Inhibitors of APE1 redox and ATM synergistically sensitize osteosarcoma cells to ionizing radiation by inducing ferroptosis.

The resistance of osteosarcoma (OS) to ionizing radiation (IR) is an obstacle for effective patient treatment. Apurinic/apyrimidinic endonuclease-reduction/oxidation factor 1 (APE1/Ref-1) is a multifunctional protein with DNA repair and reduction/oxidation (redox) activities. We previously revealed the role of APE1 in OS radioresistance; however, whether the redox activity of APE1 is involved in OS radioresistance is unclear.

mTOR Signaling Promotes Rapid m6A mRNA Methylation to Regulate NK-Cell Activation and Effector Functions.

NK cells can be rapidly activated in response to cytokines during host defense against malignant cells or viral infection. However, it remains unclear what mechanisms precisely and rapidly regulate the expression of a large number of genes involved in activating NK cells. In this study, we discovered that NK-cell N6-methyladenosine (m6A) methylation levels were rapidly upregulated upon short-term NK-cell activation and were repressed in the tumor microenvironment (TME).

The ω-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid Enhances NK-Cell Antitumor Effector Functions.

ω-3 polyunsaturated fatty acids (PUFA) are known to directly repress tumor development and progression. In this study, we explored whether docosahexaenoic acid (DHA), a type of ω-3 PUFA, had an immunomodulatory role in inhibiting tumor growth in immunocompetent mice. The number of natural killer (NK) cells but not the number of T or B cells was decreased by DHA supplementation in various tissues under physiologic conditions.

Impact of left atrial appendage occlusion device position on potential determinants of device-related thrombus: a patient-specific in silico study.

Background: Device-related thrombus (DRT) after left atrial appendage occlusion (LAAO) is potentially linked to adverse events. Although clinical reports suggest an effect of the device type and position on the DRT risk, in-depth studies of its mechanistic basis are needed. This in silico study aimed to assess the impact of the position of non-pacifier (Watchman) and pacifier (Amulet) LAAO devices on surrogate markers of DRT risk.

Genomic characteristics and prognosis of lung cancer patients with MSI-H: A cohort study.

Background: Microsatellite instability (MSI) is the first pan-cancer biomarker approved to guide immune checkpoint inhibitor therapy for MSI-high (MSI-H) solid tumors. In lung cancer, the MSI-H frequency is very low, and the genetic characteristics and prognosis of lung cancer with MSI-H were rarely reported.

Methods: Next-generation sequencing and immunohistochemistry were used detect MSI status, tumor mutation burden (TMB) and PD-L1 expression.

Neoadjuvant Anlotinib and chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced esophageal squamous cell carcinoma: Short-term results of an open-label, randomized, phase II trial.

Background: Clinical benefits of neoadjuvant Anlotinib for locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear. This study evaluated the efficacy and safety of neoadjuvant Anlotinib plus chemotherapy followed by minimally invasive esophagectomy (MIE) for the treatment of patients with locally advanced ESCC.

Methods: Patients with locally advanced ESCC were randomly assigned to neoadjuvant Anlotinib combined with chemotherapy (Anlotinib group) or neoadjuvant chemoradiotherapy alone (nCRT group) with an allocation ratio of 1:1.

Knockdown of NUSAP1 inhibits cell proliferation and invasion through downregulation of TOP2A in human glioblastoma.

Nucleolar and spindle associated protein 1 (NUSAP1), an indispensable mitotic regulator, has been reported to be involved in the development, progression, and metastasis of several types of cancer. Here, we investigated the expression and biological function of NUSAP1 in human glioblastoma (GBM), an aggressive brain tumor type with largely ineffective treatment options. Analysis of the molecular data in CGGA, TCGA and Rembrandt datasets demonstrated that NUSAP1 was significantly upregulated in GBM relative to low grade gliomas and non-neoplastic brain tissue samples.

Docosahexaenoic acid supplementation represses the early immune response against murine cytomegalovirus but enhances NK cell effector function.

Background: Docosahexaenoic acid (DHA) supplementation is beneficial for several chronic diseases; however, its effect on immune regulation is still debated. Given the prevalence of cytomegalovirus (CMV) infection and because natural killer (NK) cells are a component of innate immunity critical for controlling CMV infection, the current study explored the effect of a DHA-enriched diet on susceptibility to murine (M) CMV infection and the NK cell effector response to MCMV infection.

