinoma.

BACKGROUND: Bone morphogenetic proteins (BMPs) regulate tumor progression via binding to their receptors (BMPRs). However, the expression and clinical significance of BMPs/BMPRs in lung adenocarcinoma remain unclear due to a lack of systematic studies. METHODS: This study screened differentially expressed BMPs/BMPRs (deBMPs/BMPRs) in a training dataset combining TCGA-LUAD and GTEx-LUNG and verified them in four GEO datasets. Their prognostic value was evaluated via univariate and multivariate Cox regression analyses. LASSO was performed to construct an initial risk model. Subsequently, after weighted gene co-expression network analysis (WGCNA), differential expression analysis, and univariate Cox regression analysis, hub genes co-expressed with differentially expressed BMPs/BMPRs were filtered out to improve the risk model and explore potential mechanisms. The improved risk model was re-established via LASSO combining hub genes with differentially expressed BMPs/BMPRs as the core. In the testing cohort including 93 lung adenocarcinoma patients, immunohistochemistry (IHC) was performed to verify BMP5 protein expression and its association with prognosis. RESULTS: BMP2, BMP5, BMP6, GDF10, and ACVRL1 were verified as downregulated in lung adenocarcinoma. Survival analysis identified BMP5 as an independent protective prognostic factor. We also found that BMP5 was significantly correlated with EGFR expression and mutations, suggesting that BMP5 may play a role in targeted therapy. The initial risk model containing only BMP5 showed a significant correlation (HR: 1.71, 95% CI: 1.28-2.28, p: 3e-04) but low prognostic accuracy (AUC of 1-year survival: 0.6, 3-year survival: 0.6, 5-year survival: 0.63). Seventy-nine hub genes co-expressed with BMP5 were identified, and their functions were enriched in cell migration and tumor metastasis. The re-established risk model showed greater prognostic correlation (HR: 2.58, 95% CI: 1.92-3.46, p: 0) and value (AUC of 1-year survival: 0.72, 3-year survival: 0.69, and 5-year survival: 0.68). IHC results revealed that BMP5 protein was also downregulated in lung adenocarcinoma and higher expression was markedly associated with better prognosis (HR: 0.44, 95% CI: 0.23-0.85, p: 0.0145). CONCLUSION: BMP5 is a potential crucial target for lung adenocarcinoma treatment based on significant differential expression and superior prognostic value.

Effects of TiB2 Particles on the Microstructure Evolution and Mechanical Properties of B4C/TiB2 Ceramic Composite.

B4C/TiB2 ceramic composites reinforced with three size scales (average particle size: 7 µm, 500 nm, and 50 nm) of TiB2 were prepared by using a pressureless sintering furnace at 2100 °C under Ar atmosphere for 60 min. The results demonstrated that during the sintering process, TiB2 located on the boundaries between different B4C grains could inhibit the grain growth which improved the mass transport mechanism and sintering driving force. A semi-coherent interface between B4C and SiC was found, which is supposed to help to reduce the interface energy and obtain good mechanical properties of the B4C/TiB2 ceramic composite. On sample cooling from sintering temperature to room temperature, the residual tensile stress fields formed at the TiB2 interfaces owning to the thermo-elastico properties mismatched, which might have contributed to increase the ability of the sample to resist crack propagation. The results showed that the relative density, Vickers hardness, and fracture toughness of the composite with 20 wt.% submicron and 10 wt.% nano-TiB2 were significantly improved, which were 98.6%, 30.2 GPa, and 5.47 MPa·m1/2, respectively.

Upregulation of estrogen receptor beta protein but not mRNA predicts poor prognosis and may be associated with enhanced translation in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: An increasing number of original studies suggest that estrogen receptor beta (ERß) expression may be related to non-small cell lung cancer (NSCLC) prognosis; however, the evidence remains inconclusive and conflicting. We aimed to systematically evaluate the expression and prognostic value of ERß in NSCLC, and to explain the inconsistency between ERß protein and mRNA level. METHODS: PubMed, Embase, and Web of Science databases were searched for studies (published before October 6, 2020) reporting the prognostic value of ERß protein expression in NSCLC. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) were calculated. Transcriptome and survival data of lung adenocarcinoma patients were obtained from public databases for differential expression and survival analyses. Immunohistochemistry (IHC) was performed to examine the ERß protein expression in 39 NSCLC patients. Western blotting and RT-qPCR were performed to analyze ERß expression in two paired NSCLC and normal adjacent tissue samples. The effect of methyltransferase-like 13 (METTL3) on ERß expression was investigated in a lung cancer cell line. RESULTS: Meta-analysis of 23 studies with a total of 3744 patients demonstrated that high protein expression of overall ERß and cytoplasmic ERß indicated poor OS (HR: 1.05, 95% CI: 1.00 to 1.10; HR: 1.48, 95% CI: 1.13 to 1.95) in NSCLC. For lung adenocarcinoma especially, high protein expression of both overall/cytoplasmic ERß and nuclear ERß suggested poor OS (HR: 1.54, 95% CI: 1.05 to 2.25; HR: 1.36, 95% CI: 1.03 to 1.80). Bioinformatics analysis indicated the expression of ERß mRNA was not associated with the prognosis of lung adenocarcinoma. Analysis of public databases showed that ERß mRNA is not highly expressed in tumor tissues, however, IHC results revealed that ERß protein is highly expressed in NSCLC tissues. We validated this inconsistency in ERß expression in paired tumors and normal adjacent tissues from patients. Moreover, METTL3 knockdown in the A549 cell line downregulated ERß protein expression but not ERß mRNA expression. CONCLUSIONS: Our study elucidated the inconsistency between ERß protein and mRNA expression levels and their prognostic values. The results indicated that METTL3-driven enhanced translation in NSCLC may cause this inconsistency.