CircRNA (circ)_0007823 Contributes to Triple-Negative Breast Cancer Progression and Cisplatin Resistance via the miR-182-5p/FOXO1 Pathway.

Cisplatin (DDP) is used for the clinical management of triple-negative breast cancer (TNBC). However, the development of drug resistance limits its therapeutic efficacy. Circular RNAs (circRNAs) are known to be involved in tumor DDP resistance. In our previous study, we reported that circ_0007823 expression is downregulated and correlated with adverse prognosis in TNBC. However, its association with DDP resistance remains unclear. This study aimed to determine the role of circ_0007823 and miR-182-5p in DDP-resistant TNBC and explore the underlying mechanisms. First, expression profiles circ_0007823, microRNA (miR)-182-5p, and forkhead box O1 (FOXO1) in TNBC cells were determined. Additionally, biological characteristics of cells, including apoptosis, cell cycle, proliferation, and migration, were analyzed using various assays. Luciferase reporter and rescue assays were used to determine the correlations among circ_0007823, miR-182-5p, and FOXO1 expression. MiR-182-5p was overexpressed in DDP-resistant TNBC cells. MiR-182-5p knockdown suppressed the invasiveness and increased the apoptosis of drug-resistant cells, contributing to G1 arrest and S phase reduction. Mechanistically, circ_0007823 targeted miR-182-5p, and its overexpression drastically reduced the promotional effects of the miR-182-5p mimic on the aggression and transfer ability of drug-resistant cells. Furthermore, FOXO1 overexpression increased the sensitivity of cells to DDP and reduced their malignant progression. Therefore, FOXO1 was established as the downstream target of miR-182-5p that may be used to treat DDP-resistant TNBC. In summary, circ_0007823 overexpression attenuated DDP resistance in TNBC via the miR-182-5p-FOXO1 axis, indicating the therapeutic potential of circ_0007823 DDP-resistant TNBC treatment.

Giant photoinduced inverse spin Hall effect of the surface states in three dimensional topological insulators Bi2Te3 with different thickness.

The photoinduced inverse spin Hall effect (PISHE) has been studied in three dimensional (3D) topological insulator (TI) Bi2Te3 thin films with different thicknesses (3, 5, 12 and 20 quintuple layer (QL)). The sign of the PISHE current flips only once in the 3- and 20-QL Bi2Te3 films, but it flips three times in the 5-, 7- and 12-QL samples. The three-times sign flip is due to the superposition of the PISHE current of the top and bottom surface states in Bi2Te3 films. By analyzing the x-ray photoelectron spectroscopy (XPS) of the Bi2Te3 films, we find that the top surface of the 3- and 20-QL Bi2Te3 films are severely oxidized, leading to only one sign flip in the PISHE. The PISHE contributed by the top and bottom surface states in Bi2Te3 films have been successfully separated by fitting a theoretical model to the PISHE current. The impact of the bulk states on PISHE current has been determined. The PISHE current is also measured at different light powers, and all the measurement results are in good agreement with the theoretical model. In addition, it is found that the PISHE current in Bi2Te3 films grown on Si substrate is more than two orders larger than that grown on SrTiO3 substrates, which can be attributed to the larger absorption coefficient for Bi2Te3/Si samples. It is revealed that the PISHE current in 3D TI Bi2Te3 is as large as 140 nA/W in the 3-QL Bi2Te3 film grown on Si substrate, which is more than one order larger than that reported in GaAs/AlGaAs heterojunction (about 2 nA/W) and GaN/AlGaN heterojunction (about 1.7 nA/W). The giant PISHE current demonstrates that the TIs with strong SOC may have good application prospects in spintronic devices with high spin-to-charge conversion efficiency.

Ginsenoside Rc Promotes Bone Formation in Ovariectomy-Induced Osteoporosis In Vivo and Osteogenic Differentiation In Vitro.

