The multifaceted role of macrophage mitophagy in SiO2-induced pulmonary fibrosis: A brief review.

Prolonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully systematically summarized. Therefore, it is necessary to elucidate the role of macrophage mitophagy in SiO2-induced pulmonary fibrosis by systematic analysis on the literature reports. In this review, we first summarized the current data on the macrophage mitophagy in the development of SiO2-induced pulmonary fibrosis. Then, we introduce the molecular mechanism on how SiO2-induced mitophagy causes pulmonary fibrosis. Finally, we focus on introducing new therapies based on newly developed mitophagy-inducing strategies. We conclude that macrophage mitophagy plays a multifaceted role in the progression of SiO2-induced pulmonary fibrosis, and reprogramming the macrophage mitophagy state accordingly may be a potential means of preventing and treating pulmonary fibrosis.

Silica-induced ROS in alveolar macrophages and its role on the formation of pulmonary fibrosis via polarizing macrophages into M2 phenotype: a review.

Alveolar macrophages (AMs), the first line against the invasion of foreign invaders, play a predominant role in the pathogenesis of silicosis. Studies have shown that inhaled silica dust is recognized and engulfed by AMs, resulting in the production of large amounts of silica-induced reactive oxygen species (ROS), including particle-derived ROS and macrophage-derived ROS. These ROS change the microenvironment of the AMs where the macrophage phenotype is stimulated to swift from M0 to M1 and/or M2, and ultimately emerge as the M2 phenotype to trigger silicosis. This is a complex process accompanied by various molecular biological events. Unfortunately, the detailed processes and mechanisms have not been systematically described. In this review, we first systematically introduce the process of ROS induced by silica in AMs. Then, describe the role and molecular mechanism of M2-type macrophage polarization caused by silica-induced ROS. Finally, we review the mechanism of pulmonary fibrosis induced by M2 polarized AMs. We conclude that silica-induced ROS initiate the fibrotic process of silicosis by inducing macrophage into M2 phenotype, and that targeted intervention of silica-induced ROS in AMs can reprogram the macrophage polarization and ameliorate the pathogenesis of silicosis.

Syntheses, Structures, and Magnetic Properties of Three Cyano-Bridged FeII-MoIII Single-Molecule Magnets.

Three new cyano-bridged FeII-MoIII complexes assembled from the [MoIII(CN)7]4- unit, FeII ions, and three pentadentate N3O2 ligands, namely {[Fe2H3(dapab)2][Mo(CN)6]}n·2H2O·3.5MeCN (1), [Fe(H2dapb)(H2O)][Fe(Hdapb)(H2O)][Mo(CN)6]·4H2O·3MeCN (2), and [Fe(H2dapba)(H2O)]2[Mo(CN)7]·6H2O (3) (H2dapab = 2,6-diacetylpyridine bis(2-aminobenzoylhydrazone), H2dapb = 2,6-diacetylpyridine bis(benzoylhydrazone), H2dapba = 2,6-diacetylpyridine bis(4-aminobenzoylhydrazone)), have been synthesized and characterized. Single-crystal structure analyses suggest that complex 1 contains a one-dimensional (1D) chain structure where two FeII ions are bridged by the in situ generated [MoIII(CN)6]3- unit through two trans-cyanide groups into trinuclear Fe2IIMoIII clusters that are further linked by the amino of the ligand into an infinite chain. Complexes 2 and 3 are cyano-bridged Fe2IIMoIII trinuclear clusters with two FeII ions connected by the [MoIII(CN)6]3- and [MoIII(CN)7]4- units, respectively. Direct current magnetic studies confirmed the ferromagnetic interactions between the cyano-bridged FeII and MoIII centers and significant easy-axis magnetic anisotropy for all three complexes. Furthermore, complexes 1-3 exhibit slow magnetic relaxation under a zero dc field, with relaxation barriers of 42.3, 21.6, and 14.4 K, respectively, making them the first examples of cyano-bridged FeII-MoIII single-molecule magnets.

Zinc deficiency compromises the maturational competence of porcine oocyte by inducing mitophagy and apoptosis.

