Prediction and prognostic significance of BCAR3 expression in patients with multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is the plasma cell tumor, which is characterized by clonal proliferation of tumor cells, with high risk of progression to renal impairment, bone damage and amyloidosis. Although the survival rate of patients with MM has improved in the past decade, most people inevitably relapse. The treatment and prognosis of MM are still urgent problems. Breast Cancer Antiestrogen Resistance 3 (BCAR3) is a protein-coding gene that is associated with many tumors. However, there have been few studies on the relationship of BCAR3 and MM. METHODS: We analyzed 1878 MM patients (1930 samples) from 7 independent datasets. First, we compared the BCAR3 expression level of MM patients in different stages and MM patients with different amplification of 1q21. Second, we analyzed BCAR3 expression levels in MM patients with different molecular subtypes. Finally, we explored the event-free survival rate (EFS) and overall survival rate (OS) of MM patients with high or low BCAR3 expression, including patients before and after relapse, and their therapeutic responses to bortezomib and dexamethasone. RESULTS: The expression of BCAR3 showed a decreasing trend in stages I, II and III (P = 0.00068). With the increase of 1q21 amplification level, the expression of BCAR3 decreased (P = 0.022). Patients with high BCAR3 expression had higher EFS and OS (EFS: P < 0.0001, OS: P < 0.0001). The expression of BCAR3 gene before relapse was higher than that after relapse (P = 0.0045). BCAR3 is an independent factor affecting prognosis (EFS: P = 5.17E-03; OS: P = 3.33E-04). CONCLUSION: We found that high expression level of BCAR3 predicted better prognosis of MM patients. Low expression of BCAR3 at diagnosis can predict early relapse. BCAR3 is an independent prognostic factor for MM. BCAR3 can be used as a potential biomarker.

Identification and Validation of Immune Implication of R-Spondin 1 and an R-Spondin 1-Related Prognostic Signature in Esophagus Cancer.

R-spondin 1 (RSPO1), which encodes a secretory-activating protein, is a promising therapeutic target for various tumors. The aim of this study was to establish a robust RSPO1-related signature specific to esophageal cancer (ESCA). Our comprehensive study involved meticulous analysis of RSPO1 expression in ESCA tissues and validation across ESCA cell lines and clinical samples using The Cancer Genome Atlas (TCGA) and GTEx databases. Using TCGA-ESCA dataset, we employed single-sample gene set enrichment analysis (ssGSEA) to elucidate the complex interaction between RSPO1 expression and the abundance of 22 specific immune cell types infiltrating ESCA. The biological significance of RSPO1 was further elucidated using KEGG, GO, and GSEA, demonstrating its relevance to pivotal tumor and immune pathways. This study culminated in the construction of prognostic nomograms enriched by calibration curves, facilitating the projection of individual survival probabilities at intervals of one, three, and five years. A substantial decrease in RSPO1 expression was observed within ESCA tissues and cell lines compared to their normal esophageal counterparts, and a significant decrease in the proportion of activated dendritic cells was evident within ESCA, accompanied by an augmented presence of macrophages and naive B cells relative to normal tissue. GSEA and KEGG analyses showed that RSPO1 was associated with tumor and immune pathways. Additionally, an independent prognostic risk score based on the RSPO1-related gene signature was developed and validated for patients with ESCA. Finally, RT-qPCR and western blotting were performed to confirm RSPO1 expression in normal and ESCA cell lines and tissue samples. In summary, our investigation underscores the pivotal role of RSPO1 in orchestrating tumor immunity and proposes RSPO1 as a prospective target for immunotherapeutic interventions in ESCA. Furthermore, the intricate profile of the two RSPO1-related genes has emerged as a promising predictive biomarker with notable potential for application in ESCA.

Prognostic prediction and diagnostic role of Rspondin 1 expression in esophageal squamous cell carcinoma.