Ginsenoside Rc is one of the active components used in traditional Chinese medicine. We aim to explore how ginsenoside Rc can be used in the treatment of osteoporosis. Micro-CT demonstrated that the treatment of ovariectomized (OVX) mice with ginsenoside Rc significantly inhibited the decrease in bone mineral density, bone volumetric fraction, and trabecular number, and the increase in trabecular separation. Histological staining, qRT-PCR, and Western blot demonstrated that ginsenoside Rc enhances the microstructure of trabecular bone, and promotes the expression of bone formation-related genes. Alkaline phosphatase (ALP) staining, Alizarin Red staining, qRT-PCR, and Western blotting demonstrated that ginsenoside Rc dose-dependently promoted the osteogenic differentiation of MC3T3-E1 cells. A ginsenoside Rc-induced increase in the expression of ß-catenin, p-GSK-3ß, collagen-1, ALP, and RUNX-2 family transcription factor-2 was significantly attenuated upon 10 µM XAV-939 treatment, while the decrease in the expression of GSK-3ß and p-ß-catenin was significantly enhanced. Ginsenoside Rc promotes bone formation in ovariectomy-induced osteoporosis in vivo and promotes osteogenic differentiation in vitro via the Wnt/ß-catenin signaling pathway.

Inverse spin Hall effect induced by linearly polarized light in the topological insulator Bi2Se3.

The inverse spin Hall effect (ISHE) induced by the normal incidence of linearly-polarized infrared radiation has been observed in the topological insulator Bi2Se3. A model has been proposed to explain the phenomenon, and the spin transverse force has been determined by the model fitting. The anomalous linear photogalvanic effect (ALPGE) is also observed, and the photoinduced momentum anisotropy is extracted. Furthermore, the ISHE and ALPGE are investigated at different temperatures between 77 and 300 K, and the temperature dependence of the spin transverse force and photoinduced momentum anisotropy are obtained. This study suggests a new way to investigate the inverse spin Hall effect via linearly polarized light even at room temperature.

Photoinduced Inverse Spin Hall Effect of Surface States in the Topological Insulator Bi2Se3.

The three-dimensional (3D) topological insulator (TI) Bi2Se3 exhibits topologically protected, linearly dispersing Dirac surface states (SSs). To access the intriguing properties of these SSs, it is important to distinguish them from the coexisting two-dimensional electron gas (2DEG) on the surface. Here, we use circularly polarized light to induce the inverse spin Hall effect in a Bi2Se3 thin film at different temperatures (i.e., from 77 to 300 K). It is demonstrated that the photoinduced inverse spin Hall effect (PISHE) of the top SSs and the 2DEG can be separated based on their opposite signs. The temperature and power dependence of the PISHE also confirms our method. Furthermore, it is found that the PISHE in the 2DEG is dominated by the extrinsic mechanism, as revealed by the temperature dependence of the PISHE.

Targeting druggable enzymome by exploiting natural medicines: An in silico-in vitro integrated approach to combating multidrug resistance in bacterial infection.

CONTEXT: Antibiotic resistance is a major clinical and public health problem. Development of new therapeutic approaches to prevent bacterial multidrug resistance during antimicrobial chemotherapy has thus been becoming a primary consideration in the medicinal chemistry community. OBJECTIVE: We described a new strategy that combats multidrug resistance by using natural medicines to target the druggable enzymome (i.e., enzymatic proteome) of Staphylococcus aureus. MATERIALS AND METHODS: A pipeline of integrating in silico analysis and in vitro assay was purposed to identify antibacterial agents from a large library of natural products with diverse structures, high drug-likeness, and relatively low flexibility, with which a systematic interactome of 826 natural product candidates with 125 functionally essential S. aureus enzymes was constructed via a high-throughput cross-docking approach. The obtained docking score matrix was then converted into an array of synthetic scores; each corresponds to a natural product candidate. By systematically examining the docking results, a number of highly promising candidates with potent antibacterial activity were suggested. RESULTS: Three natural products, i.e., radicicol, jorumycin, and amygdalin, have been determined to possess strong broad-spectrum potency combating both the drug-resistant and drug-sensitive strains (MIC value <10 µg/ml). In addition, some natural products such as tetrandrine, bilobalide, and arbutin exhibited selective inhibition on different strains. DISCUSSION AND CONCLUSION: Combined quantum mechanics/molecular mechanics analysis revealed diverse non-bonded interactions across the complex interfaces of newly identified antibacterial agents with their putative targets GyrB ATPase and tyrosyl-tRNA synthetase.

