Oncogenic KPNA2 Serves as a Biomarker and Immune Infiltration in Patients With HPV Positive Tongue Squamous Cell Carcinoma.

Human tongue squamous cell carcinoma (TSCC), the most prevalent type of oral cancer, is associated with human papillomavirus (HPV) infection. Our previous work showed Karyopherin α2 (KPNA2), as an oncogene of TSCC, by relegating the p53/autophagy signaling pathway. Nevertheless, the significance of KPNA2 in TSCC pathogenesis has not been established. KPNA2 levels were evaluated via the TCGA database, and its effects on survival outcomes were assessed by LASSO, Kaplan-Meier, and COX regression analyses. CIBERSORT and ESTIMATE investigated the relationships between KPNA2 and immune infiltration. At the same time, KPNA2 and HPV infection was analyzed by immunohistochemistry. In addition, the association between downstream molecular regulation pathways and KPNA2 levels was determined by GO, GSEA, and WGCNA. In TSCC, KPNA2 levels were associated with clinical prognosis and tumor grade. Moreover, KPNA2 may be involved in cancer cell differentiation and facilitates tumor-related genes and signaling pathways, such as Cell Cycle, Mitotic G1 phase, G1/S transition, DNA Repair, and Transcriptional Regulation TP53 signaling pathways. Nevertheless, regulatory B cells, follicular helper B cells, and immune and stromal scores between low- and high-KPNA2 expression groups were insignificant. These results imply that KPNA2 is highly involved in tumor grade and prognosis of TSCC. KPNA2 levels correct with HPV 16 markedly regulated cell differentiation, several oncogenes, and cancer-related pathways.

PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells.

Filopodia, a finger-like structure and actin-rich plasma-membrane protrusion at the leading edge of the cell, has important roles in cell motility. However, the mechanisms of filopodia generation are not well-understood via the actin-related protein 2/3 (ARP2/3) complex in Non-Small Cell Lung Cancer (NSCLC) cells. We previously have demonstrated that PRR11 associates with the ARP2/3 complex to regulate cytoskeleton-nucleoskeleton assembly and chromatin remodeling. In this study, we further demonstrate that PRR11 involves in filopodia formation, focal adhesion turnover and cell motility through ARP2/3 complex. Cell phenotype assays revealed that the silencing of PRR11 increased cellular size and inhibited cell motility in NSCLC cells. Mechanistically, PRR11 recruited and co-localized with Arp2 at the membrane protrusion to promote filopodia formation but not lamellipodia formation. Notably, PRR11 mutant deletion of the proline-rich region 2 (amino acid residues 185-200) abrogated the effect of filopodia formation. In addition, PRR11-depletion inhibited filopodial actin filaments assembly and increased the level of active integrin ß1 in the cell surface, whereas reduced the phosphorylation level of focal adhesion kinase (FAKY397) to repress focal adhesion turnover and cell motility in NSCLC cells. Taken together, our findings indicate that PRR11 has critical roles in controlling filopodia formation, focal adhesion turnover and cell motility by recruiting ARP2/3 complex, thus dysregualted expression of PRR11 potentially facilitates tumor metastasis in NSCLC cells.

A newly synthesized visual bis(salamo)-based fluorescent chemosensor for exogenous detection of B4O72- in living cells and zebrafish.

A newly synthesized fluorescent chemosensor H6L was explored for detecting B4O72-, characterized by 1H NMR spectrum, mass spectrum and fluorescence spectra. During the detection process of B4O72-, the fluorescence is significantly enhanced and naked eye recognition can be performed under 365 nm UV light without any interference by other typical anions. The limit of detection is as low as 6.97 × 10-10 M. In addition, in order to broaden the application of salamo-based fluorescence sensors in the field of biology, except for the fluorescence imaging of HeLa cells, the first attempt of exogenous detection in zebrafish was conducted successfully.

Genetically increased circulating 25(OH)D level reduces the risk of type 2 diabetes in subjects with deficiency of vitamin D: A large-scale Mendelian randomization study.

