Genomic instability-associated two-miRNA signature as a novel prognostic biomarker in breast cancer.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of cancer-associated deaths among women. However, there is a lack of accurate prognostic biomarkers for BC. In the present study, we aimed to identify a genomic instability (GI)-associated microRNA signature as a novel potential prognostic biomarker in BC. METHODS: We performed an integrative analysis to investigate the relationship between GI and BC and identify GI-associated microRNAs (miRNAs). Subsequently, we conducted a discovery and validation study using multicenter cohorts. The GI-associated miRNA signature was developed in the discovery cohort and independently validated in internal and external cohorts. RESULTS: GI-associated miRNAs expression in BC showed heterogeneity and was significantly correlated with BC prognosis. We identified a GI-associated two-miRNA signature (miR-105-5p and miR-767-5p), termed GI2miR, that stratified BC patients into high-risk and low-risk groups with significantly different clinical outcomes (log-rank p = 0.027) in The Cancer Genome Atlas (TCGA) discovery cohort (n = 763). The prognostic value of GI2miR was further validated in internal TCGA validation cohort (n = 253) (log-rank p = 0.035) and independent GSE22216 cohort (n = 210) (log-rank p = 0.036). The GI2miR demonstrated independent prognostic value in multivariate Cox proportional hazard regression analyses and stratification analysis. CONCLUSIONS: We have developed a novel prognostic signature based on GI-associated two miRNAs for BC, which may lay the foundation for BC to improve prognosis prediction.

Dissection of the antitumor mechanism of tetrandrine based on metabolite profiling and network pharmacology.

RATIONALE: Tetrandrine, the Q-marker in Stephaniae Tetrandrae Radix, was proven to present an obvious antitumor effect. Until now, the metabolism and antitumor mechanism of tetrandrine have not been fully elucidated. METHODS: The metabolites of tetrandrine in rats were profiled using ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential antitumor mechanism of tetrandrine in vivo was predicted using network pharmacology. RESULTS: A total of 30 metabolites were characterized in rats after ingestion of tetrandrine (10 mg/kg), including 0 in plasma, 7 in urine, 11 in feces, 9 in liver, 8 in spleen, 4 in lung, 5 in kidney, 5 in heart, and 4 in brain. This study was the first to show the metabolic processes demethylation, hydroxylation, and carbonylation in tetrandrine. The pharmacology network results showed that tetrandrine and its metabolites could regulate AKT1, TNF, MMP9, MMP2, PAK1, and so on by involving in proteoglycan tumor pathway, PI3K-Akt signaling pathway, tumor pathway, MAPK signaling pathway, and Rap1 signaling pathway. CONCLUSIONS: The metabolism features of tetrandrine and its potential antitumor mechanism were summarized, providing data for further pharmacological validation.

Erratum: CM082 Enhances the Efficacy of Chemotherapeutic Drugs by Inhibiting the Drug Efflux Function of ABCG2.

[This corrects the article DOI: 10.1016/j.omto.2019.12.007.].

A scalable and anti-fouling silver-nickel/cellulose paper with synergy photothermal effect for efficient solar distillation.

Solar interfacial evaporation is one of the most efficient and environmentally-friendly clean freshwater production technologies. Plasma metal nanoparticles are excellent optical absorption materials, but their high cost and inherent resonance narrow bandwidth absorption limit their application. In this work, commercial cellulose papers are used as substrates to synthesize Ag-Ni/cellulose paper by the seed-mediated method. The Ag-Ni/cellulose paper exhibits high light absorption at the full wavelength (200-2500 nm) resulting from the synergistic effect of localized surface plasmon resonance (LSPR) of Ag NPs and the interband transitions (IBTs) of Ni. Under one-sun irradiation (1 kW m-2), the energy utilization efficiency of Ag-Ni/cellulose paper is as high as 93.8%, and the water evaporation rate is 1.87 kg m-2 h-1. Diffusion inhibition experiment results show that the Ag-Ni/cellulose paper exhibits excellent antibacterial performance, and the antibacterial performance is highly related with Ag NPs content. These provide new opportunities for commercial production of competitive cost, green, and portable solar evaporators for different application sceneries.