Temperature dependence of spin photocurrent spectra induced by Rashba- and Dresselhaus-type circular photogalvanic effect at inter-band excitation in InGaAs/AlGaAs quantum wells.

Spin photocurrent spectra induced by Rashba- and Dresselhaus-type circular photogalvanic effect (CPGE) at inter-band excitation have been experimentally investigated in InGaAs/AlGaAs quantum wells at a temperature range of 80 to 290 K. It is found that, the sign of Rashba-type current reverses at low temperatures, while that of Dresselhaus-type remains unchanged. The temperature dependence of ratio of Rashba and Dresselhaus spin-orbit coupling parameters, increasing from -6.7 to 17.9, is obtained, and the possible reasons are discussed. We also develop a model to extract the Rashba-type effective electric field at different temperatures. It is demonstrated that excitonic effect will significantly influence the Rashba-type CPGE, while it has little effect on Dresselhaus-type CPGE.

[Association of HLA-DQA1 gene rs9272346 polymorphism with clinical outcome of hepatitis B virus infection in ethnic Han population from Hubei].

OBJECTIVE: To assess the association of rs9272346 polymorphism of HLA-DQA1 gene with clinical outcome of hepatitis B virus (HBV) infection in ethnic Han population from Hubei, China. METHODS: A case-control study was conducted, which have involved 1028 unrelated subjects including 238 asymptomatic HBV carriers (AHC), 173 acute liver failure (ALF), 292 liver cirrhosis (LC) and 325 hepatocellular carcinoma (HCC). Genotypes of rs9272346 were determined by real-time polymerase chain reaction with a TaqMan MGB probe. Statistical results were analyzed using Chi square test, student's t test and unconditional logistic regression. RESULTS: No significant differences were detected in the frequencies of G allele between ALF, LC, HCC and AHC groups (P= 0.312, 0.314, 0.264). Compared with the AA genotype, the GG and GA genotypes were not associated with the patients groups under the dominant model: ALF group vs. AHC group (adjusted OR= 1.08, 95%CI: 0.7-1.68), LC group vs. AHC group (adjusted OR= 1.11, 95%CI: 0.87-1.26), HCC group vs. AHC group (adjusted OR= 0.93, 95%CI: 0.65-1.33). For women, the GG and GA genotypes have conferred a protective effect for the outcome of ALF (OR= 0.30, 95%CI: 0.1-1.87). CONCLUSION: Our results suggested that rs9272346 polymorphism of HLA-DQA1 may not independently influence the outcome of HBV infection in ethnic Han Chinese in Hubei, while the GG and GA genotypes may confer a protective effect against ALF in women.

Temperature dependence of anisotropic mode splitting induced by birefringence in an InGaAs/GaAs/AlGaAs vertical-cavity surface-emitting laser studied by reflectance difference spectroscopy.

The temperature dependence of the mode splitting induced by birefringence in an InGaAs/GaAs/AlGaAs vertical-cavity surface-emitting laser has been studied by reflectance difference spectroscopy at different temperatures ranging from 80 to 330 K. The anisotropic broadening width and the anisotropic integrated area of the cavity mode under different temperatures are also determined. The relation between the mode splitting and the birefringence is obtained by theoretical calculation using a Jones matrix approach. The temperature dependence of the energy position of the cavity mode and the quantum well transition are also determined by nearly normal reflectance and photoluminescence, respectively.

The ratio of lymphocyte/red blood cells and platelets/lymphocytes are predictive biomarkers for lymph node metastasis in patients with breast cancer.

