The causal effect of oxidative stress on the risk of glaucoma.

Glaucoma is a complex multifactorial disease. Oxidative stress has been implicated in its pathogenesis. However, establishing a causal relationship between oxidative stress and glaucoma is challenging due to confounding and reverse causality. In this study, we performed bidirectional two-sample Mendelian randomization (MR) analyses based on genetic instrumental variables as proxies for 11 biomarkers of oxidative stress injury to investigate the causal relationship between oxidative stress and glaucoma. Eight significant associations were identified. Increased circulating levels of catalase (OR = 0.915, 95 % CI: 0.848-0.987, P = 0.022), retinol (OR = 0.481, 95 % CI: 0.248-0.932, P = 0.044) and superoxide dismutase (OR = 0.779, 95 % CI: 0. 616-0.986, P = 0.038) are associated with a decreased risk of glaucoma, whereas an increased myeloperoxidase level (OR = 2.145, 95 % CI: 1.119-4.111, P = 0.029) is associated with an increased risk of glaucoma. Glaucoma was causally associated with lower levels of total bilirubin (OR = 0.961, 95 % CI: 0.927-0.997, P = 0.039), glutathione peroxidase (OR = 0. 934, 95 % CI: 0.890-0.981, P = 0.006), paraoxonase (OR = 0.883, 95 % CI: 0.810-0.963, P = 0.005) and albumin (OR = 0.988, 95 % CI: 0.978-0.998, P = 0.014). The bidirectional MR analysis revealed a causal relationship between oxidative stress and glaucoma. These findings provide a greater understanding of the underlying mechanisms of glaucomatous neurodegeneration and imply a potential therapeutic approach for glaucoma through targeting oxidative stress pathways.

Clinical and radiographic outcomes of lateral sinus floor elevation with simultaneous hydrophilic implants placement: A retrospective study of 2-5 years.

AIMS: To investigate the clinical and radiographic outcomes of a chemically modified sandblasted large-grit acid-etched implant (hydrophilic) in lateral sinus floor elevation (LSFE), compared with a conventional one (hydrophobic). MATERIALS AND METHODS: A retrospective study design was adopted. Patients who received LSFE with simultaneous implant placement were recruited. According to different types of implant surfaces, patients were divided into two groups (the hydrophilic group and the hydrophobic group). Implant survival rate (SR), endo-sinus bone stability on the radiographs, mean probing depths, percentage of bleeding on probing, marginal bone loss, and patient satisfaction were evaluated. RESULTS: A total of 106 patients with 180 implants (hydrophilic:101, hydrophobic:79) in 119 maxillary sinuses were included. The follow-up period ranged from 2 to 5 years. Three hydrophobic implants and one hydrophilic implant in four different patients failed. The SR of the hydrophilic group was higher than that of the hydrophobic group but without a significant difference (p > .05). The change and change rate of endo-sinus bone height (ΔESBH and RΔESBH) and bone volume (ΔESBV and RΔESBV) in the hydrophilic group were less than those in the hydrophobic group, with a significant difference at 6 months after implantation. No other significant difference was found between the two groups. CONCLUSION: Within the limitations of this study, both hydrophilic and hydrophobic implants were suitable for LSFE with predictable clinical outcomes. Meanwhile, hydrophilic implants could contribute to the grafted endo-sinus bone stability during healing time.

Effect of the gut microbiome in glaucoma risk from the causal perspective.