CONTEXT: Rspondin 1 (Rspo1), a protein family member featuring secreted furin-like domains, plays a pivotal role in cancer development and exhibits a positive correlation with tumor progression. However, its expression in esophageal squamous cell carcinoma (ESCC) is still unknown. AIMS: Here, we assessed the correlation between Rspo1 and clinicopathological features of ESCC patients, and further investigated the potential role of Rspo1 in ESCC development and clinical outcomes. SETTINGS AND DESIGN: This was a pilot study. MATERIALS AND METHODS: A total of 112 paraffin-embedded tumor samples from patients with ESCC, including 68 matched adjacent normal tissues, were collected post-surgery. Subsequently, tissue microarray (TMA) and immunohistochemistry (IHC) techniques were employed to assess the protein levels of Rspo1. STATISTICAL ANALYSIS: All statistical analyses were performed with SPSS 20.0 (SPSS, Inc., Chicago, IL). RESULTS: We found that Rspo1 expression was significantly higher in ESCC than in adjacent normal tissues (P < 0.0001). Moreover, Rspo1 was highly expressed in ESCC tumor specimens and showed a significant correlation with the T classification of ESCC (P < 0.05). Additionally, our findings indicate a positive relationship between Rspo1 and survival time in ESCC. Patients exhibiting moderate to high levels of Rspo1 expression demonstrated superior survival outcomes compared to those with low expression (P = 0.0002). CONCLUSIONS: Our investigation has demonstrated that Rspo1 is upregulated in ESCC and exhibits a positive correlation with disease progression. Furthermore, we have observed a significant association between Rspo1 overexpression and improved patient survival rates, indicating its potential as a prognostic marker and therapeutic target for ESCC treatment.

Assessing the utility of artificial intelligence throughout the triage outpatients: a prospective randomized controlled clinical study.

Currently, there are still many patients who require outpatient triage assistance. ChatGPT, a natural language processing tool powered by artificial intelligence technology, is increasingly utilized in medicine. To facilitate and expedite patients' navigation to the appropriate department, we conducted an outpatient triage evaluation of ChatGPT. For this evaluation, we posed 30 highly representative and common outpatient questions to ChatGPT and scored its responses using a panel of five experienced doctors. The consistency of manual triage and ChatGPT triage was assessed by five experienced doctors, and statistical analysis was performed using the Chi-square test. The expert ratings of ChatGPT's answers to these 30 frequently asked questions revealed 17 responses earning very high scores (10 and 9.5 points), 7 earning high scores (9 points), and 6 receiving low scores (8 and 7 points). Additionally, we conducted a prospective cohort study in which 45 patients completed forms detailing gender, age, and symptoms. Triage was then performed by outpatient triage staff and ChatGPT. Among the 45 patients, we found a high level of agreement between manual triage and ChatGPT triage (consistency: 93.3-100%, p<0.0001). We were pleasantly surprised to observe that ChatGPT's responses were highly professional, comprehensive, and humanized. This innovation can help patients win more treatment time, improve patient diagnosis and cure rates, and alleviate the pressure of medical staff shortage.

Screening of tumor antigens and immunogenic cell death landscapes of prostate adenocarcinoma for exploration of mRNA vaccine.

BACKGROUND: In this study, effective antigens of mRNA vaccine were excavated from the perspective of ICD, and ICD subtypes of PRAD were further distinguished to establish an ICD landscape, thereby determining suitable vaccine recipients. RESEARCH DESIGN AND METHODS: TCGA and MSKCC databases were applied to acquire RNA-seq data and corresponding clinical data of 554 and 131 patients, respectively. GEPIA was employed to measure prognostic indices. Then, a comparison of genetic alterations was performed utilizing cBioPortal, and correlation of identified ICD antigens with immune infiltrating cells was analyzed employing TIMER. Moreover, ICD subtypes were identified by means of consensus cluster, and ICD landscape of PRAD was depicted utilizing graph learning-based dimensional reduction. RESULTS: In total, 4 PRAD antigens were identified in PRAD, including FUS, LMNB2, RNPC3, and ZNF700, which had association with adverse prognosis and infiltration of APCs. PRAD patients were classified as two ICD subtypes based on their differences in molecular, cellular, and clinical features. Furthermore, ICD modulators and immune checkpoints were also differentially expressed between two ICD subtype tumors. Finally, the ICD landscape of PRAD showed substantial heterogeneity among individual patients. CONCLUSIONS: In summary, the research may provide a theoretical foundation for developing mRNA vaccine against PRAD as well as determining appropriate vaccine recipients.

