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SOCS3 is low-expressed in breast cancer and may be a potential target. Ultrasound targeted microbubble destruction (UTMD) improved the efficiency of gene transfection. We explored the effects of UTMD-mediated transfection of SOCS3 on the biological characteristics and epithelial-mesenchymal transition (EMT) of breast cancer stem cells (BCSCs). The expression of SOCS3 in breast cancer (BC) and its association with prognosis were evaluated by GEPIA and The Cancer Genome Atlas (TCGA) websites. BCSCs were sorted by flow cytometry and immunomagnetic bead method, followed by sphere formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and xenograft assays to test their effects in vitro and in vivo. The levels of SOCS3, EMT- and STAT3 pathway-related genes were determined by RT-qPCR and Western blot, respectively. The effects of liposome and UTMD on BCSCs and mice were compared by the gain-of-function experiments. Low expression of SOCS3 was associated with poor prognosis of BC patients, and found in BC and BCSCs. BCSCs were successfully sorted, with high viability and tumorigenicity. UTMD increased the transfection rate of SOCS3. Moreover, UTMD- and liposome-mediated SOCS3 reduced cell viability, proliferation, migration and invasion, blocked cell cycle, inhibited sphere formation in BCSCs, and retarded tumor growth in mice. Mechanistically, overexpressed SOCS3 inhibited the expressions of EMT-related genes and the activation of STAT3 pathway in BCSCs and mice. The regulatory effects of UTMD-mediated SOCS3 on the above-mentioned biological characteristics were better than liposome-mediated SOCS3. UTMD-mediated SOCS3 has a better therapeutic effect in BC, providing new experimental evidence for the treatment of BC.

Cadmium (Cd) is a toxic heavy metal, exposure to which leads to various adverse health effects including chronic kidney damage. Tremendous efforts have been explored in identifying safe chelating agents for removing accumulated Cd from kidney, but with limited success owing to their associated side effects and the ineffectiveness in eliminating Cd from the body. A newly developed chelating agent, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4(methylthio)butanoate (GMDTC), has been shown to effectively mobilize Cd from kidney. However, the mechanism(s) of removal are unclear, while it has been hypothesized that renal glucose transporters potentially play key roles mainly because GMDTC contains an open chain glucose moiety. To test this hypothesis, we utilized the CRISPR/Cas9 technology and human kidney tubule HK-2 cells, and constructed sodium-dependent glucose transporter 2 (SGLT2) or glucose transporter 2 (GLUT2) gene knockout (KO) cell lines. Our data showed that GMDTC’s ability in removing Cd from HK-2 cells was significantly reduced both in GLUT2-/- or SGLT2-/- KO cells, with a removal ratio reduced from 28.28% in the parental HK-2 cells to 7.37% in GLUT2-/- KO cells and 14.6% in SGLT2-/- KO cells. Similarly, knocking out the GLUT2 or SGLT2 gene led to a compromised protective effect of GMDTC in reducing cytotoxicity of HK-2 cells. This observation was further observed in animal studies, in which the inhibition of GLUT2 transporter by phloretin treatment resulted in a reduced efficiency of GMDTC in removing Cd from the kidney. Altogether, our results show that GMDTC is safe and highly efficient in removing Cd from the cells, and this effect is mediated by renal glucose transporters.

Background The benefit of axillary lymph node dissection (ALND) in breast cancer patients with one or two positive sentinel lymph nodes (SLNs) remains inconclusive. The purpose of this study was to identify risk factors independently associated with axillary lymph node (ALN) metastasis. Methods We retrospectively analyzed data from 389 Chinese breast cancer patients with one or two positive SLNs who underwent ALND. Univariate and multivariate logistic regression analyses were performed to identify ALN metastasis-associated risk factors. Results Among the 389 patients, 174 (44.7%) had ALN metastasis, while 215 (55.3%) showed no evidence of ALN metastasis. Univariate analysis revealed significant differences in age (P P Conclusions The risk of ALN metastasis in breast cancer patients with one or two positive SLNs can be further increased by younger age, manual labor jobs, and a high ratio of positive to total SLNs. Our findings may also aid in identifying which patients with one or two positive SLNs may not require ALND.