OBJECTIVE: Evidence from observational studies has reported possible associations between the gut microbiome (GM) and glaucoma. However, the causal effect of GM on glaucoma risk remains to be determined. METHODS AND ANALYSIS: We conducted two-sample bidirectional Mendelian randomisation (MR) analyses to explore the causal association between GM and glaucoma. Genome-wide association study summary statistics of 196 GM taxa (n=18 340) and glaucoma (18 902 cases and 358 375 controls) were obtained from MiBioGen and FinnGen Consortium. Inverse variance weighted, MR-Egger, weighted median, weighted mode, Mendelian Randomisation Pleiotropy Residual Sum and Outlier, MR-Egger intercept and Cochran's Q statistical analyses were used to supplement MR results and sensitivity analysis. An independent cohort from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol (MRC-IEU) Consortium (1715 cases and 359 479 controls) was used to validate causal effects. RESULTS: Results of the MR analysis suggested that the family Oxalobacteraceae (OR 0.900, 95% CI 0.843 to 0.961, p=0.002) and the genus Eggerthella (OR 0.881, 95% CI 0.811 to 0.957, p=0.003) had a negative effect on glaucoma, whereas the genus Bilophila (OR 1.202, 95% CI 1.074 to 1.346, p=0.001), LachnospiraceaeUCG010 (OR 1.256, 95% CI 1.109 to 1.423, p=0.0003) and Ruminiclostridium 9 (OR 1.258, 95% CI 1.083 to 1.461, p=0.003) had a positive effect on glaucoma. Among these, the positive causal effect of LachnospiraceaeUCG010 (OR 1.002, 95% CI 1.000 to 1.004, p=0.033) on glaucoma was replicated in an independent cohort. CONCLUSION: This MR analysis from large population studies demonstrated the causal effect of GM on glaucoma risk and supported the role of GM in influencing glaucoma susceptibility.

Study on the dominant mechanism of direct hole oxidation for the photodegradation of tetracycline.

Antibiotic contamination has a significant negative impact on China, one of the largest producers and consumers of antibiotics worldwide. In this study, a three-dimensional flower-like structure of CoFe-LDHs was used to efficiently degrade tetracycline (TC) in a system triggered by peroxymonosulfate (PMS) and exposed to visible light. After exploring the effects of different metal ratios, catalyst dosage, initial TC concentrations, and pH, the optimal reaction conditions were determined. In comparison to pure CoFe-LDHs, the TC elimination rate was dramatically increased by the addition of the PMS. The strong environmental resistance, excellent stability and reusability, and universal flexibility were shown. The quenching experiments and electron spin resonance detection showed that the creation of reactive oxygen species was facilitated by the synergistic transmission of electrons between the active bimetallic components. Further, photogenerated holes was the dominant oxidizing species, which contributed more to the degradation of TC. The potential degradation pathways and intermediate toxicity of TC were suggested. This work offers a new method dominated by photogenerated holes for efficiently removing TC effluent.

Self-assembly flexible SERS imprinted membrane based on Ag nanocubes for selective detection of microcystin-LR.

Silver nanocubes monolayer-modified polydimethylsiloxane (Ag NC/PDMS) flexible SERS substrates have been prepared by a three-phase interface self-assembly procedure. The combination of this method with membrane technology brings nanoparticles in close proximity, densely, and regularly arranged in monolayers over a large area, leading to excellent SERS properties. Considering the complexity of practical detection, molecular imprinted polymers (MIPs) were anchored on the surface of SERS substrate and applied to selective detection of microcystin-LR (MC-LR). It is worth mentioning that the SERS imprinted membranes (AP-MIMs) were still clearly detected at a concentration of 0.1 µg·L-1 of MC-LR in drinking water, and the detection limit was as low as 0.0067 µg·L-1. The substrate exhibited excellent uniformity with a relative standard deviation (RSD) of 6.1%. In the presence of interference molecules, AP-MIMs exhibited excellent selectivity for MC-LR. Furthermore, in the spiking and recovery tests of practical lake water samples, the method showed excellent recoveries ranging from 96.47 to 105.31%. It has been demonstrated that the prepared AP-MIMs can be applied to sensitive and specific detection of trace amounts of MC-LR in drinking water.

Study on the behavior and mechanism of NiFe-LDHs used for the degradation of tetracycline in the photo-Fenton process.