Application of 3D Slicer Combined With Simple Coordinate Method in Operation of Cerebral Arteriovenous Malformations in Functional Areas.

The authors report a case of intracranial arteriovenous malformation in functional areas, initially presenting with symptomatic epilepsy was surgically excised by the Neurosurgery Department of our hospital. The patient's head computed tomography, magnetic resonance imaging, and digital subtraction angiography examination suggested intracranial arteriovenous malformations in the left frontal functional area. A preoperative 3D-reconstruction technique was used to reconstruct the malformed vascular mass, supplying arteries, draining veins, and precise surgical resection was performed. Postoperative pathology indicated vascular malformation. No seizures occurred after surgery. There was no further neurological impairment. Preoperative use of image postprocessing techniques can facilitate precise surgical resection of brain arteriovenous malformations. Three-dimensional Slicer in cerebral arteriovenous malformations in functional areas not only shortened the preoperative planning time but also improved the efficiency of the surgery. Reduce the incidence of postoperative complications. It is helpful for further popularization and application.

Association between health literacy and dysphagia in the community-dwelling older population: a cross-sectional study.

BACKGROUND: Dysphagia, or swallowing disorders, has become a growing concern due to the aging population, and health literacy plays a crucial role in active aging. However, the relationship between them remains unclear. AIMS: To investigate the association between health literacy and dysphagia among community-dwelling older adults in China. METHODS: A survey was conducted on 4462 older adults aged 65 and above in a community in Yiwu City, China, from May 2021 to January 2022. Swallowing problems were assessed using a 30 ml water swallowing test (WST) and the Eating Assessment Tool-10 questionnaire (EAT-10). The participants' health literacy was evaluated using the Chinese Health Literacy Scale (CHLS). Logistic regression and t tests were employed to measure the association between them. RESULTS: The prevalence of dysphagia was 5.70% and 7.85% as determined by EAT-10 and 30 ml-WST, respectively. The health literacy level of community-dwelling older adults was 24.4 ± 4.93 (9-45). Participants with dysphagia exhibited lower levels of health literacy (p < 0.05). The logistic regression model demonstrated an inverse association between health literacy and dysphagia (OR = 0.94, 95%CI = 0.91-0.96 for EAT-10, and OR = 0.93, 95%CI = 0.92-0.95 for WST). Moreover, this association remained significant even after adjusting for covariates. DISCUSSION: Older adults with dysphagia have lower levels of health literacy, particularly in terms of their ability to seek medical advice, acquire and evaluate medical information, and access social support resources. CONCLUSIONS: Health literacy is associated with dysphagia among community-dwelling older adults. Effective interventions should be implemented to provide support in terms of both medical services and social support for this population.

Effect of LGR4/EGFR signaling on cell growth and cancer stem cell-like characteristics in liver cancer.

PURPOSE: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Leucine-rich repeat containing G-protein-coupled receptors 4 (LGR4) participates in tumor progression, invasion, and metastasis. Our study aimed to investigate the effect of LGR4 with epidermal growth factor receptor (EGFR) in HCC cells. METHODS: We employed Hep3B and Huh7 cells to conduct our research. Comprehensive biological activities were characterized by CCK8 and transwell assay. Molecular biology techniques were used to determine the expression of proteins. Hep3B was employed to conduct subcutaneous tumor in mice. The tumor growth and the expression levels of proteins were assessed. RESULTS: LGR4 overexpression could promote the cells proliferation, migration, and invasion ability, while siLGR4 and siEGFR could inhibit cells biological activities. In addition, LGR4 overexpression promoted the expression levels of RSPO2, ß-catenin, EGFR and cancer stem cells (CSCs) markers, whereas silence of LGR4 or EGFR could diminish the expression levels of ß-catenin and CSCs markers. Furthermore, knockdown of LGR4 or EGFR also inhibited tumor growth and reduced the expression levels of RSPO2, CD133, CD44, Nanog, ß-catenin in vivo. CONCLUSION: Our data suggest that LGR4 /EGFR signaling in HCC leads to induce tumor growth, which then contributes to stem cell characteristics. It maybe a new perspective for the targeted therapy of HCC treatment.

