BRD4L cooperates with MYC to block local tumor invasion via suppression of S100A10.

Targeted therapy based on BRD4 and MYC shows promise due to their well-researched oncogenic functions in cancer, but their tumor-suppressive roles are less understood. In this study, we employ a systematic approach to delete exons that encode the low-complexity domain (LCD) of BRD4L in cells by using CRISPR-Cas9. In particular, the deletion of exon 14 (BRD4-E14) results in cellular morphological changes towards spindle-shaped and loosely packed. BRD4-E14 deficient cells show increased cell migration and reduced cell adhesion. The expression of S100A10 was significantly increased in cells lacking E14. BRD4L binds with MYC via the E14-encoded region of the LCD to inhibit the expression of S100A10. In cancer tissues, there is a positive correlation between BRD4 and MYC, while both of these proteins are negatively associated with S100A10 expression. Finally, knocking out the BRD4-E14 region or MYC promotes tumor growth in vivo. Together, these data support a tumor-suppressive role of BRD4L and MYC in some contexts. This discovery emphasizes the significance of a discreetly design and precise patient recruitment in clinical trials that testing cancer therapy based BRD4 and MYC.

[Prognostic risk factors of catheter-related bloodstream infection in patients with maintenance hemodialysis].

OBJECTIVE: To analyze the pathogen distribution and prognostic risk factors of catheter-related bloodstream infection (CRBSI) in patients with maintenance hemodialysis (MHD) during non-hospitalization. METHODS: A retrospective comparative study was conducted. Thirty-four patients of MHD with semi-permanent catheter admitted to the department of nephrology of Gansu Provincial Hospital from January 2020 to May 2023 due to CRBSI during non-hospitalization were enrolled. The distribution characteristics of pathogens causing CRBSI in MHD patients during non-hospital period were analyzed. All patients were actively given anti-infection treatment after admission. The general data, laboratory indicators and prognosis during hospitalization were collected through the electronic medical record system. Patients were divided into poor prognosis group (14 cases) and good prognosis group (20 cases) according to the treatment results during hospitalization. Univariate and binary Logistic regression were used to analyze the risk factors affecting the prognosis of patients, and receiver operator characteristic curve (ROC curve) was drawn to evaluate its predictive value for prognosis. RESULTS: A total of 28 pathogenic bacteria were isolated from 34 patients, of which 25 were Gram-positive, Staphylococcus was the most common pathogen, accounting for 82.15% of the total, and 16 strains of Staphylococcus aureus (57.15%), including 6 methicillin-resistant Staphylococcus aureus (MRSA, 21.43%). There were 7 strains of Staphylococcus epidermidis (25.00%), including 3 strains of methicillin-resistant Staphylococcus epidermidis (MRSE, 10.71%). There were 3 strains of Gram-negative bacteria, 1 strain each of Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii. Univariate analysis showed that the fever duration of MHD patients with CRBSI in the poor prognosis group was significantly longer than that in the good prognosis group [days: 8.50 (3.75, 45.00) vs. 2.50 (1.00, 4.75), P < 0.01], serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and random blood glucose (GLU) were significantly higher than those in the good prognosis group [ESR (mm/1 h): 82.36±24.98 vs. 56.95±35.65, CRP (mg/L): 123.45±74.10 vs. 67.35±55.22, GLU (mmol/L): 8.74±3.66 vs. 6.42±1.95, all P < 0.05]. Binary Logistic regression analysis showed that serum CRP was an independent risk factor for poor prognosis in MHD patients with CRBSI [odds ratio (OR) = 1.020, 95% confidence interval (95%CI) was 1.002-1.038, P = 0.025]. ROC curve analysis showed that the area under the curve (AUC) of serum CRP in predicting poor prognosis of MHD patients with CRBSI was 0.711; when the optimal cut-off value was 104.65 mg/L, the sensitivity was 64.3% and the specificity was 85.0%, indicating that it has good predictive value. CONCLUSIONS: Gram-positive bacteria are the main pathogens of CRBSI in MHD patients during non-hospital period. The poor prognosis is mainly related to the high level of serum CRP. Serum CRP level can effectively screen the high-risk group of MHD patients with CRBSI with poor prognosis.