An environment-friendly 3D NiFe-LDHs photocatalyst was fabricated via a simple hydrothermal method and characterized by means of SEM, XRD, BET, XPS and FT-IR. It is a highly efficient heterogeneous photo-Fenton catalyst for the degradation of TC-HCl under visible light irradiation. After exploring the effects of catalyst dosage, initial concentration of TC-HCl, solution pH and H2O2 concentrations, the optimal reaction conditions were determined. The experiment results showed that the degradation efficiency can reach 99.11% through adding H2O2 to constitute a photo-Fenton system after adsorption for 30 min and visible light for 60 min. After four cycles, the degradation rate decay is controlled within 21.2%, indicating that NiFe-LDHs have excellent reusable performance. The experimental results of environmental factors indicate that Fe2+ and Ca2+ promoted the degradation of TC-HCl, both Cl- and CO32- inhibited the degradation of TC-HCl. Two other antibiotics (OTC and FT) were selected for research and found to be effectively removed in this system, achieving effective degradation of a variety of typical new pollutants. The radical trapping tests and ESR detection showed that ·OH and ·O2- were the main active substances for TC degradation in the photo-Fenton system. By further measuring the intermediate products of photodegradation, the degradation pathway of TC-HCl was inferred. The toxicity analysis demonstrated that the overall toxicity of the identified intermediates was reduced in this system. This study provides a theoretical and practical basis for the removal of TC in aquatic environments.

Synthesis and antibacterial activities of Ag-TiO2/ZIF-8.

In recent years, massive bacterial infections have led to human illness and death, reminding us of the urgent need to develop effective and long-lasting antimicrobial materials. In this paper, Ag-TiO2/ZIF-8 with good environmental friendliness and biological antibacterial activity was prepared by solvothermal method. The structure and morphology of the synthesized materials were characterized by XRD, FT-IR, SEM-EDS, TEM, XPS, and BET. To investigate the antibacterial activity of the synthesized samples, Escherichia coli and Bacillus subtilis were used as target bacteria for experimental studies of zone of inhibition, bacterial growth curves, minimum bactericidal concentration and antibacterial durability. The results demonstrated that 20 wt.%Ag-TiO2/ZIF-8 had the best bacteriostatic effect on E. coli and B. subtilis under dark and UV conditions compared to TiO2 and ZIF-8. Under the same conditions, the diameter of the inhibition circle of 20 wt% Ag-TiO2/ZIF-8 is 8.5-11.5 mm larger than that of its constituent material 4 wt% Ag-TiO2, with more obvious antibacterial effect and better antibacterial performance. It is also proposed that the excellent antibacterial activity of Ag-TiO2/ZIF-8 is due to the synergistic effect of Ag-TiO2 and ZIF-8 under UV light. In addition, the prepared material has good stability and durability with effective antimicrobial activity for more than 5 months.

The transcriptional landscape and diagnostic potential of long non-coding RNAs in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly cancer with no clinically relevant biomarkers for early detection. Here, we comprehensively characterized the transcriptional landscape of long non-coding RNAs (lncRNAs) in paired tumor and normal tissue specimens from 93 ESCC patients, and identified six key malignancy-specific lncRNAs that were integrated into a Multi-LncRNA Malignancy Risk Probability model (MLMRPscore). The MLMRPscore performed robustly in distinguishing ESCC from normal controls in multiple in-house and external multicenter validation cohorts, including early-stage I/II cancer. In addition, five candidate lncRNAs were confirmed to have non-invasive diagnostic potential in our institute plasma cohort, showing superior or comparable diagnostic accuracy to current clinical serological markers. Overall, this study highlights the profound and robust dysregulation of lncRNAs in ESCC and demonstrates the potential of lncRNAs as non-invasive biomarkers for the early detection of ESCC.

Yellow emissive nitrogen-doped carbon dots as a fluorescence probe for the sensitive and selective detection of silver ions.

