Genome-wide association study for boll weight in Gossypium hirsutum races.

High yield has always been an essential target in almost all of the cotton breeding programs. Boll weight (BW) is a key component of cotton yield. Numerous linkage mapping and genome-wide association studies (GWAS) have been performed to understand the genetic mechanism of BW, but information on the markers/genes controlling BW remains limited. In this study, we conducted a GWAS for BW using 51,268 high-quality single-nucleotide polymorphisms (SNPs) and 189 Gossypium hirsutum accessions across five different environments. A total of 55 SNPs significantly associated with BW were detected, of which 29 and 26 were distributed in the A and D subgenomes, respectively. Five SNPs were simultaneously detected in two environments. For TM5655, TM8662, TM36371, and TM50258, the BW grouped by alleles of each SNP was significantly different. The ± 550 kb regions around these four key SNPs contained 262 genes. Of them, Gh_A02G1473, Gh_A10G1765, and Gh_A02G1442 were expressed highly at 0 to 1 days post-anthesis (dpa), - 3 to 0 dpa, and - 3 to 0 dpa in ovule of TM-1, respectively. They were presumed as the candidate genes for fiber cell differentiation, initiation, or elongation based on gene annotation of their homologs. Overall, these results supplemented valuable information for dissecting the genetic architecture of BW and might help to improve cotton yield through molecular marker-assisted selection breeding and molecular design breeding.

Non-spatial and spatial heterogeneity revealed a suppressive immune feature of Siglec-15 in lung adenocarcinomas.

BACKGROUND: Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has emerged as a novel immunotherapy candidate, which deserves a comprehensive investigation in lung adenocarcinoma (LUAD). METHODS: Multiplex fluorescence-based immunohistochemistry was conducted to assess Siglec-15 expression and tumor-infiltrating immune cells in LUAD from Tianjin cohort, with validation cohorts Xinchao 04 and 07. RESULTS: This study revealed that Siglec-15 was positively correlated with CD8+ T cells and tumor-associated macrophages (TAMs) infiltration, but CD8+ T cells were mostly infiltrated in the stroma area, not in the tumor area. Spatially, fewer CD8+ T cells surrounded Siglec-15+ tumor cells in PD-L1- cells, and more TAMs surrounded Siglec-15+ tumor cells in PD-L1-/+ cells. Siglec-15+ TAMs infiltrated with more CD8+ T cells, and were closer to CD8+ T cells than Siglec-15- TAMs and Siglec-15+ tumor cells. Siglec-15+ TAMs infiltrated with more Tregs and were closer to Tregs than Siglec-15+ tumor cells. Siglec-15+ tumor cells or TAMs reversed CD8+ T cells prognosis value, and enhanced the prognosis value of Tregs and TAMs. The immunotyping based on Siglec-15 and CD8A / CD8+ T cells revealed that patients with high CD8A and Siglec-15 expression exhibited immune activation. Patients with low CD8A expression / CD8+ T cells infiltration and Siglec-15 overexpression were related to the activation of immunosuppressive signature and metabolism-related pathway, and infiltrated with more TAMs. CONCLUSIONS: We revealed the distinct characteristics between Siglec-15+ tumor cells and TAMs in relation to CD8+ T cells, and a unique relationship between Siglec-15 and immunosuppressive TIME in LUAD, which may provide potential value for anti-Siglec-15 therapy.

Rescue of autophagy and lysosome defects in salivary glands of MRL/lpr mice by a therapeutic phosphopeptide.

Sjögren's syndrome is a multifactorial systemic autoimmune disorder characterized by lymphocytic infiltrates in exocrine organs. Patients present with sicca symptoms, such as extensive dry eyes and dry mouth, and parotid enlargement. Other serious complications include profound fatigue, chronic pain, major organ involvement, neuropathies and lymphomas. Current treatments only focus on relieving symptoms and do not target the origin of the disease, which is largely unknown. The question we addressed here was whether some defects exist in autophagy processes in Sjögren's syndrome and if they can be corrected or minimized using an appropriate mechanism-driven treatment targeting this central survival pathway. Using a recognized murine model of secondary Sjögren's syndrome, we identified molecular alterations of autophagy occurring in the salivary glands of MRL/lpr mice, and discovered that opposite (up- or down-regulated) autophagy events can arise in distinct organs of the same mouse strain, here in lymphoid organs and salivary glands. We showed further that the therapeutic P140 peptide, known to directly act on chaperone-mediated autophagy, rescued MRL/lpr mice from cellular infiltration and autophagy defects occurring in salivary glands. Our findings provide a proof-of-concept that targeting autophagy might represent a promising therapeutic strategy for treating patients with Sjögren's syndrome.