Coupling metal organic frameworks nanozyme with carbon nanotubes on the gradient porous hollow fiber membrane for nonenzymatic electrochemical H2O2 detection.

In this paper, we present a gradient porous hollow fiber structure integrated the signal transduction within a microspace, serving as a platform for cellular metabolism monitoring. We developed a nonenzymatic electrochemical electrode by coupling carbon nanotubes (CNT) and metal organic frameworks (MOF) nanozyme on three-dimensional (3D) gradient porous hollow fiber membrane (GPF) for in-situ detection of cell released hydrogen peroxide (H2O2). The GPF was used as a substrate for cell culture as well as the supporting matrix of the working electrode. The ultrasonically coupled CNT@MOF composite was immobilized on the outer surface of the GPF by means of pressure filtration. Notably, the MOF, acting as a peroxidase mimic, exhibits superior stability compared to traditional horseradish peroxidase. The incorporation of CNT not only provided sufficient specific surface area to improve the uniform distribution of MOF nanozyme, but also formed 3D conductive network. This network efficiently facilitates the electrons transfer during the catalytic process of the MOF, addressing the inherent poor conductivity of MOFs. The GPF-CNT@MOF nonenzymatic bioelectrode demonstrated excellent electrocatalytic performance including rapid response, satisfactory sensing selectivity, and attractive stability, which enabled the development of a robust in-situ cellular metabolic monitoring platform.

Modular coupling MOF nanozyme with natural enzyme on hollow fiber membrane for rapid and reusable detection of H2O2 and glucose.

A novel strategy based on gradient porous hollow fiber membrane (GPF) is proposed for the modular assembly of enzyme-nanozyme cascade systems. The porous structure of GPF provided sufficient specific surface area, while the gradient structure effectively minimized the leaching of enzymes and nanozymes. To enhance stability, we prepared and immobilized metal-organic framework (MOF) nanozymes, resulting in the fabrication of GPF-MOF with excellent stability and reusability for colorimetric H2O2 detection. To improve specificity and expand the detection range, micro-crosslinked natural enzymes were modularly assembled, using glucose oxidase as the model enzyme. The assembled system, GPF-mGOx@MOF, achieved a low detection limit of 0.009 mM and a linear range of 0.2 to 11 mM. The sensor retained 87.2% and 80.7% of initial activity after being stored for 49 days and 9 recycles, respectively. Additionally, the reliability of the biosensor was validated through glucose determination of human blood and urine samples, yielding comparable results to a commercial glucose meter.

The Impact of Information Infrastructure on Air Pollution: Empirical Evidence from China.

Information infrastructure construction has become an essential support for the new global technological revolution and industrial change. To examine whether information infrastructure can mitigate the level of air pollution, this paper measures the development level of information infrastructure in each region using the entropy-TOPSIS method based on the data of 31 Chinese provinces from 2013 to 2020. On this basis, it explores the impact of information infrastructure on atmospheric pollution and its mechanism using spatial measures and mediating effects. The results show that: (1) Information infrastructure can effectively improve air quality, though its spatial spillover effect is not obvious. (2) In addition to directly reducing air pollution, information infrastructure can also improve air quality by influencing industrial structure upgrading, or by influencing technological innovation first and then industrial structure upgrading. By exploring the impact of information infrastructure on air pollution and its action path, this paper expects to provide some scientific reference value for the construction of information infrastructure under the background of the new global technological revolution.

Construction of flexible enzymatic electrode based on gradient hollow fiber membrane and multi-wall carbon tubes meshes.

In this study, we developed a convenient way to construct a flexible enzymatic electrode with excellent stability and electrochemical performance for implanted glucose monitoring. The electrode was constructed through the co-immobilization of the glucose oxidase micro-particles (GOD MPs) and multi-wall carbon nanotubes (CNT) on the inner surface of a gradient-structured hollow fiber membrane (GHM), where CNT improved the electron transport efficiency and GHM controlled the transfer of substances and interferences. GOD MPs showed higher stability under various operation conditions than the free enzymes due to the MnCO3 template method, which enabled the biosensor to remain relative sensitivity at >86% over 9 days. The GOD MPs biosensor also showed high selectivity, reproducibility, and linear sensing range from 0 mM to 24 mM (R2 = 0.9993) with a current sensitivity of 25 nA/mM. The combination of porous-structured membrane and the flexible CNT meshes ensures the electrical connections and sensing accuracy of the biosensor under the deformation status. In-vivo experiments showed reliable current responses to variations in blood glucose concentrations that were consistent with tail blood test results. This co-immobilization of enzyme micro-particles in the 3D porous structure method developed a bio-composite platform technology towards the applications in flexible sensing and implantable medical devices.