In this work, yellow emissive carbon dots (Y-CDs) were prepared via a simple hydrothermal method using catechol and hydrazine hydrate as the carbon and nitrogen sources, respectively. The average particle size was 2.99 nm. The Y-CDs demonstrate excitation-dependent emission properties, and the maximum emission wavelength is 570 nm at E x = 420 nm. The fluorescence quantum yield is calculated to be 28.2%. Ag+ could quench the fluorescence of Y-CDs with high selectivity. The quenching mechanism was further explored by various characterization techniques. A sensitive fluorescent probe for Ag+ detection was established based on Y-CDs with a linear range of 3-300 µM. The detection limit was calculated to be 1.1 µM. The proposed method shows satisfactory results in real water samples without interference by coexistence.

Fast self-curing α-tricalcium phosphate/ß-dicalcium silicate composites beneficial for root canal sealing treatment.

Objectives: α-tricalcium phosphate (α-TCP) and ß-dicalcium silicate (ß-C2S) have attracted much attention since these two types of self-curing Ca-phosphate and Ca-silicate are valuable biomaterials for bone defect or endodontic therapy. However, the injectable paste of their individual with high liquid/solid ratio is junior for root canal sealing due to very long self-setting time, low pH value and/or much volume shrinkage during paste-to-cement transformation. Methods: Our studies evaluated the effect of biphasic ratio, liquid/solid ratio and pH condition of aqueous medium on setting time and mechanical strength of this biphasic composite cement, and also the hydroxyapatite re-mineralization potential and anti-microleakage level of the cements with different α-TCP/ß-C2S ratio were explored in vitro. A control group free of paste filler was included in the extracted teeth model. Dentine re-mineralization and microleakage degree were observed by scanning electron microscopy and microCT reconstruction analysis. Results: It indicated that the weak acidic solution with pH value of 6.0 may produce a significantly shorter initial setting time (from 90 min to less 20 min) and expected final setting time (<150 min) for the biphasic composite (2:1 or 1:2) in comparison with the pure ß-C2S. Notably, the phasic composites exhibited limited microleakage and induced hydroxyapatite mineralization in the dentine tubules. These hydraulic pastes also produced strong alkaline feature and appreciable compressive resistance (12-18 MPa) after setting for a very short time stage. Moreover, a link between the addition of α-TCP leading to fast re-mineralization reaction was established. Significance: Our findings suggest that the appreciable self-setting and physicochemical properties adaption to root canal sealability make α-TCP/ß-C2S composites as preferential candidates for endodontic treatments.

A blood-based miRNA signature for early non-invasive diagnosis of preeclampsia.

BACKGROUND: Preeclampsia (PE) is a multisystemic maternal syndrome with substantial maternal and fetal morbidity and mortality. Currently, there is no clinically viable non-invasive biomarker assay for early detection, thus limiting the effective prevention and therapeutic strategies for PE. METHODS: We conducted a discovery-training-validation three-phase retrospective and prospective study with cross-platform and multicenter cohorts. The initial biomarkers were discovered and verified in tissue specimens by small RNA sequencing and qRT-PCR. A miRNA signature (miR2PE-score) was developed using Firth's bias-reduced logistic regression analysis and subsequently validated in two independent multinational retrospective cohorts and two prospective plasma cohorts. RESULTS: We initially identified five PE-associated differentially expressed miRNAs from miRNA sequencing data and subsequently validated two miRNAs (miR-196b-5p and miR-584-5p) as robust biomarkers by association analysis with clinical characteristics and qRT-PCR in tissue specimens in the discovery phase. Using Firth's bias-reduced logistic regression analysis, we developed the miR2PE-score for the early detection of PE. The miR2PE-score showed a high diagnostic performance with an area under the receiver operating characteristic curve (AUROC) of 0.920, 0.848, 0.864, and 0.812 in training, internal, and two external validation cross-platform and multicenter cohorts, respectively. Finally, we demonstrated the non-invasive diagnostic performance of the miR2PE-score in two prospective plasma cohorts with AUROC of 0.933 and 0.787. Furthermore, the miR2PE-score revealed superior performance in non-invasive diagnosis compared with previously published miRNA biomarkers. CONCLUSIONS: We developed and validated a novel and robust blood-based miRNA signature, which may serve as a promising clinically applicable non-invasive tool for the early detection of PE.

