Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation.

The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations exacerbate inflammation has not been explored. Here, using antibiotic treatment and fecal microbial transfers, we showed that sepsis susceptibility is driven by pregnancy-induced changes to gut microbiome in mice and humans. Integrative multiomics and genetically engineered bacteria revealed that reduced Parabacteroides merdae (P. merdae) abundance during pregnancy led to decreased formononetin (FMN) and increased macrophage death. Mechanistically, FMN inhibited macrophage pyroptosis by suppressing nuclear accumulation of hnRNPUL2 and subsequent binding to the Nlrp3 promoter. Treatment with FMN or deletion of murine hnRNPUL2 protected against septic inflammation. Intestinal abundances of P. merdae and FMN inversely correlated with the progression of septic patients. Our data reveal a microbe-immune axis that is disrupted in pregnant septic hosts, highlighting the potential of the FMN-hnRNPUL2-NLRP3 axis in providing promising therapeutic strategies for sepsis.

Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer.

BACKGROUND: Thrombospondin-1 (THBS1) is a secretory adhesive glycoprotein involved in the progression of multiple malignancies, including breast cancer. However, the clinical significance and prognostic role of plasma THBS1 in breast cancer have yet to be clarified. METHODS: Plasma THBS1 levels in 627 breast cancer patients were analyzed by enzyme-linked immunosorbent assay. Bone marrow blood was drawn from the anterior/posterior superior iliac spine to detect the presence of disseminated tumor cells (DTCs). The effects of plasma THBS1 on the clinicopathological characteristics and survival prediction of breast cancer patients were explored. RESULTS: Plasma THBS1 did not correlate with overall survival, breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) in the entire breast cancer cohort. Notably, HER2-enriched patients with high-plasma THBS1 levels had significantly shorter BCSS (P = 0.027) and DDFS (P = 0.011) than those with low levels. Multivariate analyses revealed that plasma THBS1 was an independent prognostic marker of BCSS (P = 0.026) and DDFS (P = 0.007) in HER2-enriched patients. THBS1 levels were 24% higher in positive DTC patients than in negative DTC patients (P = 0.031), and high levels were significantly associated with poor BCSS in positive DTC patients (HR 2.08, 95% CI 1.17-3.71; P = 0.019). Moreover, high-plasma THBS1 levels were specifically associated with an increased occurrence of brain metastasis in HER2-enriched patients (P = 0.041). CONCLUSION: These findings suggest that plasma THBS1 may be serving as an unfavorable prognosis predictor for HER2-enriched breast cancer and justifies the need for further research.

Preliminary exploration of the effects of environmental factors on the microsatellite status of BRAF-mutated colorectal cancer.

BACKGROUND: To investigate the expression of EBV products and frequency of gallstone disease (GD) among different microsatellite status in colorectal cancer (CRC) with BRAFV600E mutation. METHODS: We collected 30 CRC patients with BRAFV600E mutation and 10 BRAF ( -) CRC patients as well as 54 healthy subjects. Tumor tissue samples were collected to detect the mutation of BRAF, KRAS, and TP53. Microsatellite status was determined by immunohistochemistry and PCR. EBER in situ hybridization was performed to detect EBV. In addition, we also collected clinical information about the patients. RESULTS: We found that although EBV products were detected in CRC, there were no significant differences in the EBV distribution between the different BRAF groups. Our study demonstrated that BRAFV600E mutation and BRAFV600E with MSI were significantly more frequent in the right CRC. Furthermore, the KRAS mutation rate in the BRAF-wild-type group was proved to be significantly higher than that in the BRAF mutation group. In addition, we revealed that BRAF mutation and MSI were independent risk factors of TNM stage. The frequency of GD was higher in CRC patients than in general population, and although there was no significant difference between CRC with or without BRAFV600E mutation, the highest frequency of GD was found in MSS CRC with BRAFV600E mutation. CONCLUSIONS: EBV plays a role in CRC, but is not a determinant of different microsatellite status in CRC with BRAFV600E mutation. The frequency of GD in MSS CRC with BRAFV600E mutation is significantly higher than that in the general population.