All-optical reconstruction of k-dependent transition dipole moment by solid harmonic spectra from ultrashort laser pulses.

Band structure and transition dipole moment play important roles in high-order harmonic generation from solid materials. In this work we provide a new all-optical technique to reconstruct the momentum-dependent transition dipole moment using the harmonic spectrum from MgO crystal driven by an ultrashort mid-infrared laser pulse. Under the influence of the ultrashort laser pulse, the emitted photon energy and the crystal momentum form a one-to-one match, in the same way between the intensity of the harmonic above the minimum bandgap and the square of the amplitude of the transition dipole moment, resulting in a realization of directly probing the transition dipole moment. Our all-optical method paves a way to image the two-dimensional transition dipole moment of crystals with the inversion symmetry.

M860, a Monoclonal Antibody against Human Lactoferrin, Enhances Tumoricidal Activity of Low Dosage Lactoferrin via Granzyme B Induction.

Lactoferrin (LF) is a soluble glycoprotein of the transferring family found in most biological fluids, functioning as a major first line defense molecule against infection in mammals. It also shows certain anti-tumor activity, but its clinical application in tumor therapy is limited because high dosage is required. In this study, we demonstrate that M860, a monoclonal antibody against human LF (hLF), could significantly increase the anti-tumor potential of low dosage hLF by forming LF-containing immune complex (IC). Human monocytes primed with LF-IC, but not hLF or M860 alone, or control ICs, showed strong tumoricidal activity on leukemia cell lines Jurkat and Raji through induction of secreted Granzyme B (GzB). LF-IC is able to colligate membrane-bound CD14 (a TLR4 co-receptor) and FcγRIIa (a low affinity activating Fcγ receptor) on the surface of human monocytes, thereby triggering the Syk-PI3K-AKT-mTOR pathway leading to GzB production. Our work identifies a novel pathway for LF-mediated tumoricidal activity and may extend the clinical application of LF in tumor therapy.

Pivotal role of cAMP-PKA-CREB signaling pathway in manganese-induced neurotoxicity in PC12 cells.

Manganese (Mn) plays a critical role in individual growth and development, yet excessive exposure can result in neurotoxicity, especially cognitive impairment. Neuronal apoptosis is considered as one of the mechanisms of Mn-induced neurotoxicity. Recent evidence suggests that cAMP-PKA-CREB signaling regulates apoptosis and is associated with cognitive function. However, whether this pathway participates in Mn-induced neurotoxicity is not completely understood. To fill this gap, in vitro cultures of PC12 cells were exposed to 0, 400, 500, and 600 µmol/L Mn for 24 hours, respectively. Another group of cells were pretreated with 10.0 µmol/L rolipram (a phosphodiesterase-4 [PDE4] inhibitor) for 1 hour followed by 500 µmol/L Mn exposure for 24 hours. Flow cytometry, immunofluorescence staining, enzyme-linked immunosorbent assay, and Western blot analysis were used to detect the apoptosis rate, protein levels of PDE4, cAMP signaling, and apoptosis-associated proteins, respectively. We found that Mn exposure significantly inhibited cAMP signaling and protein expression of Bcl-2, while increasing apoptosis rate, protein levels of PDE4, Bax, activated caspase-3, and activated caspase-8 in PC12 cells. Pretreatment of rolipram ameliorated Mn-induced deficits in cAMP signaling and apoptosis. These findings demonstrate that cAMP-PKA-CREB signaling pathway-induced apoptosis is involved in Mn-induced neurotoxicity.

Top-Down Strategy of Implantable Biosensor Using Adaptable, Porous Hollow Fibrous Membrane.

