Orbital-dependent electron correlation in double-layer nickelate La3Ni2O7.

The latest discovery of high temperature superconductivity near 80 K in La3Ni2O7 under high pressure has attracted much attention. Many proposals are put forth to understand the origin of superconductivity. The determination of electronic structures is a prerequisite to establish theories to understand superconductivity in nickelates but is still lacking. Here we report our direct measurement of the electronic structures of La3Ni2O7 by high-resolution angle-resolved photoemission spectroscopy. The Fermi surface and band structures of La3Ni2O7 are observed and compared with the band structure calculations. Strong electron correlations are revealed which are orbital- and momentum-dependent. A flat band is formed from the Ni-3d z 2 orbitals around the zone corner which is ~ 50 meV below the Fermi level and exhibits the strongest electron correlation. In many theoretical proposals, this band is expected to play the dominant role in generating superconductivity in La3Ni2O7. Our observations provide key experimental information to understand the electronic structure and origin of high temperature superconductivity in La3Ni2O7.

Observation of flat band, Dirac nodal lines and topological surface states in Kagome superconductor CsTi3Bi5.

Kagome lattices of various transition metals are versatile platforms for achieving anomalous Hall effects, unconventional charge-density wave orders and quantum spin liquid phenomena due to the strong correlations, spin-orbit coupling and/or magnetic interactions involved in such a lattice. Here, we use laser-based angle-resolved photoemission spectroscopy in combination with density functional theory calculations to investigate the electronic structure of the newly discovered kagome superconductor CsTi3Bi5, which is isostructural to the AV3Sb5 (A = K, Rb or Cs) kagome superconductor family and possesses a two-dimensional kagome network of titanium. We directly observe a striking flat band derived from the local destructive interference of Bloch wave functions within the kagome lattice. In agreement with calculations, we identify type-II and type-III Dirac nodal lines and their momentum distribution in CsTi3Bi5 from the measured electronic structures. In addition, around the Brillouin zone centre, [Formula: see text] nontrivial topological surface states are also observed due to band inversion mediated by strong spin-orbit coupling.

Short-term toxicity assessment of combined use of zidovudine, lamivudine and lopinavir/ritonavir in vitro and in vivo.

INTRODUCTION: A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. METHOD: An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity. RESULTS: In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P < 0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P < 0.05); the relative weights of the liver, kidney, spleen and brain increased (P < 0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P < 0.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P < 0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P < 0.05). CONCLUSION: The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.

Titanium doped kagome superconductor CsV3-xTixSb5 and two distinct phases.

The vanadium-based kagome superconductor CsV3Sb5 has attracted tremendous attention due to its unexcepted anomalous Hall effect (AHE), charge density waves (CDWs), nematicity, and a pseudogap pair density wave (PDW) coexisting with unconventional strong-coupling superconductivity. The origins of CDWs, unconventional superconductivity, and their correlation with different electronic states in this kagome system are of great significance, but so far, are still under debate. Chemical doping in the kagome layer provides one of the most direct ways to reveal the intrinsic physics, but remains unexplored. Here, we report, for the first time, the synthesis of Ti-substituted CsV3Sb5 single crystals and its rich phase diagram mapping the evolution of intertwining electronic states. The Ti atoms directly substitute for V in the kagome layers. CsV3-xTixSb5 shows two distinct superconductivity phases upon substitution. The Ti slightly-substituted phase displays an unconventional V-shaped superconductivity gap, coexisting with weakening CDW, PDW, AHE, and nematicity. The Ti highly-substituted phase has a U-shaped superconductivity gap concomitant with a short-range rotation symmetry breaking CDW, while long-range CDW, twofold symmetry of in-plane resistivity, AHE, and PDW are absent. Furthermore, we also demonstrate the chemical substitution of V atoms with other elements such as Cr and Nb, showing a different modulation on the superconductivity phases and CDWs. These findings open up a way to synthesise a new family of doped CsV3Sb5 materials, and further represent a new platform for tuning the different correlated electronic states and superconducting pairing in kagome superconductors.