Zinc, an essential trace mineral, plays a pivotal role in cell proliferation, maintenance of redox homeostasis, apoptosis, and aging. Serum zinc concentrations are reduced in patients with polycystic ovary syndrome (PCOS). However, the underlying mechanism of the effects of zinc deficiency on the female reproductive system, especially oocyte quality, has not been fully elucidated. Thus, we established an in vitro experimental model by adding N,N,N',N'-Tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) into the culture medium, and to determine the potential regulatory function of zinc during porcine oocytes maturation. In the present study, we found that zinc deficiency caused aberrant meiotic progress, accompanied by the disrupted cytoskeleton structure in porcine oocytes. Zinc deficiency impaired mitochondrial function and dynamics, leading to the increase of reactive oxygen species (ROS) and acetylation level of the antioxidative enzyme superoxide dismutase 2 (SOD2), eventually induced the occurrence of oxidative stress and early apoptosis. Moreover, zinc deficiency perturbed cytosolic Ca2+ homeostasis, lipid droplets formation, demonstrating the aberrant mitochondrial function in porcine oocytes. Importantly, we found that zinc deficiency in porcine oocytes induced the occurrence of mitophagy by activating the PTEN-induced kinase 1/Parkin signaling pathway. Collectively, our findings demonstrated that zinc was a critical trace mineral for maintaining oocyte quality by regulating mitochondrial function and autophagy in porcine oocytes.

Simazine perturbs the maturational competency of mouse oocyte through inducing oxidative stress and DNA damage.

Simazine is a triazine pesticides that typically detected in ground water and soil, and can reportedly affect reproductive health in humans and animals. However, the effect of simazine on female germ cell development remains unclear. In the present study, we observed that simazine exposure decreased oocyte maturation competence and embryonic developmental capacity. Importantly, simazine exposure disrupted microtubule stability and actin polymerization, resulting in failure of spindle assembly and migration. In addition, simazine exposure impaired mitochondrial function and cytosolic Ca2+ homeostasis in both oocyte and 2-cell embryos, thus increasing the levels of reactive oxygen species (ROS). Moreover, simazine exposure induced DNA damage and early apoptosis during oocyte maturation. Collectively, our results demonstrate that simazine exposure-induced mitochondrial dysfunction and apoptosis are major causes of poor oocytes quality.

Formation and control of disinfection byproducts and toxicity during reclaimed water chlorination: A review.

Chlorination is essential to the safety of reclaimed water; however, this process leads to concern regarding the formation of disinfection byproducts (DBPs) and toxicity. This study reviewed the formation and control strategies for DBPs and toxicity in reclaimed water during chlorination. Both regulated and emerging DBPs have been frequently detected in reclaimed water during chlorination at a higher level than those in drinking water, indicating they pose a greater risk to humans. Luminescent bacteria and Daphnia magna acute toxicity, anti-estrogenic activity and cytotoxicity generally increased after chlorination because of the formation of DBPs. Genotoxicity by umu-test and estrogenic activity were decreased after chlorination because of destruction of toxic chemicals. During chlorination, water quality significantly impacted changes in toxicity. Ammonium tended to attenuate toxicity changes by reacting with chlorine to form chloramine, while bromide tended to aggravate toxicity changes by forming hypobromous acid. During pretreatment by ozonation and coagulation, disinfection byproduct formation potential (DBPFP) and toxicity formation potential (TFP) occasionally increase, which is accompanied by DOC removal; thus, the decrease of DOC was limited to indicate the decrease of DBPFP and TFP. It is more important to eliminate the key fraction of precursors such as hydrophobic acid and hydrophilic neutrals. During chlorination, toxicities can increase with the increasing chlorine dose and contact time. To control the excessive toxicity formation, a relatively low chlorine dose and short contact time were required. Quenching chlorine residual with reductive reagents also effectively abated the formation of toxic compounds.

[Synthesis and Luminescence Properties of BiOCL: Dy3⁺Phosphors for NUV Excited White Light-Emitting Diodes].

Abstract In the present paper, we reported the luminescence properties of BiOCl:Dy(3+) and BiOCl:Dy(3+), Li+ phosphor synthesized by conventional solid state method. X-ray diffraction (XRD) and excitation and emission spectroscopy were used to characterize the samples. Results show that pure tetragonal BiOCl:Dy(3+) crystals can be synthesized successfully at 500 °C, and Li+ ion dopant improves the crystallinity of samples furtherly. Under near UV light excitation, the samples,give the characteristic luminescence of Dy(3+) ions located at 478 (blue) and 574 nm (yellow), which show a low yellow-to-blue intensity ratio (Y/B) of Dy(3+) emission and white light emission. Moreover, codoping of Li+ ion can realize the enhancement of emission intensity and the adjustment of emission color. The characteristics of BiOCl:Dy(3+) phosphor, low temperature preparation, good near ultraviolet excitation and white light emission make it to a promising near-ultraviolet WLED phosphor.