BACKGROUND: Axillary lymph node metastasis (LNM) affects the progression of breast cancer. However, it is difficult to preoperatively diagnose axillary lymph node status with high sensitivity. Therefore, we hypothesized that platelets/lymphocytes ratio (PLR) and lymphocytes/ red blood cells ratio (LRR) might help in the prognosis of lymph node metastasis in T1-T2 breast cancer. METHODS: 166 patients (Chang Ning Maternity & Infant Health Institute) were included in our study, and the associations of PLR and LPR with lymph node metastasis were investigated. Peripheral blood was collected one week before the surgery, and the patients were divided into different categories based on their PLR and LRR. RESULTS: The incidence of LNM was significantly increased in the high PLR group (p= 0.002) compared with the low PLR group; LNM was also significantly increased in the low LRR group (p= 0.036) compared with the high LPR group. Further, our study revealed that high PLR (p< 0.001, OR = 4.397, 95% CI = 2.005-9.645), low LRR (p= 0.017, OR = 0.336, 95%CI = 0.136-0.825) and high clinical T stage (p< 0.001, OR = 3.929, 95%CI = 1.913-8.071) are independent predictors of LNM. CONCLUSIONS: PLR and LRR could be identified as predictors of LNM in patients with T1/T2 breast cancer.

Bioinformatics Analysis to Identify Intersection Genes, Associated Pathways and Therapeutic Drugs between COVID-19 and Oral Candidiasis.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a serious threat to human health. Oral candidiasis (OC) may be one of the causes of morbidity in severe COVID-19 patients. However, there is currently no treatment for oral candidiasis and COVID-19 (OC/COVID-19). The purpose of this study was to use text mining and data analysis to investigate the target genes for treatment and explore potential therapeutic drugs for OC/COVID-19. METHODS: We used the text mining tool pubmed2ensembl to detect genes associated with OC, and the dataset GSE164805 was used for the data analysis. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on two intersection genes using the Database of Annotation, Visualization and Integrated Discovery (DAVID) platform. The protein-protein interaction (PPI) networks were constructed by STRING software, and gene module analysis was performed using Molecular Complex Detection (MCODE), a plug-in in Cytoscape. The most significant genes were selected as hub genes and their functions and pathways were analyzed using Metascape. We revealed the upstream pathway activity of the hub genes. The drug-gene interaction database (DGIdb) and the traditional Chinese medicines integrated database (TCMID) were used to discover potential drugs for the treatment of OC/COVID-19. RESULTS: The analysis indicated that there were 2869 differentially expressed genes (DEGs) in GSE164805. We identified 161 unique genes associated with oral candidiasis through text mining. A total of 20 intersection genes were identified as the therapeutic targets for OC/COVID-19. Based on the bioinformatics analysis, nine genes (TNF, IL1B, IFNG, CSF2, ELANE, CCL2, MMP9, CXCR4, and IL1A) were identified as hub genes that were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications and NOD-like receptor signaling pathway. We identified four of the nine genes that target five existing drugs, including BKT140, mavorixafor, sivelestat, canakinumab, and rilonacept. Furthermore, twenty herb ingredients were also screened as potential drugs. CONCLUSION: In this study, TNF, IL1B, IFNG, CSF2, ELANE, CCL2, MMP9, CXCR4, and IL1A were potentially key genes involved in the treatment of OC/COVID-19. Taken together five drugs and twenty herb ingredients were identified as potential therapeutic agents for OC/COVID-19 treatment and management.

Hsa_circ_0007823 Overexpression Suppresses the Progression of Triple-Negative Breast Cancer via Regulating miR-182-5p-FOXO1 Axis.

Background: This study aimed to analyze the specific expression of hsa_circ_0007823 in triple-negative breast cancer (TNBC) and explore the roles and related molecular mechanisms of hsa_circ_0007823 in TNBC. Materials and Methods: Relative hsa_circ_0007823 levels in TNBC tissues and cell lines were examined by reverse transcription-quantitative polymerase chain reaction. The value of hsa_circ_0007823 levels was evaluated in patients' clinicopathological characteristics and prognostic prediction. A dual-luciferase reporter assay was used to determine the relationship between hsa_circ_0007823, miR-182-5p, and FOXO1. The effect of circ_0007823 overexpression on the growth of TNBC cells was investigated in vitro and in vivo. Results: Lower levels of hsa_circ_0007823 were found in TNBC tissues and cell lines and were closely associated with lymph node metastasis, poorer overall and disease-free survival rates. MiR-182-5p was significantly up-regulated, whereas FOXO1 was down-regulated in TNBC cell lines. The miR-182-5p inhibition up-regulated FOXO1 in TNBC cells. Dual-luciferase reporter assays showed that hsa_circ_0007823, miR-182-5p, and FOXO1 interacted with each other. Overexpression of circ_0007823 significantly inhibited the viability, migration, and invasion of TNBC cell lines, but promoted apoptosis. In vivo experiments showed that circ_0007823 overexpression inhibited tumor growth and down-regulated miR-182-5p and up-regulated FOXO1. Conclusion: Hsa_circ_0007823 overexpression could suppress the growth, invasion, and migration of TNBC cells, and inhibit tumor growth by regulating miR-182-5p/FOXO1.