Blockade of macrophage autophagy ameliorates activated lymphocytes-derived DNA induced murine lupus possibly via inhibition of proinflammatory cytokine production.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a typical inflammatory autoimmune disease for its unknown pathogenesis and potential fatality. It has been reported that autophagy has a crosstalk with autoimmunity, but its impact on the pathogenesis of SLE remains unclear. Here, we investigated the role of autophagy in inflammatory response of macrophages under SLE conditions. METHODS: First, we detected the expression of autophagy-related genes (Atg5, Atg12 and Beclin 1) in the macrophages derived from activated lymphocytes-derived DNA (ALD-DNA) induced murine lupus as well as in the PBMC from SLE patients. And then through adoptive transfer of Beclin 1 knockdown macrophages, we further investigated the potential effect of macrophage autophagy on the SLE-associated inflammatory response and disease severity by evaluating serum anti-dsDNA antibodies and proteinuria levels, immune complex deposition as well as renal pathological changes. RESULTS: We found that autophagy related genes were significantly upregulated in the splenic and renal macrophages of lupus mice and in the PBMC of SLE patients. Adoptive transfer of Beclin 1 knockdown macrophages could significantly decrease the anti-dsDNA antibodies and proteinuria levels, robustly reduce renal immune complex deposition and remit glomerulonephritis, indicating the amelioration of murine lupus. This protective effect was associated with the obviously decreased production of proinflammatory cytokines IL-6 and TNF-α. CONCLUSIONS: Our results suggested that aberrant activated autophagy in macrophages contributed to the pathogenesis of murine lupus possibly via promoting the production of proinflammatory cytokines TNF-α and IL-6, and inhibition of autophagy might represent a novel regulation strategy for excessive activation of proinflammatory macrophages and a new therapeutic regime for SLE.

Siglec-15 on macrophages suppress the immune microenvironment in patients with PD-L1 negative non-metastasis lung adenocarcinoma.

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immune checkpoint molecule with sequence homology to programmed cell death ligand 1 (PD-L1), which is mainly expressed on macrophages and tumor cells. However, whether Siglec-15-induced immunosuppression and poor prognosis are independent of PD-L1 remains unclear. In this study, we collected samples of 135 non-small cell lung cancers and found that Siglec-15 and PD-L1 expression were independent in non-small cell lung cancer by multiple immunofluorescence staining. Siglec-15 on macrophages (Mφ-Siglec-15) was significantly associated with DFS (p < 0.05) in PD-L1- patients with non-metastasis lung adenocarcinoma, not in PD-L1+ or lung squamous cell carcinoma patients. Moreover, stromal Siglec-15+ macrophages of Mφ-Siglec-15+PD-L1- patients were significantly more than those of Mφ-Siglec-15-PD-L1- patients (p = 0.002). We further found that Siglec-15+ macrophages polarized toward M2 and produced more IL-10, negatively associated with inflamed immunophenotype in PD-L1- patients and may inhibit CD8+T cells infiltration. In conclusion, PD-L1-independent Siglec-15+ macrophages contribute to the formation of an immunosuppressive microenvironment in non-metastasis lung adenocarcinoma patients, which may cause a higher risk of recurrence. Siglec-15 could be a potential target for normalizing cancer immunotherapy, benefiting patients who fail to respond to anti-PD-L1 therapy.

Liquid-liquid phase separation of immiscible polymers at double emulsion interfaces for configurable microcapsules.