Electronic nature of charge density wave and electron-phonon coupling in kagome superconductor KV3Sb5.

The Kagome superconductors AV3Sb5 (A = K, Rb, Cs) have received enormous attention due to their nontrivial topological electronic structure, anomalous physical properties and superconductivity. Unconventional charge density wave (CDW) has been detected in AV3Sb5. High-precision electronic structure determination is essential to understand its origin. Here we unveil electronic nature of the CDW phase in our high-resolution angle-resolved photoemission measurements on KV3Sb5. We have observed CDW-induced Fermi surface reconstruction and the associated band folding. The CDW-induced band splitting and the associated gap opening have been revealed at the boundary of the pristine and reconstructed Brillouin zones. The Fermi surface- and momentum-dependent CDW gap is measured and the strongly anisotropic CDW gap is observed for all the V-derived Fermi surface. In particular, we have observed signatures of the electron-phonon coupling in KV3Sb5. These results provide key insights in understanding the nature of the CDW state and its interplay with superconductivity in AV3Sb5 superconductors.

Impact of Lead Exposure on Thyroid Status and IQ Performance among School-age Children Living Nearby a Lead-Zinc Mine in China.

BACKGROUND: Lead exposure is one of the most concerning public health problems worldwide, particularly among children. Yet the impact of chronic lead exposure on the thyroid status and related intelligence quotient performance among school-age children remained elusive. OBJECTIVE: The aim of this study was to evaluate the influence of lead exposure on the thyroid hormones, amino acid neurotransmitters balances, and intelligence quotient (IQ) among school-age children living nearby a lead-zinc mining site. Other factors such as rice lead levels, mothers' smoking behavior, and diet intake were also investigated. METHODS: A total of 255 children aged 7-12 years old were recruited in this study. Blood lead level (BLL), thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH), and amino acid neurotransmitters such as glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA) were measured using graphite furnace atomic absorption spectroscopy (GFAAS), chemiluminescence immunoassay, high performance liquid chromatography (HPLC). Raven's standard progressive matrices (SPM) and the questionnaire were used to determine IQ and collect related influence factors. RESULTS: The average BLL of children was 84.8 µg/L. The occurrence of lead intoxication (defined as the BLL ≥ 100 µg/L) was 31.8%. Serum TSH levels and IQ of lead-intoxicated children were significantly lower than those without lead toxicity. The GABA level of girls with the lead intoxication was higher than those with no lead-exposed group. Correlation analyses revealed that BLL were inversely associated with the serum TSH levels (R= -0.186, p < 0.05), but positively related with IQ grades (R = 0.147, p < 0.05). Moreover, BLL and Glu were inversely correlated with IQ. In addition, this study revealed four factors that may contribute to the incidence of lead intoxication among children, including the frequency of mother smoking (OR = 3.587, p < 0.05) and drinking un-boiled stagnant tap water (OR = 3.716, p < 0.05); eating fresh fruits and vegetables (OR = 0.323, p < 0.05) and soy products regularly (OR = 0.181, p < 0.05) may protect against lead intoxication. CONCLUSION: Lead exposure affects the serum TSH, GABA levels and IQ of school-aged children. Developing good living habits, improving environment, increasing the intake of high-quality protein and fresh vegetable and fruit may improve the condition of lead intoxication.

Author Correction: Universal mechanical exfoliation of large-area 2D crystals.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Universal mechanical exfoliation of large-area 2D crystals.

