Significant Enhancement of Negative Thermal Expansion Under Low Pressure in Cu2P2O7.

Much effort is made to achieve the negative thermal expansion (NTE) control, but rare methods reached the improvement of intrinsic NTE. In the present work, a significantly enhanced NTE is realized in Cu2P2O7 by applying low pressure. Especially, the volumetric coefficient of thermal expansion (CTE) of Cu2P2O7 reached to -50.0 × 10-6 K-1 (150-325K) under 0.25 GPa, which is increased by 47.5% compared to its NTE in a similar temperature range under atmosphere pressure. This character enables a more effective manifestation of the thermal compensation role of Cu2P2O7 in composites. The enhanced NTE mechanisms are analyzed by high pressure synchrotron X-ray diffraction, neutron diffraction at variable temperature and pressure, as well as density functional theory (DFT) calculations. The results show that applied pressure accelerates the contraction of the distance between adjacent CuO layers and CuO columns. Meanwhile, the low-frequency phonon contribution to NTE in α-Cu2P2O7 is improved. This work is meaningful for the exploration of methods to enhance NTE and the practical application of NTE materials.

The Prognostic Significance of Nomogram-Based Pretreatment Inflammatory Indicators in Patients With Esophageal Squamous Cell Carcinoma Receiving Intensity-Modulated Radiotherapy.

BACKGROUND: At present, there is no objective prognostic index available for patients with esophageal squamous cell carcinoma (ESCC) who underwent intensity-modulated radiotherapy (IMRT). This study is to develop a nomogram based on hematologic inflammatory indices for ESCC patients treated with IMRT. METHODS: 581 patients with ESCC receiving definitive IMRT were enrolled in our retrospective study. Of which, 434 patients with treatment-naïve ESCC in Fujian Cancer Hospital were defined as the training cohort. Additional 147 newly diagnosed ESCC patients were used as the validation cohort. Independent predictors of overall survival (OS) were employed to establish a nomogram model. The predictive ability was evaluated by time-dependent receiver operating characteristic curves, the concordance index (C-index), net reclassification index (NRI), and integrated discrimination improvement (IDI). Decision curve analysis (DCA) was performed to assess the clinical benefits of the nomogram model. The entire series was divided into 3 risk subgroups stratified by the total nomogram scores. RESULTS: Clinical TNM staging, primary gross tumor volume, chemotherapy, neutrophil-to-lymphocyte ratio and platelet lymphocyte ratio were independent predictors of OS. Nomogram was developed incorporating these factors. Compared with the 8th American Joint Committee on Cancer (AJCC) staging, the C-index for 5-year OS (.627 and .629) and the AUC value of 5-year OS (.706 and .719) in the training and validation cohorts (respectively) were superior. Furthermore, the nomogram model presented higher NRI and IDI. DCA also demonstrated that the nomogram model provided greater clinical benefit. Finally, patients with <84.8, 84.8-151.4, and >151.4 points were categorized into low-risk, intermediate-risk, and high-risk groups. Their 5-year OS rates were 44.0%, 23.6%, and 8.9%, respectively. The C-index was .625, which was higher than the 8th AJCC staging. CONCLUSIONS: We have developed a nomogram model that enables risk-stratification of patients with ESCC receiving definitive IMRT. Our findings may serve as a reference for personalized treatment.

Comparative study of first-principles approaches for effective Coulomb interaction strength Ueff between localized f-electrons: Lanthanide metals as an example.

As correlation strength has a key influence on the simulation of strongly correlated materials, many approaches have been proposed to obtain the parameter using first-principles calculations. However, a comparison of the different Coulomb strengths obtained using these approaches and an investigation of the mechanisms behind them are still needed. Taking lanthanide metals as an example, we research the factors that affect the effective Coulomb interaction strength, Ueff, by local screened Coulomb correction (LSCC), linear response (LR), and constrained random-phase approximation (cRPA) in the Vienna Ab initio Simulation Package. The Ueff LSCC value increases from 4.75 to 7.78 eV, Ueff LR is almost stable at about 6.0 eV (except for Eu, Er, and Yb), and Ueff cRPA shows a two-stage decreasing trend in both light and heavy lanthanides. To investigate these differences, we establish a scheme to analyze the coexistence and competition between the orbital localization and the screening effect. We find that LSCC and cRPA are dominated by the orbital localization and the screening effect, respectively, whereas LR shows the balance of the competition between the two factors. Additionally, the performance of these approaches is influenced by different starting points from the Perdew-Burke-Ernzerhof (PBE) and PBE + U, especially for cRPA. Our results provide useful knowledge for understanding the Ueff of lanthanide materials, and similar analyses can also be used in the research of other correlation strength simulation approaches.