Purpose Breast cancer (BC) is the most common malignant cancer in women worldwide. Recently, long non-coding RNAs (LncRNAs) have been reported to have essential roles in BC tumorigenesis. Patients and methods Tumor and adjacent non-tumor tissue samples were collected from patients with BC (n = 168) for comparison of LncRNA and miRNA expression levels. Patient clinical, demographic, and molecular data were analyzed by univariate and multivariate methods to identify factors associated with patient survival, and a nomogram was generated using significant risk/protective factors. Further, analyses of LINC00461 and miR-411-5p expression and function were conducted in BC and normal breast epithelial cell lines, by quantitative RT-PCR, cell proliferation, wound-healing, RNA pull-down, RNA immunoprecipitation, and luciferase assays. Docetaxel (DTX)-resistant BC cell lines were also generated and used to assess the roles of LINC00461 and miR-411-5p in drug resistance. Results LINC00461 was up-regulated in BC tissues relative to adjacent non-tumor samples, and expression of LINC00461 was correlated with poor patient prognosis. LINC00461 knockdown could inhibit proliferation of BC cells in vitro. Further, LINC00461 expression was higher in DTX-resistant than in non-resistant BC cell lines. Our data support a role for LINC00461 as a competitive endogenous RNA sponge involved in regulation of miR-411-5p expression in BC. miR-411-5p was down-regulated in both BC tissues and cell lines, with levels negatively correlated with those of LINC00461. Moreover, miR-411-5p was down-regulated in DTX-resistant BC cell lines compared with non-resistant cell lines. Conclusion In conclusion, LINC00461 promotes proliferation, migration, and DTX-resistance in BC by acting as a sponge for miR-411-5p. This process represents a potential therapeutic target for patients with BC.

The characteristics of dust coagulation process in gravitational direction are investigated in an ethylene RF (radio frequency) discharge plasma system. The experiment shows that dust particles can aggregate into the huge fractal structure (centimeter scale). The coagulation process is mainly characterized by the scattering laser intensity, the distribution of dust clouds, and the fractal dimension. In this experiment, the rotational characteristics of the huge fractal structure can be observed and investigated by the oscillation of the scattering spectrum. These results provide an experimental basis for the investigation of dust coagulations.

As an aggressive breast cancer (BCa) subtype, triple-negative breast cancer (TNBC) responses poorly to chemotherapy and endocrine therapy, and usually has a worse prognosis. This is largely due to the lack of specific therapeutic targets, laying claim to an imperious demand to clarify the key signaling pathways potentiating TNBC progression. Herein, we report that expression levels of the liver-specific bHLH-Zip transcription factor (LISCH7), a recently identified key player in cancerous progression, preferentially enriched in TNBC in comparison with other BCa subtypes, and this upregulation was observed to be correlated to a poor survival outcome in patients with TNBC. Ablation of LISCH7 in TNBC cells impaired cell proliferation, reduced cell invasiveness, and enhanced sensitivity to the first-line chemotherapeutic drug docetaxel at both in vitro and in vivo levels. Importantly, concurrent induction of TGFB1, the gene encoding transforming growth factor-β1 (TGF-β1), an essential multipluripotent regulator of TNBC, was accompanied with these alterations in cancerous properties. We further showed that LISCH7 could directly bind to the TGFB1 promoter and stimulate TGFB1 transcription in TNBC cells. The recruitment of LISCH7 onto the TGFB1 chromatin and transactivation of TGFB1 were substantially augmented by treatment with the exogenous TGF-β1 in a time- and dose-dependent manner. Collectively, these findings suggest that LISCH7 and TGF-β1 form a reciprocal positive regulatory loop and cooperatively regulate cancerous progression in TNBC cells. Thus, simultaneous inhibition of both LISCH7 and TGF-β1 signaling may represent a more effective approach to counteract advanced TNBC.

Cancer remains one of the top culprits causing disease-related deaths. A lack of effective multi-cancer therapeutic targets has limited the prolongation of cancer patients’ survival. Therefore, it is important to explore novel oncogenic genes or versatile targets and perform a comprehensive analysis to assess their roles in the process of tumorigenesis. OSBPL3 protein is an intracellular lipid receptor of the oxysterol-binding protein superfamily, which participates in some pathological and physiological processes in tumor progression. However, its clinical roles and potential mechanisms in cancers remain unknown. Thus, we aimed to systematic explore the potential oncogenic roles of OSBPL3 across thirty-three tumors using multiple web-based and publicly available tools, including the Cancer Genome Atlas, Gene Expression Omnibus, Genotype-Tissue Expression, cBioPortal, and Human Protein Atlas database. OSBPL3 is highly expressed in major subtypes of cancers, distinctly associated with the prognosis of tumor patients. We observed X676_splice/V676G alteration in the oxysterol domain and frequent mutations of OSBPL3 involve cell survival in skin cutaneous melanoma. We also first presented that the expression of OSBPL3 was associated with tumor mutational burden (TMB) in nine cancer types. Additionally, OSBPL3 shows an enhanced phosphorylation level at S426, S251, and S273 loci within the pleckstrin homology domain in multiple tumors, such as breast cancer or lung adenocarcinoma. And OSBPL3 expression was associated with active immune cells (CD8+ T cells) and cancer-associated fibroblasts in breast cancer, colon adenocarcinoma, and kidney renal clear cell carcinoma and immune checkpoint genes in more than 30 tumors, but weakly associated with immune suppressive cells (myeloid-derived suppressor cells, T regulatory cells). Moreover, protein processing and mRNA metabolic signaling pathways were involved in the functional mechanisms of OSBPL3. Our study first demonstrated that a novel agent OSBPL3 plays an important role in tumorigenesis from the perspective of publicly available databases and clinical tumor samples in various cancers, which comprehensively provide insights into its biological functions and may be helpful for further investigation.