Combined analysis of imaging tumor capsule with imaging tumor size guides the width of resection margin for solitary hepatocellular carcinoma.

BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.

MRP8/14 mediates macrophage efferocytosis through RAGE and Gas6/MFG-E8, and induces polarization via TLR4-dependent pathway.

Myeloid-related protein 8/14 (MRP8/14) participates in various inflammatory responses, however, its effect on macrophage efferocytosis remains unclear. Here, we demonstrate that MRP8/14 significantly inhibits the efferocytosis of apoptotic thymocytes by mouse bone marrow-derived macrophages (BMDMs), which later proves to be associated with the receptor for advanced glycation end products (RAGE) or for reducing the expression of growth arrest-specific protein 6 and milk fat globule epidermal growth factor 8, independent of RAGE. Furthermore, MRP8/14 promotes polarization of BMDMs from the M2 - to M1 -like phenotype by upregulating expression of M1 -related surface receptor proteins and signature M1 -marker genes and by downregulating signature M2 -marker gene expression, which depends on Toll-like receptor 4 and p38 mitogen-activated protein kinase/nuclear factor κB pathways. Thus, we report a significant inhibitory effect of MRP8/14 on macrophage efferocytosis and MRP8/14-mediated phenotypic polarization, which may be helpful in developing novel therapeutic strategies leading to inflammation resolution.

Reabsorption of bile acids regulated by FXR-OATP1A2 is the main factor for the formation of cholesterol gallstone.

The purpose of this study was to demonstrate the aberrant metabolism of bile acids in patients with cholesterol gallstone and explore for its underlying mechanisms. The composition of bile acids collected from the patients with cholelithiasis and the control individuals was analyzed by LC-MS. The expression of genes regulating the metabolism of bile acids was quantitatively determined by real-time PCR or Western blot analysis. Cholesterol saturation index of patients with gallstone was significantly higher than that of the controls. The concentrations of taurodeoxycholic acid and taurolithocholic acid in the bile of patients were significantly higher than that of the controls. When compared with the controls, it was remarkable in the patients that the mRNA expression of farnesoid X receptor (FXR) was lower, whereas that of organic anion transporting polypeptide (OATP1A2) was higher. However, the expressions of both mRNA and protein of cytochrome P-450 family 8 subfamily B member 1 (CYP8B1) did not differ between the patients and the controls. Although the protein level of CYP8B1 was significantly lower in the subjects with single nucleotide polymorphism (SNP) rs3732860(G), the composition of bile acids and the ratio of CA to CDCA remained unaltered in the patients with different SNP genotype of CYP8B1. In conclusion, the axis of FXR-OATP1A2 that physiologically regulated the reabsorption of bile acids might play an important role in the composition of bile acids and the development of gallstone. CYP8B1 gene was irrelevant to the altered composition of bile acids in patients with gallstone.NEW & NOTEWORTHY For the first time, our results indicate that the axis of farnesoid X receptor-organic anion transporter polypeptide 1A2 that physiologically regulates the reabsorption of bile acids might play an important role in the regulation of the composition of bile acids and make contribution to the development of cholelithiasis.

Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis-Induced Liver Injury by Granisetron Generation in Mice.

Sepsis-induced liver injury is recognized as a key problem in intensive care units. The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis-induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis-induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was used to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis-resistant (Res; survived to 7 days after CLP) and sepsis-sensitive (Sen; moribund before or approximately 24 hours after CLP) mice. Mice gavaged with feces from Sen mice displayed more-severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5-hydroxytryptamine 3 (5-HT3 ) receptor antagonist, than the microbiota from Sen mice. Granisetron protected mice against CLP-induced death and liver injury. Moreover, proinflammatory cytokine expression by macrophages after lipopolysaccharide (LPS) challenge was markedly reduced in the presence of granisetron. Both treatment with granisetron and genetic knockdown of the 5-HT3A receptor in cells suppressed nuclear factor kappa B (NF-кB) transactivation and phosphorylated p38 (p-p38) accumulation in macrophages. Gut microbial granisetron levels showed a significantly negative correlation with plasma alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels in septic patients. Conclusion: Our study indicated that gut microbiota plays a key role in the sensitization of sepsis-induced liver injury and associates granisetron as a hepatoprotective compound during sepsis development.