Prognostic significance of SH2D5 expression in lung adenocarcinoma and its relation to immune cell infiltration.

Objective: Through analyzing the SH2D5 expression profiles, clinical features, and immune infiltration in lung adenocarcinoma (LUAD), the study was intended to discuss the correlations of SH2D5 with prognosis and immune infiltration in LUAD. Methods: We downloaded transcriptome and clinical data of LUAD patients from TCGA, GEO, and CCLE databases. Sangerbox, R language, GEPIA, UALCAN, and Kaplan-Meier Plotter were adopted to analyze the SH2D5 expression patterns, prognosis, and clinical features. Spearman correlation analysis was performed to determine the association between SH2D5 expression and immune cell infiltration and immune checkpoint genes. The miRNA-SH2D5 relations were predicted by miRDB and starbase. Lastly, quantitative PCR, IHC and Western blot were implemented for validation. Results: A prominent up-regulation of SH2D5 was noted in the LUAD group relative to the normal group, which was validated by quantitative PCR, IHC and Western blot. SH2D5 expression was inversely related to overall survival (OS) of LUAD patients as well as B cell immune infiltration. Additionally, SH2D5 expression was negatively correlated with dendritic cells resting (p < 0.001), plasma cells (p < 0.001), mast cells resting (p = 0.031) and T cells CD4 memory resting (p = 0.036) in LUAD patients with abundant SH2D5 expression correlated with poor prognosis. Furthermore, enrichment analysis suggested that SH2D5 was associated with lung cancer and immunity. Lastly, we investigated the relationship between the expression of SH2D5 and the use of antitumor drugs. Conclusion: High SH2D5 expression shares an association with unfavorable prognosis in LUAD, and SH2D5 may also provide new ideas for immunotherapy as a potential therapeutic target.

Bovine Serum Albumin Molecularly Imprinted Electrochemical Sensors Modified by Carboxylated Multi-Walled Carbon Nanotubes/CaAlg Hydrogels.

In this paper, sodium alginate (NaAlg) was used as functional monomers, bovine serum albumin (BSA) was used as template molecules, and calcium chloride (CaCl2) aqueous solution was used as a cross-linking agent to prepare BSA molecularly imprinted carboxylated multi-wall carbon nanotubes (CMWCNT)/CaAlg hydrogel films (MIPs) and non-imprinted hydrogel films (NIPs). The adsorption capacity of the MIP film for BSA was 27.23 mg/g and the imprinting efficiency was 2.73. The MIP and NIP hydrogel film were loaded on the surface of the printed electrode, and electrochemical performance tests were carried out by electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) using the electrochemical workstation. The loaded MIP film and NIP film effectively improved the electrochemical signal of the bare carbon electrode. When the pH value of the Tris HCl elution solution was 7.4, the elution time was 15 min and the adsorption time was 15 min, and the peak currents of MIP-modified electrodes and NIP-modified electrodes reached their maximum values. There was a specific interaction between MIP-modified electrodes and BSA, exhibiting specific recognition for BSA. In addition, the MIP-modified electrodes had good anti-interference, reusability, stability, and reproducibility. The detection limit (LOD) was 5.6 × 10-6 mg mL-1.

Stable Harsh-Temperature Lithium Metal Batteries Enabled by Tailoring Solvation Structure in Ether Electrolytes.