Liquid-liquid phase separation at complex interfaces is a common phenomenon in biological systems and is also a fundamental basis to create synthetic materials in multicomponent mixtures. Understanding the liquid-liquid phase separation in well-defined macromolecular systems is anticipated to shed light on similar behaviors in cross-disciplinary areas. Here we study a series of immiscible polymers and reveal a generic phase diagram of liquid-liquid phase separation at double emulsion interfaces, which depicts the equilibrium structures by interfacial tension and polymer fraction. We further reveal that the interfacial tensions in various systems fall on a linear relationship with spreading coefficients. Based on this theoretical guideline, the liquid-liquid phase separation can be modulated by a low fraction of amphiphilic block copolymers, leading the double emulsion droplets configurable between compartments and anisotropic shapes. The solidified anisotropic microcapsules could provide unique orientation-sensitive optical properties and thermomechanical responses. The theoretical analysis and experimental protocol in this study yield a generalizable strategy to prepare multiphase double emulsions with controlled structures and desired properties.

Cartilage Regeneration Units Based on Hydrogel Microcarriers for Injectable Cartilage Regeneration in an Autologous Goat Model.

Despite numerous studies on tissue-engineered injectable cartilage, it is still difficult to realize stable cartilage formation in preclinical large animal models because of suboptimal biocompatibility, which hinders further application in clinical settings. In this study, we proposed a novel concept of cartilage regeneration units (CRUs) based on hydrogel microcarriers for injectable cartilage regeneration in goats. To achieve this goal, hyaluronic acid (HA) was chosen as the microparticle to integrate gelatin (GT) chemical modification and a freeze-drying technology to create biocompatible and biodegradable HA-GT microcarriers with suitable mechanical strength, uniform particle size, a high swelling ratio, and cell adhesive ability. CRUs were then prepared by seeding goat autologous chondrocytes on the HA-GT microcarriers and culturing in vitro. Compared with traditional injectable cartilage methods, the proposed method forms relatively mature cartilage microtissue in vitro and improves the utilization rate of the culture space to facilitate nutrient exchange, which is necessary for mature and stable cartilage regeneration. Finally, these precultured CRUs were used to successfully regenerate mature cartilage in nude mice and in the nasal dorsum of autologous goats for cartilage filling. This study provides support for the future clinical application of injectable cartilage.

Risk factors for totally implantable access ports-associated thrombosis in pediatric oncology patients.

The application of totally implantable access ports (TIAPs) reduces treatment-related discomfort; however, the existence of catheter may cause side effects, with the most common one being the occurrence of TIAPs-associated thrombosis. The risk factors for TIAPs-associated thrombosis in pediatric oncology patients have not been fully described. A total of 587 pediatric oncology patients undergoing TIAPs implantation at a single center over a 5-year period were retrospectively analyzed in the present study. We investigated the risk factors for thrombosis, emphasizing the internal jugular vein distance, by measuring the vertical distance from the highest point of the catheter to the upper border of the left and right extremitas sternalis claviculae on chest X-ray images. Among 587 patients, 143 (24.4%) had thrombosis. Platelet count, C-reactive protein, and the vertical distance from the highest point of the catheter to the upper border of the left and right extremitas sternalis claviculae were demonstrated to be the main risk factors for the development of TIAPs-associated thrombosis. TIAPs-associated thrombosis, especially asymptomatic events, is common in pediatric cancer patients. The vertical distance from the highest point of the catheter to the upper border of the left and right extremitas sternalis claviculae was a risk factor for TIAPs-associated thrombosis, which deserved additional attention.

Somatic copy number alteration predicts clinical benefit of lung adenocarcinoma patients treated with cytokine-induced killer plus chemotherapy.

Somatic copy number alterations (SCNA), which are widespread in cancer, can predict the efficacy of immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC). However, the usefulness of SCNA for predicting the survival of patients treated with cytokine-induced killer (CIK) cells or chemotherapy (CT) is unknown. This study aimed to explore the correlation between SCNA and clinical outcome in NSCLC patients treated with CIK + CT or CT alone. We performed whole-exome sequencing on 45 NSCLC patients treated with CIK + CT, as well as 305 NSCLC patients treated with CT alone, from The Cancer Genome Atlas, which showed SCNA had a superiority in predicting the progression-free survival (PFS) over tumor mutation burden (TMB) and SCNA + TMB in NSCLC patients treated with CIK + CT, especially in lung adenocarcinoma, while SCNA could not predict the efficacy of CT alone. Additionally, we investigated the association between SCNA and immune cell infiltration by RNA sequencing and immunohistochemistry. The results revealed that SCNA was negatively associated with the expression of dendritic cells. Collectively, this study revealed a negative correlation between SCNA and response to CIK + CT and showed that SCNA is a predictive indicator in LUAD patients treated with CIK + CT.