OBJECTIVES: The objective of our study was to evaluate the association between occupational exposure to trichloroethylene (TCE), a suspected lymphomagen, and serum levels of miRNAs in a cross-sectional molecular epidemiology study of TCE exposed workers and comparable unexposed controls in China. METHODS: Serum levels of 40 miRNAs were compared in 74 workers exposed to TCE (median: 12 ppm) and 90 unexposed control workers. Linear regression models were used to test for differences in serum miRNA levels between exposed and unexposed workers and to evaluate exposure-response relationships across TCE exposure categories using a three-level ordinal variable (i.e., unexposed

With the rapid development of 4G/5G technology and the Internet of Things (IoT), data security and privacy problems are becoming more serious. Wireless sensor networks (WSNs), as the main data source of IoT, are an important stage to ensure data availability and data privacy protection. In this paper, a novel deployment algorithm for 3D WSNs based on the Voronoi diagram is proposed. The algorithm uses the characteristics of adjacency and fast partition of the Voronoi diagram to realize fast division of the 3D monitoring area, calculates the center of each Voronoi area as the latest position of node, repeatedly builds the Voronoi diagram to maximize the coverage of the monitoring area, and maximizes the availability and integrity of data. At the same time, the 4G/5G communication technology is used to realize communication between nodes, and data encryption is used to improve data security. An improved algorithm is also proposed to adapt to different deployment conditions. In this paper, data and privacy security are protected from data sources, and the effectiveness of the algorithm is tested by computer simulation.

Immunochromatographic strips (ICSs) are inexpensive, simple, portable, and robust, and therefore have many uses in the medicinal, agricultural, and environmental industries. For detection of small molecules, current ICSs are competitive format (competitive ICSs, CICSs), which only offer a turn-off readout mode, and therefore lead to low sensitivity when evaluating results by the naked eye. To overcome this problem, we report a turn-on CICSs that relies on the ability of gold nano-stars (AuNSs) quenching the signal of quantum dots (QDs). This turn-on CICSs device was applied to detect cadmium ions (Cd2+). The linear detection range (LDR) of the turn-on CICSs was 0.25ng/mL-8ng/mL, and the detection of limit (LOD) was 0.18ng/mL. Compared with traditional turn-off CICSs, the sensitivity of the turn-on CICSs was enhanced by 32 times. The turn-on CICSs also has a high specificity and high recovery for the detection of Cd2+ in Pearl River (95-112%) and tap water samples (103.5-116.67%). Therefore, we believe the turn-on CICSs offers great potential for the detection of other small molecules in clinical diagnostics, food safety investigations, and environment pollution monitoring.

Background: Parkinson’s disease (PD) is a degenerative disorder of the central nervous system mainly affecting the motor system. Presently, there is no effective and safe drug to treat patients with PD. Ginkgo biloba extract (GBE), obtained from leaves of the Ginkgo biloba tree, is a complex mixture of ingredients primarily containing two active components: flavonoids and terpenoids. In this study, we investigated the effects of GBE on A53T α-synuclein transgenic mice, a PD model that has better simulated the progression of PD patients than other models such as the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine–induced PD model. Methods: Fifty α-synuclein A53T transgenic mice were fed and treated with GBE, and locomotor activity was detected by pole test, forced swim test, and wire-hang test. The expression of tyrosine hydroxylase and dopamine transporters was detected using immunohistochemistry. Superoxide dismutase activity, glutathione peroxidase activity, and malondialdehyde expression were detected using an assay kit. Results: Our results show that GBE treatment improved locomotor activity and that superoxide dismutase and glutathione peroxidase inhibited the expression of methane dicarboxylic aldehyde and recovered the expression of tyrosine hydroxylase and dopamine transporters. Conclusions: The GBE treatment improved locomotor activity and inhibited the development of PD in the A53T α-synuclein transgenic mice, which may be partly responsible for decreased oxidative damage and maintain the normal dopamine homeostasis.

