An innovative model based on N7-methylguanosine-related lncRNAs for forecasting prognosis and tumor immune landscape in bladder cancer.

BACKGROUND: As a novel type of the prevalent post-transcriptional modifications, N7-methylguanosine (m7G) modification is essential in the tumorigenesis, progression, and invasion of many cancers, including bladder cancer (BCa). However, the integrated roles of m7G-related lncRNAs in BCa remain undiscovered. This study aims to develop a prognostic model based on the m7G-related lncRNAs and explore its predictive value of the prognosis and anti-cancer treatment sensitivity. METHODS: We obtained RNA-seq data and corresponding clinicopathological information from the TCGA database and collected m7G-related genes from previous studies and GSEA. Based on LASSO and Cox regression analysis, we developed a m7G prognostic model. The Kaplan-Meier (K-M) survival analysis and ROC curves were performed to evaluate the predictive power of the model. Gene set enrichment analysis (GSEA) was conducted to explore the molecular mechanisms behind apparent discrepancies between the low- and high-risk groups. We also investigated immune cell infiltration, TIDE score, TMB, the sensitivity of common chemotherapy drugs, and the response to immunotherapy between the two risk groups. Finally, we validated the expression levels of these ten m7G-related lncRNAs in BCa cell lines by qRT-PCR. RESULTS: We developed a m7G prognostic model (risk score) composed of 10 m7G-related lncRNAs that are significantly associated with the OS of BCa patients. The K-M survival curves revealed that the high-risk group patients had significantly worse OS than those in the low-risk group. The Cox regression analysis confirmed that the risk score was a significant independent prognostic factor for BCa patients. We found that the high-risk group had higher the immune scores and immune cell infiltration. Furthermore, the results of the sensitivity of common anti-BCa drugs showed that the high-risk group was more sensitive to neoadjuvant cisplatin-based chemotherapy and anti-PD1 immunotherapy. Finally, qRT-PCR revealed that AC006058.1, AC073133.2, LINC00677, and LINC01338 were significantly downregulated in BCa cell lines, while the expression levels of AC124312.2 and AL158209.1 were significantly upregulated in BCa cell lines compared with normal cell lines. CONCLUSION: The m7G prognostic model can be applied to accurately predict the prognosis and provide robust directions for clinicians to develop better individual-based and precise treatment strategies for BCa patients.

A cuproptosis-related LncRNA signature: Integrated analysis associated with biochemical recurrence and immune landscape in prostate cancer.

Background: As a new form of regulated cell death, cuproptosis differs profoundly from apoptosis, ferroptosis, pyroptosis, and necroptosis. The correlation between cuproptosis and long non-coding RNAs (lncRNAs) has been increasingly studied recently. In this study, a novel cuproptosis-related lncRNA prognostic signature was developed to investigate biochemical recurrence (BCR) and tumor immune landscape in prostate cancer (PCa). Methods and Materials: The transcriptome data and clinicopathologic information of PCa patients were downloaded from The Cancer Genome Atlas (TCGA). Pearson's correlation analysis was applied to identify lncRNAs associated with cuproptosis. Based on Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis, we developed a cuproptosis-related lncRNA prognostic model (risk score) to predict the BCR of PCa patients. Additionally, we also constructed a nomogram with the risk score and clinicopathologic features. The biological function, tumor mutation burden (TMB), immune cell infiltration, expression levels of immune checkpoint genes, and anti-cancer drug sensitivity were investigated. Results: We constructed and validated the cuproptosis-related lncRNA signature prognostic model (risk score) by six crlncRNAs. All patients were divided into the low- and high-risk groups based on the median risk score. The Kaplan-Meier (KM) survival analysis revealed that the high-risk group had shorter BCR-free survival (BCRFS). The risk score has been proven to be an independent prognostic factor of BCR in PCa patients. In addition, a nomogram of risk scores and clinicopathologic features was established and demonstrated an excellent predictive capability of BCR. The ROC curves further validated that this nomogram had higher accuracy of predicting the BCR compared to other clinicopathologic features. We also found that the high-risk group had higher TMB levels and more infiltrated immune cells. Furthermore, patients with high TMB in the high-risk group were inclined to have the shortest BCRFS. Finally, patients in the high-risk group were more susceptible to docetaxel, gefitinib, methotrexate, paclitaxel, and vinblastine. Conclusion: The novel crlncRNA signature prognostic model shows a greatly prognostic prediction value of BCR for PCa patients, extends our thought on the association of cuproptosis and PCa, and provides novel insights into individual-based treatment strategies for PCa.