Two-dimensional materials provide extraordinary opportunities for exploring phenomena arising in atomically thin crystals. Beginning with the first isolation of graphene, mechanical exfoliation has been a key to provide high-quality two-dimensional materials, but despite improvements it is still limited in yield, lateral size and contamination. Here we introduce a contamination-free, one-step and universal Au-assisted mechanical exfoliation method and demonstrate its effectiveness by isolating 40 types of single-crystalline monolayers, including elemental two-dimensional crystals, metal-dichalcogenides, magnets and superconductors. Most of them are of millimeter-size and high-quality, as shown by transfer-free measurements of electron microscopy, photo spectroscopies and electrical transport. Large suspended two-dimensional crystals and heterojunctions were also prepared with high-yield. Enhanced adhesion between the crystals and the substrates enables such efficient exfoliation, for which we identify a gold-assisted exfoliation method that underpins a universal route for producing large-area monolayers and thus supports studies of fundamental properties and potential application of two-dimensional materials.

Effect of manganese on neural endocrine hormones in serum of welders and smelters.

BACKGROUND: Although manganese (Mn)-induced neurotoxicity effects are well known among occupational Mn exposure, few reports have investigated the effects on endocrine systems among welders and smelters. OBJECTIVE: To determine the effect of high level occupational manganese (Mn) exposure on neuropsychological parameters and hormonal status. METHODS: We used a cross-sectional design with 52 welders, 48 smelters and 43 age-matched office workers from the same factory in China. We analyzed serum endocrine hormones level and airborne Mn concentrations. Erythrocyte and urine Mn levels were quantified using inductively-coupled plasma atomic emission spectroscopy. RESULTS: The geometric mean of air Mn concentrations for the welders and smelters were 19.7 and 273.1 µg/m3, respectively. Mn concentrations in erythrocytes of smelters were markedly greater than those in controls and welders, but there was no difference between the erythrocytes Mn levels of Control and welders. We also found an increase of Mn levels in the urine of both welders and smelters vs. controls; Mn levels in urine of smelters were higher than in welders. Self-reported neurobehavioral symptoms were higher in welders and smelters than in controls. Finally, thyroid-stimulating hormone (TSH) levels of welders were significantly lower than in controls, whereas smelters had lower prolactin (PRL), testosterone (TST) and follicle-stimulating hormone (FSH) concentrations than either controls or welders. CONCLUSIONS: These results show that smelters have higher Mn exposure than do welders, and that Mn levels in erythrocytes or urine can be a marker for exposure. Moreover, high level occupational Mn exposure increases adverse neurobehavioral effects, and also may disrupt endocrine systems.

Sodium p-Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels.

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl2 (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABAA) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism.

Sodium P-Aminosalicylic Acid Improved Manganese-Induced Learning and Memory Dysfunction via Restoring the Ultrastructural Alterations and γ-Aminobutyric Acid Metabolism Imbalance in the Basal Ganglia.

Excessive intake of manganese (Mn) may cause neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has been used successfully in the treatment of Mn-induced neurotoxicity. The γ-aminobutyric acid (GABA) is related with learning and memory abilities. However, the mechanism of PAS-Na on improving Mn-induced behavioral deficits is unclear. The current study was aimed to investigate the effects of PAS-Na on Mn-induced behavioral deficits and the involvement of ultrastructural alterations and γ-aminobutyric acid (GABA) metabolism in the basal ganglia of rats. Sprague-Dawley rats received daily intraperitoneally injections of 15 mg/kg MnCl2.4H2O, 5d/week for 4 weeks, followed by a daily back subcutaneously (sc.) dose of PAS-Na (100 and 200 mg/kg), 5 days/week for another 3 or 6 weeks. Mn exposure for 4 weeks and then ceased Mn exposure for 3 or 6 weeks impaired spatial learning and memory abilities, and these effects were long-lasting. Moreover, Mn exposure caused ultrastructural alterations in the basal ganglia expressed as swollen neuronal with increasing the electron density in the protrusions structure and fuzzed the interval of neuropil, together with swollen, focal hyperplasia, and hypertrophy of astrocytes. Additionally, the results also indicated that Mn exposure increased Glu/GABA values as by feedback loops controlling GAT-1, GABAA mRNA and GABAA protein expression through decreasing GABA transporter 1(GAT-1) and GABA A receptor (GABAA) mRNA expression, and increasing GABAA protein expression in the basal ganglia. But Mn exposure had no effects on GAT-1 protein expression. PAS-Na treatment for 3 or 6 weeks effectively restored the above-mentioned adverse effects induced by Mn. In conclusion, these findings suggest the involvement of GABA metabolism and ultrastructural alterations of basal ganglia in PAS-Na's protective effects on the spatial learning and memory abilities.