Results: Male C57BL/6 mice fed a control or DHA-enriched diet for 3 weeks were infected with MCMV and sacrificed at the indicated time points postinfection.

Whole exome and transcriptome sequencing reveal clonal evolution and exhibit immune-related features in metastatic colorectal tumors.

Liver is the most common site where metastatic lesions of colorectal cancer (CRC) arise. Although researches have shown mutations in driver genes, copy number variations (CNV) and alterations in relevant signaling pathways promoted the tumor evolution and immune escape during colorectal liver metastasis (CLM), the underlying mechanism remains largely elusive. Tumor and matched metastatic tissues were collected from 16 patients diagnosed with colorectal cancer and subjected to whole-exome sequencing (WES) and RNA sequencing (RNA-seq) for studying colorectal cancer clonal evolution and immune escape during CLM.

Identification of a Five-Autophagy-Related-lncRNA Signature as a Novel Prognostic Biomarker for Hepatocellular Carcinoma.

Although great progresses have been made in the diagnosis and treatment of hepatocellular carcinoma (HCC), its prognostic marker remains controversial. In this current study, weighted correlation network analysis and Cox regression analysis showed significant prognostic value of five autophagy-related long non-coding RNAs (AR-lncRNAs) (including TMCC1-AS1, PLBD1-AS1, MKLN1-AS, LINC01063, and CYTOR) for HCC patients from data in The Cancer Genome Atlas. By using them, we constructed a five-AR-lncRNA prognostic signature, which accurately distinguished the high- and low-risk groups of HCC patients.

Mediating effects of general self-efficacy on the relationship between the source of meaning in life and prosocial behaviours in vocational college nursing students: A cross-sectional study.

Objectives: To examine the mediating effect of general self-efficacy on the relationship between the source of meaning in life (SML) and prosocial behaviours in vocational college nursing students.

Methods: Between March and June 2019, a cross-sectional descriptive study was conducted, and 799 nursing students from three vocational colleges completed the Source of Meaning in Life Scale, General Self-Efficacy Scale and Prosocial Behaviours Scale. Data were analyzed using structural equation modelling and statistical analysis by SPSS (version 23.

Landscape of active enhancers developed de novo in cirrhosis and conserved in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) patients always have a background of cirrhosis. Aberrant epigenetic changes in cirrhosis provide a conductive environment for HCC tumorigenesis. Active enhancers (AEs) are essential for epigenetic regulation and play an important role in cell development and the progression of many diseases.

Mitochondrial APE1 promotes cisplatin resistance by downregulating ROS in osteosarcoma.

Apurinic/apyrimidinic endonuclease 1 (APE1) is a primary nuclear‑localized multifunctional protein in osteosarcoma. However, the cytoplasmic localization of APE1 was found to be functional and to increase with cisplatin resistance, yet the molecular mechanism is unknown. In the present study, we explored the cisplatin resistance mechanism in osteosarcoma from the new perspective of APE1 extranuclear biological activity.

ADAMTS12 acts as a cancer promoter in colorectal cancer via activating the Wnt/β-catenin signaling pathway .

Background: ADAMTS12, a member of the ADAMTS family, is reported to be associated with the clinic outcome of colorectal cancer (CRC) patients. However, the functions and precise mechanism in CRC progression have yet to be fully understood.

Methods: By analyzing The Cancer Genome Atlas (TCGA) database, we examined the mRNA level of ADAMTS12 and assessed the prognostic value of ADAMTS12 in CRC patients using a tissue microarray containing 41 CRC patient samples.

Challenge of parents caring for children or adolescents with early-stage schizophrenia in China: A qualitative study.

Purpose: To explore the challenges of parents caring for early-stage schizophrenia (ESS) children/adolescents in China.

Design And Methods: Thirteen parents of ESS subjects completed semi-structured interviews. Thematic analysis was used to analyze data.

Control of thermal deformation with photonic sintering of ultrathin nanowire transparent electrodes.

Development of electronic devices on ultrathin flexible plastic substrates is of great value in terms of portability, cost reduction, and mechanical flexibility. However, because thin plastic substrates with low heat capacity can be more easily damaged by thermal energy, their use is limited. Highly flexible nanowire (NW) transparent conductive electrodes on ultrathin (∼10 μm) low cost polyethylene terephthalate (PET) substrates are fabricated.

Cytoplasmic APE1 promotes resistance response in osteosarcoma patients with cisplatin treatment.