HDAC1 overexpression promoted by METTL3-IGF2BP2 inhibits FGF21 expression in metabolic syndrome-related liver injury.

Metabolic syndrome (MetS) represents a cluster of diseases that includes diabetes and insulin resistance. A combination of these metabolic disorders damages liver function. We hypothesized here that histone deacetylase 1 (HDAC1) inhibits fibroblast growth factor 21 (FGF21) expression through histone deacetylation, thereby accentuating liver injury in rats with MetS. MetS rats induced by a high-fat diet were monitored weekly for blood pressure and body weight measurement. The changes of hepatic injury parameters were also measured. The pathological changes in the liver were observed by HE staining and oil red O staining. We found that HDAC1 was increased in the liver of rats with MetS, while sh-HDAC1 reduced blood pressure, body weight, and hepatic injury parameters. Improvement of structural pathological alterations and reduction of lipid deposition were observed after HDAC1 inhibition. Notably, HDAC1 inhibited FGF21 expression through histone deacetylation. The hepatoprotective effects of sh-HDAC1 on rats were reversed by adenovirus-mediated knockdown of FGF21. Moreover, methyltransferase-like 3 (METTL3) mediated the N6-methyladenosine (m6A) modification of HDAC1 mRNA and increased its binding to IGF2BP2. Consistently, sh-METTL3 inhibited HDAC1 and increased FGF21 expression, thereby ameliorating liver injury in MetS rats. This study discovered that HDAC1 is capable of managing liver injury in MetS. Targeting HDAC1 may be an optimal treatment for MetS-related liver injury.

Ultrahigh Polarization Response along Large Energy Storage Properties in BiFeO3-BaTiO3-Based Relaxor Ferroelectric Ceramics under Low Electric Field.

BiFeO3-BaTiO3 (BF-BT) dielectric ceramics are receiving more and more concern for advanced energy storage devices owing to their excellent ferroelectric properties and environmental sustainability. However, the energy density and efficiency are limited in spite of the large remanent polarization. Herein, we proposed a multiscale optimization strategy via a local compositional disorder with a Birich content and nanodomain engineering by introducing the Sr0.7Bi0.2Ca0.1TiO3 (SBCT) into BF-BT ceramics. Interestingly, an extraordinary energy storage property (ESP) with a high reversible energy storage density (Wrec) of ∼3.79 J/cm3 and an ultrahigh polarization discrepancy (ΔP) of ∼58.5 µC/cm2 were obtained in the SBCT-modified BF-BT ceramics under 160 kV/cm. The boosted ESP should be attributed to the fact that the replacement of A/B-sites cations could transform the long-range ferroelectric order of the BF-BT system into polar nanoregions (PNRs) along with the refined grain size, decreased leakage current, and broadened energy band gap. Moreover, good frequency (1-103 Hz) and temperature (25-125 °C) stabilities, high fatigue resistance (× 105), large power density (∼31.1 MW/cm3), and fast discharge time (∼97 ns) were also observed for the optimized ceramics. These results illustrate a potentially effective method for creating high ESP lead-free ceramics at a low electric field.

Stromal cell-derived factor-1 exerts opposing roles through CXCR4 and CXCR7 in angiotensin II-induced adventitial remodeling.