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma.

MicroRNAs (miRNAs) are well known as important regulators in various cancer development. In the present study, we focused on the expression and biological function of miR-1291 in esophageal squamous cell carcinoma (ESCC). Compared with adjacent non-tumorous tissue samples, qRT-PCR data showed significant downregulation of miR-1291 in 54 ESCC tissue samples (P<0.05), which was also significantly associated with lymph node metastases and clinical stage (P<0.05). Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometric apoptosis assays were performed to detect the effect of miR-1291 upregulation, and the results showed inhibition of the proliferation, invasion and promotion of apoptosis in EC9706 and EC-1 cells. Using bioinformatic analyses, we found that mucin 1 (MUC1) was a potential target for miR-1291. Luciferase assays were performed to reveal that miR-1291 inhibited MUC1 expression by targeting the seed region of MUC1 3'-untranslated region (3'UTR). We also found that the expression of MUC1 lacking in 3'UTR abrogated the anti-invasion and pro-apoptosis function of miR-1291. Our results demonstrated the importance of miR-1291 in targeting MUC1 for the regulation of esophagus cancer growth, invasion and apoptosis, and may be helpful for developing new targets for early diagnosis or new therapeutic targets for ESCC.

Upregulation of miR-513b inhibits cell proliferation, migration, and promotes apoptosis by targeting high mobility group-box 3 protein in gastric cancer.

The high mobility group-box 3 (HMGB3) protein belongs to the high mobility group box (HMG-box) subfamily, and recent studies have shown that HMGB3 is an oncogene for leukemia. HMGB3 is also expressed at a high level in the progression phase of breast and gastric cancer (GC). Using bioinformatic analyses, we found that HMGB3 is a potential target for miR-513b. However, the pathophysiological role of miR-513b and its relevance to the growth and development of GC have yet to be investigated. This study focuses on whether miR-513b acts as a tumor suppressor in GC. Compared with non-malignant adjacent tissues samples, qRT-PCR data showed significant downregulation of miR-513b in 74 GC tissue samples (P < 0.01). Furthermore, western blotting revealed that HMGB3 protein was overexpressed in tumor samples relative to matched, non-malignant adjacent tissues. Western blotting and qRT-PCR results showed that high expression of HMGB3 and low expression of miR-513b were both significantly associated with primary tumors, lymph node metastases, and the clinical stage (P < 0.01). MiR-513b was shown to not only inhibit the proliferation and migration of gastric cancer cells (MKN45 and SGC7901) in the CCK-8 and transwell assays, but also to promote cell apoptosis in a flow-cytometric apoptosis assay. In western blot and luciferase assays, HMGB3 was identified as a major target of miR-513b. Moreover, we also found that the expression of HMGB3 lacking in 3' UTR could abrogate the anti-migration and pro-apoptosis function of miR-513b. These findings suggest the importance of miR-513b targeting of HMGB3 in the regulation of growth, migration and apoptosis of GC, improve our understanding of the mechanisms of GC pathogenesis, and may promote the development of novel targeted therapies.

Silencing BMP-2 expression inhibits A549 and H460 cell proliferation and migration.