Fabrication of an outer membrane is crucial for an implantable biosensor to enhance the long-term stability and accuracy of sensors. Herein, an adaptable, controllable, porous outer membrane for an implantable biosensor was fabricated using a "top-down" method, allowing maximum retention of enzyme activity and fine control over membrane microstructure. Polysulfone hollow fibrous membranes with different pore sizes and porosities were used as a base membrane. Chitosan (CH) and sodium alginate (SA) were self-assembled on the inner surface of PSfHM to construct a biocompatible and conductive interface between PSfHM and the electrode. In vitro and in vivo experiments were used to evaluate the performance of implantable glucose biosensors with PSfHM and CH/SA modified PSfHM (PSfHM-CH/SA). The glucose biosensor with PSfHM-CH/SA exhibited a more stable output current than bare sensors and a quick response time (<50 s). The glucose biosensor with PSfHM-CH/SA linear sensing range was between 0 and 22 mM ( R2 = 0.9905), and relative sensitivity remained at >87% within 7 days and >76% within 15 days. Furthermore, response currents recorded by implanted sensors closely followed the blood glucose trend from the tail vein blood during in vivo experiments.

Identification of key pathways regulated by a set of competitive long non-coding RNAs in oral squamous cell carcinoma.

OBJECTIVE: The aim of this study was to identify important pathways regulated by a set of long non-coding RNAs (lncRNAs) in oral squamous cell carcinoma (OSCC). METHODS: A lncRNA-mediated competitive endogenous RNA network (LMCN) was constructed using information on microRNA (miRNA)-mRNA interactions and lncRNA-miRNA intersections from the E-GEOD-37991 transcription profiling data in the ArrayExpress database. A random walk with restart ranking algorithm was then applied to evaluate the influences of protein-coding genes regulated by competitive lncRNAs. Pathway enrichment scores were calculated based on the propagation scores of protein-coding genes. Finally, permutation tests were used to estimate the significance of the pathways. RESULTS: We obtained lncRNA-mRNA interactions based on miRNAs common to both miRNA-mRNA interactions and lncRNA-miRNA intersections, and used interactions with a z-score > 0.7 to construct a LMCN. Ten lncRNAs were identified as source nodes in the LMCN, and nine pathways with enrichment scores >0.8, including 'Cell cycle', 'Endocytosis', and 'Pathways in cancer', were significantly enriched by these source nodes. CONCLUSIONS: Nine significant pathways regulated by a set of competitive lncRNAs were identified in OSCC, which may play important roles in the development of OSCC via the cell cycle and endocytosis.

Combination of in situ metathesis reaction with a novel "magnetic effervescent tablet-assisted ionic liquid dispersive microextraction" for the determination of endogenous steroids in human fluids.

Herein, a novel magnetic effervescence tablet-assisted microextraction coupled to in situ metathesis reaction of ionic liquid (IS-META-ILDM) is presented for the determination of four endogenous steroids in human urine, pregnant women's blood, and fetal umbilical cord blood. The magnetic effervescent tablets, which were composed of Fe3O4 nanoparticles, sodium carbonate (alkaline source), and tartaric acid (acidic source), were used to disperse the extractant and for convenient magnetic separation. After the effervescent reaction, in situ reaction between NH4PF6 and [C6MIM]BF4 was adopted to change hydrophilic ionic liquid to hydrophobic liquid, which could be separated from the aqueous phase. The newly developed method has three obvious advantages: (1) combination of effervescent dispersion and magnetic nanoparticles' retrieval is cost-effective and the dispersion and collection of the extractant can be completed almost simultaneously; (2) as compared to temperature-controlled ionic liquid dispersive microextraction and cold-induced solidified microextraction, this method avoids a heating and cooling process which significantly reduces the extraction time and energy cost; and (3) the combination of adsorption by magnetic nanoparticles with extraction by in situ metathesis reaction easily produces high recoveries for target analytes. The optimized composition of effervescent tablet and experimental parameters are as follows: 0.64 g mixture of sodium carbonate and tartaric acid, 7 mg of Fe3O4 (20 nm) as magnetic sorbents, 40 µL of [C6MIM]BF4 as the extraction solvent, 0.15 g NH4PF6, and 300 µL of elution solvent. Under the optimized conditions, the newly developed method provided high extraction recoveries (90.0-118.5%) and low LODs (0.14-0.17 µg L-1) in urine and blood samples. In total, this IS-META-ILDM method provided high extraction efficiency, fast and convenient separation, and underutilization of any organic solvent, and thus it has great potential for the determination of trace endogenous steroids in complex human fluids. Graphical abstract The newly developed method has three obvious advantages: combination of effervescent dispersion and magnetic nanoparticles' retrieval is cost-effective and the dispersion and collection of the extractant can be completed almost simultaneously. It avoids a heating and cooling process which significantly reduces the extraction time and energy cost and easily produces high recoveries for target analytes.