Impact of professional identity on learner well-being of undergraduate nursing students of "double tops" universities: Mediating effect of self-regulated learning.

OBJECTIVES: The pressure of internal competition at the college level has increased in recent years in China with an impact on nursing students' learning and well-being. This study aimed to investigate the current situation and factors affecting professional identity, learner well-being and self-regulated learning of undergraduate nursing students in the Neijuan ecology of the "double tops" universities, and to explore the relationships between these three variables. METHODS: A cross-sectional design was adopted to conduct an online survey of 322 Chinese undergraduate nursing students from seven "double tops" universities. The survey included socio-demographics characteristics, students' professional identity, learner well-being, and self-regulated learning. RESULTS: Results of Pearson correlation analysis showed that professional identity was significantly and positively correlated with learner well-being (R = 0.795, p < 0.001); professional identity was significantly and positively correlated with self-regulated learning (R = 0.843, p < 0.001); and, self-regulated learning was significantly and positively correlated with learner well-being (R = 0.852, p < 0.001). After mediation effect testing, self-regulated learning had a mediating effect between professional identity and learner well-being (95 % CI 0.366-0.548, p < 0.001). Professional identity had a positive predictive effect on self-regulated learning (a = 0.570, p < 0.001), and self-regulated learning also had a positive predictive effect on learner well-being (b = 0.798, p < 0.001). The direct effect of professional identity on learner well-being (0.225) and its mediating effect (0.455) account for 33.1 % and 66.9 % of the total effect (0.680), respectively. CONCLUSIONS: The learner well-being of undergraduate Chinese nursing students is in the middle to upper range, and it is crucial to enhance professional identity and develop students' self-regulated learning to improve their learner well-being. This study provides empirical evidence to support the mediating effect of self-regulated learning on the relationship between professional identity and learner well-being among undergraduate nursing students in "double tops" universities. Universities are expected to strengthen career planning guidance and professional competence training for students as early as possible in order to develop quality nursing education programs that produce graduates who enter and remain in the workforce.

Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer: study protocol for a randomised controlled trial.

BACKGROUND: A single injection of local anaesthetic (LA) in the erector spinae plane block (ESPB) can reduce pain after modified radical mastectomy (MRM) surgery, but the duration of analgesia is affected by the duration of the LA. The aim of this study is to investigate the effect of continuous ESPB on acute and chronic pain and inflammatory response after MRM surgery. METHODS: In this prospective, randomised, controlled trial, we will recruit 160 patients, aged 18-80 years, scheduled for elective MRM surgery under general anaesthesia. They will be randomly assigned to two groups: a continuous ESPB group (group E) and a sham block group (group C). Both groups of patients will have a nerve block (group C pretended to puncture) and an indwelling catheter fixed prior to surgery. Electronic pumps containing LA are shielded. The primary outcome is the total consumption of analgesic agents. The secondary outcomes include the levels of inflammation-related cytokines; the occurrence of chronic pain (post-mastectomy pain syndrome, PMPS); static and dynamic pain scores at 2, 6, 12, 24 and 48 h postoperatively; and post-operative and post-puncture adverse reactions. DISCUSSION: Analgesia after MRM surgery is important and chronic pain can develop when acute pain is prolonged, but the analgesic effect of a nerve block with a single injection of LA is limited by the duration of drug action. The aim of this trial is to investigate whether continuous ESPB can reduce acute pain after MRM surgery and reduce the incidence of chronic pain (PMPS), with fewer postoperative analgesic drug-related complications and less inflammatory response. Continuous ESPB and up to 12 months of follow-up are two innovations of this trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ) ChiCTR2200061935. Registered on 11 July 2022. This trial is a prospective registry with the following registry names: Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer.

Inactivation of microglia dampens blood-brain barrier permeability and loss of dopaminergic neurons in paraquat-lesioned mice.