Preparation and Characterization of DNA-assembled GRS-DNA-CuS Nanodandelions.

In this study, we introduce a detailed protocol for the preparation of DNA-assembled GRS-DNA-copper sulfide (CuS) nanodandelion, a multifunctional theranostics nanoparticle. Using transmission electron microscope (TEM) and dynamic light scattering techniques, we characterize the physicochemical property of DNA-assembled GRS-DNA-CuS nanodandelions and their dissociation property after the first near-infrared (NIR) light irradiation. In addition, we systematically monitor the processes of tumor accumulation and uniform intratumoral distribution (UITD) of ultrasmall CuS photothermal agents (PAs), which are dissociated from GRS-DNA-CuS nanodandelions, by Raman imaging and photoacoustic imaging, respectively. The UITD of the dissociated ultrasmall CuS PAs can enhance the therapeutic efficiency of photothermal treatment under the second NIR light irradiation. Overall, this protocol provides a powerful tool to achieve UITD of PAs by explosively breaking the hydrogen bonds of DNA in GRS-DNA-CuS nanodandelions under NIR light irradiation. We expect DNA-assembled nanotheranostics to serve as a robust platform for a variety of biomedical applications related to photothermal therapy in the oncology field. This protocol can increase experimental reproducibility and contribute to efficient theranostics nanomedicine.

Function and prognosis analysis of nucleolus protein DCAF13 in breast cancer.

Background: Breast cancer is one of the main causes of death among women. RNA binding proteins (RBPs) play a crucial role in the progression of breast cancer, with increasingly detailed understanding of RBP functional molecular mechanisms in breast cancer, the functional research of RBPs may help elucidate the potential mechanisms of tumor occurrence, development, invasion, metastasis and prognosis. DDB1- and CUL4-associated factor 13 (DCAF13) is an RBPs has been identified as a substrate receptor for the CUL4-DDB1 E3 ligase complex. Its expression is related to the prognosis of certain cancer. We tried to explore both co-expressed network and biological functions of DCAF13 in breast cancer. Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the different expression of DCAF13 messenger RNA (mRNA) between normal breast tissue and breast carcinoma tissue, and the clinical data about 960 samples were downloaded from the cBio Cancer Genomics Portal (cBioPortal). The expression level of DCAF13, co-expression network, and survival were analyzed. Those with a fold change ≥1 and FDR <0.05 were considered to have statistical significance. Unsupervised clustering of differentially expressed RBPs was performed based on log2-transformed FPKM values using the "pheatmap" package in R. Genes with a Spearman score >0.55 were regarded as moderately co-expressed genes. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a co-expression network. Meanwhile, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to identify the biological process cluster and pathway cluster, respectively. Results: Compared with normal breast tissue, DCAF13 mRNA expression was significantly increased in breast cancer tissue (P<0.01). The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to identify the functions of the co-expressed network. These genes were mainly enriched in mitosis, nuclear division, metabolic process, recombination, replication and repair of DNA, double-strand break repair, posttranscriptional regulation of gene expression, regulation of cell cycle, division and proliferation, regulation of protein stability and also participation in in regulation of poly(A) RNA binding, mRNA binding, tRNA binding, adenosine triphosphate (ATP) binding. KEGG pathway analysis revealed that the genes were mainly enriched in cell cycle, oocyte meiosis and oxidative phosphorylation. According to survival analysis, upregulation of DCAF13 mRNA was significant for overall survival (OS) (P=0.0163). Conclusions: DCAF13 is up-regulated in breast cancer, the OS of patients with DCAF13 up-regulation was obviously reduced. DCAF13 was used as a diagnostic marker and therapeutic target for breast cancer. By building a co-expression network of DCAF13 and conducting bioinformatics analysis, it is possible to find the biomarker to evaluate patient prognosis. This finding provides a new target in mechanism and cell research of breast cancer.