BACKGROUND: Bone morphogenetic protein 2 (BMP-2) is a member of the TGF-ß superfamily that is closely correlated with many malignancies, particularly lung cancer. However, the effects of silenced BMP-2 on lung cancer cell proliferation and migration are not clear. METHODS: Using quantitative real-time RT-PCR, BMP-2 mRNA expression was detected in 61 non-small cell lung cancer (NSCLC) samples. Survival curves were generated using follow-up data. Relationships between clinical or pathological characteristics and prognosis were analyzed. Cell viability assays and transwell migration assays were used to evaluate the effects of BMP-2 silencing on cell proliferation and migration of A549 and H460 cells. RESULTS: BMP-2 mRNA expression was higher in NSCLC tissues compared to matched adjacent normal tissues (P<0.01). High BMP-2 expression levels were significantly associated with the occurrence of lymph node metastases and tumor stage (P<0.05). There were significant differences in survival curves between groups with metastatic lymph nodes and non-metastatic lymph nodes, as well as between groups with low BMP-2 expression and groups with high BMP-2 expression. In addition, we observed decreased proliferation and migration rates of the NSCLC-derived cell lines A549 and H460 that were transfected with siBMP-2 (P<0.05). CONCLUSION: BMP-2 mRNA is overexpressed in NSCLC samples and is a risk factor for survival in patients with NSCLC. BMP-2 silencing can significantly inhibit A549 and H460 cell proliferation and migration. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4263254471298866.

Vulnerability of welders to manganese exposure--a neuroimaging study.

Increased manganese (Mn) exposure is known to cause cognitive, psychiatric and motor deficits. Mn exposure occurs in different occupational settings, where the airborne Mn level and the size of respirable particulates may vary considerably. Recently the importance of the role of the cerebral cortex in Mn toxicity has been highlighted, especially in Mn-induced neuropsychological effects. In this study we used magnetic resonance imaging (MRI) to evaluate brain Mn accumulation using T1 signal intensity indices and to examine changes in brain iron content using T2* contrast, as well as magnetic resonance spectroscopy (MRS) to measure exposure-induced metabolite changes non-invasively in cortical and deep brain regions in Mn-exposed welders, Mn-exposed smelter workers and control factory workers with no measurable exposure to Mn. MRS data as well as T1 signal intensity indices and T2* values were acquired from the frontal cortex, posterior cingulate cortex, hippocampus, and thalamus. Smelters were exposed to higher air Mn levels and had a longer duration of exposure, which was reflected in higher Mn levels in erythrocytes and urine than in welders. Nonetheless, welders had more significant metabolic differences compared to controls than did the smelter workers, especially in the frontal cortex. T1 hyperintensities in the globus pallidus were observed in both Mn-exposed groups, but only welders showed significantly higher thalamic and hippocampal T1 hyperintensities, as well as significantly reduced T2* values in the frontal cortex. Our results indicate that (1) the cerebral cortex, in particular the frontal cortex, is clearly involved in Mn neurotoxic effects and (2) in spite of the lower air Mn levels and shorter duration of exposure, welders exhibit more extensive neuroimaging changes compared to controls than smelters, including measurable deposition of Mn in more brain areas. These results indicate that the type of exposure (particulate sizes, dust versus fume) and route of exposure play an important role in the extent of Mn-induced toxic effects on the brain.

Pallidal index as biomarker of manganese brain accumulation and associated with manganese levels in blood: a meta-analysis.

OBJECTIVE: The current study was designed to evaluate the sensitivity, feasibility, and effectiveness of the pallidal index (PI) serving as a biomarker of brain manganese (Mn) accumulation, which would be used as an early diagnosis criteria for Mn neurotoxicity. METHODS: The weighted mean difference (WMD) of the PI between control and Mn-exposed groups was estimated by using a random-effects or fixed-effects meta-analysis with 95% confidence interval (CI) performed by STATA software version 12.1. Moreover, the R package "metacor" was used to estimate correlation coefficients between PI and blood Mn (MnB). RESULTS: A total of eight studies with 281 occupationally Mn-exposed workers met the inclusion criteria. Results were pooled and performed with the Meta-analysis. Our data indicated that the PI of the exposed group was significantly higher than that of the control (WMD: 7.76; 95% CI: 4.86, 10.65; I2 = 85.7%, p<0.0001). A random effects model was used to perform meta-analysis. These findings were remarkably robust in the sensitivity analysis, and publication bias was shown in the included studies. Seven out of the eight studies reported the Pearson correlation (r) values. Significantly positive correlation between PI and MnB was observed (r = 0.42; 95% CI, 0.31, 0.52). CONCLUSIONS: PI can be considered as a sensitive, feasible, effective and semi-quantitative index in evaluating brain Mn accumulation. MnB can also augment the evaluation of brain Mn accumulation levels in the near future. However, the results should be interpreted with caution.

