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To investigate the clinical effect of Shenkang injection on chronic renal insufficiency. Methods 88 patients with chronic renal insufficiency were selected as the research object and randomly divided into observation group and control group. The control group was given routine treatment, and the observation group was given Shenkang injection on this basis. The total effective rate, hemoglobin level (Hb), red blood cell count (RBC), urea nitrogen (BUN), serum creatinine (SCr) and endogenous creatinine clearance (Ccr) were compared between the two groups. Results The total effective rate of the observation group (93.18%) was significantly higher than that of the control group (77.27%), and all observation indexes were significantly better than the control group, the difference was statistically significant (P

A new deployable warhead-like decoy is proposed in this study. It consists of a rigid deployable skeleton in the center, a cable net system, and a membrane connected to the outer part of the decoy. First, the structural design of the decoy is presented, and its spatial geometry relationship is described. Compared with the existing decoy design, the decoy has high structural stiffness and surface similarity. Furthermore, the large storage ratio ensures that the space it occupies and its weight do not exceed those of the conventional decoy. Then, the structural characteristics and deployment dynamics of the ground and air conditions are analyzed considering the difference between the actual working condition and ground condition. Finally, a prototype is developed to verify the feasibility of the design, and an experimental test is conducted. The test results show that the decoy can be deployed successfully under its passive power and that its structure has good repeatability and surface similarity.

3,4-Dihydroxyphenylacetaldehyde synthase (DHPAAS) catalyzes the direct conversion of 3,4-dihydroxyphenylalanine to 3,4-dihydroxyphenylacetaldehyde (DHPAA), an important intermediate in the formation of flexible insect cuticle. In order to clarify the precise roles DHPAAS plays in insect development and survival, DHPAAS was characterized throughout the physiological to the molecular levels. Extensive in vivo experiments in Aedes aegypti confirm that DHPAAS is essential for blood feeding, egg development and cuticle structure formation. The crystal structure of insect DHPAAS was then solved to reveal the structural basis underlying the catalytic production of the key cuticle intermediate DHPAA. The molecular view shows a DHPAAS active site that is distinct from that of the homologous enzyme 3,4-dihydroxyphenylalanine decarboxylase. Stabilization of the flexible 320–350 region is observed to position the 350–360 loop towards the catalytic asparagine residue, and these distinct features are suggested to promote pyridoxal 5'-phosphate-dependent amine oxidation. Additional molecular dynamics simulations further support the involvement of Phe82, Tyr83 and Asn195 in substrate binding and catalysis, and also shows increased fluctuations limited to loop residues 330–345 in Aedes aegypti DHPAAS.

Background N-hexane, with its metabolite 2,5-hexanedine (HD), is an industrial hazardous material. Chronic hexane exposure causes segmental demyelination in the peripheral nerves, and high-dose intoxication may also affect central nervous system. Demyelinating conditions are difficult to treat and stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) is a promising novel strategy. Our previous study found that BMSCs promoted motor function recovery in rats modeling hexane neurotoxicity. This work aimed to explore the underlying mechanisms and focused on the changes in spinal cord. Methods Sprague Dawley rats were intoxicated with HD (400 mg/kg/day, i.p, for 5 weeks). A bolus of BMSCs (5 × 107 cells/kg) was injected via tail vein. Demyelination and remyelination of the spinal cord before and after BMSC treatment were examined microscopically. Cultured oligodendrocyte progenitor cells (OPCs) were incubated with HD ± BMSC-derived conditional medium (BMSC-CM). OPC differentiation was studied by immunostaining and morphometric analysis. The expressional changes of Hes1, a transcription factor negatively regulating OPC-differentiation, were studied. The upstream Notch1 and TNFα/RelB pathways were studied, and some key signaling molecules were measured. The correlation between neurotrophin NGF and TNFα was also investigated. Statistical significance was evaluated using one-way ANOVA and performed using SPSS 13.0. Results The demyelinating damage by HD and remyelination by BMSCs were evidenced by electron microscopy, LFB staining and NG2/MBP immunohistochemistry. In vitro cultured OPCs showed more differentiation after incubation with BMSC-CM. Hes1 expression was found to be significantly increased by HD and decreased by BMSC or BMSC-CM. The change of Hes1 was found, however, independent of Notch1 activation, but dependent on TNFα/RelB signaling. HD was found to increase TNFα, RelB and Hes1 expression, and BMSCs were found to have the opposite effect. Addition of recombinant TNFα to OPCs or RelB overexpression similarly caused upregulation of Hes1 expression. The secretion of NGF by BMSC and activation of NGF receptor was found important for suppression of TNFα production in OPCs. Conclusions Our findings demonstrated that BMSCs promote remyelination in the spinal cord of HD-exposed rats via TNFα/RelB-Hes1 pathway, providing novel insights for evaluating and further exploring the therapeutical effect of BMSCs on demyelinating neurodegenerative disease.