The Fry gene, located on chromosome 13, is an evolutionarily conserved large protein from yeast to human. Our previous study genetically linked the Fry gene with differential susceptibility to mammary carcinogenesis, but whether Fry affects mammary gland development and function, as well as the growth of breast cancer cells, is largely unknown. To define the consequences of Fry loss in the mammary glands, we have generated mice conditionally deficient of the Fry gene in the mammary glands using the Cre-loxP recombination system. We examined multiple phenotypes with male and female homozygous Fry conditional knockout mice (Mfry) and control mice (WT), including body weight, preliminary observations (health and neurological flexes), open field locomotion, sensory abilities, auditory threshold, and glucose metabolism. The loss of Fry in the mammary glands didn't cause a significant difference in these genotypes between Mfry and WT mice. However, our data showed that Fry was required during pregnancy, while it was functionally dispensable in virgin mammary gland development. Loss of Fry led to more lateral buds, and the lobuloalveoli were smaller and showed undistended morphology in mammary glands during late pregnancy. in vitro experiment, ectopic expression of FRY could alter the morphology and significantly suppress the growth and proliferation of the breast cancer cell lines, MDA-MB-231 (ER-/PR-/HER2-, Basal-like) and BT474 (ER+/PR+/HER2+, Luminal B). The following genome-wide transcriptomic analysis of these cells suggested that FRY interacted with protein kinases relevant signaling pathways and induced massive changes in gene expression, including the activation of the Hippo/Yap pathway. Together, our data suggest that the FRY is required for mammary glands developments during pregnant periods, and affects breast cancer cell growth and proliferation.

Human exposure to trichloroethylene (TCE) is linked to kidney cancer, autoimmune diseases, and probably non-Hodgkin lymphoma. Additionally, TCE exposed mice and cell cultures show altered DNA methylation. To evaluate associations between TCE exposure and DNA methylation in humans, we conducted an epigenome-wide association study (EWAS) in TCE exposed workers using the HumanMethylation450 BeadChip. Across individual CpG probes, genomic regions, and globally (i.e., the 450K methylome), we investigated differences in mean DNA methylation and differences in variability of DNA methylation between 73 control (< 0.005 ppm TCE), 30 lower exposed (< 10 ppm TCE), and 37 higher exposed ( ≥ 10 ppm TCE) subjects' white blood cells. We found that TCE exposure increased methylation variation globally (Kruskal-Wallis p-value = 3.75e-3) and in 25 CpG sites at a genome-wide significance level (Bonferroni p-value < 0.05). We identified a 609 basepair region in the TRIM68 gene promoter that exhibited hypomethylation with increased exposure to TCE (FWER = 1.20e-2). Also, genes that matched to differentially variable CpGs were enriched in the 'focal adhesion' biological pathway (p-value = 2.80e-2). All in all, human exposure to TCE was associated with epigenetic alterations in genes involved in cell-matrix adhesions and interferon subtype expression, which are important in the development of autoimmune diseases; and in genes related to cancer development. These results suggest that DNA methylation may play a role in the pathogenesis of TCE exposure-related diseases and that TCE exposure may contribute to epigenetic drift.

Cisplatin is a platinum-based chemotherapeutic drug widely used in the treatment of various cancers such as testicular, ovarian, lung, bladder, and cervical cancers. However, its use and the dosage range applied have been limited by severe side effects (e.g., nephrotoxicity and ototoxicity) and by the development of resistance to cisplatin in patients during treatment. Metal chelators have shown promising potential in overcoming these problems often associated with platinum drugs. Previously, a new chelating agent, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)-4(methylthio)butanoate (GMDTC), was developed. In this study, we examined the effect of GMDTC in modifying cisplatin-induced toxicities following in vitro and in vivo exposures. GMDTC treatment dramatically reduced cisplatin-induced apoptosis and cytotoxicity in HK2 cells by decreasing the amount of intracellular platinum. In the 4T1 breast cancer mouse model, GMDTC reduced cisplatin-induced nephrotoxicity by reducing cisplatin deposition in the kidney. GMDTC attenuated cisplatin-induced elevations in blood urea nitrogen and plasma creatinine, ameliorated renal tubular dilation and vacuolation, and prevented necrosis of glomeruli and renal tubular cells. GMDTC also inhibited cisplatin-induced ototoxicity as shown by improved hearing loss which was assessed using the auditory brainstem response test. Furthermore, GMDTC attenuated cisplatin-induced hematotoxicity and hepatotoxicity. Importantly, co-treatment of cisplatin with GMDTC did not affect cisplatin antitumor efficacy. Tumor growth, size, and metastasis were all comparable between the cisplatin only and cisplatin-GMDTC co-treatment groups. In conclusion, the current study suggests that GMDTC reduces cisplatin-induced systemic toxicity by preventing the accumulation and assisting in the removal of intracellular cisplatin, without compromising cisplatin therapeutic activity. These results support the development of GMDTC as a chemotherapy protector and rescue agent to overcome the toxicity of and resistance to platinum-based antineoplastic drugs.