Alpha-Lipoic Acid Suppresses Extracellular Histone-Induced Release of the Infammatory Mediator Tumor Necrosis Factor-α by Macrophages.

BACKGROUND/AIMS: This study investigated signaling pathways via which extracellular histones induce the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) release from the macrophage cell line RAW 264.7 and the anti-inflammatory efficacy of the antioxidant alpha-lipoic acid (ALA). METHODS: ELISA and western blotting analyses were conducted to detect the release of TNF-α from histone-stimulated RAW 264.7 macrophages and the associated phospho-activation of MAPKs (ERK and p38) and NF-κB p65. The effects of ALA on the release of TNF-α and phospho-activation of the MAPKs and NF-κB p65 were studied. P < 0.05 was considered statistically significant. RESULTS: Extracellular histones dose-dependently induced TNF-α release from RAW 264.7 cells and increased the phosphorylation of p38, ERK, and NF-κB p65. TNF-α release was markedly suppressed by p38, ERK, and NF-kB inhibitors. ALA reduced histone-induced TNF-α release, ERK/p38 MAPK activation, and NF-kB activation without affecting macrophage viability. CONCLUSION: Histones induce TNF-α release from macrophages by activating the MAPK and NF-kB signaling pathways, while ALA suppresses this response by inhibiting ERK, p38 and NF-kB. These findings identify potentially critical inflammatory signaling pathways in sepsis and molecular targets for sepsis treatment.

Polydatin post-treatment alleviates myocardial ischaemia/reperfusion injury by promoting autophagic flux.

Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation. We noted that PD enhanced autophagy and decreased apoptosis during I/R or hypoxia/reoxygenation (H/R), and this effect was antagonized by co-treatment with adenovirus carrying short hairpin RNA for Beclin 1 and 3-methyladenine (3-MA), an autophagic inhibitor. Compared with vehicle-treated mice, PD-treated mice had a significantly smaller myocardial infarct size (IS) and a higher left ventricular fractional shortening (LVFS) and ejection fraction (EF), whereas these effects were partly reversed by 3-MA. Furthermore, in the PD-treated NRCs, tandem fluorescent mRFP-GFP-LC3 assay showed abundant clearance of autophagosomes with an enhanced autophagic flux, and co-treatment with Bafilomycin A1 (Baf), a lysosomal inhibitor, indicated that PD promoted the degradation of autolysosome. In addition, PD post-treatment reduced mitochondrial membrane potential and cellular reactive oxygen species (ROS) production in NRCs, and these effects were partially blocked by Baf. These findings indicate that PD post-treatment limits myocardial I/R injury by promoting autophagic flux to clear damaged mitochondria to reduce ROS and cell death.

Molecular subtypes predict the prognosis of male breast cancer: a retrospective cohort study.