Anchoring Filament Protein Ladinin-1 is an Immunosuppressive Microenvironment and Cold Tumor Correlated Prognosticator in Lung Adenocarcinoma.

Anchoring filament protein ladinin-1 (LAD1) codes for an anchor filament protein in the basement membrane. Here, we have aimed to determine its potential role in LUAD. According to the comprehensive analyses conducted in this study, we studied the expression, prognostic significance, function, methylation, copy number variations, and the immune cell infiltration of LAD1 in LUAD. A higher level of LAD1 gene expression was observed in the LUAD tumor tissues compared to the normal lung tissues (p < 0.001). Furthermore, the multivariate analysis indicated that a higher LAD1 gene expression level was the independent prognostic factor. Additionally, the DNA methylation level of the LAD1 was inversely linked to its expression (p < 0.001). We noted that the patients affected due to LAD1 hypomethylation showed a very low overall survival rate compared to the patients with a higher LAD1 methylation score (p < 0.05). Moreover, the results of the immunity analysis indicated that the LAD1 expression might be inversely linked to the immune cell infiltration degree, expression of the infiltrated immune cells, and the PD-L1 levels. Lastly, we supplemented some verification to increase the rigor of the study. The results suggested that high expression of LAD1 may be related to cold tumors. Hence, this indirectly reflects that the immunotherapy effect of LUAD patients with high LAD1 expression might be worse. Based on the role played by the LAD1 in the tumor immune microenvironment, it can be considered a potential biomarker for predicting the immunotherapy response to LUAD.

Plasma Epstein-Barr Virus MicroRNA BART8-3p as a Diagnostic and Prognostic Biomarker in Nasopharyngeal Carcinoma.

BACKGROUND: Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor that is highly common in southern China. Our previous sequencing data demonstrated that the EBV-encoded microRNA BART8-3p was most upregulated in nasopharyngeal carcinoma (NPC) and was closely associated with the metastasis of NPC. However, the values of plasma BART8-3p in NPC patients have not yet been well characterized. MATERIAL AND METHODS: We quantified plasma BART8-3p expression by quantitative real-time PCR in 205 newly diagnosed NPC patients. Kaplan-Meier analysis was used to compare overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) between the groups. RESULTS: Plasma pretreatment BART8-3p was highly expressed in NPC patients compared with healthy controls. Pretreatment BART8-3p yielded a 92% predictive value for detecting NPC. Importantly, BART8-3p decreased dramatically after therapy relative to pretreatment levels. High levels of pretreatment or post-treatment BART8-3p were associated with worse OS, DMFS, and LRRFS. Multivariate analysis showed that high pretreatment or post-treatment BART8-3p was an independent unfavorable prognostic marker for OS (HR 3.82, 95% CI 1.77-8.24, P = .001 or HR 2.74, 95% CI 1.27-5.91, P = .010), DMFS (HR 2.82, 95% CI 1.36-5.85, P = .005 or HR 3.27, 95% CI 1.57-6.81, P = .002), and LRRFS (HR 1.94, 95% CI 1.12-3.35, P = .018 or HR 2.03, 95% CI 1.14-3.62, P = .016) in NPC. Subgroup analysis revealed that for patients with locally advanced NPC with high levels of pretreatment BART8-3p (n = 58), more cycles of chemotherapy (≥6 cycles) tended to prolong OS (P = .070). Over 50% (6/11) patients with high levels of post-treatment BART8-3p presented distant metastasis. CONCLUSION: Plasma BART8-3p is a promising biomarker for the detection and prognosis of NPC.

Activatable Nanoprobe with Aggregation-Induced Dual Fluorescence and Photoacoustic Signal Enhancement for Tumor Precision Imaging and Radiotherapy.