ABSTRACT: Observational studies have reported that Vitamin D deficiency and the risk type 2 diabetes are associated, but the causation is unclear. Mendelian randomization (MR) involving genetic variants as instrument variables (IVs) overcomes the reverse-casualty and unmeasured confounding. However, with limited sample size and IVs, previous MR studies showed inconsistent results. Leveraging by a largely increased sample size for both stages, we aim to provide an updated and precise estimate for the causality between Vitamin D and type 2 diabetes.A 2-sample multi-IVs MR was performed. IVs for circulating 25-hydroxyvitamin D (25(OH)D) were obtained from a genome-wide association study from UK biobank involving 329,247 subjects of European ancestry. The causal effect of 25(OH)D and type 2 diabetes was estimated using traditional inverse variance weighting and MR pleiotropy residual sum and outlier (MR-PRESSO) framework which provides a robust estimate by systematically filtering out IVs identified with potential pleiotropy effects.A higher genetically instrumented 25(OH)D was causally linked to reduced risk of type 2 diabetes risk by MR-PRESSO [odds ratio (OR) per standard deviation (SD) = 0.950, 95% confidence interval (CI) = 0.913-0.988, P = .010] after removing 13 (13/193) invalid IVs. In addition, we confirmed the causal role Vitamin D using 2 synthesis-related single-nucleotide polymorphisms (SNPs) which are consistent with previous MR studies [OR per SD = 0.894, 95% CI = 0.816-0.979, P = .016].With a largely improved sample size, our results confirmed that genetically increased 25(OH)D concentration reduced the risk of type 2 diabetes and provided a more precise estimate for the effect size. The updated result empowers the role of Vitamin D and provides nontrivial evidence for interventional studies.

Synthesis and characterization for a highly selective bis(salamo)-based chemical sensor and imaging in living cell.

A new sensor H5L for continuous identification of Cu2+, Al3+ and lysine was synthesized by Schiff base reactions. The sensor could specifically recognized Cu2+ in the EtOH/H2O (1:1 v/v) solution by UV-vis spectra, and the binding constant with Cu2+ can reach 1011 M-1, meanwhile, it was found by the naked-eye that the color of the solution was changed from colorless to yellow. The copper complex L-Cu2+ formed by the sensor H5L and Cu2+ could further recognize Al3+ and lysine in the fluorescence spectra. The LOD values of the three objects were 2.67 × 10-8, 1.96 × 10-8 and 5.59 × 10-9 M, respectively. In addition, fluorescence intracellular images of Al3+ and lysine were performed and obtained satisfactory results.

The short-term and long-term outcomes of transcatheter or surgical aortic valve replacement in elderly patients: A protocol for a systematic review.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an essential alternate option for people suffering from aortic stenosis. However, the efficacy and safety of TAVR for elderly population (aged over 80 years) is still unclear. METHODS: We plan to perform a systematic review and meta-analysis of clinical controlled trials and propensity-match cohort studies to evaluate the short- and long-term outcomes in elderly aortic stenosis patients who undergo a transcatheter or surgical aortic valve replacement. We will search PubMed, EMBASE, and Cochrane Library using a comprehensive strategy. The related conference proceedings and reference lists of the included studies will also be checked to identify additional studies. Two reviewers will screen retrieved records, extract information, and assess the risk of bias independently. STATA software will be used to conduct data synthesis. There is no requirement of ethical approval and informed consent. RESULTS: This study will be submitted to a peer-reviewed journal for publication. CONCLUSION: This is the first systematic assessment of TAVR for elderly patients with aortic stenosis. We hope it will provide a relatively comprehensive reference for clinical practice and future relevant clinical trials. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is a systematic review and meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42019140857. STUDY PROTOCOL REGISTRY: The protocol has been registered in PROSPERO, which is an International Prospective Register of Systematic Reviews. The registration number is CRD42019140857.

MicroRNA-107 is a novel tumor suppressor targeting POU3F2 in melanoma.