A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis.

Tofacitinib (CP-690550), an oral Janus kinase inhibitor, has shown significant efficacy in the treatment of rheumatoid arthritis through blocking the signaling pathways of pro-inflammatory cytokines. However, recent evidence suggests that long-term tofacitinib treatment is associated with increased risk of infection (e.g. tuberculosis) in patients. In the present study, we illustrate that tofacitinib administration significantly reduced the survival rate of mice given lethal or sub-lethal dose challenge with Candida albicans. This was related to the ability of tofacitinib to reverse TNFα- and IFNγ-enhanced candidacidal activity of murine polymorph nuclear cells (PMNs) and also to suppress chemokine CXCL5 expression and PMN infiltration in the infected tissues of mice. More importantly, tofacitinib significantly antagonized the ability of TNFα, IFNγ and GM-CSF to boost human PMNs in phagocytosis and direct killing of C. albicans in vitro. It also down-regulated reactive oxygen production and neutrophil extracellular trap formation by human PMNs stimulated with yeast-derived ß-glucans in the presence of TNFα, IFNγ or GM-CSF. Our data emphasizes a significantly increased risk for opportunistic fungal infection associated long-term tofacitinib treatment in humans, likely through antagonizing the PMN-boosting effect of pro-inflammatory cytokines.

Oxidative Stress and Genotoxicity of Long-Term Occupational Exposure to Low Levels of BTEX in Gas Station Workers.

Atmospheric benzene, toluene, ethylbenzene, and xylenes (BTEX) can lead to multiple health injuries. However, what remains uncertain is the effect of long-term exposure to low levels of BTEX. Thus, we determined the BTEX levels in the air from the refueling and office areas in gas stations. Then we collected workers' (200 refueling vs. 52 office workers) peripheral blood samples to analyze the serum total-superoxide dismutase (T-SOD), glutathione (GSH), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) levels. DNA damage was analyzed by the comet assay and micronucleus test in buccal epithelial cells. We found that the levels of BTEX in refueling areas were significantly higher than those in office areas (p < 0.001). The serum T-SOD and GSH of refueling workers were significantly lower than those in office workers (p < 0.001). By contrast, the serum MDA and 8-OHdG of refueling workers were significantly higher than those of office workers (p < 0.001, MDA; p = 0.025, 8-OHdG). Furthermore, tail and Olive tail moments in refueling workers were longer (p = 0.004, tail moment; p = 0.001, Olive tail moment), and the micronucleus rate was higher (p < 0.001) than those in office workers. Taken together, long-term exposure to low levels of BTEX may reduce the antioxidant ability and increase the risk of DNA damage in refueling workers of gas stations.

Manganese accumulation in hair and teeth as a biomarker of manganese exposure and neurotoxicity in rats.

Manganese (Mn) is an essential trace element to humans. However, excessive Mn causes cognitive impairment resulting from injury to the central nervous system within the hippocampus. No ideal biomarker is currently available for evaluating Mn exposure and associated neurotoxicity in the body. Hence, this study used Mn levels in the serum (MnS), teeth (MnT), and hair (MnH) as biomarkers for evaluating the association between Mn exposure and cognitive impairment in Mn-treated rats. A total of 32 male Sprague-Dawley rats were randomly divided into four groups, received 0, 5, 10, and 20 mg/(kg day) of MnCl2·4H2O for 5 days a week for 18 weeks, respectively. Lifetime Mn cumulative dose (LMCD) was used to evaluate external Mn exposure. Hippocampus, serum, teeth, and hair specimens were collected from the rats for Mn determination by graphite furnace atomic absorption spectrometry. Learning and memory functions were assessed using the Morris water maze test. Results showed that chronic Mn exposure increased the hippocampus (MnHip), MnS, MnT, and MnH levels, as well as impaired learning and memory function in rats. MnHip, MnT, and MnH levels were positively correlated with LMCD (r = 0.759, r = 0.925, and r = 0.908, respectively; p < 0.05), escape latency (r = 0.862, r = 0.716, and r = 0.814, respectively; p < 0.05), and the number of platform crossings (r = -0.734, r = -0.514, and r = -0.566, respectively; p < 0.05). No association was observed between MnS levels and the number of platform crossings (r = -0.286, p > 0.05). Thus, MnT and MnH detected long-term low-dose Mn exposure. These parameters can be reliable biomarkers for Mn exposure and associated neurotoxicity in Mn-treated rats.