Owing to the high sensitivity and high spatial resolution, fluorescence (FL) imaging has been widely applied for visualizing biological processes. To gain insight into molecular events on deeper tissues, photoacoustic (PA) imaging with better deep-tissue imaging capability can be incorporated to provide complementary visualization and quantitative information on the pathological status. However, the development of activatable imaging probes to achieve both FL and PA signal amplification remains challenging because the enhancement of light absorption in PA imaging often caused the quenching of FL signal. Herein, we first developed a caspase-3 enzyme activatable nanoprobe of a nanogapped gold nanoparticle coated with AIE molecule INT20 and DEVD peptides (AuNNP@DEVD-INT20) for tumor FL and PA imaging and subsequent imaging-guided radiotherapy. The nanoprobe could interact with GSH and caspase-3 enzyme to liberate INT20 molecules, leading to AIE. Simultaneously, the in situ self-assembly of AuNPs was achieved through the cross-linking reaction between the sulfhydryl and the maleimide, resulting in ratiometric PA imaging in tumor. Remarkably, the nanoprobe can generate richful ROS for cancer radiotherapy under X-ray irradiation. The platform not only achieves the aggregation-induced FL and PA signal enhancement but also provides a general strategy for imaging of various biomarkers, eventually benefiting precise cancer therapy.

SASS6 promotes proliferation of esophageal squamous carcinoma cells by inhibiting the p53 signaling pathway.

SASS6 encodes for the Homo sapiens SAS-6 centriolar assembly protein and is important for proper centrosome formation. Although centrosomes are amplified in a wide variety of tumor types, abnormally high SASS6 expression had previously only been identified in colon cancer. Moreover, the role of SASS6 in esophageal squamous cell carcinoma (ESCC) pathogenesis has not yet been elucidated. The aim of this study was to investigate the role and mechanisms of SASS6 in ESCC. In this study, we found that the mRNA and protein levels of SASS6 were increased in human ESCC samples. In addition, SASS6 protein expression was associated with the esophageal cancer stage and negatively affected survival of patients with ESCC. Furthermore, silencing of SASS6 inhibited cell growth and promoted apoptosis of ESCC cells in vitro and inhibited xenograft tumor formation in vivo. A genetic cluster and pathway analysis showed that SASS6 regulated the p53 signaling pathway. Western blot demonstrated that CCND2, GADD45A and EIF4EBP1 protein expression decreased and that TP53 protein expression increased after the knockdown of SASS6 in ESCC cells. Therefore, SASS6 promoted the proliferation of esophageal cancer by inhibiting the p53 signaling pathway. SASS6 has potential as a novel tumor marker and a therapeutic target for ESCC.

Identification of potential plasma biomarkers in early-stage nasopharyngeal carcinoma-derived exosomes based on RNA sequencing.

BACKGROUND: Early diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC. METHODS: Exosomes in plasma were extracted by ultra-high-speed centrifugation. Western blot and transmission electron microscopy (TEM) were used to verify the purity of exosomes. The sequencing data (6 plasma samples from healthy volunteers vs. 6 NPC plasma samples) were analyzed by principal component analysis (PCA), DESeq2, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and TargetScan. The differentially expressed miRNAs (DEmiRNAs) were obtained from the dataset (GSE118720) downloaded from the Gene Expression Omnibus (GEO) repository. Additionally, the datasets downloaded from the GEO database (GSE12452, GSE13597, GSE53819, GSE64634) were used to predict the target genes and functions of hsa-miR-1301-3p. qPCR was applied to verify the differences in the expressions of hsa-miR-1301-3p between 10 normal plasma and 10 NPC plasma samples. RESULTS: Western blot, TEM, and Nanoparticle Tracking Analysis showed adequate purity of the extracted exosomes. RNA-seq analysis revealed 21 upregulated miRNAs, and 10 downregulated miRNAs in plasma exosomes of early-stage NPC patients. GO analysis showed that the target genes of DEmiRNAs were mainly enriched in DNA synthesis and transcription regulation. KEGG analysis revealed that DEmiRNAs were mainly enriched in PI3K-Akt and MAPK signaling pathways. Moreover, the expression of hsa-mir-1301-3p was verified to be significantly upregulated in enlarged samples of plasma exosomes. CONCLUSIONS: We identified several DEmiRNAs extracted from tumor-derived exosomes between normal plasma and early-stage NPC plasma. Bioinformatics analyses indicated that these DEmiRNAs may be related to NPC development. Our study may provide novel insights into underlying biomarkers and mechanisms of plasma exosomes in early-stage NPC.

Prognostic value of serum uric acid and tumor response to induction chemotherapy in locally advanced nasopharyngeal carcinoma.