Electric Control of Helicity-Dependent Photocurrent and Surface Polarity Detection on Two-Dimensional Bi2O2Se Nanosheets.

Bismuth oxyselenide (Bi2O2Se) is a two-dimensional (2D) layered semiconductor material with high electron Hall mobility and excellent environmental stability as well as strong spin-orbit interaction (SOI), which has attracted intense attention for application in spintronic and spin optoelectronic devices. However, a comprehensive study of spin photocurrent and its microscopic origin in Bi2O2Se is still missing. Here, the helicity-dependent photocurrent (HDPC) was investigated in Bi2O2Se nanosheets. By analyzing the dependence of HDPC on the angle of incidence, we find that the HDPC originates from surface states with Cs symmetry in Bi2O2Se, which can be attributed to the circular photogalvanic effect (CPGE) and circular photon drag effect (CPDE). It is revealed that the HDPC current almost changes linearly with the source-drain voltage. Furthermore, we demonstrate effective tuning of HDPC in Bi2O2Se by ionic liquid gating, indicating that the spin splitting of the surface electronic structure is effectively tuned. By analyzing the gate voltage dependence of HDPC, we can unambiguously identify the surface polarity and the surface electronic structure of Bi2O2Se. The large HDPC in Bi2O2Se nanosheets and its efficient electrical tuning demonstrate that 2D Bi2O2Se nanosheets may provide a good platform for opto-spintronics devices.

Cuproptosis-Related lncRNAs are Biomarkers of Prognosis and Immune Microenvironment in Head and Neck Squamous Cell Carcinoma.

Background: Cuproptosis is a new type of cell death that induces protein toxic stress and eventually leads to cell death. Hence, regulating cuproptosis in tumor cells is a new therapeutic approach. However, studies on cuproptosis-related long noncoding RNA (lncRNA) in head and neck squamous cell carcinoma (HNSC) have not been found. This study aimed to explore the cuproptosis-related lncRNAs prognostic marker and their relationship to immune microenvironment in HNSC by using bioinformatics methods. Methods: RNA sequencing, genomic mutations, and clinical data of TCGA_HNSC were downloaded from The Cancer Genome Atlas. HNSC patients were randomly assigned to either a training group or a validation cohort. The least absolute shrinkage and selection operator Cox regression and multivariate Cox regression models were used to determine the prognostic model in the training cohort, and its independent prognostic effect was further confirmed in the validation and entire cohorts. Results: Based on previous literature, we collected 19 genes associated with cuproptosis. Afterward, 783 cuproptosis-related lncRNAs were obtained through coexpression. Cox model revealed and constructed eight cuproptosis-related lncRNAs prognostic marker (AL132800.1, AC090587.1, AC079160.1, AC011462.4, AL157888.1, GRHL3-AS1, SNHG16, and AC021148.2). Patients were divided into high- and low-risk groups based on the median risk score. The Kaplan-Meier survival curve revealed that the overall survival between the high- and low-risk groups was statistically significant. The receiver operating characteristic curve and principal component analysis demonstrated the accurate prognostic ability of the model. Univariate and multivariate Cox regression analysis showed that risk score was an independent prognostic factor. In addition, we used multivariate Cox regression to establish a nomogram of the predictive power of prognostic markers. The tumor mutation burden showed significant differences between the high- and low-risk groups. HNSC patients in the high-risk group responded better to immunotherapy than those in the low-risk group. We also found that risk scores were significantly associated with drug sensitivity in HNSC. Conclusion: In summary, our study identified eight cuprotosis-related lncRNAs signature of HNSC as the prognostic predictor, which may be promising biomarkers for predicting the benefit of HNSC immunotherapy as well as drug sensitivity.