Background: Male breast cancer is rare, and something different from female breast cancer. The characteristics of molecular subtype in male breast cancer is unclear and lack of large-sample study. Methods: A retrospective study was conducted to investigate the characteristics and prognosis of patients with male breast cancer using the data recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2014. A total of 1,597 cases were enrolled with median age of 66 years. The study endpoint was considered as patient death. The molecular subtype was defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, hormone receptor (HR) positive was defined as ER positive with or without PR positive, including 1,373 cases of HR+/HER2- tumor (86%), 182 cases of HR+/HER2+ tumor (11.4%), 13 cases of HR-/HER2+ tumor (0.8%) and 29 cases with triple negative (TN) tumor (1.8%), respectively. Results: There were significant differences in distributions of age, race, grade, tumor size and American Joint Committee on Cancer (AJCC) stage between different molecular subtypes. Patients of different molecular subtypes differed significantly in 5 years overall survival and cause-specific survival (CSS). Five-year CSS (5y-CSS) rates of different molecular subtypes was 89.2% (HER2-/HR+), 78.4% (HER2+/HR+), 72.6% (HER2+/HR-) and 43.2% (TN), respectively. According to Cox regression, age ≥65 years [P=0.001, hazard ratio (HR) =2.136 (1.372, 3.324)], ER negative [P=0.02, HR =2.481 (1.159, 5.319)], PR negative [P=0.007, HR =2.294 (1.256, 4.184)], TN subtype [P<0.001, HR =10.676 (4.441, 25.665)], AJCC stage IV [P<0.001, HR =21.222 (10.377, 43.4)], tumor size >5 cm or T4 [P<0.001, HR =2.577 (0.978, 6.792)], Stage M1 [P=0.001, HR =4.519 (1.929, 10.587)] and Black race [P=0.002, HR =2.322 (1.442, 3.74)] were independent prognostic factors for poorer CSS. Conclusions: Just like female, molecular subtypes also varied in male breast cancer. It could be a predictor for survival and improve the strategy making in clinical practice.

Erratum: High-background parenchymal enhancement in the contralateral breast is an imaging biomarker for favorable prognosis in patients with triple-negative breast cancer treated with chemotherapy.

[This corrects the article on p. 4422 in vol. 13, PMID: 34150024.].

Prediction of target genes in community-acquired pneumonia based on the bioinformatics method.

Background: To screen the related genes of community-acquired pneumonia (CAP) by bioinformatics technology, and to analyze the clinical value of key genes. Methods: Gene chip data sets containing CAP patients and normal controls were screened from the Gene Expression Omnibus (GEO) database. The downregulated differentially expressed genes (DEGs) were screened using a gene expression analysis tool (GEO2R). Simultaneously, gene set enrichment analysis (GSEA) was used to explore the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and core genes related to CAP. The candidate genes were then intersected with the genes reported in Online Mendelian Inheritance in Man (OMIM), and the clinical value of these candidate genes was examined based on a literature search. Finally, the clinical data of the CAP patients were retrospectively analyzed. Detect the type of pathogenic bacteria in bronchial-alveolar lavage fluid (BALF) using metagenomics next-generation sequencing (mNGS) high throughput sequencing technology, and detect the expression of key genes through liquid based cell immunohistochemistry to analyze the correlation between pathogenic bacteria and key genes. Results: Through the intersection of Venn diagrams, 175 co-expressed downregulated DEGs related to CAP were identified. A total of 4 candidate genes, including ICOS, IL7R, ITK, and ZAP70, were obtained by constructing the protein mutual aid network and conducting a module analysis of the common differentially expressed genes. The core genes in the GSEA enrichment pathways were intersected with the CAP-related genes reported in the relevant literature retrieved from the OMIM database. In the Venn diagram, two genes that coexist with OMIM include IL7R and PIK3R1. After considering our findings and the relevant literature, we determined that the key gene related to the occurrence and development of CAP was IL7R. The mNGS detected 13 kinds of bacteria, 4 kinds of fungi, and 2 kinds of viruses. Based on immunohistochemical results, it was found that there were relatively more bacteria detected in the IL7R high expression group. Conclusions: The identification of the key gene IL7R and the related signaling pathways extend understanding of the pathogenesis of CAP and provide a theoretical basis for clinical targeted therapy research.

Sustained induction of IP-10 by MRP8/14 via the IFNß-IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice.