BACKGROUND: To explore the combined predictive value of serum uric acid (SUA) and tumor response to induction chemotherapy (IC) in locally advanced nasopharyngeal carcinoma (LANPC) patients receiving IC followed by concurrent chemoradiation therapy (CCRT). METHODS: A total of 341 LANPC patients treated with IC + CCRT were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared by the Kaplan-Meier analysis and the log-rank test, and multivariable survival analysis was carried out to investigate the independent prognostic factors. RESULTS: Univariate analysis showed that a low SUA level and unsatisfactory tumor response to two cycles of IC both were negative predictors for OS, PFS, and DMFS in patients with LANPC. multivariable analysis demonstrated that the SUA level after two cycles of IC was an independent prognostic factor for OS (P = 0.012) but of borderline significance for PFS and DMFS (P = 0.055 and P = 0.067, respectively). Furthermore, tumor response to IC was of independent significance for predicting OS, PFS, and DMFS, respectively. Finally, LANPC patients with satisfactory tumor response and a high SUA level after two cycles of IC had a better OS, PFS, and DMFS than those with unsatisfactory tumor response and a low SUA level. CONCLUSION: The SUA level and the tumor response to two cycles of IC had predictive value for LANPC patients treated with IC plus CCRT. However, more aggressive therapeutic strategies are recommended for those with a low SUA level and unsatisfactory tumor response to two cycles of IC.

Primary gross tumor volume is prognostic and suggests treatment in upper esophageal cancer.

BACKGROUND: To aid clinicians strategizing treatment for upper esophageal squamous cell carcinoma (ESCC), this retrospective study investigated associations between primary gross tumor volume (GTVp) and prognosis in patients given surgical resection, radiotherapy, or both resection and radiotherapy. METHODS: The population comprised 568 patients with upper ESCC given definitive treatment, including 238, 216, and 114 who underwent surgery, radiotherapy, or combined radiotherapy and surgery. GTVp as a continuous variable was entered into the multivariate Cox model using penalized splines (P-splines) to determine the optimal cutoff value. Propensity score matching (PSM) was used to adjust imbalanced characteristics among the treatment groups. RESULTS: P-spline regression revealed a dependence of patient outcomes on GTVp, with 30 cm3 being an optimal cut-off for differences in overall and progression-free survival (OS, PFS). GTVp ≥30 cm3 was a negative independent prognostic factor for OS and PFS. PSM analyses confirmed the prognostic value of GTVp. For GTVp < 30 cm3, no significant survival differences were observed among the 3 treatments. For GTVp ≥30 cm3, the worst 5-year OS rate was experienced by those given surgery. The 5-year PFS rate of patients given combined radiotherapy and surgery was significantly better than that of patients given radiotherapy. The surgical complications of patients given the combined treatment were comparable to those who received surgery, but radiation side effects were significantly lower. CONCLUSION: GTVp is prognostic for OS and PFS in upper ESCC. For patients with GTVp ≥30 cm3, radiotherapy plus surgery was more effective than either treatment alone.

Circulating Epstein-Barr virus microRNAs BART7-3p and BART13-3p as novel biomarkers in nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) BamHI A rightward transcripts (BART) encoded microRNAs (EBV-miR-BARTs) are abnormally highly expressed in nasopharyngeal carcinoma (NPC). This study aims to investigate the diagnostic and prognostic performance of miR-BART7-3p and miR-BART13-3p. Plasma levels of EBV DNA, miR-BART7-3p, and miR-BART13-3p were examined by quantitative PCR in 483 treatment-naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow-up. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for plasma miR-BART7-3p, 0.973 for miR-BART13-3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above-median miR-BART7-3p and EBV DNA were independent risk for shorter distant metastasis-free survival (DMFS) (hazard ratio [HR] = 2.94, 95% confidence interval [CI], 1.44-5.97, P = .003; HR = 2.27, 95% CI, 1.26-4.10, P = .006) in multivariate Cox regression. Epstein-Barr virus DNA, miR-BART7-3p, and miR-BART13-3p after radiotherapy were detectable in 28.6%, 17.6%, and 54.7% of patients, respectively. In multivariate Cox regression, detectable miR-BART7-3p and EBV DNA were independent risks for shorter DMFS (HR = 4.13, 95% CI, 1.89-9.01, P < .001; HR = 2.14, 95% CI, 1.04-4.42, P = .039). The 4-year DMFS rate was 92.0% in subjects (n = 156) with neither detectable miR-BART7-3p nor EBV DNA, 80.0% in subjects (n = 65) with either detectable miR-BART7-3p or EBV DNA, and 52.9% in subjects (n = 24) with both detectable miR-BART7-3p and EBV DNA after radiotherapy (P < .001). Circulating levels of miR-BART7-3p and miR-BART13-3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR-BART7-3p and EBV DNA at diagnosis and after radiotherapy could help stratify patients by risk of poor DMFS.