Ball Milling Medium May Tune the Self-Curing Property and Root Canal Microleakage of ß-Dicalcium Silicate-Based Cement.

It is still a challenge to overcome the extended setting process of pure Ca-silicate as root canal fillers. We investigated the effects of attapulgite (a basic hydrous silicate of magnesium and aluminum) and ball-milling liquid medium on the self-curing properties of conventional ß-dicalcium silicate (C2Si)-based cements. It was shown that a minor amount of attapulgite nanofibers (1-4%) had only a slight influence on setting time but caused a large increase in compressive resistance and structural stability. In particular, the ball milling media with different acetone/water ratios (3:0, 2:1, 1:2, 0:3) could directly influence the particle size distribution of C2Si powders, and the co-existence of liquid media (2:1 or 1:2) may be beneficial for shortening the setting time, enhancing early-stage compressive strength, and significantly improving the anti-microleakage ability of cement. Moreover, the composite cements also exhibited appreciable antibacterial efficacy in vitro. These findings demonstrated that the physicochemical properties of the Ca-silicate powders could be tuned by adding a minor amount of inorganic silicate nanofibers and a simple ball milling condition, and such a facile strategy is favorable for developing novel (pre-mixed) Ca silicate-based cements as root canal sealers.

Computational elucidation of spatial gene expression variation from spatially resolved transcriptomics data.

Recent advances in spatially resolved transcriptomics (SRT) have revolutionized biological and medical research and enabled unprecedented insight into the functional organization and cell communication of tissues and organs in situ. Identifying and elucidating gene spatial expression variation (SE analysis) is fundamental to elucidate the SRT landscape. There is an urgent need for public repositories and computational techniques of SRT data in SE analysis alongside technological breakthroughs and large-scale data generation. Increasing efforts to use in silico techniques in SE analysis have been made. However, these attempts are widely scattered among a large number of studies that are not easily accessible or comprehensible by both medical and life scientists. This study provides a survey and a summary of public resources on SE analysis in SRT studies. An updated systematic overview of state-of-the-art computational approaches and tools currently available in SE analysis are presented herein, emphasizing recent advances. Finally, the present study explores the future perspectives and challenges of in silico techniques in SE analysis. This study guides medical and life scientists to look for dedicated resources and more competent tools for characterizing spatial patterns of gene expression.

Deep learning-based advances and applications for single-cell RNA-sequencing data analysis.

The rapid development of single-cell RNA-sequencing (scRNA-seq) technology has raised significant computational and analytical challenges. The application of deep learning to scRNA-seq data analysis is rapidly evolving and can overcome the unique challenges in upstream (quality control and normalization) and downstream (cell-, gene- and pathway-level) analysis of scRNA-seq data. In the present study, recent advances and applications of deep learning-based methods, together with specific tools for scRNA-seq data analysis, were summarized. Moreover, the future perspectives and challenges of deep-learning techniques regarding the appropriate analysis and interpretation of scRNA-seq data were investigated. The present study aimed to provide evidence supporting the biomedical application of deep learning-based tools and may aid biologists and bioinformaticians in navigating this exciting and fast-moving area.

Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes.

The emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level. These TIME lncRNA modifiers (TIL-lncRNAs) were able to subclassify various tumors into three de novo pan-cancer subtypes characterized by distinct immunological features, biological behaviors, and disease prognoses. Finally, a TIL-lncRNA-derived immune state index (TISI) that was reflective of immunological and oncogenic states but also predictive of patients' prognosis was proposed. Furthermore, the TISI provided additional prognostic value for existing tumor immunological and molecular subtypes. By applying the TISI to tumors from different clinical immunotherapy cohorts, the TISI was found to be significantly negatively correlated with immune-checkpoint genes and to have the ability to predict the effectiveness of immunotherapy. In conclusion, the present study provided comprehensive resources and insights for future functional and mechanistic studies on lncRNA-mediated cancer immunity and highlighted the potential of the clinical application of lncRNA-based immunotherapeutic strategies in precision immunotherapy.

Circulating exosomal miR-363-5p inhibits lymph node metastasis by downregulating PDGFB and serves as a potential noninvasive biomarker for breast cancer.

Sentinel lymph node (LN) biopsy is currently the standard procedure for clinical LN-negative breast cancer (BC) patients but it is prone to false-negative results and complications. Thus, an accurate noninvasive approach for LN staging is urgently needed in clinical practice. Here, circulating exosomal microRNA (miRNA) expression profiles in peripheral blood from BC patients and age-matched healthy women were obtained and analyzed. We identified an exosomal miRNA, miR-363-5p, that was significantly downregulated in exosomes from plasma of BC patients with LN metastasis which exhibited a consistent decreasing trend in tissue samples from multiple independent datasets. Plasma exosomal miR-363-5p achieved high diagnostic performance in distinguishing LN-positive patients from LN-negative patients. The high miR-363-5p expression level was significantly correlated with improved overall survival. Functional assays demonstrated that exosomal miR-363-5p modulates platelet-derived growth factor (PDGF) signaling activity by targeting PDGFB to inhibit cell proliferation and migration. Our study revealed, for the first time, plasma exosomal miR-363-5p plays a tumor suppressor role in BC and has the potential for noninvasive LN staging and prognosis prediction of BC.

Light-induced degradation of rhodamine B by tellurium quantum dots.

Tellurium quantum dots (Te QDs) were prepared using bulk tellurium as the precursor. Te QDs can be a highly active photocatalyst for boosting the photocatalytic degradation of rhodamine B (RhB) under visible light irradiation. The morphology and composition of Te QDs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The results showed that in the presence of H2O2, the photocatalytic efficiency of Te QDs on RhB could achieve a good degradation effect within a very short time (30 min). The effects of initial dye concentration, pH value, light intensity, catalyst dosage and H2O2 concentration on dye degradation were successively studied. The effects of inorganic ions (NO3-, Cl-, SO42-, Ca2+, Mg2+ and Fe3+) on photocatalytic degradation were also discussed. Experimental results of free radical capture showed that OH• and O2•- played important roles in photocatalytic degradation. More importantly, Te QDs efficiency still remained above 85% after four cycles of use, indicating good stability, recyclability and utility. This work may inspire further design of other semiconductor QDs for highly efficient dye degradation.

Photoconversion of polychlorinated naphthalenes in organic solvents under simulated sunlight: Solvent effect and mechanism.

In this work, the organic solvent effect on the photoconversion of polychlorinated naphthalenes (PCNs) under the simulated sunlight, as well as the mechanism and influence factor were studied. Eight organic solvents were selected to demonstrate the solvent effect on the photoconversion by the theoretical calculation method. It was found that the photoconversion rates of 1-chloronaphthalene (CN-1) in different organic solvents were in the order of dimethyl sulfoxide > methanol > acetonitrile > ethanol > dichloromethane > toluene > n-hexane > acetone. The result, obtained by the density functional theory (DFT) computation and the polarized continuum model (PCM) analysis in the framework of self-consistent reaction field (SCRF), indicated that the photoconversion was affected by the hydrogen-donating ability and electron-withdrawing potential of the solvents, as well as non-specific solute-solvent interactions. The photoconversion in acetonitrile for the five PCNs (1-chloronaphthalene, 2-chloronaphthalene, 2,3-dichloronaphthalene, 1,2,3,4-tetrachloronaphthalene, and 1,2,3,4,5,6,7,8- octachloronaphthalene) all fitted well with the first-order kinetic equation; and the reaction rate decreased with the increasing of number of chlorine atoms of the PCNs. Products analysis proved that the photoconversion process of PCNs went through two stages, namely the initial stage of dechlorination and the later stage of oxidative ring opening. It was found that inorganic ions (NO3-, Cl-, Fe3+, and Fe2+) promoted or inhibited the photoconversion by generating or quenching of the reactive oxygen species, and chlorophyll a promoted the photoconversion through the generation of singlet oxygen.