Expression Profiles of Long Noncoding RNAs and Messenger RNAs in Mn-Exposed Hippocampal Neurons of Sprague-Dawley Rats Ascertained by Microarray: Implications for Mn-Induced Neurotoxicity.

Manganese (Mn) is an essential trace element, while excessive expose may induce neurotoxicity. Recently, lncRNAs have been extensively studied and it has been confirmed that lncRNAs participate in neural functions and aberrantly expressed lncRNAs are involved in neurological diseases. However, the pathological effects of lncRNAs on Mn-induced neurotoxicity remain unclear. In this study, the expression profiles of lncRNAs and messenger RNAs (mRNAs) were identified in Mn-treated hippocampal neurons and control neurons via microarray. Bioinformatic methods and intersection analysis were also employed. Results indicated that 566, 1161, and 1474 lncRNAs meanwhile 1848, 3228, and 4022 mRNAs were aberrantly expressed in low, intermediate, and high Mn-exposed groups compared with the control group, respectively. Go analysis determined that differentially expressed mRNAs were targeted to biological processes, cellular components, and molecular functions. Pathway analysis indicated that these mRNAs were enriched in insulin secretion, cell cycle, and DNA replication. Intersection analysis denominated that 135 lncRNAs and 373 mRNAs were consistently up-regulated while 150 lncRNAs and 560 mRNAs were consistently down-regulated. Meanwhile, lncRNA BC079195 was significantly up-regulated while lncRNAs uc.229- and BC089928 were significantly down-regulated in three comparison groups. The relative expression levels of 3 lncRNAs and 4 mRNAs were validated through qRT-PCR. To the best of our knowledge, this study is the first to identify the expression patterns of lncRNAs and mRNAs in hippocampal neurons of Sprague-Dawley rats. The results may provide evidence on underlying mechanisms of Mn-induced neurotoxicity, and aberrantly expressed lncRNAs/mRNAs may be useful in further investigations to detect early symptoms of Mn-induced neuropsychiatric disorders in the central nervous system.

Effects of chronic manganese exposure on the learning and memory of rats by observing the changes in the hippocampal cAMP signaling pathway.

Chronic manganese exposure can produce cognitive deficits; however, the underlying mechanism remains unclear; reliable peripheral biomarker of Mn neurotoxicity have not yet been fully developed. Hence, this study aimed to investigate the mechanism of Mn-induced cognitive deficits and the potential biomarker of Mn neurotoxicity in rats. Thirty-two male Sprague Dawley rats were divided into four groups; these groups received intraperitoneal injections of 0, 5, 10 and 20 mg Mn/kg once daily, five days/week for 18 weeks. Learning and memory were assessed via Morris water maze test. Hippocampal and plasma Mn concentrations were measured through graphite furnace atomic absorption spectrometry. The levels of plasma BDNF, hippocampal BDNF, cAMP, protein kinase A, and pCREB were assessed through ELISA or Western blot. Results showed that the Mn concentrations in the hippocampus and plasma of the Mn-treated rats were higher than those of the control rats. Mn exposure impaired the learning and memory of rats. Plasma BDNF levels and hippocampal BDNF, cAMP, protein kinase A, and pCREB levels were significantly lower in the Mn-treated rats than in the control rats. Plasma BDNF levels were negatively correlated with the escape latency and the hippocampal and plasma Mn concentrations. By contrast, plasma BDNF levels were positively correlated with the number of platform crossings and the hippocampal cAMP and BDNF levels. Therefore, Mn impaired learning and memory probably by inhibiting the hippocampal cAMP signaling pathway in rats. Plasma BDNF levels may also be a potential effect biomarker of Mn neurotoxicity.