Background: As a damage-associated molecular pattern, the myeloid-related protein 8/14 (MRP8/14) heterodimer mediates various inflammatory diseases, such as sepsis. However, how MRP8/14 promotes lung injury by regulating the inflammatory response during endotoxemia remains largely unknown. This study aims at illuminating the pathological functions of MRP8/14 in endotoxemia. Methods: An endotoxemic model was prepared with wild-type and myeloid cell-specific Mrp8 deletion (Mrp8ΔMC) mice for evaluating plasma cytokine levels. Lung injury was evaluated by hematoxylin and eosin (H&E) staining, injury scoring and wet-to-dry weight (W/D) ratio. The dynamic profile of interferon γ (IFNγ)-inducible protein 10 (IP-10) mRNA expression induced by macrophage MRP8/14 was determined by quantitative real-time polymerase chain reaction (qPCR). Immunoblotting was used to evaluate the increase in IP-10 level induced by activation of the JAK-STAT signaling pathway. Luciferase reporter assay was performed to detect the involvement of IRF7 in Ip-10 gene transcription. In vivo air pouch experiments were performed to determine the biological function of IP-10 induced by MRP8/14. Results: Experiments with Mrp8ΔMC mice showed that MRP8/14 promoted the production of cytokines, including IP-10, in the bronchoalveolar lavage fluid (BALF) and lung injury in endotoxic mice. The result of qPCR showed sustained expression of Ip-10 mRNA in macrophages after treatment with MRP8/14 for 12 h. Neutralization experiments showed that the MRP8/14-induced Ip-10 expression in RAW264.7 cells was mediated by extracellular IFNß. Western blotting with phosphorylation-specific antibodies showed that the JAK1/TYK2-STAT1 signaling pathway was activated in MRP8/14-treated RAW264.7 cells, leading to the upregulation of Ip-10 gene expression. IRF7 was further identified as a downstream regulator of the JAK-STAT pathway that mediated Ip-10 gene expression in macrophages treated with MRP8/14. In vivo air pouch experiments confirmed that the IFNß-JAK1/TYK2-STAT1-IRF7 pathway was required for chemokine (C-X-C motif) receptor 3 (CXCR3)+ T lymphocyte migration, which promoted lung injury in the context of endotoxemia. Conclusions: In summary, our study demonstrates that MRP8/14 induces sustained production of IP-10 via the IFNß-JAK1/TYK2-STAT1-IRF7 pathway to attract CXCR3+ T lymphocytes into lung tissues and ultimately results in lung injury by an excessive inflammatory response in the context of endotoxemia.

Downregulation of ZNF280A inhibits proliferation and tumorigenicity of colorectal cancer cells by promoting the ubiquitination and degradation of RPS14.

Colorectal cancer (CRC), one of the cancers with highest mortality, involves complicated molecular mechanisms leading to the onset of malignant phenotypes. ZNF280A, a member of the zinc-finger protein family, was shown to be a promotor of oncogenesis in CRC in this study. ZNF280A was remarkably upregulated in CRC tissues, which was meaningfully associated with tumor progression and poor prognosis in patients with CRC. Loss-of-function studies revealed that ZNF280A knockdown inhibited the development and progression of CRC as evident by the inhibition of cell proliferation, colony formation, cell apoptosis, cell cycle distribution, and cell migration in vitro and the repressed tumorigenesis of CRC cells in vivo. Next, we showed that RPS14 was the downstream target of ZNF280A and ZNF280A knockdown promoted the ubiquitination as well as degradation of RPS14 in CRC. Additionally, we demonstrated that RPS14 regulated the development of CRC via PI3K-Akt signaling pathway. Taken together, our findings provide a novel clear insight into ZNF280A/RPS14/PI3K-Akt axis in CRC for the first time, offering a potential target for early detection, diagnosis and treatment of CRC in future clinical applications.

A novel function of ATF3 in suppression of ferroptosis in mouse heart suffered ischemia/reperfusion.