CuS-131I-PEG Nanotheranostics-Induced "Multiple Mild-Hyperthermia" Strategy to Overcome Radio-Resistance in Lung Cancer Brachytherapy.

Brachytherapy is one mainstay treatment for lung cancer. However, a great challenge in brachytherapy is radio-resistance, which is caused by severe hypoxia in solid tumors. In this research, we have developed a PEGylated 131I-labeled CuS nanotheranostics (CuS-131I-PEG)-induced "multiple mild-hyperthermia" strategy to reverse hypoxia-associated radio-resistance. Specifically, after being injected with CuS-131I-PEG nanotheranostics, tumors were irradiated by NIR laser to mildly increase tumor temperature (39~40 °C). This mild hyperthermia can improve oxygen levels and reduce expression of hypoxia-induced factor-1α (HIF-1α) inside tumors, which brings about alleviation of tumor hypoxia and reversion of hypoxia-induced radio-resistance. During the entire treatment, tumors are treated by photothermal brachytherapy three times, and meanwhile mild hyperthermia stimulation is conducted before each treatment of photothermal brachytherapy, which is defined as a "multiple mild-hyperthermia" strategy. Based on this strategy, tumors have been completely inhibited. Overall, our research presents a simple and effective "multiple mild-hyperthermia" strategy for reversing radio-resistance of lung cancer, achieving the combined photothermal brachytherapy.

Association of copper exposure with prevalence of chronic kidney disease in older adults.

BACKGROUND & AIMS: Metal exposure is suspected to be associated with the risk of chronic kidney disease (CKD). Copper (Cu) is an essential yet toxic trace element in humans. Epidemiological evidence on the association of Cu exposure with CKD remains inconsistent. This study aims to investigate the association of blood Cu and its co-exposure to other metals with CKD. METHODS: A cross-sectional study was conducted among 3285 older participants in Zhejiang, China. The whole blood levels of Cu as well as other 10 metals were measured using the inductively coupled plasma mass spectrometry (ICP-MS). CKD events were defined as the presence of albuminuria or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Multivariable logistic regression and linear regression models were applied to assess the association of Cu with kidney function. The Bayesian kernel machine regression (BKMR) was used to examine the association of metal interactions with CKD. RESULTS: In logistic models, we found a dose-dependent positive association between blood Cu and the prevalence of CKD. Compared to the lowest quartile of blood Cu, the odds ratio (OR) of CKD in the highest quartile was 1.65 (95% confidence interval, CI: 1.25, 2.17), and the ß of eGFR was -1.74 (95% CI: -3.15, -0.34) after adjusting for multiple covariates. The positive linear dose-response association was found between blood Cu and the OR of CKD, and negative linear association was found between Cu and the ß of eGFR. The positive association between blood Cu and CKD risk was stronger at lower level of manganese (Mn) in the BKMR model. CONCLUSION: The whole blood level of Cu was remarkably associated with the risk of CKD and showed positive dose-response relationships in the older Chinese population. The toxicity of Cu on kidney function could be antagonized by the exposure of Mn. These findings shed new light on the potential role of Cu in kidney health.

Molecular Planarization of Raman Probes to Avoid Background Interference for High-Precision Intraoperative Imaging of Tumor Micrometastases and Lymph Nodes.

The intraoperative imaging applications of a large number of Raman probes are hampered by the overlap of their signals with the background Raman signals generated by biological tissues. Here, we describe a molecular planarization strategy for adjusting the Raman shift of these Raman probes to avoid interference. Using this strategy, we modify the backbone of thiophene polymer-poly(3-hexylthiophene) (P3HT), and obtain the adjacent thiophene units planarized polycyclopenta[2,1-b;3,4-b']dithiophene (PCPDT). Compared with P3HT whose signal is disturbed by the Raman signal of lipids in tissues, PCPDT exhibits a 60 cm-1 blueshift in its characteristic signal. Therefore, the PCPDT probe successfully avoids the signal of lipids, and achieves intraoperative imaging of lymph nodes and tumor micrometastasis as small as 0.30 × 0.36 mm. In summary, our study presents a concise molecular planarization strategy for regulating the signal shift of Raman probes, and brings a tunable thiophene polymer probe for high-precision intraoperative Raman imaging.