Comprehensive analysis of key genes associated with ceRNA networks in nasopharyngeal carcinoma based on bioinformatics analysis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with high morbidity rates in the east and southeast Asia. The molecular mechanisms of NPC remain largely unknown. We explored the pathogenesis, potential biomarkers, and prognostic indicators of NPC. METHODS: We analyzed mRNAs, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) in the whole transcriptome sequencing dataset of our hospital (five normal tissues vs. five NPC tissues) and six microarray datasets (62 normal tissues vs. 334 NPC tissues) downloaded from the Gene Expression Omnibus (GSE12452, GSE13597, GSE95166, GSE126683, and GSE70970, GSE43039). Differential expression analyses, gene ontology (GO) enrichment, kyoto encyclopedia of genes and genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were conducted. The lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks were constructed using the miRanda and TargetScan database, and a protein-protein interaction (PPI) network of differentially expressed genes (DEGs) was built using Search Tool for the Retrieval of Interacting Genes (STRING) software. Hub genes were identified using Molecular Complex Detection (MCODE), NetworkAnalyzer, and CytoHubba. RESULTS: We identified 61 mRNAs, 14miRNAs, and 10 lncRNAs as shared DEGs related to NPC in seven datasets. Changes in NPC were enriched in the chromosomal region, sister chromatid segregation, and nuclear chromosome segregation. GSEA indicated that the mitogen-activated protein kinase (MAPK) pathway, phosphatidylinositol-3 OH kinase/protein kinase B (PI3K-Akt) pathway, apoptotic pathway, and tumor necrosis factor (TNF) were involved in the initiation and development of NPC. Finally, 20 hub genes were screened out via the PPI network. CONCLUSIONS: Several DEGs and their biological processes, pathways, and interrelations were found in our current study by bioinformatics analyses. Our findings may offer insights into the biological mechanisms underlying NPC and identify potential therapeutic targets for NPC.

Quasi-Two-Dimensional Fermi Surfaces and Unitary Spin-Triplet Pairing in the Heavy Fermion Superconductor UTe_{2}.

We report first-principles and strongly correlated calculations of the newly discovered heavy fermion superconductor UTe_{2}. Our analyses reveal three key aspects of its magnetic, electronic, and superconducting properties that include (i) a two-leg ladder-type structure with strong magnetic frustrations, which might explain the absence of long-range orders and the observed magnetic and transport anisotropy, (ii) quasi-two-dimensional Fermi surfaces composed of two separate electron and hole cylinders with similar nesting properties as in UGe_{2}, which may potentially promote magnetic fluctuations and help to enhance the spin-triplet pairing, and (iii) a unitary spin-triplet pairing state of strong spin-orbit coupling at zero field, with point nodes presumably on the heavier hole Fermi surface along the k_{x} direction, in contrast to the previous belief of nonunitary pairing. Our proposed scenario is in excellent agreement with latest thermal conductivity measurement and provides a basis for understanding the peculiar magnetic and superconducting properties of UTe_{2}.

Intraarticular gene transfer of SPRY2 suppresses adjuvant-induced arthritis in rats.

AKT and ERK pathways have been implicated as therapeutic targets for human rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) inhibition, and thus RA treatment. Sprouty2 (SPRY2) has been known as a tumor suppressor by blocking both ERK and AKT signaling cascades. Whether SPRY2 can function as a suppressor of tumor-like inflammatory FLS and RA through negatively regulating AKT and ERK activation has not been reported. The purpose of this study was to determine whether SPRY2 might have antiarthritic effects in experimental animal model of RA. We first determined that expression of SPRY2 mRNA was decreased in FLS from patients with RA compared with patients with osteoarthritis (OA). Further studies demonstrated that intraarticular gene transfer with AdSPRY2, the recombinant adenovirus containing SPRY2 complementary DNA, resulted in a significant suppression of rat adjuvant-induced arthritis (AIA) compared with the control AdGFP, the adenoviral vector encoding green fluorescent protein, as reflected in both clinical and histological observations. AdSPRY2 suppressed the production of proinflammatory cytokines and matrix metalloproteinases (MMPs), and the activation of ERK and AKT signals in AIA ankle joints. These results suggest that using SPRY2 to block the AKT and ERK pathways effectively reduces the inflammatory responses and arthritic progression in AIA. Thus, the development of an immunoregulatory strategy based on SPRY2 may therefore have therapeutic potential in the treatment of RA.