CD4+ T cells are required to improve the efficacy of CIK therapy in non-small cell lung cancer.

As a widely studied adoptive treatment method, CIK (cytokine-induced killer cells) treatment has shown clinical benefits in many clinical trials on non-small cell lung cancer. As a heterogeneous cell population, however, CIK cells have a strong instability and individual differences in their efficacies, which are collaboratively regulated by the tumor microenvironment and CIK subpopulations. Among them, CD4+ T cells belong to a crucial subgroup of the CIK cell population, and their influence on CIK therapy is still unclear. Herein, we show how CD4+ T cells positively regulate the functions of CD3+CD56+ T and CD3+CD8+ T cells. During this process, we found that Th1/Th17 CD4+ subgroups can induce the phosphorylation of the AKT pathway by secreting IL-17A, and upregulate the expression of T-bet/Eomes transcription factors, thereby restoring the function of CD8+/CD3+CD56+ T cells and reversing the exhaustion of PD-1+Tim-3+ T cells. These findings will provide guidance for the clinical screening of suitable populations for CIK treatment and formulation of strategies for CIK therapy plus immune checkpoint treatment. Based on these findings, we are conducting an open-label phase II study (NCT04836728) is to evaluate the effects of autologous CIKs in combination with PD-1 inhibitor in the first-line treatment of IV NSCLC, and hope to observe patients' benefits in this clinical trial.

Signatures of Multi-Omics Reveal Distinct Tumor Immune Microenvironment Contributing to Immunotherapy in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) contains a variety of genomic and epigenomic abnormalities; the effective tumor markers related to these abnormalities need to be further explored. Methods: Clustering analysis was performed based on DNA methylation (MET), DNA copy number variation (CNV), and mRNA expression data, and the differences in survival and tumor immune microenvironment (TIME) between subtypes were compared. Further, we evaluated the signatures in terms of both prognostic value and immunological characteristics. Results: There was a positive correlation between MET and CNV in LUAD. Integrative analysis of multi-omics data from 443 samples determined molecular subtypes, iC1 and iC2. The fractions of CD8+ T cells and activated CD4+ T cells were higher, the fraction of Tregs was lower, and the expression level of programmed death-ligand 1 (PD-L1) was higher in iC2 with a poor prognosis showing a higher TIDE score. We selected PTTG1, SLC2A1, and FAM83A as signatures of molecular subtypes to build a prognostic risk model and divided patients into high-risk group and low-risk group representing poor prognosis and good prognosis, respectively, which were validated in 180 patients with LUAD. Further, the low-risk group with lower TIDE score had more infiltrating immune cells. In 100 patients with LUAD, the high-risk group with an immunosuppressive state had a higher expression of PD-L1 and lower counts of CD8+ T cells and dendritic cells. Conclusions: These findings demonstrated that combined multi-omics data could determine molecular subtypes with significant differences of prognosis and TIME in LUAD and suggested potent utility of the signatures to guide immunotherapy.

SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7.

The protein methyltransferase SET and MYND domain-containing protein 2 (SMYD2) is a transcriptional regulator that methylates histones and nonhistone proteins. As an oncogene, SMYD2 has been investigated in numerous types of cancer. However, its involvement in lung cancer remains elusive. The prognostic value of SMYD2 expression in lung adenocarcinoma (LUAD) was determined through bioinformatics analysis, reverse-transcription polymerase chain reaction, western blotting, and immunohistochemistry. The effect of SMYD2 on LUAD cell proliferation and metastasis was explored in vivo and in vitro, and the underlying mechanisms were investigated via RNA-seq, and chromatin immunoprecipitation-quantitative PCR. SMYD2 expression was significantly upregulated in LUAD cell lines and tissues. High SMYD2 expression was associated with shorter overall and disease-free survival in LUAD patients. Inhibition of SMYD2 with SMYD2 knockdown or AZ505 dramatically inhibited the proliferation, migration, and invasion ability of GLC-82 and SPC-A1 cells and remarkably reduced tumor growth in mice. Mechanically, SMYD2 may activate the transcription of ribosomal small subunit protein 7 (RPS7) by binding to its promoter. Following overexpression of SMYD2, the proliferation, migration, and invasion of cells increased, which was partially reversed by RPS7. Thus, SMYD2 might modulate tumorigenesis and metastasis mediated by RPS7 LUAD. SMYD2 might be a prognostic biomarker and therapeutic target in LUAD.