Change of water sources reduces health risks from heavy metals via ingestion of water, soil, and rice in a riverine area, South China.

This study evaluates the effect of water source change on heavy metal concentrations in water, paddy soil, and rice, as well as the health risks to residents of three riverine communities in South China. The results show that after substituting the sources of drinking water, heavy metal levels (except for Pb at Tangjun) in drinking water were below WHO guideline values and the potential risk from drinking water may be negligible. The As (46.2-66.8%), Pb (65.7-82.6%), Cd (50.8-55.0%), and Hg (28.3-32.6%) concentrations in paddy soils in Sanhe and Lasha significantly (p<0.05) decreased with a change of irrigation water sources compared to Tangjun, without change of irrigation water source. Similarly, the Cd (39.1-81.3%) and Hg (60.0-75.0%) concentrations in rice grown at Sanhe and Lasha significantly (p<0.05) decreased compared to those at Tangjun. Consequently, replacing irrigation water source significantly (p<0.05) reduced the hazard quotient (HQ) and cancer risk for the corresponding single metal via soil ingestion and rice consumption. Despite that total non-carcinogenic and carcinogenic risks at Sanhe and Lasha were significantly decreased, they still exceeded the maximum acceptable limits recommended by US EPA, indicating that residents of these two communities remain at high risks of both non-cancer and cancer effects.

Synergistic impaired effect between smoking and manganese dust exposure on pulmonary ventilation function in Guangxi manganese-exposed workers healthy cohort (GXMEWHC).

PURPOSE: The aims of this study were to investigate the effects of manganese (Mn) dust exposure on lung functions and evaluate the potential synergistic effect between smoking and Mn dust exposure among refinery workers. METHODS: A retrospective study including 1658 workers in a ferromanganese refinery was conducted, with subjects who were from the Guangxi manganese-exposed workers healthy cohort (GXMEWHC). Based on the Mn manganese cumulative exposure index (Mn-CEI), all subjects were divided into the low exposure group (n = 682) and the high exposure group (n = 976). A pulmonary function test was performed using an electronic spirometer, including the values and percentages of FVC, FEV1, FEV1/FVC, MMEF, PEFR, MVV, respectively. RESULTS: No significant effect of Mn dust exposure on the pulmonary function was found in the female workers (all p>0.05). However, there was an obvious decrease in the male workers in the high exposure group compared with those in the low exposure group (FVC -60 ml, FEV1 -120 ml, MMEF -260 ml/s, MVV -5.06 L, all p<0.05). In the high exposure group, the reduction in FVC% predicted, MMEF and MMEF% predicted was 1.0%, 210 mL/s, and 4.9%, respectively. In particular, among the exposed subjects smokers had a statistically significant decrease in lung function compared with non-smokers and the reduction in FVC% predicted, MMEF and MMEF% predicted was 1.0%, 210 mL/s, and 4.9%, respectively (p<0.05). Partial correlation analysis showed that there was also negative correlation between Mn-CEI and decreased changes in MMEF (r = -0.159, p = 0.018) and also MMEF% predicted (r = -0.163, p = 0.015). CONCLUSIONS: Mn dust can impair the pulmonary ventilation function of male workers but not females, and individual smoking habits and manganese exposure had a synergistic effect on the lung function decrease.

Establishment of reproducible xenotransplantation model of T cell acute lymphoblastic leukemia in NOD/SCID mice.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia. However the poor prognosis and low morbidity restrict further analysis of the disease. Therefore there is an increasing demand to develop animal models for identifying novel therapeutic approaches. In this study, we inoculated the anti-mouse CD122 monoclonal antibody conditioned NOD/SCID mice with the leukemia cells from 9 T-ALL patients and 1 cell line via the tail vein. Four of the 9 patients and the cell line were successfully engrafted. Flow cytometry detected high percentage of human CD45(+) cells in recipient mice. Immunohistochemistry showed infiltration of human CD45(+) cells in different organs. Serial transplantation was also achieved. In vivo drug treatment showed that dexamethasone could extend survival, which was consistent with clinical observation. These results demonstrated that we successfully established 5 xenotransplantation models of T-ALL in anti-mCD122 mAb conditioned NOD/SCID mice, which recapitulated the characteristics of original disease.