Advantages of intensity modulated radiotherapy in recurrent T1-2 nasopharyngeal carcinoma: a retrospective study.

BACKGROUND: Recurrent T1-2 Nasopharyngeal Carcinoma (rT1-2) may be salvaged by 3D - CRT (3D-Conformal Radiotherapy), IMRT (Intensity Modulated Radiotherapy), Brachytherapy (BT), BT with external radiotherapy. The purpose of this study is to address the efficacy and toxicity profile of aforementioned four modalities for rT1-2 NPC. METHODS: 168 patients, median age 48 years (range 16-75 years) proven rT1-2 NPC were diagnosed and treated with four different irradiation modalities (3D-CRT, IMRT, BT, BT with external radiotherapy). Median time to recurrence was 30 months (range 1-180 months). The median follow-up time was 28 months (range, 4-135 months). RESULTS: 161 patients completed a median dose of 6445 cGy (ranging 30 to 87 Gy). Seven patients prematurely terminated their treatment due to acute side-effects and received 30-49 Gy. The 1- and 3-year local regional recurrent free survival (LRRFS), distant free survival (DFS), and overall survival (OS) rates were 82.03% vs. 82.03% vs. 82.58%, 51.33% vs. 51.33% vs. 53.41, respectively. Gender and recurrence T-classification were the two significant adverse prognostic factors for LRRFS, DFS, and OS rates. Grade 3 or 4 toxicities were tolerable. CONCLUSION: 3D-CRT, IMRT, BT, BT with external radiotherapy are feasible and efficacious for rT1-2 NPC. In toxicity 3D-CRT/IMRT group is lower than BT group. IMRT is superior for rT1-2 NPC.

Optical Nanobiosensor Based on Surface-Enhanced Raman Spectroscopy and Catalytic Hairpin Assembly for Early-Stage Lung Cancer Detection via Blood Circular RNA.

Lung cancer has become the leading cause of cancer-related deaths globally. However, early detection of lung cancer remains challenging, resulting in poor outcomes for the patients. Herein, we developed an optical biosensor integrating surface-enhanced Raman spectroscopy (SERS) with a catalyzed hairpin assembly (CHA) to detect circular RNA (circRNA) associated with tumor formation and progression (circSATB2). The signals of the Raman reporter were considerably enhanced by generating abundant SERS "hot spots" with a core-shell nanoprobe and 2D SERS substrate with calibration capabilities. This approach enabled the sensitive (limit of detection: 0.766 fM) and reliable quantitative detection of the target circRNA. Further, we used the developed biosensor to detect the circRNA in human serum samples, revealing that patients with lung cancer had higher circRNA concentrations than healthy subjects. Moreover, we characterized the unique circRNA concentration profiles of the early stages (IA and IB) and subtypes (IA1, IA2, and IA3) of lung cancer. These results demonstrate the potential of the proposed optical sensing nanoplatform as a liquid biopsy and prognostic tool for the early screening of lung cancer.

A novel amino acid metabolism-related gene signature to predict the overall survival of esophageal squamous cell carcinoma patients.