Identification of Potential miRNA-mRNA Regulatory Network in Denervated Muscular Atrophy by Bioinformatic Analysis.

Muscle atrophy caused by long-term denervation leads to the loss of skeletal muscle mass and strength, resulting in a poor recovery of functional muscles and decreasing quality of life. Increasing differentially expressed microRNAs (DEMs) have been reported to be involved in the pathogenesis of denervated muscle atrophy. However, there is still insufficient evidence to explain the role of miRNAs and their target genes in skeletal muscle atrophy. Therefore, an integrative exploration of the miRNA-mRNA regulatory network in denervated muscle atrophy is necessary. A total of 21 (16 upregulated and 5 downregulated) DEMs were screened out in the GSE81914 dataset. Med1, Myod1, Nfkb1, Rela, and Camta1 were predicted and verified to be significantly upregulated in denervated muscle atrophy, from which 6 key TF-miRNA relationship pairs, including Med1-mir-1949, Med1-mir-146b, Myod1-mir-29b, Nfkb1-mir-21, Rela-mir-21, and Camta1-mir-132, were obtained. 60 target genes were then predicted by submitting candidate DEMs to the miRNet database. GO and KEGG pathway enrichment analysis showed that target genes of DEMs were mainly enriched in the apoptotic process and PI3K/Akt signaling pathway. Through the PPI network construction, key modules and hub genes were obtained and potentially modulated by mir-29b, mir-132, and mir-133a. According to the qRT-PCR results, the expression of COL1A1 and Ctgf is opposite to their related miRNAs in denervated muscle atrophy. In the study, a potential miRNA-mRNA regulatory network was firstly constructed in denervated muscle atrophy, in which the mir-29b-COL1A1 and mir-133a-Ctgf pathways may provide new insights into the pathogenesis and treatment.

Optical properties of soot aggregates with different monomer shapes.

The monomer of soot fractal aggregate is usually considered to be sphere, but the monomer shapes are cube and hexagon by some transmission electron microscope (TEM) and scanning electron microscope (SEM) observation. In this paper, the fractal soot models of different monomer shapes (sphere, cube, ellipsoid, hexagonal prism) were established. And the optical properties of models are calculated by discrete dipole approximation (DDA). After systematically comparing the Muller matrix and optical cross section properties between the models, we find that monomer deviation from sphericity does not necessarily lead to further decline of F22(π)/F11(π) even at shorter wavelengths. In other words, the non-sphericity of monomers does not necessarily affect the non-sphericity of whole soot particle. This can provide some implication for lidar remote sensing observation. However, other light scattering matrix elements can keep good consistency. The maximum deviation of extinction cross section of hexagonal prism model is 11.2%. The more the monomer shape deviates from the sphere, the more the optical integral properties of the non-spherical monomer model deviates from the optical integral properties of sphere monomer model. Hence, the difference in optical properties caused by different monomer shapes cannot be neglected when the monomer deviates significantly from a spherical shape. This work is helpful to evaluate the optical properties of soot aggregates more precisely.

Trace gas emissions from laboratory combustion of leaves typically consumed in forest fires in Southwest China.