The number of shared bicycles is large and the parking is not standardized. Accurate position prediction of the bicycle can effectively prevent the collision between the number of vehicles and the parking position. The traditional machine learning algorithm is slowly to process and can not meet the accuracy requirements. Therefore, the Boosting algorithm which promote the weak learner to a strong learner is adopted to enhance running speed and accuracy. At the same time, the way of constructing feature groups is proposed, and the importance of features is evaluated. The comparison experiment compares the prediction capabilities of the three Boosting algorithms, XGboost, LightGBM and Catboost. The example verification shows that the LightGBM algorithm has the highest test accuracy, and then this algorithm is used to predict the dynamic distribution of the Mobike in Beijing throughout the day. And show the heat distribution map of the prediction results of Mobike in different time periods.

Chemotherapy is the predominant treatment option for patients with breast cancer. Selection of patients according to biomarker will improve chemotherapy efficacy. In the present study, we examined the relations of the expression of candidate genes and 21-recurrence score (RS) results to patients' demographic characteristics, histopathological factors, and outcomes.A total of 146 patients were enrolled in this study. The patients underwent 21-gene RS testing. In addition, expressions of candidate genes, TYMS, RRM1, TUBB3, TOP2A, PTEN, were detected. Information was obtained on age, tumor size, TMN stage, tumor grade, and status of Ki-67, HER2, ER and PR. The treatment information on the type of endocrine therapy was also obtained.Results clearly showed that the 21-gene RS significantly correlated with the TNM stage of breast cancer (P = 0.047). The RS also correlated with the number of sentinel lymph node (P = 0.038). The pathological type of tumors was strongly associated with the expression of RRM1 (P 0.015), and slightly correlated with TYMS (P = 0.095) and tumor size (P = 0.061). Further analysis showed that TYMS and RRM1 were two independent factors affecting the disease progression of patients. Besides, for HER-2 stain, staining of grade 2 or above significantly increased the risk of disease progression.Our studies showed that TNM stage and sentinel lymph node were important clinical parameters correlated with 21-gene RS results. Also, RRM1, TYMS and HER2 expressions were independent factors associated with disease progression in breast cancer patients. Future study is warranted to investigate the usefulness of these genes in treatment efficacy.

For the node deployment problem in three-dimensional heterogeneous sensor networks, the traditional virtual force method is prone to local optimization and the parameters required for calculation are uncertain. A spatial deployment algorithm for 3D mobile wireless sensor networks based on weighted Voronoi diagram is proposed (TDWVADA) to solve the problem. Based on the positions and weights of all nodes in the monitoring area, a three-dimensional weighted Voronoi diagram is constructed. Next, the central position of each node’s the Voronoi region is calculated and the position is regarded as target position of the node movement. Each node moves from the original position to the target position to complete one iteration. After multiple iterations, each node is moved to the optimal deployment location and network coverage is improved. In view of the initial centralized placement of sensor nodes, the addition of virtual force factors is added to the TWDVDA algorithm. An improved algorithm TDWVADA-I was proposed. The algorithm enables nodes that are centrally placed to spread quickly and speeds up deployment. The simulation results show that TDWVADA and TDWVADA-I effectively improve the network coverage of the monitored area compared to the virtual force algorithm and the unweighted Voronoi method. Compared with the virtual force method, the coverage of TDWVADA has increased from 90.53% to 96.70%, and the coverage of TDWVADA-I has increased from 81.12% to 96.56%. Compared with the Voronoi diagram method, the coverage of TDWVADA has increased from 85.01% to 96.70%, and the coverage of TDWVADA-I has increased from 80.82% to 96.56%. TDWVADA and TDWVADA-I also greatly reduce the energy consumption of the network. Experimental results demonstrate the effectiveness of the algorithms.

Accumulated evidence indicates that aberrant microRNAs (miRNAs) expression plays an important role in the initiation and progression of various cancers, including breast cancer. Previous studies suggested that miR‑139‑3p might serve as a tumor suppressor and is downregulated in several cancer types. However, the expression patterns and exact role of miR‑139‑3p in breast cancer remain to be elucidated. In this study, we aimed to analyze the effect of miR‑139‑3p on the progression of breast cancer and the mechanism involved. Through bioinformatics analysis and in vitro experimental studies, we found that miR‑139‑3p was decreased in breast cancer tissues and cell lines, and decreased miR‑139‑3p is associated with a poor prognosis in breast cancer patients. Overexpression of miR‑139‑3p by transfection significantly inhibits cell proliferation, migration, and invasion of breast cancer cells. Bioinformatics analysis and luciferase reporter gene assay confirmed that RAB1A was a potential target of miR‑139‑3p. Furthermore, overexpression of RAB1A counteracted the suppressing effects of miR‑139‑3p on breast cancer cell migration, invasion and epithelial‑to‑mesenchymal transition (EMT). Taken together, these data suggest that miR‑139‑3p plays a tumor suppressive role in breast cancer by targeting RAB1A and may serve as a potential new biomarker for breast cancer prognosis.