Recent studies have emphasized the role of vascular adventitia inflammation and immune response in hypertension. It has been reported that stromal cell-derived factor-1 (SDF-1) plays various biological functions through its receptors C-X-C motif chemokine receptor 4 (CXCR4) and CXCR7 in tumor growth and tissue repair. However, it is unclear that whether SDF-1/CXCR4/CXCR7 axis is involved in hypertensive vascular remodeling. In the present study, the involvement of SDF-1/CXCR4/CXCR7 axis was evaluated with lentivirus-mediated shRNA of SDF-1 and CXCR7, CXCR4 antagonist AMD3100 and CXCR7 agonist VUF11207 in angiotensin II (AngII)-induced hypertensive mice and in cultured adventitial fibroblasts (AFs). Results showed that AngII infusion markedly increased SDF-1 expressed in vascular adventitia, but not in media and endothelium. Importantly, blockade of SDF-1/CXCR4 axis strikingly potentiated AngII-induced adventitial thickening and fibrosis, as indicated by enhanced collagen I deposition. In contrast, CXCR7 shRNA largely attenuated AngII-induced adventitial thickness and fibrosis, whereas CXCR7 activation with VUF11207 significantly potentiated AngII-induced adventitial thickening and fibrosis. In consistent with these in vivo study, CXCR4 inhibition with AMD3100 and CXCR7 activation with VUF11207 aggravated AngII-induced inflammation, proliferation and migration in cultured AFs. In summary, these results suggested that SDF-1 exerted opposing effects through CXCR4 and CXCR7 in AngII-induced vascular adventitial remodeling.

Enhanced Charge Transport in Conventional Polymer Solar Cells with a Perovskite-Type LaNiO3 Layer.

In this study, a novel metal oxide, lanthanum nickelate (LNO) with a perovskite structure, was introduced into a polymer solar cell (PSC) device, replacing the PEDOT:PSS hole transport layer (HTL). The results show that the LNO-based PTB7-Th:PC71BM solar cell exhibits a higher circuit current density, power conversion efficiency, and stability compared with a device with PEDOT:PSS HTL. To understand the effect of LNO HTL on the performance of devices, the active layer morphology and charge transport characteristics in PSCs were systematically analyzed. The morphology of active layer was affected by the HTL, which further regulated the generation and transport processes of charge carrier in the PSC device. For the LNO HTL, an appropriate thickness (8 nm) and a small surface roughness (Sq = 0.7 nm) can coordinate the energy-level structure of device and improve the interface contact between the FTO electrode and PTB7-Th:PC71BM active layer, promoting the charge transport performance of device. Therefore, this work provides a new consideration for the preparation of efficient, stable, and low-cost polymer solar cells.

Hybrid coronary revascularization versus off-pump coronary artery bypass grafting and percutaneous coronary intervention for the treatment of two-vessel coronary artery disease with proximal left anterior descending artery stenosis.

BACKGROUND: This study sought to compare clinical outcomes of hybrid coronary revascularization (HCR) with off-pump coronary artery bypass grafting (OPCAB) and percutaneous coronary intervention (PCI) for the treatment of two-vessel coronary artery disease (CAD) including proximal LAD stenosis. METHODS: From January 2009 to December 2016, 52 patients of two-vessel CAD including proximal LAD stenosis underwent HCR at Rui Jin Hospital. Using propensity score methodology, these patients were matched with those in the OPCAB and PCI cohorts. The primary endpoint during follow-up was main adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: The intensive care unit (ICU) length of stay (LOS) and the hospital LOS were shorter in the HCR group than in the OPCAB group (ICU LOS: P<0.001; hospital LOS: P=0.027). The mean follow-up time was 59 months (interquartile range, 42 to 79 months). The 8-year freedom from MACCE of the HCR group was higher than that of the PCI group (P=0.008), but similar to that of the OPCAB group (P=0.893). CONCLUSIONS: HCR provides favorable outcomes for selected patients with two-vessel CAD including proximal LAD stenosis.

Multi-depth three-dimensional image encryption based on the phase retrieval algorithm in the Fresnel and fractional Fourier transform domains.