INTRODUCTION: Ferroptosis, a newly identified type of programmed cell death type, has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury. However, little is known about ferroptosis regulation in I/R injury. OBJECTIVES: We identified activating transcription factor 3 (ATF3) as a vital regulator of I/R induced ferroptosis and investigated the effects and potential mechanism of ATF3 in cardiac ferroptosis. METHODS: In this study, the dynamic RNA-sequencing (RNA-seq) analysis were performed on mouse hearts exposed to different I/R schedules to identify that ATF3 represents an important modulatory molecule in myocardial I/R injury. Then knockout, rescue and overexpression methods were used in mice and neonatal mouse cells (NMCs) to illustrate the effect of ATF3 on myocardial I/R injury. Loss/gain of function techniques were used both in vivo and in vitro to explore the effects of ATF3 on ferroptosis in I/R injury. Furthermore, chromatin immunoprecipitation sequence (ChIP-seq) analysis was performed in the AC16 human cardiomyocyte cell line to investigate potential genes regulated by ATF3. RESULTS: ATF3 expression reached highest level at early stage of reperfusion, knockout of ATF3 significantly aggravated I/R injury, which could be rescued by ATF3 re-expression. Knockout and the re-expression of ATF3 changed the transcription levels of multiple ferroptosis genes. In addition, results showed that overexpression of ATF3 inhibits cardiomyocyte ferroptosis triggered by erastin and RSL3. Lastly, ChIP-seq and dual luciferase activity analysis revealed ATF3 could bind to the transcription start site of Fanconi anaemia complementation group D2 (FANCD2) and increased the FANCD2 promoter activity. Furthermore, we first demonstrated that overexpression of FANCD2 exerts significant anti-ferroptosis and cardioprotective effect on AC16 cell H/R injury. CONCLUSION: ATF3 inhibits cardiomyocyte ferroptotic death in I/R injury, which might be related with regulating FANCD2. Our study provides new insight into the molecular target for the therapy of myocardial I/R injury.

Recognition of industrial machine parts based on transfer learning with convolutional neural network.

As the industry gradually enters the stage of unmanned and intelligent, factories in the future need to realize intelligent monitoring and diagnosis and maintenance of parts and components. In order to achieve this goal, it is first necessary to accurately identify and classify the parts in the factory. However, the existing literature rarely studies the classification and identification of parts of the entire factory. Due to the lack of existing data samples, this paper studies the identification and classification of small samples of industrial machine parts. In order to solve this problem, this paper establishes a convolutional neural network model based on the InceptionNet-V3 pretrained model through migration learning. Through experimental design, the influence of data expansion, learning rate and optimizer algorithm on the model effectiveness is studied, and the optimal model was finally determined, and the test accuracy rate reaches 99.74%. By comparing with the accuracy of other classifiers, the experimental results prove that the convolutional neural network model based on transfer learning can effectively solve the problem of recognition and classification of industrial machine parts with small samples and the idea of transfer learning can also be further promoted.

High-background parenchymal enhancement in the contralateral breast is an imaging biomarker for favorable prognosis in patients with triple-negative breast cancer treated with chemotherapy.

This study aimed to analyze the association between background parenchymal enhancement (BPE) in the contralateral breast tissue on magnetic resonance imaging (MRI) and clinicopathologic parameters in patients with unilateral breast carcinoma and to investigate its potential prognostic significance. A total of 467 patients who were pathologically confirmed to have unilateral breast cancer and underwent breast MRI were recruited to participate in this cohort study. BPE was assessed in the healthy contralateral breast. Minimal and mild levels were classified as low BPE, whereas moderate and marked levels were classified as high BPE. The effects of BPE on clinicopathologic parameters, overall survival (OS), and invasive disease-free survival (IDFS) were determined. Among the 467 patients, 327 cases were classified into the low-BPE group, whereas 140 cases were classified into the high-BPE group. The high-BPE pattern markedly correlated with age at diagnosis, menopausal status, histologic grading, and estrogen receptor status. BPE pattern did not correlate with OS and IDFS in the entire breast cancer cohort, regardless of whether adjuvant chemotherapy was received. Notably, BPE in the healthy contralateral breast on MRI is markedly related to OS and IDFS in triple-negative breast cancer (TNBC) cases who received chemotherapy. High BPE is related to chemotherapeutic benefits and can be an independent favorable prognostic factor for TNBC patients. Thus, our observations suggest that high BPE pattern can potentially be used as an imaging biomarker for relatively favorable prognosis in TNBC cases receiving chemotherapy. However, the findings need to be verified in a large-scale study.

MicroRNA-107 may regulate lung cancer cell proliferation and apoptosis by targeting TP53 regulated inhibitor of apoptosis 1.