Molecular subtypes based on CNVs related gene signatures identify candidate prognostic biomarkers in lung adenocarcinoma.

The classical factors for predicting prognosis currently cannot meet the developing requirements of individualized and accurate prognostic evaluation in lung adenocarcinoma (LUAD). With the rapid development of high-throughput DNA sequencing technologies, genomic changes have been discovered. These sequencing data provide unprecedented opportunities for identifying cancer molecular subtypes. In this article, we classified LUAD into two distinct molecular subtypes (Cluster 1 and Cluster 2) based on Copy Number Variations (CNVs) and mRNA expression data from the Cancer Genome Atlas (TCGA) based on non-negative matrix factorization. Patients in Cluster 1 had worse outcomes than that in Cluster 2. Molecular features in subtypes were assessed to explain this phenomenon by analyzing differential expression genes expression pattern, which involved in cellular processes and environmental information processing. Analysis of immune cell populations suggested different distributions of CD4+ T cells, CD8+ T cells, and dendritic cells in the two subtypes. Subsequently, two novel genes, TROAP and RASGRF1, were discovered to be prognostic biomarkers in TCGA, which were confirmed in GSE31210 and Tianjin Medical University Cancer Institute and Hospital LUAD cohorts. We further proved their crucial roles in cancers by vitro experiments. TROAP mediates tumor cell proliferation, cycle, invasion, and migration, not apoptosis. RASGRF1 has a significant effect on tumor microenvironment. In conclusion, our study provides a novel insight into molecular classification based on CNVs related genes in LUAD, which may contribute to identify new molecular subtypes and target genes.

Somatic copy number alterations are predictive of progression-free survival in patients with lung adenocarcinoma undergoing radiotherapy.

OBJECTIVE: Lung cancer is the most common cause of cancer-related deaths worldwide. Somatic copy number alterations (SCNAs) have been used to predict responses to therapies in many cancers, including lung cancer. However, little is known about whether they are predictive of radiotherapy outcomes. We aimed to understand the prognostic value and biological functions of SCNAs. METHODS: We analyzed the correlation between SCNAs and clinical outcomes in The Cancer Genome Atlas data for 486 patients with non-small cell lung cancer who received radiotherapy. Gene set enrichment analyses were performed to investigate the potential mechanisms underlying the roles of SCNAs in the radiotherapy response. Our results were validated in 20 patients with lung adenocarcinoma (LUAD) receiving radiotherapy. RESULTS: SCNAs were a better predictor of progression-free survival (PFS) in LUAD (P = 0.024) than in lung squamous carcinoma (P = 0.18) in patients treated with radiotherapy. Univariate and multivariate regression analyses revealed the superiority of SCNAs in predicting PFS in patients with LUAD. Patients with stage I cancer and low SCNA levels had longer PFS than those with high SCNA levels (P = 0.022). Our prognostic nomogram also showed that combining SCNAs and tumor/node/metastasis provided a better model for predicting long-term PFS. Additionally, high SCNA may activate the cell cycle pathway and induce tumorigenesis. CONCLUSIONS: SCNAs may be used to predict PFS in patients with early-stage LUAD with radiotherapy, in combination with TNM, with the aim of predicting long-term PFS. Therefore, SCNAs are a novel predictive biomarker for radiotherapy in patients with LUAD.

Spontaneous Creation of Anisotropic Polymer Crystals with Orientation-Sensitive Birefringence in Liquid Drops.

It remains a grand challenge to prepare anisotropic crystal superstructures with sensitive optical properties in polymer science and materials field. This study demonstrates that semicrystalline polymers develop into anisotropic hollow spherulitic crystals spontaneously at interfaces of liquid drops. In contrast to conventional spherulites with centrosymmetric optics and grain boundaries, these anisotropic spherulitic crystals have vanished boundary defects, tunable aspect ratios, and noncentrosymmetric, orientation-sensitive birefringence. The experimental finding is elaborated in poly(l-lactic acid) crystals and is further verified in a broad class of semicrystalline polymers, irrespective of molecular chirality, chemical constitution, or interfacial modification. The facile methods and general mechanism revealed in this study shed light on developing new types of optical microdevices and synthesis of anisotropic semicrystalline particles from liquid emulsions.