We propose a multi-depth three-dimensional (3D) image cryptosystem by employing the phase retrieval algorithm in the Fresnel and fractional Fourier (Fr-FrF) domains. Encryption was realized by applying the phase retrieval algorithm based on the double-random-phase-encoding architecture in which two encryption keys will be incessantly updated in each iteration loop. The phase-only functions (POFs) are generated in two cascaded Fr-FrF transforms (Fr-FrFT), serving as decryption keys to efficiently reduce the speckle noise and crosstalk between encrypted 3D image depths. The use of Fr-FrFT position parameters and fractional order as decryption keys further extended the key space, enhancing the cryptosystem's security level. Numerical simulations demonstrated the feasibility and robustness of our proposed scheme.

Mid-term results of coronary bypass graft surgery in patients with ischaemic left ventricular systolic dysfunction and no detected myocardial viability.

OBJECTIVES: There are concerns about effects of surgical revascularization on patients with ischaemic systolic dysfunction when no signs of myocardial viability have been detected by nuclear imaging preoperatively. We reviewed our data to determine the efficacy of coronary bypass graft in this special patient cohort. METHODS: A retrospective review with prospectively collected clinical data was conducted on 87 consecutive patients between 2000 and 2012 whose left ventricular ejection fraction was less than 40%. All patients received positron emission tomography examination before undergoing coronary artery bypass graft and showed no signs of myocardial viability. Improvements in ejection fraction, postoperative re-examination of myocardial viability by nuclear imaging and freedom from major cardiac events were observed. Survival was calculated using Kaplan-Meier analysis. RESULTS: The 30-day mortality rate was 7%. Ejection fraction improvement (defined as over 5%) was observed in 13 (16%) patients within 6 months postoperatively. Ejection fraction improvement was observed in 46 (58%) patients by the end of the first year and 50 (63%) patients by the second year. It was noted that 25 (32%) and 43 (54%) patients progressed to heart functional class I or II at 1 and 5 years, respectively. Positron emission tomography examination showed enhanced myocardial viability in the non-viable ventricular wall segment in 53 (67%) patients at 1 year. Freedom from major adverse cardiac events was observed in 56 (71%) patients at 1 year and 47 (60%) patients at 5 years. Survival rates were 82 and 66% at 1 and 5 years, respectively. CONCLUSIONS: Coronary artery bypass graft proved to be a positive choice of treatment for patients with severe ischaemic systolic dysfunction when there was no viable myocardium detected through nuclear imaging.

Comparison of graft patency between off-pump and on-pump coronary artery bypass grafting: an updated meta-analysis.

BACKGROUND: Currently, off-pump coronary artery bypass grafting (OPCAB) and on-pump coronary artery bypass grafting (ONCAB) are 2 well-established therapeutic strategies for patients with coronary artery disease, and debate regarding which strategy provides superior graft patency is ongoing. The current study is a meta-analysis of randomized controlled trials that compared the graft patency between OPCAB and ONCAB. METHODS: Data sources were PubMed, the Cochrane Library, Google Scholar, and ISI Web of Knowledge (1966-2013). We identified studies comparing graft patency after the 2 procedures as the primary intervention for patients with multivessel coronary artery disease and conducted a meta-analysis of randomized controlled trials on graft patency. RESULTS: A literature search yielded 12 randomized controlled trials, for a total of 3,894 and 4,137 grafts performed during OPCAB and ONCAB procedures, respectively. Meta-analysis of these studies showed an increased risk of occlusion of all grafts (risk ratio [RR], 1.35; 95% confidence interval [CI], 1.16-1.57) and saphenous vein grafts (SVGs) (RR, 1.41; 95% CI, 1.24-1.60) in the OPCAB group, whereas there was no significant difference in graft occlusion of left internal mammary artery (LIMA) (RR, 1.15; 95% CI, 0.83-1.59) and radial artery (RR, 1.37; 95% CI, 0.76-2.47) grafts between OPCAB and ONCAB. CONCLUSIONS: Meta-analysis of currently available randomized controlled trials on graft patency shows that ONCAB reduces the incidence of SVG graft occlusion significantly but does not affect LIMA and radial artery graft patency compared with OPCAB.

Role of surgical ventricular restoration in the treatment of ischemic cardiomyopathy.