Plasma cell mastitis (PCM) is a special form of mastitis characterized by periductal inflammation and large-scale plasma cell infiltration. At present, the recurrence rate of PCM after excision is quite high, making PCM a major problem for mammary surgeons. However, no effective drug exists for the treatment of PCM. Numerous studies have demonstrated that Sinomenine hydrochloride (SH) has potent anti-inflammatory and immunoregulatory properties. However, the efficacy and the underlying mechanisms of SH in the treatment of PCM remain unclear. In the present study, we first investigated the therapeutic effects of SH in the PCM mouse model and clarified the possible mechanisms. We found that the levels of plasmocytes and lymphocytes infiltration were alleviated significantly in the 100 mg/kg SH group compared to the control group. In addition, few CD138+ plasma cells were found in the mammary glands of the 100 mg/kg SH group. The levels of Bcl-2 in the 100 mg/kg SH group were dramatically decreased compared with those in the saline group. Mechanistically, we demonstrated that SH inhibited the progression of PCM mainly through downregulating IL-6/JAK2/STAT3 levels. Collectively, our results suggested that SH could inhibit the progression of PCM by suppressing IL-6/JAK2/STAT3 cascades and ultimately achieve a therapeutic effect in PCM. This study provides theoretical support for the clinical application of SH in the treatment of PCM.

Plasma cell mastitis (PCM) is a chronic mastitis with limited treatment options and common recurrence. A histopathological hallmark of PCM is the infiltration of numerous plasma cells surrounding the mammary duct. Our previous study showed that the activity of the IL-6/STAT3 signaling pathway was elevated in patients with PCM. However, the etiology of PCM remains largely unclear. In this study, we sought to explore the effects of IL-6/JAK2/STAT3 signaling pathway in the pathogenesis of PCM. Histological analysis showed that the mammary glands of mice that received human breast tissue homogenates, followed by an injection of IL-6, exhibited features of PCM similar to human PCM. The IL-6/JAK2/STAT3 signaling activity was significantly elevated and Bcl-2 was highly expressed in CD138 + plasma cells in the mammary glands of mice with PCM. Furthermore, treatment with AG-490, an inhibitor of JAK family kinases, suppressed activation of the IL-6/JAK2/STAT3 signaling cascade, in turn resulting in a decreased number of plasma cells in the mammary gland and reversing the pathogenesis of PCM. Taken together, our study indicated that a PCM mouse model was successfully established through activation of the IL-6/JAK2/STAT3 pathway by injecting IL-6 into the mammary gland of mouse that had received homogenates of human breast tissue. Thus, the IL-6/JAK2/STAT3 signaling pathway plays a critical role in orchestrating the pathogenesis of PCM.

Even though early detection methods and treatment options are greatly improved, chemoresistance is still a tremendous challenge for breast cancer therapy. Breast cancer stem cells (BCSCs) represent a subpopulation that is central to chemoresistance. We aim to investigate the relationship between SLC34A2 and chemoresistance in BCSCs and identify the underlying mechanisms by which SLC34A2 regulates chemoresistance in BCSCs. Fluorescence Activated Cell Sorting (FACS) analysis showed the presence of a variable fraction of CD44(+)CD24(-) cells in 25 out of 25 breast cancer samples. We cultured primary breast cancer sample cells and breast cancer cell line cells to induce sphere formation in serum-free medium. Following sorting of CD44(+)CD24(-) cells from spheres, we showed that CD44(+)CD24(-) cells displayed stem cell-like features and were resistant to chemotherapy drug doxorubicin. Significantly, enhanced SLC34A2 expression correlated with chemoresponse and survival of breast cancer patients. We subsequently indicated that increased SLC34A2 expression in BCSCs directly contributed to their chemoresistance by a series of in vitro and in vivo experiments. Furthermore, we demonstrated that SLC34A2 induced chemoresistance in BCSCs via SLC34A2-Bmi1-ABCC5 signaling. Finally, we showed that ABCC5 was a direct transcriptional target of Bmi1 by chromatin immunoprecipitation (ChIP). In conclusion, our work indicated that decreased SLC34A2 expression sensitized BCSCs to doxorubicin via SLC34A2-Bmi1-ABCC5 signaling and shed new light on understanding the mechanism of chemoresistance in BCSCs. This study not only bridges the missing link between stem cell-related transcription factor (Bmi1) and ABC transporter (ABCC5) but also contributes to development of potential therapeutics against breast cancer.