Prior studies indicated the involvement of neuroinflammation in the dopaminergic neurodegeneration in mice of paraquat (PQ)-induced Parkinson's disease (PD), but the underlying mechanisms remain to be elucidated. The present study explored whether microglia-mediated inflammation disrupted blood-brain barrier (BBB) and its related mechanism. C57BL/6 mice were injected intraperitoneally with PQ, twice a week for six weeks, following with or without minocycline (intraperitoneal injection, once every two days). The microglial activation, BBB permeability, expression of tight junctions (TJs) proteins and matrix metalloproteinase (MMP), as well as the loss of dopaminergic neurons and neurological deficits assessment, were evaluated. Minocycline efficiently restrained nigral microglial activation induced by PQ in mice. PQ-induced increase of EB content in the brain and excessive expression of zonula occludin-1 (ZO-1), claudin-5 and occludin were significantly dampened by minocycline treatment. Inhibition of microglial activation by minocycline greatly ameliorated the loss of dopaminergic neurons and neurological dysfunctions in PQ-exposed mice. Also, microglial inactivation downregulated the expression of MMP-2/9 in PQ-lesioned mice. These findings suggested the potential protection of suppressing microglia-mediated neuroinflammation against dopaminergic neurodegeneration through attenuating BBB disruption in a mouse of PQ-induced PD, and MMP-2/9 might involve in the contribution, which needs to be verified in future study.

Comprehensive treatment strategy for diesel truck exhaust.

At present, diesel vehicles still play an irreplaceable role in the traditional energy field in China. Diesel vehicle exhaust contains hydrocarbons, carbon monoxide, nitrogen oxides, and particulate matter, which can lead to haze weather, photochemical smog, and the greenhouse effect; endanger human health; and damage the ecological environment. In 2020, the number of motor vehicles in China reached 372 million, and the number of automobiles reached 281 million, of which 20.92 million are diesel vehicles, accounting for only 5.6% of the number of motor vehicles and 7.4% of the number of automobiles. Nevertheless, diesel vehicles emitted 88.8% of nitrogen oxides and 99% of particulate matter in total vehicle emissions. Diesel vehicles, especially diesel trucks, have become the top priority of motor vehicle pollution control. However, there are few reviews on the comprehensive treatment of diesel vehicle exhaust. This review provides an overview of exhaust gas composition, hazards, and treatment techniques. Phytoremediation, three-way catalytic conversion, rare earth catalytic degradation, and nanoscale TiO2 catalytic degradation are briefly described.

Perfluorooctanoic acid (PFOA) exposure affects early embryonic development and offspring oocyte quality via inducing mitochondrial dysfunction.

Perfluorooctanoic acid (PFOA) is a synthetic perfluorinated compound that is extensively used as an integral surfactant in commercial production. Owing to its hydrophilicity and persistence, PFOA can accumulate in living organisms and induce severe disease in animals and humans. It has been reported that PFOA exposure can affect ovarian function and induce reproductive toxicity; however, the effects and potential mechanism of PFOA exposure during gestation on early embryonic development and offspring remain unclear. This study found that PFOA exposure in vitro disrupted spindle assembly and chromosome alignment during the first cleavage of early mouse embryos, which impacted early embryonic cleavage and blastocyst formation. Moreover, PFOA exposure caused mitochondrial dysfunction and oxidative stress by inducing aberrant Ca2+ levels, liquid drops(LDs), and mitochondrial membrane potential in the 2-cell stage. Furthermore, we found that PFOA exposure resulted in DNA damage, autophagy, and apoptosis in 2-cell stage by inhibiting SOD2 function. Gestational exposure to PFOA significantly increased ovarian apoptosis and disrupted follicle development in F1 offspring. In addition, oocyte maturation competence was decreased in F1 offspring. Finally, single-cell transcriptome analysis revealed that PFOA-induced oocyte deterioration was caused by mitochondrial dysfunction and apoptosis in the F1 offspring. In summary, our results indicated that gestational exposure to PFOA had potential toxic effects on ovarian function and led to a higher incidence of meiotic defects in F1 female offspring.

A time-course study of microglial activation and dopaminergic neuron loss in the substantia nigra of mice with paraquat-induced Parkinson's disease.