Association between levels of blood trace minerals and periodontitis among United States adults.

Aim: Evidence linking trace minerals and periodontitis is limited. To investigate the relationship between trace minerals (selenium, manganese, lead, cadmium, and mercury) and periodontitis, data from the National Health and Nutrition Examination Survey (NHANES) were analyzed after accounting for potential confounding factors. No known studies have explored the relationship between these five trace minerals and periodontitis. Materials and methods: A total of 4,964 participants who had undergone a full-mouth periodontal examination and laboratory tests for five trace minerals were studied in a cross-sectional study. Clinical attachment loss (CAL) and periodontitis grading were used to measure periodontitis severity. Linear and logistic regression models were used to evaluate the association between trace minerals and periodontitis. Further subgroup analyses were performed. Results: Blood lead and cadmium levels were positively associated with mean CAL, and blood selenium was negatively associated with mean CAL; however, blood mercury, blood manganese, and mean CAL were not significantly associated. The association between trace minerals and mean CAL was more significant in males, the elderly, and patients with diabetes. There was a threshold effect between blood cadmium levels and mean CAL. Among the Black population, the relationship between blood cadmium levels and mean CAL followed an inverted U-shaped curve. There was a saturation effect in the study of blood lead in people aged 45-59 years old. Conclusion: Our study highlighted that blood selenium, lead, and cadmium levels were significantly associated with periodontitis in a nationally representative sample of United States adults.

Effects of variant rs346473 in ARHGAP24 gene on disease progression of HBV infection in Han Chinese population.

Host genetic, environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus (HBV) infection. The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24 (ARHGAP24) gene and disease progression of HBV infection in Han Chinese population. These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers, and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers (AsC) in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase. Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase (OR, 2.693; 95% CI, 1.928-3.760; P=6.2×10(-9); additive model) and the replication phase (OR, 1.490; 95% CI, 1.104-2.012; P=9.0×10(-3); additive model). These two SNPs were in strong linkage disequilibrium with D'=0.99 and r (2)=0.951, and haplotype TT disclosed an increased susceptibility to HBV progression (OR, 1.980; 95% CI, 1.538-2.545; P=8.1×10(-8)). These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.

The efficacy and safety of silver needle in the treatment of rheumatoid arthritis: A protocol of randomized controlled trial.

BACKGROUND: Rheumatoid arthritis is a kind of chronic crippling disease, the condition is complex, the course of the disease is repeated, seriously affecting the quality of life of patients. Adverse reactions and drug resistance associated with conventional treatment can no longer meet the clinical need. Therefore, complementary and alternative therapies need to be explored. The evidence shows that silver needle therapy has advantages in the treatment of rheumatoid arthritis, but there is a lack of standard clinical studies to verify this conclusion. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of silver needles in the treatment of rheumatoid arthritis. Approved by the Clinical Research Ethics Committee of our hospital. The patients are randomly divided into a treatment group (silver needle treatment group) or control group (routine western medicine treatment group). The patients are followed up for 2 months after 4 weeks of treatment. Observation indicators include: TCM symptom score, HAQDI score, DAS-28 score, laboratory indicators, adverse reactions and so on. Data will be analyzed using the statistical software package SPSS version 18.0 (Chicago, IL). DISCUSSION: This study will evaluate the clinical efficacy of a silver needle in the treatment of rheumatoid arthritis. The results of this study will provide a reliable reference for the clinical use of a silver needle in the treatment of rheumatoid arthritis. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/4X5QB.

Fabrication of a novel core-shell-shell temperature-sensitive magnetic composite with excellent performance for papain adsorption.