Prodigiosin found in Serratia marcescens y2 initiates phototoxicity in the cytomembrane

Background: Light can be absorbed by bacterial pigment and affects its growth. Prodigiosin is a red pigment found in various bacterial species. The purpose of this study was to investigate the impacts of light on prodigiosin production, biomass formation, and membrane integrity of Serratia marcescens y2. Results: S. marcescens y2 grew better and produced more intracellular prodigiosin in darkness than in illumination. The pigment leakage ratio from cells was detected more in light than in darkness conditions. Ethidium bromide uptake assay could visually prove the prodigiosin-related loss of membrane integrity under illumination. A higher concentration of malondialdehyde (MDA) was detected in light-treated culture than in darkness. Tests of different light treatments (red, yellow, blue and green) showed that the maximum extracellular pigment and the minimum biomass formation and intracellular pigment were obtained in green light. Conclusions: Prodigiosin could absorb light, and then initiate phototoxicity damage of the cytomembrane.

[Effect of sodium para-aminosalicylic on concentrations of amino acid neurotransmitters in basal ganglia of manganese-exposed rats].

OBJECTIVE: To probe the effect of sodium para-aminosalicylate (PAS-Na) on concentration of amino acid neurotransmitters including glutamate (Glu), glutamine (Gln), glycine (Gly) and gamma-aminobutyric acid (GABA) in basal ganglia of subacute manganese (Mn)-exposed rats. METHODS: Forty Sprague-Dawley male rats were randomly divided into the control, Mn-exposed, low dose PAS-Na (L-PAS) and high dose PAS-Na (H-PAS) groups. Rats in experiment groups received daily intraperitoneally injections of manganese chloride (MnCl2 · 4H2O, 15 mg/kg), while rats in control group received daily intraperitoneally injections of normal saline (NS), all at 5 days/week for 4 weeks. Then the rats in PAS groups followed by a daily subcutaneously dose of PAS-Na (100 and 200 mg/kg as the L-PAS and H-PAS groups, respectively) for another 3 and 6 weeks; while the rats in Mn-exposed and control group received NS. The concentrations of Glu, Gln, Gly and GABA in basal ganglia of rat was detected by the high performance liquid chromatography fluorescence detection technique. RESULTS: After treating with PAS-Na for 3 weeks, the concentration of Gly in the Mn-exposed rats decreased to (0.165 ± 0.022) µmol/L (control = (0.271 ± 0.074) µmol/L, Mn vs control, t = 4.65, P < 0.05). After the further 6-week therapy with PAS-Na, the concentrations of Glu, Gln, Gly in the Mn-exposed rats were lower than those of the control rats ((0.942 ± 0.121), (0.377 ± 0.070), (0.142 ± 0.048), (1.590 ± 0.302), (0.563 ± 0.040), (0.247 ± 0.084) µmol/L; t = 7.72, 5.85, 4.30, P < 0.05); and also lower than in L-PAS and H-PAS groups, whose concentrations were separately (1.268 ± 0.124), (1.465 ± 0.196), (0.497 ± 0.050), (0.514 ± 0.103), (0.219 ± 0.034) µmol/L (L-PAS Glu and Gln vs Mn, t = 3.87, 3.77, P < 0.05; H-PAS Glu, Gln and Gly vs Mn, t = 6.78, 4.70, 3.42, P < 0.05). CONCLUSION: The toxic effect of manganese on Glu, Gln and Gly in basal ganglia of Mn-exposed rats is obvious, especially appears earlier on Gly. The toxic effect still continues to develop when relieved from the exposure. PAS-Na may play an antagonism role in toxic effect of manganese on concentration of Glu, Gln and Gly in basal ganglia of Mn-exposed rats.