Spinosad has been extensively used for insect control in agricultural crops. In the present study, a novel succinic derivative of spinosyn A as the hapten was synthesized, and an indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed using a new monoclonal antibody (designed as mAb3E6) specifically against spinosyn A. A mAb3E6-based immunoaffinity column was developed for enrichment extraction of spinosyn A and reduction of matrix interference. The half maximum inhibitory concentration and limit of detection (LOD) of the icELISA were 4.11 ng/mL and 0.63 ng/mL, respectively. The icELISA had average fortified recoveries from 78.1% to 103.2% and the validation results correlated well with high-performance liquid chromatography. The mAb3E6 showed cross reactivity of 80.4%, 75.7% and less than 0.1% with spinosyns B, D and other macrolides, respectively. Interactions of the antibody and macrolides were further analyzed by molecular docking. The developed immunoaffinity chromatography-assisted icELISA is potentially a sensitive and convenient tool for monitoring spinosad residues in milk, fruits, and vegetables.

To compare the clinical efficacy, heart and kidney function, calcium and phosphorus metabolism, serological indicators, and the effects of micro-inflammatory status after two hemodialysis treatments to evaluate the best treatment for patients with end-stage renal disease. According to the criteria for inclusion and exclusion, collected in the Department of Nephrology, third People's Hospital of Gansu Province, patients were selected and received treatment between July 2019 and July 2021. A total of 60 cases were randomized. The urea nitrogen (BUN), blood creatinine (Scr), calcium and phosphorus metabolism levels, inflammation-related factors, and serum-related indicators of the two groups of patients before and after the treatment were detected for half a year. The effective rate (83.33%) of the observation group was higher than that of the control group (66.67%). After treatment, the iPTH, β2-MG, Hcy of the observation group were lower than those of the control group, and ALB was higher than that of the control group. The inflammation-related index observation group was significantly lower than the control However, the difference in Scr and BNU index levels between the two groups of patients after treatment was not so obvious that they could not be evaluated. In terms of all indicators and parameters, high-flux hemodialysis can better treat ESRD and improve the heart and kidney function of patients.

To study the Sustained Low Efficiency Dialysis (SLED) in the treatment of end-stage renal disease with refractory heart failure and the clinical curative effect of refractory hypertension. choose department of Nephrology, third People's Hospital of Gansu Province of 54 cases of end-stage renal disease with refractory heart failure. The patients with intractable hypertension were randomly divided into control group and observation group, with 27 cases in each group. The control group was treated with Intermittent HemoDialysis (IHD), the observation group was treated with SLED for 2 weeks. The levels of Scr, mean arterial pressure (MAP), BUN, heart rate (HR), CRP, IL-1β, TNF-α, TP, Alb and Hb in the observation group were better than those in the control group, and Closer to normal. The continuous low-efficiency and slow approach is better than the intermittent approach for hemodialysis in the treatment of end-stage renal disease complicated by refractory heart failure and refractory hypertension, which has a better treatment and prognostic effect, and can be promoted in clinical treatment.

2,5-hexanedione (HD) is the ultimate neurotoxic metabolite of hexane, causing the progression of nerve diseases in human. It was reported that HD induced apoptosis and oxidative stress. Taurine has been shown to be a potent antioxidant. In the present study, we investigated the protection of taurine against HD-induced apoptosis in PC12 cells and the underlying mechanism. Our results showed the decreased viability and increased apoptosis in HD-exposed PC12 cells. HD also induced the disturbance of Bax and Bcl-2 expression, the loss of MMP, the release of mitochondrial cytochrome c and caspase-3 activation in PC12 cells. Moreover, HD resulted in an increase in reactive oxygen species (ROS) level and a decline in the activities of superoxidedismutase and catalase in PC12 cells. However, taurine pretreatment ameliorated the increased apoptosis and the alterations in key regulators of mitochondria-dependent pathway in PC12 exposed to HD. The increased ROS level and the decreased activities of the antioxidant enzymes in HD group were attenuated by taurine. These results indicate that pretreatment of taurine may, at least partly, prevent HD-induced apoptosis via inhibiting mitochondria-dependent pathway. It is also suggested that the potential of taurine against HD-induced apoptosis may benefit from its anti-oxidative property.