Design, synthesis and biological evaluation of novel 3,4-dihydro-2(1H)-quinolinone derivatives as potential chitin synthase inhibitors and antifungal agents.

A series of 3,4-dihydro-2(1H)-quinolinone derivatives contained butenediamide fragment were designed and synthesized. Their inhibition potency against chitin synthase and antimicrobial activities were screened in vitro. The enzymatic assays showed that all the synthesized compounds had inhibition potency against chitin synthase at concentration of 300 µg/mL. Compound 2d displayed excellent potency with inhibition percentage (IP) value of 82.3%, while IP value of the control polyoxin B was 87.5%. Compounds 2b, 2e and 2s whose IP values were above 70% showed good inhibition potency against chitin synthase. Moreover, the IC50 value of 2b was comparable with that of polyoxin B (0.09 mM). The Ki of compound 2b was 0.12 mM and the result from Lineweaver-Burk plot showed that 2b was non-competitive inhibitor to bind chitin synthase. The antifungal experiment showed that these compounds had excellent antifungal activity against fungal strains, especially for candida albicans. The antifungal activities against C .albicans of compounds 2b, 2d, 2e and 2l were comparable with that of fluconazole and were superior to that of polyoxin B. Meanwhile, the other compounds against C. albicans showed better antifungal activity (MIC 2 µg/mL) than polyoxin B except for compound 2n (MIC 4 µg/mL). The trial of drug combination use showed that these synthesized compounds had synergistic effects with fluconazole and polyoxin B. It indicated that these compounds were not competing with polyoxin B to bind with chitin synthase, which was also consistence with the result of enzymatic assays. The antibacterial experiment showed that these compounds had no activity against selected strains including three Gram-positive and three Gram-negative bacteria. These results showed that the designed compounds were chitin synthase inhibitors and had selective antifungal activity.

TOP2A Promotes Lung Adenocarcinoma Cells' Malignant Progression and Predicts Poor Prognosis in Lung Adenocarcinoma.

Background: Topoisomerase IIA (TOP2A) gene encodes DNA topoisomerase enzyme and has been reported that TOP2A is broadly expressed in many types of cancers. Our study aims to investigate the prognostic effect of TOP2A on lung adenocarcinoma (LUAD) and the potential molecular mechanism of TOP2A to tumorigenesis. Methods: Bioinformatical analysis, real-time PCR and Western blot were applied to explore the expression level of TOP2A. Kaplan-Meier survival analysis was used to evaluate the effect of TOP2A on patients' prognosis. Cell proliferation, migration and invasion ability were examined by colony-formation, Cell Counting Kit-8 (CCK8) assay, wound healing assay and transwell invasion assay, respectively. Results: We firstly investigated differentially expressed genes in lung adenocarcinoma and normal tissues of GEO (tumor = 666, normal = 184) and TCGA (tumor = 517, normal = 59) and these data showed that TOP2A is broadly expressed in LUAD and the expression level of TOP2A is associated with poor prognosis, which indicated that TOP2A is an upregulated prognostic related gene in LUAD. Then we identified that the expression level of TOP2A was upregulated in both surgically removed lung cancer tissues and lung cancer cell lines. Knockdown of TOP2A in A549 and GLC82 cells inhibited cell proliferation, migration and invasion. Inhibition of TOP2A reduced the expression levels of CCNB1 and CCNB2, which indicated that TOP2A targeting CCNB1 and CCNB2 promotes GLC82 and A549 cells proliferation and metastasis. Conclusions: Our study revealed an important role of TOP2A in LUAD, and may provide a potential prognostic indicator and target for cancer therapy.

Comprehensive Analysis of lncRNA-Mediated ceRNA Crosstalk and Identification of Prognostic Biomarkers in Wilms' Tumor.