For lithium metal batteries (LMBs), the elevated operating temperature results in severe capacity fading and safety issues due to unstable electrode-electrolyte interphases and electrolyte solvation structures. Therefore, it is crucial to construct advanced electrolytes capable of tolerating harsh environments to ensure stable LMBs. Here, we proposed a stable localized high-concentration electrolyte (LHCE) by introducing the highly solvating power solvent diethylene glycol dimethyl ether (DGDME). Computational and experimental evidence discloses that the original DGDME-LHCE shows favorable features for high-temperature LMBs, including high Li+-binding stability, electro-oxidation resistance, thermal stability, and nonflammability. The tailored solvated sheath structure achieves the preferred decomposition of anions, inducing the stable (cathode and Li anode)/interphases simultaneously, which enables a homogeneous Li plating-stripping behavior on the anode side and a high-voltage tolerance on the cathode side. For the Li||Li cells coupled with DGDME-LHCE, they showcase outstanding reversibility (a long lifespan of exceeding 1900 h). We demonstrate exceptional cyclic stability (∼95.59%, 250 cycles), high Coulombic efficiency (>99.88%), and impressive high-voltage (4.5 V) and high-temperature (60 °C) performances in Li||NCM523 cells using DGDME-LHCE. Our advances shed light on an encouraging ether electrolyte tactic for the Li-metal batteries confronted with stringent high-temperature challenges.

BTN3A2 Expression Is Connected With Favorable Prognosis and High Infiltrating Immune in Lung Adenocarcinoma.

Background: Butyrophilin subfamily 3 member A2 (BTN3A2) is an important mediator in immune activation, and it is reported to be linked to many cancer progresses. However, the relation with infiltrating immune and prognosis of BTN3A2 in lung adenocarcinoma are not clear. Methods: In our study, we checked the mRNA expression and protein expression profile of BTN3A2 in lung adenocarcinoma (LUAD) and its relation to clinical outcomes using TIMER and UALCAN databases. In addition, we analyzed the survival of BTN3A2 in LUAD using the Kaplan-Meier Plotter database and PrognoScan database. Moreover, we analyzed gene set enrichment analysis (GSEA) of the BTN3A2. Next, we explored the relation of BTN3A2 expression with the immune infiltration by TIMER. At last, in order to enrich the regulatory mechanism of BTN3A2, we used miRarbase, starbase, and miRDB databases to look for miRNA targets of BTN3A2. Results: The mRNA along with the protein expression of BTN3A2 in the LUAD group was lower than that in the normal group. In addition, high BTN3A2 expression was connected with good first progression (FP) and overall survival (OS) in LUAD. Then, the GSEA analysis demonstrated that T-cell receptor signaling cascade, B-cell receptor signaling cascade, natural killer cell-mediated cytotoxicity, immune receptor activity, immunological synapse, and T-cell activation were enriched differentially in the BTN3A2 high expression phenotype of LUAD. Moreover, BTN3A2 expression is a remarkable positive correlation with invading levels of tumor purity, B cells, neutrophils, CD4+ T cells, dendritic cells, macrophages, and CD8+ T cells in LUAD, and B cells and dendritic cells were linked with a good prognosis of LUAD. To further enrich the possible regulatory mechanisms of BTN3A2, we analyzed the miRNA targets. The results showed that hsa-miR-17-5p may be miRNA targets of BTN3A2. Conclusion: Taking together, we provide evidence of BTN3A2 as possible prognosis biomarkers of LUAD. In addition, high BTN3A2 expression in LUAD may influence the prognosis because of immune invasion. Moreover, our findings provide a potential mechanism that hsa-miR-17-5p may be miRNA targets of BTN3A2.

Ultra-stable Li||LiFePO4 batteries via advanced designing of localized high concentration electrolyte.