Lung cancer causes over 1.6 million mortalities worldwide annually. MicroRNAs (miRs) are involved in various types of cancer-associated processes. The present study investigated the possible mechanism of miR-107 in the development of lung cancer in order to identify novel targets for clinical treatment. The expression levels of miR-107 and its putative target gene TP53 regulated inhibitor of apoptosis 1 (TRIAP1) were measured in lung cancer tumor tissues and non-tumor adjacent tissues. Subsequently, the association between TRIAP1 and miR-107 was investigated using a dual-luciferase reporter assay. Following transfection, the effects of miR-107 and TRIAP1 on the proliferation and apoptosis of lung cancer cell lines in vitro were investigated using Cell Counting Kit-8 and flow cytometry assays, respectively. Furthermore, the regulatory effect of miR-107 on the expression levels of TRIAP1 and associated proteins was analyzed using a western blot assay. The results revealed lower expression levels of miR-107 and higher expression levels of TRIAP1 in lung cancer tumor tissues compared with non-tumor adjacent tissues. The dual-luciferase reporter assay demonstrated that TRIAP1 is a target gene of miR-107. Additionally, the results revealed that overexpression of miR-107 resulted in a lower proliferation rate and higher apoptosis rate of A549 cells, compared with the negative control (NC) and control groups (P<0.01). The variation of cell proliferation and apoptosis induced by miR-107 mimics was reversed by co-transfection with pcDNA3.1-TRIAP1. Furthermore, the expression levels of cyclin D1 and proliferating cell nuclear antigen were markedly decreased in the miR-107 mimics group compared with the NC group (P<0.01). The expression levels of BCL2 associated X apoptosis regulator, tumor protein p53 and caspase 3 were upregulated and the expression levels of TRIAP1 and BCL2 apoptosis regulator were significantly reduced in the miR-107 mimics group compared with the NC group (P<0.01). The results of the present study suggested that miR-107 regulates lung cancer cell proliferation and apoptosis by targeting TRIAP1.

Soyasaponin II protects against acute liver failure through diminishing YB-1 phosphorylation and Nlrp3-inflammasome priming in mice.

Acute liver failure is characterized by the rapid development of liver dysfunction and remarkably high mortality. Accumulating evidence suggests that soyasaponin possesses potential anti-inflammatory activities. Here, we aimed to investigate the potential role of soyasaponin II in acute liver failure and establish the underlying mechanism. Methods: Lipopolysaccharide/D-galactosamine (LPS/GalN) was employed to induce acute liver failure. We applied liquid chromatography and mass spectrometry (LC/MS) to characterize the changes of soyasaponin II levels in the cecal content and liver. Transcriptomics and proteomics analysis were used to evaluate the functional molecule mediated by soyasaponin II in macrophages. Results: LPS/GalN administration markedly decreased fecal and hepatic soyasaponin II levels. Soyasaponin II treatment protected mice against LPS/GalN induced acute liver injury. Additionally, soyasaponin II markedly diminished Y-Box Binding Protein 1 (YB-1) phosphorylation and nuclear translocation, Nlrp3 inflammasome priming, and interleukin 1ß (Il-1ß) production in macrophages. Phosphorylated YB-1 could activate Nlrp3 mRNA transcription by binding the promoter region. Finally, immunofluorescence analysis showed elevated p-YB-1 nuclear translocation in macrophages of acute liver failure patients compared to controls. Conclusion: Our data shows that soyasaponin II which serves as a novel inhibitor for YB-1 phosphorylation and Nlrp3 inflammasome priming could protect mice against LPS/GalN induced acute liver failure.

Study on the activity and mechanism of skimmianine against human non-small cell lung cancer.

The present research was to investigate the effects of skimmianine (SK) in four non-small cell lung cancer (NSCLC) cells. We found that SK can significantly inhibit the growth of NSCLC cells and markedly induce apoptosis in NSCLC cells. The effects of growth inhibition and apoptosis induction were in a concentration-response relationship and caspase-dependent manner.