In three-dimensional space, the traditional algorithm of virtual force applies to continuous target tracking process is prone to problems of distraction and short time in keeping tracking of the target in the process of. This paper proposed a three-dimensional space deployment algorithm applies to continuous target tracking to solve these problems. The combine virtual force in this algorithm is generated by the inter-node force, the obstacle repulsive force, monitored-path attractive force and the tracking target together. It makes the target path covering evenly, continuous and sustained. Moreover, remove the "coverage holes" caused by following the continuous target. Performance of simulations show that, this algorithm obtains obvious improvement in continuous target tracking compared to the traditional virtual force, as it enhanced the effective time of tracking process and shorten the time of losing target.

Increasing evidence confirms that aberrant miRNA expression contributes to breast cancer (BC) development and progression. However, the roles of different miRNAs in BC remain to be explored. In the present study, we demonstrated that miR-1297 expression was increased in BC tissues and cell lines. Our clinical analysis revealed that the upregulated miR-1297 expression was significantly correlated with poor prognostic features including advanced TNM stage and larger tumor size. Moreover, we found that miR-1297 was a novel independent prognostic marker for predicting 5-year survival of BC patients. The ectopic overexpression of miR-1297 promoted cell proliferation, cell cycle progression and inhibited apoptosis while miR-1297 knockdown reversed the effect. In addition, miR-1297 modulated PTEN by directly binding to its 3'-UTR, resulting in activation of AKT signaling. In clinical samples of BC, miR-1297 inversely correlated with PTEN, which was downregulated in BC. Alternation of PTEN expression or AKT inhibitor at least partially abolished the biological effects of miR-1297 on BC cells. In conclusion, our results indicated that miR-1297 functioned as an oncogene in regulating the proliferation, cell cycle and apoptosis of BC via targeting PTEN/PI3K/AKT signaling, and may represent a novel potential therapeutic target and prognostic marker for BC.

Contrast to the two-dimensional directional sensor networks, the three-dimensional directional sensor networks increases complexity and diversity. External environment and sensor limitations impact the target monitoring and coverage. Adjustment strategies provide better auxiliary guide in the process of self-deployment, while strengthen the monitoring area coverage rate and monitoring capability of sensor nodes. We propose a path self-deployment algorithm TPSA (Three-dimension Path Self-Deployment Algorithm) based on above issues. The concept of virtual force extends from two-dimensional to three-dimensional, includes target path control. The node gets locational information about monitoring target and target path in the initialization, calculates the virtual force of them, finally obtains the next movement location and direction. We analyse the process of self-deployment of both static and polymorphic nodes. The simulation results verify the proposed algorithm enables better node control in the deployment process, and improves the efficiency of the sensor node deployment.

To evaluate the immunotoxicity of trichloroethylene (TCE), we conducted a cross-sectional molecular epidemiology study in China of workers exposed to TCE. We measured serum levels of IL-6, IL-10, and TNF-α, which play a critical role in regulating various components of the immune system, in 71 exposed workers and 78 unexposed control workers. Repeated personal exposure measurements were taken in workers before blood collection using 3 M organic vapor monitoring badges. Compared to unexposed workers, the serum concentration of IL-10 in workers exposed to TCE was decreased by 70% (P = 0.001) after adjusting for potential confounders. Further, the magnitude of decline in IL-10 was >60% and statistically significant in workers exposed to

Nephrolithiasis (kidney stones) is a common disease with the prevalence that is increasing globally. We previously found that trimethyltin (TMT), a by-product of plastic stabilisers, can inhibit the H(+)/K(+) ATPase activity in renal intercalated cells and alter urinary pH, which is a known risk factor for nephrolithiasis. In this study, we conducted a cross-sectional analysis to evaluate the impact of chronic low level occupational TMT exposure on nephrolithiasis.This study included 216 healthy workers with TMT exposure and 119 workers as controls with no TMT exposure. All study participants were administered a questionnaire and underwent a routine clinical examination including an ultrasonographic screening for kidney stones. Exposures were assessed by measuring TMT concentrations in personal air samples, blood and urine. Logistic regression analysis was used to estimate the ORs and 95% CIs for the risk of kidney stones.TMT exposed workers had a higher prevalence of kidney stones (18.06%) in comparison with control workers (5.88%). High TMT concentrations in personal air samples, blood and urines were positively associated with increased prevalence of kidney stones in workers exposed to TMT compared with controls workers (p-trend values=0.005, 0.008 and 0.002, respectively). The length of employment in plants with elevated TMT levels (duration of the exposure) was significantly associated with the increased prevalence of kidney stones (p trend=0.001). The ORs were 2.66 for3 years, 3.73 for 3-10 years and 7.89 for 10+ years of employment compared with control workers.To our knowledge, this is the first report to demonstrate that occupational exposure to TMT is a potential risk factor for nephrolithiasis.