Forest fires are becoming increasingly severe and frequent due to global climate change. Trace gases emitted from forest fires significantly affect atmospheric chemistry and climate change on a regional and global scale. Forest fires occur frequently in Southwest China, but systematic studies on trace gas emissions from forest fires in Southwest China are rare. Leaves of seven typical vegetation fuels based on their prominence in forest fires consumption in Southwest China were burned in a self-designed combustion device and the emission factors of eighteen trace gases (greenhouse gases, non-methane organic gases, nitrogenous gases, hydrogen chloride, and sulfur dioxide) at specific combustion stages (flaming and smoldering) were determined by using Fourier transform infrared spectroscopy, respectively. The emission factors data presented were compared with previous studies and can aid in the construction of an emission inventory. Pine needle combustion released a greater amount of methane in the smoldering stage than other broadleaf combustion. Peak values of emission factors for methane and non-methane organic gas are emitted by the smoldering of vegetation (Pinus kesiya and Pinus yunnanensis), which is endemic to forest fires in Southwest China. The emission factor for oxygenated volatile organic compounds (OVOCs) in the smoldering stage is greater than the flaming stage. This work established the relationship between modified combustion efficiency (MCE) with emission factors of hydrocarbons (except acetylene) and OVOCs. The results show that exponential fitting is more suitable than linear fitting for the seven leaf fuels (four broadleaf and three coniferous). However, the emission factors from the combustion of three coniferous fuels relative to all fuels are linear with MCE. Findings demonstrated that different combustion stages and fuel types have significant impacts on the emission factors, which also highlighted the importance of studying regional emissions.

Investigation of the effects of high cervical spinal cord electrical stimulation on improving neurological dysfunction and its potential mechanism in rats with traumatic brain injury.

To explore the effects of high cervical spinal cord electrical stimulation (cSCS) on the recovery of neurological function and its possible mechanism in rats with traumatic brain injury (TBI). 72 rats were randomly divided into: (1) a sham group; (2) a traumatic brain injury (TBI) group; (3) a TBI+cSCS group; (4) a LY294002+TBI+cSCS group. The degree of neurological dysfunction was evaluated by modified Neurological severity score (mNSS). The pathological changes of the brain tissue in the injured area were observed by HE staining, and the apoptosis of neuron cells were observed by TUNEL staining. The expressions of BDNF and VEGFmRNA were detected by polymerase chain reaction (PCR), and the expressions of p-AKT, AKT, Bcl-2, Bax and caspase-3 proteins were detected by western blot. Compared with that of the TBI and LY294002+TBI+cSCS groups, the mNSS of the TBI+cSCS group were significantly lower on day 3 and 7 ( P <0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the apoptosis of neuron cells in the TBI+cSCS group decreased significantly ( P < 0.05). Compared with the TBI and LY294002+TBI+cSCS group, the expression of Bcl-2 protein increased and the expressions of Bax and Caspase-3 proteins decreased in the TBI+cSCS group ( P < 0.05). Compared with that in the TBI and LY294002+TBI+cSCS groups, the intensity of p-Akt/Akt in the TBI+cSCS group increased ( P < 0.05). We found that cSCS had a protective effect on neuron cells after craniocerebral injury and could improve neurological dysfunction in rats, the mechanism of which might be that cSCS made the PI3K/Akt pathway more active after TBI.

Laboratory investigation of pollutant emissions and PM2.5 toxicity of underground coal fires.

Widespread underground coal fires (UCFs) release large amounts of pollutants, thus leading to air pollution and health impacts. However, this topic has not been widely investigated, especially regarding the potential health hazards. We quantified the pollutant emissions and analyzed the physicochemical properties of UCF PM2.5 in a laboratory study of coal smoldering under a simulated UCF background. The emission factors of CO2, CO, and PM2.5 were 2489 ± 35, 122 ± 9, 12.90 ± 1.79 g/kg, respectively. UCF PM2.5 are carbonaceous particles with varied morphology and complex composition, including heavy metals, silica and polycyclic aromatic hydrocarbons (PAHs). The main PAHs components were those with 2-4 rings. Benzoapyrene (BaP) and indeno[1,2, 3-cd]pyrene (IcdP) were important contributors to the carcinogenesis of these PAHs. We quantitatively evaluate the toxicity of inhaled UCF PM2.5 using a nasal inhalation exposure system. The target organs of UCF PM2.5 are lungs, liver, and kidneys. UCF PM2.5 presented an enriched chemical composition and induced inflammation and oxidative stress, which together mediated multiple organ injury. Long-term PM2.5 metabolism is the main cause of persistent toxicity, which might lead to long-term chronic diseases. Therefore, local authorities should recognize the importance and effects of UCF emissions, especially PM2.5, to establish control and mitigation measures.