BACKGROUND: Surgical ventricular restoration (SVR) has been applied as a valuable adjunct procedure for patients undergoing coronary artery bypass grafting (CABG) to correct the geometry of the left ventricle on the basis of myocardial revascularization. It is necessary to find out at least which patient cohort is more likely to benefit from this procedure. METHODS: A case-control study was conducted on 221 patients with ejection fraction (EF)≤0.35 and New York Heart Association (NYHA) class III or IV, who received CABG+SVR or CABG alone from 1998 to 2008. Comparisons were made between CABG+SVR and CABG alone within two groups of patients: group 1 (preoperative left ventricular end-systolic volume index [LVESVI]<80 mL/m2, n=127) and group 2 (preoperative LVESVI≥80 mL/m2, n=94). Outcomes included improvement in EF, NYHA class, readmissions, and survival. RESULTS: Patients in either group receiving SVR achieved significant LVESVI reduction postoperatively (p<0.001). In group 1, EF improvement (defined as over .05 improvement in EF) was observed in 53.7% of CABG+SVR patients compared with 48.5% for CABG patients (p 0.570). A similar percentage of patients improved to NYHA class I or II (63.0% for CABG+SVR versus 55.9% for CABG, p=0.430). Readmissions after CABG+SVR were 27.8% compared with 38.2% after CABG (p=0.225). There was no difference in survival between CABG+SVR and CABG (p=0.709). In group 2, the CABG+SVR patients showed greater EF improvement (55.6% versus 30.8%, p=0.020) and were more likely to improve to NYHA class I or II (58.3% versus 36.5%, p=0.044). Readmissions were fewer for the CABG+SVR patients than for the CABG patients (30.6% versus 57.7%, p=0.012). CABG+SVR yielded better survival than did CABG (p=0.031). CONCLUSIONS: Patients with much advanced LVESVI are more likely to benefit from surgical ventricular restoration, and this surgical procedure still holds its ground in the treatment of ischemic cardiomyopathy.

Effect of prepro-calcitonin gene-related peptide-expressing endothelial progenitor cells on pulmonary hypertension.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is a potent smooth muscle cell proliferation inhibitor and vasodilator. It is now believed that CGRP plays an important role in maintaining a low pulmonary vascular resistance. We evaluated the therapeutic effect of intravenously administered CGRP-expressing endothelial progenitor cells (EPCs) on left-to-right shunt-induced pulmonary hypertension in rats. METHODS: Endothelial progenitor cells were obtained from cultured human peripheral blood mononuclear cells. The genetic sequence for CGRP was subcloned into cultured EPCs by human expression plasmid. Pulmonary hypertension was established in immunodeficient rats with an abdominal aorta to inferior vena cava shunt operation. The transfected EPCs were injected through the left jugular vein at 10 weeks after the shunt operation. Mean pulmonary artery pressure and total pulmonary vascular resistance were detected with right cardiac catheterization at 4 weeks. The distribution of EPCs in the lung tissue was examined with immunofluorescence technique. Histopathologic changes in the structure of the pulmonary arteries was observed with electron microscopy and subjected to computerized image analysis. RESULTS: The lungs of rats transplanted with CGRP-expressing EPCs demonstrated a decrease in both mean pulmonary artery pressure (17.64 +/- 0.79 versus 22.08 +/- 0.95 mm Hg; p = 0.018) and total pulmonary vascular resistance (1.26 +/- 0.07 versus 2.45 +/- 0.18 mm Hg x min/mL; p = 0.037) at 4 weeks. Immunofluorescence revealed that intravenously administered cells were incorporated into the pulmonary vasculature. Pulmonary vascular remodeling was remarkably attenuated with the administration of CGRP-expressing EPCs. CONCLUSIONS: The transplantation of CGRP-expressing EPCs may effectively attenuate established pulmonary hypertension and exert reversal effects on pulmonary vascular remodeling. Our findings suggest that the therapy based on the combination of both CGRP transfection and EPCs may be a potentially useful strategy for the treatment of pulmonary hypertensive disorders.