Trichloroethylene (TCE) has been associated with a variety of immunotoxic effects and may be associated with an increased risk of non-Hodgkin lymphoma (NHL). Altered serum immunoglobulin (Ig) levels have been reported in NHL patients and in animals exposed to TCE. Recently, we reported that occupational exposure to TCE is associated with immunosuppressive effects and immune dysfunction, including suppression of B-cell counts and activation, even at relatively low levels. We hypothesized that TCE exposure would also affect Ig levels in humans. We measured serum levels of IgG, IgM and IgE, by enzyme-linked immunosorbent assay, in TCE-exposed workers (n = 80) and unexposed controls (n = 45), matched by age and gender, in a cross-sectional, molecular epidemiology study of occupational exposure to TCE in Guangdong, China. Exposed workers had about a 17.5% decline in serum levels of IgG compared with unexposed controls (P = 0.0002). Similarly, serum levels of IgM were reduced by about 38% in workers exposed to TCE compared with unexposed controls (P < 0.0001). Serum levels of both IgG and IgM were significantly decreased in workers exposed to TCE levels below 12 p.p.m., the median exposure level. Adjustment for B-cell counts had minimal impact on our findings. IgE levels were not significantly different between exposed and control subjects. These results provide further evidence that TCE is immunotoxic at relatively low exposure levels and provide additional biologic plausibility for the reported association of TCE with NHL.

// Xiao Li 1 , Pingping Li 2 , Chao Liu 3 , Yu Ren 1 , Xiaojiang Tang 1 , Ke Wang 1 , Jianjun He 1 1 Department of Breast Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China 2 Translational Medical Center, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China 3 Department of Vascular Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P.R. China Correspondence to: Jianjun He, email: chinahjj@163.com Ke Wang, email: 979915080@qq.com Keywords: sinomenine hydrochloride, breast cancer, metastasis, EMT, CSC Received: July 04, 2016 Accepted: January 03, 2017 Published: January 10, 2017 ABSTRACT Sinomenine hydrochloride (SH) has been investigated for its anti-tumor growth effect. We have previously reported that SH inhibited breast cancer cell proliferation via MAPKs signaling. However, whether SH could inhibit tumor metastasis has not been fully explored. In this study, we found that SH suppressed the metastasis potential of breast cancer cells. The wound healing and transwell assays showed that SH inhibited the migration and invasion ability of both 4T1 and MDA-MB-231 breast cancer cells. The orthotopic mouse model of 4T1 and the experimental mouse model of MDA-MB-231-luc (MDA-MB-231 cell line expressing firefly luciferase) demonstrated that SH treatment inhibited breast cancer metastasis by inhibiting epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties without obvious hepatotoxicity and renal toxicity. We also found that SH decreased spleen volume and weight in both mouse models, especially in the 4T1 mouse model. IL-6, a strong inflammatory factor causing EMT, was remarkably reduced. Overall, this anti-metastasis effect of SH could be possibly caused by attenuating inflammatory reaction, which led to inhibition of EMT and CSC characteristics of breast cancer cells. This study, together with our previous one, provides more evidence of SH as a potential drug for breast cancer therapy.

Trimethyltin chloride (TMT), a byproduct of plastic stabilizers, has caused 67 poisoning accidents in the world; more than 98% (1814/1849) of the affected patients since 1998 have been in China. As a long-established toxic chemical, TMT severely affects the limbic system and the cerebellum; however, its relationship with hypokalemia, a condition observed in the majority of the cases in the last decade, remains elusive. To understand the mechanism underlying hypokalemia induced by TMT, Sprague-Dawley (SD) rats were administered TMT to determine the relationship between H(+)/K(+)-ATPase activity and the blood and urine K(+) concentration and pH, respectively. H(+)/K(+)-ATPase protein and mRNA were observed too. In vitro changes to intracellular pH, K(+) channels in renal cells were measured. The results showed that TMT increased potassium leakage from the kidney, raised urine pH, and inhibited H(+)/K(+)-ATPase activity both in vitro and in vivo. In the tested animals, H(+)/K(+)-ATPase activity was positively correlated with the decrease of plasma K(+) and blood pH but was negatively correlated with the increase of urine K(+) and urine pH (P