Background: Esophageal squamous cell carcinoma (ESCC) has a poor early detection rate, prognosis, and survival rate. Effective prognostic markers are urgently needed to assist in the prediction of ESCC treatment outcomes. There is accumulating evidence of a strong relationship between cancer cell growth and amino acid metabolism. This study aims to determine the relationship between amino acid metabolism and ESCC prognosis. Methods: This study comprehensively evaluates the association between amino acid metabolism-related gene (AAMRG) expression profiles and the prognosis of ESCC patients based on data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify the expression of prognosis-related genes. Results: A univariate Cox regression analysis of TCGA data identified 18 prognosis-related AAMRGs. The gene expression profiles of 90 ESCC tumor and normal tissues were obtained from the GSE20347 and GSE67269 datasets. Two differently expressed genes (DEGs) were considered as ESCC prognosis-related genes; and they were branched-chain amino acid transaminase 1 (BCAT1) and methylmalonic aciduria and homocystinuria type C protein (MMACHC). These two AAMRGs were used to develop a novel AAMRG-related gene signature to predict 1- and 2-year prognostic risk in ESCC patients. Both BCAT1 and MMACHC expression were verified by RT-qPCR. A prognostic nomogram that incorporated clinical factors and BCAT1 and MMACHC gene expression was constructed, and the calibration plots showed that it had good prognostic performance. Conclusions: The AAMRG signature established in our study is efficient and could be used in clinical settings to predict the early prognosis of ESCC patients.

Tunable positions of Weyl nodes via magnetism and pressure in the ferromagnetic Weyl semimetal CeAlSi.

The noncentrosymmetric ferromagnetic Weyl semimetal CeAlSi with simultaneous space-inversion and time-reversal symmetry breaking provides a unique platform for exploring novel topological states. Here, by employing multiple experimental techniques, we demonstrate that ferromagnetism and pressure can serve as efficient parameters to tune the positions of Weyl nodes in CeAlSi. At ambient pressure, a magnetism-facilitated anomalous Hall/Nernst effect (AHE/ANE) is uncovered. Angle-resolved photoemission spectroscopy (ARPES) measurements demonstrated that the Weyl nodes with opposite chirality are moving away from each other upon entering the ferromagnetic phase. Under pressure, by tracing the pressure evolution of AHE and band structure, we demonstrate that pressure could also serve as a pivotal knob to tune the positions of Weyl nodes. Moreover, multiple pressure-induced phase transitions are also revealed. These findings indicate that CeAlSi provides a unique and tunable platform for exploring exotic topological physics and electron correlations, as well as catering to potential applications, such as spintronics.

Design, expression and characterization of a novel coexpression system of two antiarthritic molecules.

The complexity of rheumatoid arthritis (RA) pathogenesis makes combined blockade of multiple targets an attractive therapeutic strategy. The combination therapy with anti-TNF plus anti-T-cell has been mostly reported to provide greater efficacy than anti-TNF alone. TNFR (p75)-Fc fusion protein, which has been proven effective in clinics, is chosen as the TNF antagonist in this study. CTLA4-FasL fusion molecule, which has been well characterized in our previous studies for its suppressive effect in rat arthritis model, is chosen as the T-cell antagonist. In this study, furin cleavage site and 2A self-processing sequence were introduced to link upstream TNFR-Fc and downstream CTLA4-FasL and mediate separate coexpression of the two fusion proteins in a single recombinant adeno-associated virus (rAAV) vector. Using this expression system, we generated two fusion proteins with same size as their individual counterparts in vitro and in vivo, and the proteins desirably retained their parent biological activities. In vivo results demonstrated that furin-2A technology is able to regulate separate coexpression of these proteins under arthritic inflammatory conditions. This study describes a single rAAV vector for production of two antiarthritic molecules antagonizing both TNF and T cells, which may serve as an attractive expression system for RA gene therapy.

Characterization of the Immune Infiltration Landscape and Identification of Prognostic Biomarkers for Esophageal Cancer.

Immunotherapy is an effective treatment for esophageal cancer (ESCA) patients. However, there are no dependable markers for predicting prognosis and immunotherapy responses in ESCA. Our study aims to explore immune gene prognostic models and markers in ESCA as well as predictors for immunotherapy. The expression profiles of ESCA were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases. Cox regression analysis was performed to construct an immune gene prognostic model. ESCA was grouped into three immune cell infiltration (ICI) clusters by CIBERSORT algorithm. The immunotherapy response of patients in different ICI score clusters was also compared. The copy number variations, somatic mutations, and single nucleotide polymorphisms were analyzed. Enrichment analyses were also performed. An immune gene prognostic model was successfully constructed. The ICI score may be used as a predictor independent of tumor mutation burden. Enrichment analyses showed that the differentially expressed genes were mostly enriched in microvillus and the KRAS and IL6/JAK/STAT3 pathways. The top eight genes with the highest mutation frequencies in ESCA were identified and all related to the prognosis of ESCA patients. Our study established an effective immune gene prognostic model and identified markers for predicting the prognosis and immunotherapy response of ESCA patients.