Wilms' tumor (WT) is the most common type of childhood kidney cancer, and most cases present with favorable histology and respond well to standard treatment. However, a subset of patients with WT is diagnosed with bilateral, relapsed, and high-risk tumors which remain the leading cause of cancer-related death in children. Long noncoding RNAs (lncRNAs) and their aberrant expression have currently been attracting great attention as oncogenes or tumor suppressors during tumor initiation and progression. So far, their roles and related competitive endogenous RNA (ceRNA) network remain unelucidated in nephroblastoma pathogenesis. We comprehensively integrated lncRNA, microRNA (miRNA), and messenger RNA (mRNA) expression profiles from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and screened out differentially expressed mRNAs (DEMs), lncRNAs (DELs), and miRNAs (DEMis) to construct a ceRNA network based on the information generated from miRcode, miRTarBase, TargetScan, and miRDB. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the functional characteristics of DEMs in the ceRNA network. The interaction between protein molecules was also analyzed by establishing a protein-protein interaction network. Finally, prognosis-related biomarkers were identified via survival analysis. Initially, 1647 DELs, 115 DEMis, and 3280 DEMs (|log FC| > 2; FDR < 0.01) were obtained using the R package. Next, we constructed a lncRNA-miRNA-mRNA network (ceRNA network), in which 176 DELs, 24 DEMis, and 141 DEMs were identified. Furthermore, 148 functional enrichment terms from GO were identified and 29 KEGG pathways were found to be significantly enriched. We also integrated patient clinical information to analyze the association between DERNAs and patient prognosis. We found that high expression of 8 DELs (LINC00473, AL445228.2, DENND5B-AS1, DLEU2, AC123595.1, AC135178.1, LINC00535, and LMO7-AS1) and 4 DEMs (CEP55, DEPDC1, PHF19, and TRIM36) correlated with poor survival in a patient with WT, whereas high expression of 2 DELs (MEG3 and RMST), 1 DEM (KIAA0922), and 1 DEMi (hsa-mir-200a) could possibly lead to better clinical outcomes. For the first time, the present study provided a novel insight into lncRNA-related ceRNA networks and identified potential prognostic biomarkers in Wilms' tumor.

Expression signature, prognosis value, and immune characteristics of Siglec-15 identified by pan-cancer analysis.

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is considered a novel anti-tumor target comparable to programmed cell death 1 ligand 1(PD-L1). However, little is known about Siglec-15. Our study aims to understand its expression signature, prognosis value, immune infiltration pattern, and biological function using multi-omic bioinformatics from public databases and verify them in lung cancer patients. Integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals showed Siglec-15 was overexpressed across cancers. Genetic and epigenetic alteration analysis was performed using cBioportal and UALCAN, showed Siglec-15 was regulated at the genetic and epigenetic levels. Survival estimated using Kaplan-Meier plotter indicated high Siglec-15 expression correlated with favorable or unfavorable outcomes depending on the different type and subtype of cancer. Components of immune microenvironment were analyzed using CIBERSORT, and the correlation between immune cells and Siglec-15 was found to be distinct across cancer types. Based on Gene Set Enrichment Analysis, Siglec-15 was implicated in pathways involved in immunity, metabolism, cancer, and infectious diseases. Lung cancer patients with positive Siglec-15 expression showed significantly short survival rates in progression-free survival concomitant with reduced infiltration of CD20 + B, and dendritic cells by immunohistochemistry. Quantitative real-time PCR results indicated the overexpression of Siglec-15 was correlated with activation of the chemokine signaling pathway. In conclusion, Siglec-15 could serve as a vital prognostic biomarker and play an immune-regulatory role in tumors. These results provide us with clues to better understand Siglec-15 from the perspective of bioinformatics and highlight the importance of Siglec-15 in many types of cancer.

Metalized Alkanedithiol Self-Assembled Monolayers (SAM) on Au Surfaces by an In Situ Autocatalytic Mechanism.

Here, a simple and general approach was developed for depositing metal nanoparticles on alkanedithiol self-assembled monolayers (SAMs) based on the spontaneous reduction of metal ions by the free SH sites of SAMs. By immersing the alkanedithiol SAM/Au in a corresponding metalcontaining solution (HAuCl4, AgNO3, H2PtCl6 and PdSO4), Au, Ag, Pt and Pd clusters, respectively, could be formed on top of the SAM/Au(111) electrode surface, which was confirmed by STM characterization. The size, morphology and coverage of clusters/islands can be tuned by modulating the immersion time, which allows for possible utilization of the metal/SAM/Au(111) in catalysis, nanoelectronics and biodetection.