Recombinant MafA protein containing its own protein transduction domain stimulates insulin gene expression in IEC-6 cells.

AIMS: MafA, a basic leucine zipper (bZIP) transcription factor, functions as a potent activator of insulin gene transcription in ß-cell. In this paper, we aimed to investigate whether the entire MafA protein has the self-delivery activity, and that the arginine- and lysine-rich sequence in MafA bZIP domain is an efficient protein transduction domain (PTD). MAIN METHODS: Entire MafA protein internalization was evaluated with Western blot and immunofluorescence. The distribution of the PTD-EGFP (enhanced green fluorescence protein) was examined by fluorescent microscope observation. Luciferase reporter assay was used to investigate the effect of the transduced MafA protein on insulin 2 promoter activity. Additionally, we conducted RT-PCR to detect the expression of insulin mRNA in MafA treated IEC-6 cells. KEY FINDINGS: The arginine- and lysine-rich peptide of MafA serves as a novel PTD. PTD-EGFP can permeate into various cell types including Min6 (a ß-cell line), and transduce in a dose- and time-dependent manner. The cellular uptake of MafA PTD can be completely blocked by heparin, whereas cytochalasin D and amiloride were partially effective in blocking the PTD-EGFP protein entry. Transduced intact MafA protein behaves in the same way as the endogenous MafA, stimulating the transcription of insulin promoter and further inducing insulin expression in treated non-ß-cell line (IEC-6). SIGNIFICANCE: These results indicate that the MafA PTD could serve as a therapeutic delivery vehicle, and further suggest that MafA protein transduction could be a valuable strategy for enhancing insulin gene transcription without requiring gene transfer technology.

[Effects of low level manganese exposure on the serum neuroendocrine hormones in the welders].

OBJECTIVE: To study the effects of low level manganese (Mn) exposure on the serum neuroendocrine hormones levels of the welders. METHODS: The exposure group consisted of 41 male welders, 40 male workers without exposing to harmful agents served as controls. The serum contents of prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (TST) and thyroid stimulating hormone (TSH) of 81 subjects were detected by chemiluminescence immunoassay. RESULTS: The geometric mean value of airborne Mn concentrations was 0.03 mg/m(3) (0.003 - 0.519 mg/m(3)) in the welding circumstances. The levels of Mn in red blood cells (RBCs) and urinary Mn of the exposure group were significantly higher than those of control group (P < 0.01). The contents of serum LH and TSH of the exposure group were 2.89 ± 0.69 mIU/ml and 1.45 ± 0.56 uIU/ml, which were significantly lower than those (3.82 ± 1.61 mIU/ml and 2.19 ± 1.28 µIU/ml) of control group (P < 0.01). The serum contents of LH, FSH and TSH of the group exposed to Mn for < 5 years were significantly lower than those of the control group, The serum TST level of the group exposed to Mn for < 5 years was significantly higher than those of the control group and group exposed to Mn for 5 ∼ years, the serum FSH level of the group exposed to Mn for < 5 years was significantly lower than that of the group exposed to Mn for 10 years (P < 0.05 or P < 0.01). The serum contents of LH and TSH of the group exposed to Mn for 5 ∼ years were significantly lower than those of the control group (P < 0.05 or P < 0.01). The serum contents of PRL, LH and TSH of the group exposed to Mn for 10 years were significantly lower than those of the control group (P < 0.05). There was negative correlation between blood (RBC) Mn and urinary Mn (r = -0.310, P < 0.05), also there was negative correlation between serum PRL and serum TST (r = -0.409, P < 0.01), the positive correlation between serum LH and serum FSH was observed (r = 0.361, P < 0.05). CONCLUSION: The results of present study showed that the long exposure to low level of Mn may decrease the levels of serum PRL, LH and TSH in workers occupationally exposed to Mn, which can influence the metabolism of neuroendocrine hormones to certain extent.