BACKGROUND: Melanoma is one of the major types of skin cancer. The metastatic melanoma is among the most lethal forms of malignant skin tumors. We hereby aimed to characterize a novel microRNA (miR) in the metastatic melanoma model. METHODS: First, we evaluated the expression of miR-107 in melanoma cells and tumor tissues. The comparison between primary and metastatic cancer tissues was also accessed. Next, we examined the impact of miR-107 on melanoma cell proliferation, cell cycle, colony formation, apoptotic activity, migration and matrix invasion. A downstream target of miR-107 was also predicted and validated functionally in melanoma cells. RESULTS: Our findings showed miR-107 was significantly downregulated in melanoma. Its expression was lowest in metastatic form. Over-expression of miR-107 reduced melanoma cell proliferation, migration and invasion. POU3F2 was identified as the downstream target of miR-107. Over-expression of POU3F2 antagonized miR-107-mediated inhibitory effect on melanoma cells. CONCLUSION: Our study has reported miR-107 as a novel tumor suppressive factor in the metastatic melanoma model. It has provided new avenue to manage melanoma and improve the survival rate in the advanced stage.

Proline-rich 11 (PRR11) drives F-actin assembly by recruiting the actin-related protein 2/3 complex in human non-small cell lung carcinoma.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100-184 or 100-200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

Two highly sensitive and efficient salamo-like copper(II) complex probes for recognition of CN.

Two salamo-like copper(II) complex probes, L1-Cu2+ and L2-Cu2+, were designed and synthesized for sensitive and efficient identification of CN-. UV spectroscopy, high resolution mass spectrometry, RGB analysis and naked eye recognition were performed to explore their recognition mechanisms. High resolution mass spectra indicated that the probes L1-Cu2+ and L2-Cu2+ formed complexes with CN-. The two probes could recognize CN- by the naked eye and the color of the solution changed from light yellow to red. In terms of application, the contents of CN- in the environmental water samples were tested. In addition, the optimal pH ranges for probe detection of CN- were investigated by pH value measurement.

MicroRNA-107 is a novel tumor suppressor targeting POU3F2 in melanoma

BACKGROUND: Melanoma is one of the major types of skin cancer. The metastatic melanoma is among the most lethal forms of malignant skin tumors. We hereby aimed to characterize a novel microRNA (miR) in the metastatic melanoma model. METHODS: First, we evaluated the expression of miR-107 in melanoma cells and tumor tissues. The comparison between primary and metastatic cancer tissues was also accessed. Next, we examined the impact of miR-107 on melanoma cell proliferation, cell cycle, colony formation, apoptotic activity, migration and matrix invasion. A downstream target of miR-107 was also predicted and validated functionally in melanoma cells. RESULTS: Our findings showed miR-107 was significantly downregulated in melanoma. Its expression was lowest in metastatic form. Over-expression of miR-107 reduced melanoma cell proliferation, migration and invasion. POU3F2 was identified as the downstream target of miR-107. Over-expression of POU3F2 antagonized miR-107-mediated inhibitory effect on melanoma cells. CONCLUSION: Our study has reported miR-107 as a novel tumor suppressive factor in the metastatic melanoma model. It has provided new avenue to manage melanoma and improve the survival rate in the advanced stage.

A high-efficiency salamo-based copper(ii) complex double-channel fluorescent probe.

In this paper, a salamo-based copper(ii) complex probe L-Cu2+ was synthesized, which combined with copper(ii) ions to form L-Cu2+ for the detection of S2- and had a good fluorescence chemical response. Through spectral analysis, we found that S2- could be identified with high sensitivity and selectivity in the presence of various anions and could be used for the detection of S2- by the naked eye. With the addition of S2-, the solution color changed from colorless to bright yellow. UV absorption, fluorescence and other characterization methods were carried out, and the mechanism of action was determined. In addition, we performed a visual inspection of H2S gas, and the probe L-Cu2+ could detect S2- in the gas molecules, revealing its potential application value in biology and medicine.

Homo- and heterometallic Cu(II)-M(II) (M = Ca, Sr and Ba) bis(salamo)-based complexes: Syntheses, structures and fluorescent properties.