Chemotherapy resistance has become a hold back and major clinical challenge in osteosarcoma cancer. The alteration and subcellular distribution of apurinic/apyrimidinic endonuclease 1 (APE1) has been reported to be involved in chemotherapy resistance in many cancers. Here, we report that the cytoplasmic distribution of APE1 plays a key role in the sensitivity of combination platinum chemotherapy in osteosarcoma.

Satisfactory short-term outcome after anlotinib and docetaxel chemotherapy in tongue cancer with N3 cervical lymph node metastasis: A case report.

Patients with tongue squamous cell carcinoma (TSCC) and cervical lymph node metastasis are particularly difficult to treat. This is the first report of about anlotinib combined with docetaxel chemotherapy for chemotherapy-refractory TSCC with cervical lymph node metastasis, may provide a new, suitable therapeutic option for these patients.

MicroRNA-765 sensitizes osteosarcoma cells to cisplatin via downregulating APE1 expression.

Objectives: Osteosarcoma (OS) is the most common bone cancer diagnosed in children and adolescents. Expression of APE1 is commonly increased in OS, and this is negatively correlated with a sensitivity to platinum and a favorable prognosis. However, the mechanism underlying high APE1 expression in OS is not fully understood.

Distinct APE1 Activities Affect the Regulation of VEGF Transcription Under Hypoxic Conditions.

Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF), a crucial factor in tumor angiogenesis, has been reported to be transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1). An 8-oxo-G or apurinic/apyrimidinic (AP) site, which is frequently associated with DNA damage, has been identified in the promoter region of VEGF.

Erlotinib versus gemcitabine/cisplatin in Chinese patients with EGFR mutation-positive advanced non-small-cell lung cancer: Crossover extension and post-hoc analysis of the ENSURE study.

Objectives: Sequential combination of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy has shown greater benefits than either treatment alone in non-small-cell lung cancer (NSCLC). In this follow-up of the ENSURE study, we evaluated progression-free survival (PFS) with first-line erlotinib followed by chemotherapy at progression versus the inverse treatment sequence in 175 Chinese patients with EGFR mutation-positive NSCLC.

Materials And Methods: Forty-five of the 175 patients included in the follow-up analysis experienced progressive disease (PD).

Three-Dimensionally Printed Stretchable Conductors from Surfactant-Mediated Composite Pastes.

A stretchable conductor is a critical prerequisite to achieve various forms of stretchable electronics. In particular, directly printable stretchable conductors have gathered considerable attention with recent growing interest in a variety of large-area, deformable electronics. In this study, we have developed a chemical pathway of incorporating a surfactant with a moderate hydrophilic-lipophilic balance in formulating composite pastes for printed stretchable conductors, with a possibility of a vertically stackable, three-dimensional printing process.

The flutter-by effect: a comprehensive study of the fluttering cusps of the Perceval heart valve prosthesis.

Objectives: Sutureless aortic valve prostheses are gaining popularity due to the substantial reduction in cross-clamp time. In this study, we report our observations on the cusp-fluttering phenomenon of the Perceval bioprosthesis (LivaNova, London, UK) using a combination of technical and medical perspectives.

Methods: Between August 2014 and December 2016, a total of 108 patients (69% women) with a mean age of 78 years had aortic valve replacement using the Perceval bioprosthesis (34 combined procedures).

Defect-Free, Highly Uniform Washable Transparent Electrodes Induced by Selective Light Irradiation.

A simple route to fabricate defect-free Ag-nanoparticle-carbon-nanotube composite-based high-resolution mesh flexible transparent conducting electrodes (FTCEs) is explored. In the selective photonic sintering-based patterning process, a highly soft rubber or thin plastic substrate is utilized to achieve close and uniform contact between the composite layer and photomask, with which uniform light irradiation can be obtained with diminished light diffraction. This well-controlled process results in developing a fine and uniform mesh pattern (≈12 μm).

A photonic sintering derived Ag flake/nanoparticle-based highly sensitive stretchable strain sensor for human motion monitoring.

Recently, the demand for stretchable strain sensors used for detecting human motion is rapidly increasing. This paper proposes high-performance strain sensors based on Ag flake/Ag nanocrystal (NC) hybrid materials incorporated into a polydimethylsiloxane (PDMS) elastomer. The addition of Ag NCs into an Ag flake network enhances the electrical conductivity and sensitivity of the strain sensors.