The High-Performance Li-LiFePO4 batteries (Li||LFP) realized by highly compatible electrolytes are considered to be the breakthrough point to achieve the stability and high energy density of lithium-ion battery (LIB) systems. However, the current prevailing commercial electrolytes can hardly be compatible with both LFP cathode and lithium anode simultaneously to an ideal extent. On this very note, we designed an advanced ether-based localized high concentration electrolyte (abbreviated as "ADE"), which exhibits extreme compatibility with LFP-based lithium metal batteries (Fb-LMBs). Equipped with ADE-electrolyte, the Li||LFP coin cell system can carry out more than 4000 fast-charging/discharging (3C for charge and 6C for discharge, respectively) rigorously cycles. Each cycle can not only sacrifice just 0.145‱ capacity on average compared with the original value, but also cycle at elevated temp (>200 fast charging/discharging cycles under 60 °C). This performance remains rare in liquid electrolyte systems in previous reports. The significantly enhanced electrochemical performance can be ascribed to the stabilization of both LFP-cathode/electrolyte and Li-metal-anode/electrolyte interphases. In addition, due to its specific solvated sheath structure, its wettability and flame-retarding properties are superior to those of the control group. This work expands the space for designing a stable fast-charge LFP-based system and sheds light on the possibility of replacing the most popular graphite||LFP system with Li ||LFP configuration with high energy density and stable cyclic performance.

Integrative Multi-Omics Analysis of Identified SKA3 as a Candidate Oncogene Correlates with Poor Prognosis and Immune Infiltration in Lung Adenocarcinoma.

Background: Spindle and kinetochore-associated complex subunit 3 (SKA3) plays important roles in promoting the migration and the invasion of various human cancer cells. There are a few studies on SKA3 in lung adenocarcinoma (LUAD), but the in-depth analysis of the expression of SKA3 and the correlated possible immune mechanism of SKA3 in LUAD are not clear. Methods: In our study, the expression and survival data of SKA3 were analyzed in LUAD using TIMER, Oncomine, UALCAN, cBioPortal, LinkedOmics, Human Protein Atlas, and Kaplan-Meier plotter. Then, quantitative PCR was used to verify the expression differences of SKA3 between LUAD tissues of mice and the normal tissues. Results: We established that the expression of SKA3 in the LUAD group was remarkably higher than that in the normal group. Additionally, high SKA3 expression was linked to poorer survival in LUAD. Moreover, SKA3 expression had a remarkable negative correlation with the immune infiltration of B cells, macrophages, and CD4+ T cells. SKA3 was markedly negatively related to the immune type biomarkers of T cells and B cells in LUAD. The elevated expression of SKA3 with LUAD in enriched B cells, CD4+ T cells, CD8+ T cells, macrophages and Treg cells had worse prognosis, respectively. Functional network analysis showed that SKA3 regulated the mitotic cell cycle, mitosis, chromosome segregation and cell division via pathways. Conclusion: In summary, our study suggested that SKA3 was highly expressed in LUAD and SKA3 might function as a prognostic biomarker in LUAD. Besides, SKA3 may be a candidate oncogene, which correlates with poor prognosis and immune infiltration in lung adenocarcinoma.

Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) correlates with poor prognosis and immune infiltration in lung adenocarcinoma.

The protein phosphatase 1 regulatory subunit 3 G (PPP1R3G) participates in many tumor biological processes; however, its effects on lung adenocarcinoma (LUAD) have not been clarified. Therefore, this study aimed to explore the correlation between PPP1R3G and the prognosis and immune invasion of LUAD. We evaluated the relationship between PPP1R3G and LUAD using a wide range of databases and analysis tools, including UALCAN, TIMER, miRDB, The Human Protein Atlas and the MethSurv database. First, we explored the mRNA and protein expression levels of PPP1R3G in LUAD, and results were validated using real-time PCR. Next, we explored the relationship between PPP1R3G expression and clinical features. Finally, Kaplan-Meier curves and Cox regression were employed to investigate the prognostic significance of PPP1R3G in LUAD. In addition, we explored the relationship between the expression of PPP1R3G and immune infiltration using the TIMER database. We analyzed the relationship between PPP1R3G and methylation using MethSurv database. Results showed that PPP1R3G expression in LUAD tissues was higher than that in normal tissues, and high expression was suggestive of a poor prognosis. Moreover, PPP1R3G expression was positively correlated with the immune infiltration of CD4 + T cells, macrophages, neutrophils, and dendritic cells. PPP1R3G copy number variations also demonstrated remarkable associations with the levels of B cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells. Finally, a PPP1R3G-associated regulatory network was constructed. Overall, PPP1R3G might be a poor prognostic biomarker for LUAD and is associated with tumor immune cell infiltration.Abbreviations: LUAD: Lung adenocarcinoma; PPP1R3G: The protein phosphatase 1 regulatory subunit 3G; OS: overall survival; CI: confidence interval; CNV: copy number variance; HR: Hazard Ratio; ROC: receiver operating characteristic curve; AUC: area under the curve; TCGA: The Cancer Genome Atlas.