Activated microglia play an active role in the pathogenesis of PD and paraquat (PQ) induces PD. The study was to understand the time relationship between microglial activation and dopaminergic neuron loss in the substantia nigra (SN) of PQ-induced PD mice. Male C57BL/6 mice were injected intraperitoneally with PQ, twice a week for six weeks. Some mice underwent behavioral assessments each week and were sacrificed for SN tissues, in which histopathological analysis, dopaminergic neuron loss, microglial activation and phenotypic characteristics were evaluated. The results showed that motor retardation, coordination disorders and limb stiffness occurred four weeks after PQ exposure, as well as the degeneration and loss of dopaminergic neurons in the SN. Activated microglia and increased CD68 expression appeared two weeks after PQ exposure in time-dependent manners. Increased CD86 and decreased CD206 expression were observed four weeks after PQ exposure, accompanied by increased TNF-α and IL-6 levels and decreased IL-10 and TGF-ß levels. These results indicate that PQ can activate microglia in vivo, and microglial activation precedes neuronal loss in the SN. Activated microglia are characterized by mixed M1/M2 polarization in the early stage and M1 polarization in the late stage of PQ-induced PD development.

Design, synthesis, and anticancer activity of three novel palbociclib derivatives.

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

Application of ESR spin label oximetry in food science.

Lipid oxidation attributed to the presence of oxygen has long been a focal area for food science research due in early years mainly to its broad impact on the quality and shelf stability. The need to effectively strategize interventions to detect and eventually eliminate lipid oxidation in food remains as evidence on nutritional and health implications continue to accumulate. Electron spin resonance (ESR) spin label oximetry has been shown capable of detecting dissolved oxygen concentration in both liquid and gaseous phases based on the collision between oxygen and stable free radicals. This review aimed to summarize not just the principles and rationale of ESR spin label oximetry but also the wide spectrum of ESR spin label oximetry applications to date. The feasibility to identify in very early stage oxygen generation and consumption offers a promising tool for controlling lipid oxidation in food and biological systems.

Surrogates for the removal by ozonation of the cytotoxicity and DNA double-strand break effects of wastewater on mammalian cells.

Effluents from wastewater treatment plants (WWTPs) may contain various pollutants with potential toxic effects. Ozonation is widely applied to purify wastewater, which may influence the toxicity and water quality indices simultaneously. The main goal of this study was to reveal influence of ozonation on toxicity of WWTP effluents and to find the surrogates for toxicity changes. Cytotoxicity and DNA double-strand break (DSB) effect of WWTP effluents were measured based on Chinese hamster ovary (CHO) cells. Changes of water quality parameters and molecular weight distribution of WWTP effluents were also measured. The organic extracts in WWTP effluents were shown to decrease the cell viability. Besides, an increased level of DNA DSBs was found in cells when exposed to the organic extracts. Ozonation significantly eliminated cytotoxicity and DNA DSB-based genotoxicity of WWTP effluents, with removal rates of 53-66% and 51-76% for cytotoxicity and genotoxicity, respectively, with 10 mg/L ozone dose. Although the DOC contents in WWTP effluents were hardly removed by ozonation, the chromophores and fluorophores were significantly eliminated. Organic matter in WWTP effluents mainly consists of fractions with molecular weight (MW) < 500 Da. Ozonation generally decreased the fluorescence intensity and UV254 values of all the MW fractions, but increased the DOC contents of the 100-500 Da fraction. During ozonation, the removal rates of UV254 and SUVA254 were significantly correlated to the removal rates of both cytotoxicity and genotoxicity. UV254 might be an ideal surrogate for cytotoxicity and genotoxicity reduction during wastewater ozonation.

Corrigendum: Sperm Protein Antigen 17 Expression Correlates With Lymph Node Metastasis and Worse Overall Survival in Patients With Breast Cancer.

[This corrects the article DOI: 10.3389/fonc.2019.00710.].

Homotherapy for heteropathy active components and mechanisms of Qiang-Huo-Sheng-Shi decoction for treatment of rheumatoid arthritis and osteoarthritis.