2,5-Hexanedione (HD) is an important bioactive metabolite of n-hexane, which mediates the neurotoxicity of the parent compound. Increasing evidence suggests that over-activated autophagy can lead to autophagic neuronal death; however, whether the excessive autophagy is involved in HD-induced neurotoxicity remains unknown. To investigate the effect of HD on autophagy and to find its underlying mechanism, we respectively treated VSC4.1 cells with 5, 15 and 25 mM HD for 24 h. Our results show that HD induced excessive autophagy of VSC4.1 cells in a dose-dependent manner, also, the over-activated autophagy was significantly mitigated in the presence of PI3K activator or Akt activator or mTOR activator. These results indicate that HD induces excessive autophagy of VSC4.1 cells by repressing the PI3K/Akt/mTOR signaling pathway. LDH assay showed that HD contributed to a concentration dependent increase in VSC4.1 cell death, which was significantly reduced by the administration of PIK-III, an autophagy inhibitor. These results also indicate that HD induces autophagic death of VSC4.1 cells via the signaling pathway.

The entry of industrial and commercial capital into China’s “three rural” area can promote rural economic growth, helping to revitalize the rural stock assets, and it is one of the important ways to double the income of the farmer in China. Under the actual situation of the change of the marginal rate of return of traditional agriculture and the continuous promotion of agricultural industrialization in China, the industrial and commercial capital in traditional industry seeks new profit space and forms the endogenous driving force to enter the “three rural” area. The government’s policy support forms the exogenous driving force, which makes it possible for industrial and commercial capital to promote the doubling of the farmer’s income.

Single-crystal or coarse-grained nanoporous gold (NPG) prepared by dealloying is considered stable against sintering or densification during annealing. Herein, we report that this phenomenon only applies to high-density NPG with relative density ( φ ) exceeding a critical value of 0.31, which densifies very slightly during annealing. In low-density NPG with φ 0.31, annealing induces excessive shrinkage that increases with decreasing φ . Sintering along grain boundaries may account for the small densification of high-density NPG, but it fails to explain the excessive shrinkage of low-density NPG. This densification may be linked to ligament pinch-off, which dominates the coarsening of NPG with φ below ∼ 0.30. However, ligament pinch-off does not directly lead to densification. Instead, we suggest that reattachment of dangling ligaments (generated by pinch-offs) is responsible for the large shrinkage in low-density NPG. This break-and-reconnect scenario is supported by quasi-in situ scanning electron microscopy observations and the evolution of scaled genus density for different type of NPGs during annealing. Our findings suggest that annealing-induced densification can be suppressed by increasing the relative density of NP metals to above 0.31, which is critical to many mechanical and functional explorations.

Keap1 is deemed as a suppressor of Nrf2 in cytoplasm by sequestrating Nrf2 to proteolysis as an adapter of the Cul3-Rbx1 E3 ubiquitin ligase complex. In the study, it was proposed that post-translational modification might affect the interaction between Nrf2 and Keap1, and the profiles of the phosphorylation of amino acid residues of Keap1 and its effects on the binding of Keap1 to Nrf2 was investigated. A mass spectrometry analysis revealed that S53 and S293 were phosphorylated upon an oxidative stress. Using Keap1 proteins with amino acid residues mutated to glutamate to simulate the introduction of a negative charge by phosphorylation, it was found that a potential phosphorylation of S53 affected Keap1-Nrf2 binding in the pull-down assay, and induced nuclear translocation of Nrf2 in the electrophoretic mobility shift assay. Sequence homology analysis showed that S53 was highly conserved. Structural modeling around BTB domain of wild type and S53E-mutant Keap1 showed that the negative charge introduced by S53E mutation generates a salt bridge between E53 and ionized guanidine group of Arg50. Real-time qRT-PCR for transcription levels of antioxidant genes that are modulated by Nrf2 further proved the effects of the potential phosphorylation of S53 under an oxidative stress condition. In summary, S53 is a potential phosphorylation site of Keap1, and the phosphorylation could enhance the antioxidative capacity of cells in response to an oxidative stress.