Herein, a novel temperature-sensitive magnetic composite (Fe3O4@SiO2@P(NIPAM-co-VI)/Cu2+) with a uniform core-shell-shell structure was successfully prepared via a layer-by-layer method. The resulting magnetic composite revealed good magnetic properties and remarkable affinity to papain with a maximum adsorption capacity of 199.17 mg g-1. The adsorption equilibrium data fitted the pseudo-second-order kinetic and Freundlich models well, and the major thermodynamics parameters indicated that adsorption was an endothermic and spontaneous process. Fe3O4@SiO2@P(NIPAM-co-VI)/Cu2+ could thermally protect papain, which is attributed to the reversible hydrophilic-hydrophobic transition of the composite at temperatures below and above the lower critical solution temperature. More importantly, the magnetic composite could be recycled at least six times without a remarkable loss in its adsorption capacity, and the process of adsorption and elution had no significant effect on the activity and structure of papain. This work could provide a novel separation method for papain without loss of its activity.

Long Non-coding RNA Expression Patterns in Stomach Adenocarcinoma Serve as an Indicator of Tumor Mutation Burden and Are Associated With Tumor-Infiltrating Lymphocytes and Microsatellite Instability.

Long non-coding RNAs (lncRNAs) are crucial in controlling important aspects of tumor immunity. However, whether the expression pattern of lncRNAs in stomach adenocarcinoma (STAD) reflects tumor immunity is not fully understood. We screened differentially expressed lncRNAs (DElncRNAs) between high and low tumor mutation burden (TMB) STAD samples. Using the least absolute shrinkage and selection operator method, 33 DElncRNAs were chosen to establish a lncRNA-based signature classifier for predicting TMB levels. The accuracy of the 33-lncRNA-based signature classifier was 0.970 in the training set and 0.950 in the test set, suggesting the expression patterns of the 33 lncRNAs may be an indicator of TMB in STAD. Survival analysis showed that a lower classifier index reflected better prognosis for STAD patients, and the index showed correlation with expression of immune checkpoint molecules (PD1, PDL1, and CTLA4), tumor-infiltrating lymphocytes, and microsatellite instability. In conclusion, STAD samples with different tumor mutation burdens have different lncRNA expression patterns. The 33-lncRNA-based signature classifier index may be an indicator of TMB and is associated expression of immune checkpoints, tumor-infiltrating lymphocytes, and microsatellite instability.

Metastasis suppressor 1 acts as a tumor suppressor by inhibiting epithelial-to-mesenchymal transition in triple-negative breast cancer.

OBJECTIVE: This study aimed to analyze the function of metastasis suppressor 1 (MTSS1) in triple negative breast cancer (TNBC). METHODS: MTSS1 expression in 30 TNBC and paracancerous tissues was measured by quantitative reverse transcriptase polymerase chain reaction. The prognostic value of MTSS1 was assessed by Kaplan-Meier analysis followed by the log-rank test. MCF7 cells were transfected with si-MTSS1, while MDA-MB-231 cells were transfected with pcDNA3.1-MTSS1. Cell proliferation assay and transwell assay were performed to investigate the effects of MTSS1 on the biological behavior of breast cancer cells. Immunofluorescence and western blot were used to detect the influence of MTSS1 on epithelial-mesenchymal transition (EMT) markers. RESULTS: MTSS1 expression was significantly lower in TNBC tissues compared with that in paracancerous tissues (0.012 vs. 0.370; P = 0.006). A lower MTSS1 expression level was also found in tumor tissues of patients with lymph node metastasis (P = 0.002) or tumor node metastasis stage (P = 0.010). Patients with low expression of MTSS1 (⩽ 0.009) had shorter disease-free survival (47.4 vs. 56.0 months; P = 0.012). The knockdown of MTSS1 in MCF7 cells inhibited cell proliferation, enhanced cell migration and invasion capacities, decreased the E-cadherin level, and increased the vimentin level, whereas overexpression of MTSS1 in MDA-MB-231 cells had the opposite effects (P < 0.05). CONCLUSIONS: Our findings demonstrated that MTSS1 regulates proliferation, invasion, migration, and EMT in TNBC, and that decreased MTSS1 is associated with shorter disease-free survival.