H19 Knockdown Suppresses Proliferation and Induces Apoptosis by Regulating miR-130a-3p/SATB1 in Breast Cancer Cells.

PURPOSE: Breast cancer (BC) is the most common cancer in women. Emerging evidence has demonstrated that lncRNAs play an important role in BC. The objective of this study was to investigate the impact of the long non-coding RNA (lncRNA), H19/miRNA-130a-3P/special AT-rich sequence-binding protein-1 (SATB1) axis on BC progression. MATERIALS AND METHODS: Expression of lncRNA and RNA was quantified via RT-qPCR. CCK-8, colony formation, wound healing, transwell, and flow cytometric analyses were used to analyze the proliferation, migration, invasion and apoptosis of cells. A dual-luciferase reporter assay and a RNA immunoprecipitation (RIP) assay were used to assess molecular binding. Protein levels were measured by Western blotting. The function of the lncRNA H19 (hereafter referred to as H19) was examined by xenotransplantation. RESULTS: We demonstrated that H19 expression was higher in cancer tissues and cancer cell lines than in adjacent non-tumor tissues and normal cell lines, respectively. H19 silencing inhibited the proliferation, migration and invasion of BC cells, and induced apoptosis. In addition, H19 directly bound to miR-130a-3p and downregulated its expression. We further demonstrated that H19 sponged miRNA-130a-3p, which resulted in SATB1 upregulation, thus promoting BC progression. Silencing of H19 substantially suppressed BC tumorigenesis in vivo. CONCLUSION: Our data uncovered a novel mechanism of BC progression based on the H19-miR-130a-3p-SATB1 axis.

Self-organization of dragon king failures.

The mechanisms underlying cascading failures are often modeled via the paradigm of self-organized criticality. Here we introduce a simple network model where nodes self-organize to be either weakly or strongly protected against failure in a manner that captures the trade-off between degradation and reinforcement of nodes inherent in many network systems. If strong nodes cannot fail, any failure is contained to a single, isolated cluster of weak nodes and the model produces power-law distributions of failure sizes. We classify the large, rare events that involve the failure of only a single cluster as "black swans." In contrast, if strong nodes fail once a sufficient fraction of their neighbors fail, then failure can cascade across multiple clusters of weak nodes. If over 99.9% of the nodes fail due to this cluster hopping mechanism, we classify this as a "dragon king," which are massive failures caused by mechanisms distinct from smaller failures. The dragon kings observed are self-organized, existing over a wide range of reinforcement rates and system sizes. We find that once an initial cluster of failing weak nodes is above a critical size, the dragon king mechanism kicks in, leading to piggybacking system-wide failures. We demonstrate that the size of the initial failed weak cluster predicts the likelihood of a dragon king event with high accuracy and we develop a simple control strategy that can dramatically reduce dragon kings and other large failures.

Compounds interaction on the biodegradation of butanol mixture in a biofilter.

Compounds interaction on the biodegradation of n-butanol and sec-butanol mixture in a composite bead biofilter was investigated. The biodegradation rate of compounds in the exponential growth phase and stationary phase for the single compound and two compounds mixing systems was determined. The microbial growth rate and biochemical reaction rate of two compounds decreased with increasing compound inlet concentration for the single compound system. The microbial metabolic activity of sec-butanol biodegraded in the microbial growth process and biochemical reaction process was inhibited as n-butanol was introduced. This inhibitive effect was more pronounced at higher n-butanol inlet concentration and lower sec-butanol inlet concentration for the two compounds mixing system.