Four homo/heterometallic complexes [Cu3(L)(µ2-OAc)9(CH3OH) 9]·3CHCl3 (1), [Cu2(L)Ca(µ2-NO3)9] (9), [{Cu2(L)Sr(µ2-NO3)9}9]·CH3CH2OH (11) and [Cu2(L)Ba(µ2-OAc)9(OAc)] (14), containing an acyclic naphthalenediol-based ligand H4L, were synthesized and characterized by elemental analyses, IR, UV-Vis, fluorescence spectra, TG-DTA and X-ray crystallography. The complex 1 was obtained by the reaction of H4L with 11 equivalents of Cu(OAc) 9·2H2O. The heterometallic complexes 9, 11, 14 were acquired by the reaction of H4L with 9 equivalents of Cu(OAc)9·2H2O or Cu(NO3)9·2H2O and 1 equivalent of M(OAc)9 (M = Ca, Sr and Ba). Owing to the different coordination cavities of the N2O2 and O6 of the completely deprotonated (L)14- unit, the crystal structures showed the N2O2 sites were occupied by Cu(II) atoms, alkaline earth metal(II) atoms occupied the O6 site of the ligand (L)14- unit, respectively. Furthermore, the fluorescence properties and TG-DTA analyses were discussed.

Synthesis and Fluorescence Properties of Structurally Characterized Heterobimetalic Cu(II)⁻Na(I) Bis(salamo)-Based Complex Bearing Square Planar, Square Pyramid and Triangular Prism Geometries of Metal Centers.

A novel heterotrinuclear complex [Cu2(L)Na(µ-NO3)]∙CH3OH∙CHCl3 derived from a symmetric bis(salamo)-type tetraoxime H4L having a naphthalenediol unit, was prepared and structurally characterized via means of elemental analyses, UV-Vis, FT-IR, fluorescent spectra and single-crystal X-ray diffraction. The heterobimetallic Cu(II)⁻Na(I) complex was acquired via the reaction of H4L with 2 equivalents of Cu(NO3)2·2H2O and 1 equivalent of NaOAc. Clearly, the heterotrinuclear Cu(II)⁻Na(I) complex has a 1:2:1 ligand-to-metal (Cu(II) and Na(I)) ratio. X-ray diffraction results exhibited the different geometric behaviors of the Na(I) and Cu(II) atoms in the heterotrinuclear complex; the both Cu(II) atoms are sited in the N2O2 coordination environments of fully deprotonated (L)4− unit. One Cu(II) atom (Cu1) is five-coordinated and possesses a geometry of slightly distorted square pyramid, while another Cu(II) atom (Cu2) is four-coordination possessing a square planar coordination geometry. Moreover, the Na(I) atom is in the O6 cavity and adopts seven-coordination with a geometry of slightly distorted single triangular prism. In addition, there are abundant supramolecular interactions in the Cu(II)⁻Na(I) complex. The fluorescence spectra showed the Cu(II)⁻Na(I) complex possesses a significant fluorescent quenching and exhibited a hypsochromic-shift compared with the ligand H4L.

Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma.

PURPOSE: The aim of this study was to investigate expression of CD147 and MMP-9 in salivary duct carcinoma (SDC) so as to determine whether these two genes may be correlated with poor prognosis of SDC. METHODS: We examined the significance of the CD147 and MMP-9 expression in SDC (n = 35), non-cancerous salivary tissue (n = 20) in previously untreated patients using immunohistochemical staining. Furthermore, we analyzed the correlation between the expression of these two genes and various clinicopathologic factors including survival status of patients with SDC. RESULTS: Positive stain of CD147 and MMP-9 was seen in all 35 cases of tumor samples. A statistical correlation was observed between CD147 and MMP-9 expression in SDC tissues. The incidences of high expression were 45.71% for CD147 and 51.43% for MMP-9 in 35 SDC tissues, respectively. High expression of CD147 and MMP-9 was significantly correlated with clinical feature and shorter progression-free survival (PFS) (P (CD147) = 0.031; P (MMP-9) = 0.020) and overall survival (OS) (P (CD147) = 0.044; P (MMP-9) = 0.013). CONCLUSION: CD147 and MMP-9 expression is correlated with invasion, metastasis and shorter PFS/OS of SDC. Patients with high expression of CD147 and MMP-9 had poor prognosis than SDC patients with low expression.