OBJECTIVES The aim of this study was to identify whether arsenic (As) exposure could induce hippocampal neural apoptosis in vivo. METHODS Sixty-four mice were randomly divided into 4 groups of 16 each. Group 1 orally received drinking water alone as a control. Groups 2-4 were given arsenic trioxide (As2O3) orally at the doses of 1 ppm, 2 ppm and 4 ppm, respectively. All the treatments continued for 60 days. Morphological changes in the hippocampus were observed by HE staining. Apoptosis in the hippocampus was examined by TUNEL assay and transmission electron microscopy. The expression levels of Bcl-2 and Bax genes and their proteins in the hippocampus were determined by real-time PCR and Western blotting. The activity of caspase-3 was determined by spectrophotometry. RESULTS Abnormal histopathological changes and apoptosis were found in the hippocampus of As-exposed mice. The expressions of the Bcl-2 gene and its protein in the hippocampus of As-exposed mice were significantly lower than those in the control group (p

Sojae Semen Praeparatum (SSP) is commonly used as a type of dietetic Chinese herb. By collecting and analyzing ancient and recent literatures, a textual criticism was conducted on the historical evolution of the processing of SSP. Fermented soybean was recorded in Shijing, and relevant rational processing was described in Qimin Yaoshu. In the early time, fermented soybean included the type of "salty" and "light". After the Ming Dynasty, "light" fermented soybean or SSP was recognized as a better medicinal matter than salty fermented soybean, and the fermentation processing was recorded more clearly. In modern time, many characteristic methods for processing SSP have been developed. Today, the processing of SSP is mainly based on the Chinese Pharmacopoeia, which records soybean as a main ingredient and Artemisiae Annuae Herba, Mori Folium as excipients.

To evaluate protection of taurine against arsenic (As)-induced impairment of learning and memory as well as explore its protective mechanism, mice were divided into control, As and taurine protection groups. Mice of As exposure group exposed to drinking water containing 4 ppm As

Expression of enhancer of zeste homolog 2 (EZH2) has been implicated in cancer pathology, but research on its mechanistic activity is limited. The present study sought to assess the levels expression of EZH2 in patients with endometrial carcinoma (EC) and to explore the effects of EZH2 downregulation on the biological behavior of endometrial carcinoma RL-952 cells. Samples were obtained from a total of 104 patients with EC and an immunohistochemical assay was used to detect the expression of EZH2 in cancer and adjacent tissues. The relationship between the expression of EZH2 and the clinicopathological features was analyzed. Endometrial carcinoma RL-952 cells were transfected with chemically synthesized siRNA to conduct targeting inhibition of EZH2 expression. The expression levels of EZH2 protein were detected by immunoblotting. MTT and Transwell assays were used to detect the changes of cell proliferation and invasion after EZH2 downregulation. Of the 104 cases of endometrial carcinoma samples, 71 cases showed positive expression of EZH2, with an expression rate of 68.27%. In 104 cases of adjacent tissue samples, 25 cases showed positive expression of EZH2, with an expression rate of 24.03%. The expression of EZH2 in endometrial carcinoma tissue was significantly higher than that in adjacent tissue (P0.05), but was correlated with the histological grade, depth of tumor invasion, lymph node metastasis and TNM stage (P

To evaluate protection of taurine against arsenic (As)-induced impairment of learning and memory as well as explore its protective mechanism, mice were divided into control, As and taurine protection groups. Mice of As exposure group exposed to drinking water containing 4 ppm As2O3. Mice of taurine protective group received both 4 ppm As2O3 and 150 mg taurine per kilogram. Mice of control group only drank double-distilled water. All animals were treated for 60 days. Morphology of brain was observed by HE staining. Morris water maze (MWM) tests and step-down passive avoidance task were performed to examine cognition function. Moreover, expressions of some genes and proteins related to regulation learning and memory in brain were tested by Real Time RT-PCR and Western Blot. As a result, abnormal morphologic changes in brain tissue and poor performance in cognition functions were observed in As-exposed mice. The expression of TRβ protein, a regulator of CaMK IV gene, significantly decreased in brains of As-exposed mice than in controls. By contrast, impairment in learning and memory, change in brain morphology and disturbance in protein expression were significantly mitigated in mice of taurine protective group. Our results suggest that taurine supplementation protects against neurotoxicity induced by As in mice.