Phototransformation of three polychlorinated naphthalenes on surface of atmospheric particulate matter.

Polychlorinated naphthalenes (PCNs) are a new class of persistent organic pollutants. Photoconversion is an important pathway for their transformation in the environment. In this work, silica gel was used to simulate atmospheric mineral particles, and the photochemical reaction of three PCNs 1-chloronaphthalene (CN-1), 2-chloronaphthalene (CN-2) and 2,3-dichloronaphthalene (CN-10)) on silica gel surface was studied under the irradiation of high-pressure mercury lamp, the phototransformation intermediates and pathways of PCNs were investigated, effects of reactive oxygen species (ROS, ·OH, 1O2 and O2-·) were proved by free radical scavenging method and the effects of co-existing components (water, inorganic ions and fulvic acid) were examined. The results showed that all the three PCNs could be photochemical degraded on silica gel surface. The order of the apparent rate constants was CN-2 ≈ CN-1 > CN-10. ROS accelerated the photochemical reaction. The three PCNs didn't produce completely identical photoproducts, but all underwent a series of reactions such as reductive dechlorination, hydroxylation, oxidation, decarboxylation and ring opening. In addition, for the photoconversion of CN-1, the presence of water, NO3- or fulvic acid all promoted the photochemical transformation, while the presence of Cu2+ had an inhibitory effect.

Genomic instability-derived plasma extracellular vesicle-microRNA signature as a minimally invasive predictor of risk and unfavorable prognosis in breast cancer.

BACKGROUND: Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-associated deaths in women. Recent studies have indicated that microRNA (miRNA) regulation in genomic instability (GI) is associated with disease risk and clinical outcome. Herein, we aimed to identify the GI-derived miRNA signature in extracellular vesicles (EVs) as a minimally invasive biomarker for early diagnosis and prognostic risk stratification. EXPERIMENTAL DESIGN: Integrative analysis of miRNA expression and somatic mutation profiles was performed to identify GI-associated miRNAs. Then, we constructed a discovery and validation study with multicenter prospective cohorts. The GI-derived miRNA signature (miGISig) was developed in the TCGA discovery cohort (n = 261), and was subsequently independently validated in internal TCGA validation (n = 261) and GSE22220 (n = 210) cohorts for prognosis prediction, and in GSE73002 (n = 3966), GSE41922 (n = 54), and in-house clinical exosome (n = 30) cohorts for diagnostic performance. RESULTS: We identified a GI-derived three miRNA signature (MIR421, MIR128-1 and MIR128-2) in the serum extracellular vesicles of BC patients, which was significantly associated with poor prognosis in all the cohorts tested and remained as an independent prognostic factor using multivariate analyses. When integrated with the clinical characteristics, the composite miRNA-clinical prognostic indicator showed improved prognostic performance. The miGISig also showed high accuracy in differentiating BC from healthy controls with the area under the receiver operating characteristics curve (ROC) with 0.915, 0.794 and 0.772 in GSE73002, GSE41922 and TCGA cohorts, respectively. Furthermore, circulating EVs from BC patients in the in-house cohort harbored elevated levels of miGISig, with effective diagnostic accuracy. CONCLUSIONS: We report a novel GI-derived three miRNA signature in EVs, as an excellent minimally invasive biomarker for the early diagnosis and unfavorable prognosis in BC.