Qiang-Huo-Sheng-Shi decoction (QHSSD), a classic traditional Chinese herbal formula, which has been reported to be effective in rheumatoid arthritis (RA) and osteoarthritis (OA). However, the concurrent targeting mechanism of how the aforementioned formula is valid in the two distinct diseases OA and RA, which represents the homotherapy-for-heteropathy principle in traditional Chinese medicine (TCM), have not yet been clarified. In the present study, network pharmacology was adopted to analyze the potential molecular mechanism, and therapeutic effective components of QHSSD on both OA and RA. A total of 153 active ingredients in QHSSD were identified, 142 of which associated with 59 potential targets for the two diseases were identified. By constructing the protein-protein interaction network and the compound-target-disease network, 72 compounds and 10 proteins were obtained as the hub targets of QHSSD against OA and RA. The hub genes of ESR1, PTGS2, PPARG, IL1B, TNF, MMP2, IL6, CYP3A4, MAPK8, and ALB were mainly involved in osteoclast differentiation, the NF-κB and TNF signaling pathways. Moreover, molecular docking results showed that the screened active compounds had a high affinity for the hub genes. This study provides new insight into the molecular mechanisms behind how QHSSD presents homotherapy-for-heteropathy therapeutic efficacy in both OA and RA. For the first time, a two-disease model was linked with a TCM formula using network pharmacology to identify the key active components and understand the common mechanisms of its multi-pathway regulation. This study will inspire more innovative and important studies on the modern research of TCM formulas.

Sperm Protein Antigen 17 Expression Correlates With Lymph Node Metastasis and Worse Overall Survival in Patients With Breast Cancer.

Purpose: The expression and role of sperm protein antigen 17 (SPA17), which has been confirmed to be immunogenic, in breast cancer remain unclear. We examined the expression of SPA17 in breast cancer and assessed its effect on patient prognosis and its function in breast cancer development. Methods: SPA17 expression was evaluated by immunohistochemistry and Q-RT-PCR in 120 breast tissue samples. Correlation of SPA17 expression with the patients' clinicopathological parameters and overall survival was assessed. The function of SPA17 was also explored. Results: By reviewing Gene Expression Omnibus datasets, we found that SPA17 expression in ductal breast carcinoma in situ (log2[fold change] = 1.14, p-value = 0.004) and invasive ductal breast cancer (log2[fold change] = 1.03, p-value = 0.016) tissues was 2.20 and 2.05 times higher, respectively, than that in normal breast tissues. Our result also showed that 27% (27/100) of breast cancer samples expressed SPA17 but none of the normal breast (0/20) samples did. Lymph node metastasis (p < 0.001) and molecular subtyping (p = 0.002) were independent factors associated with SPA17 expression. Most importantly, SPA17 expression resulted in poor prognosis. In addition, cell function assay validated that SPA17 increased the migration (p < 0.001) and invasion (p = 0.007) of breast cancer cells, but not affected the proliferation of breast cancer cells. Conclusion: Our results demonstrated the vital role of SPA17 in the development and metastasis of breast cancer and that SPA17 may be a new therapeutic target in improving breast cancer prognosis.

Underestimated risk from ozonation of wastewater containing bromide: Both organic byproducts and bromate contributed to the toxicity increase.

Ozonation is widely used in wastewater treatment but the associated byproduct formation is a concern. When ozonation is used in the presence of bromide, bromate is generally considered as a major byproduct, and few studies have examined the toxicity of organic byproducts. This study was designed to investigate the cytotoxicity, genotoxicity and DNA/RNA oxidative damage to Chinese hamster ovary (CHO) cells of organic extracts from ozonated wastewater in the absence or presence of bromide. Ozonation effectively detoxified secondary effluents containing no bromide. However, ozonation significantly increased the cytotoxicity and genotoxicity of the effluents spiked with a bromide concentration as low as 100 µg/L, compared with the bromide-free effluent. When the bromide concentration in the effluent was increased to 2000 µg/L, ozonation resulted in 1.4-1.5 times the cytotoxicity and 1.5-5.0 times the genotoxicity of the non-ozonated secondary effluent. Besides, the oxidative stress (including reactive oxygen species and reactive nitrogen species) and DNA/RNA oxidative damage also became more severe and a high level of 8-hydroxy-(deoxy)guanosine was detected in the CHO cell nucleus in the presence of bromide. Cytotoxicity and genotoxicity were found to increase with the formation of total organic bromine (TOBr). When the CHO cells were exposed to both the organic byproducts and bromate formed from wastewater containing 500 and 2000 µg/L bromide, bromate significantly increased oxidative stress and DNA/RNA oxidative damage at relatively high concentration factors, suggesting both organic byproduct and bromate can contribute to toxicity increase. During ozonation of the effluent containing bromide, particular attention should be paid to the organic byproducts such as TOBr.