When rotor exist eccentricity, there will be mutual effect between bending vibratory and torsion vibration. This kind of mutual effect will generate bending-torsion coupling vibration. At present, the majority research on the bending-torsion coupling vibration are focus on the nonlinear characteristics, but seldom on the coupling resonance amplitude of the bending-torsion coupling vibration. Given this situation, this article starts with resonance amplitude have further research on the bending-torsion coupling vibration. Firstly, a model of eccentric rotor with coupled bending and torsion vibrations was built and the vibration equation was solved by small parameter method. Then considering the forcing frequency and dynamic tress of the existing equipment can provide,the main resonance of bending-torsion coupling vibration stress relief was determined, and the mechanism of bending-torsion coupling vibration stress relief was put forward. Finally, the example demonstrated the theoretical analysis. The research provide thought and basis for the bending-torsion coupling vibration.

Recently, long term arsenic exposure was considered to be associated with an increased risk of diabetes mellitus. While a relation of cause-and-effect between apoptosis of pancreatic β-cells and arsenic exposure, the precise mechanisms of these events remains unclear. The aim of this study was to explore arsenic-induced pancreatic β-cell apoptosis and the mechanisms of through the possible link between lysosomal and the mitochondrial apoptotic pathway. After exposure to 10 μM of arsenic, the reactive oxygen species (ROS) level was significantly increased at 12 h, while the mitochondrial membrane potential was reduced at 24 h and the lysosomal membrane integrity was disrupted at 48 h. A significant increase in protein expression for cytochrome c was also observed using Western blot analysis after exposure to arsenic for 48 h. To further demonstrate that arsenic reduced the lysosomal membrane integrity, cells pretreated with NH4 Cl and exposed to arsenic harbored a lower fluorescence increase than cells that were only exposed to arsenic. In addition, apoptosis was mesured using Hoechst 33342/PI dual staining by microscopy and annexin V-FITC/propidium iodide dual staining by flow cytometry. The results show an increased uptake of the arsenic dose and the cells changed from dark blue to light blue, karyopyknosis, nuclear chromatin condensation, side set or fracture, and a correlation was found between the number of apoptotic cells and arsenic dose. The result of present study suggest that arsenic may induce pancreatic β-cell apoptosis through activation of the lysosome-mitochondrial pathway.

Adrenocorticotropic hormone (ACTH) is the only medicine for treating infantile spasms, however, it is catabolized rapidly. In order to make an ACTH derivative with prolonged effects, we prepared genetically engineered wild type (WT) and mutant ACTH candidates based on protease database analysis, and compared their stability and pharmacological effects. For analysis of stability, serum concentration of WT and mutant ACTH candidates were tested at different time after intravenous injection, and elimination curves were calculated to compare pharmacokinetic properties of WT and E5D-mutant ACTH. For comparison of their pharmacological effects, levels of glucocorticoids (GC) in the blood serum and secreted from cultured Y1 mouse adrenal cells were tested, and their effects on the signaling pathway mediating the expression of genes critical for GC synthesis were analyzed. The effects of ACTHs on transcription levels of the genes involved in GC synthesis were tested by qPCR. The blood concentration of E5D ACTH is higher than the WT after injection, and E5D mutation increased the t1/2 and AUC of ACTH. Pharmacological experiments showed that the effects of E5D and Y2S mutant ACTH on the production of GC and the critical signal transduction were equivalent to those of WT. WT, E5D and Y2S ACTH also have similar effects on the transcriptional levels of the genes for GC synthesis, including STAR, P450-scc, 3β-HSD, and SF-1. The stability of E5D mutant ACTH is higher than WT ACTH. The pharmacological effects of E5D ACTH is equivalent to those of WT ACTH.

To evaluate prenatal exposure to arsenic in the general population and its effects on birth size, we conducted a cross-sectional study in Dalian, China. Arsenic concentration in maternal and cord blood was detected by inductively coupled plasma-mass spectrometry and its effects on birth size were analyzed by multivariate analysis and multiple linear regression analysis. Arsenic concentrations in cord blood were significantly lower than those in maternal blood. A significant positive correlation was shown between maternal and cord blood arsenic concentrations. Maternal arsenic concentration was negatively associated with birth weight, height and chest circumference, and fetal arsenic concentration was negatively associated with head circumference. Our results indicate that arsenic exposure at environmental levels in uterus may pose adverse effects on fetal development.

Following determination of trypsin inhibitory activity, a serine protease inhibitor was purified and characterized from frog Duttaphrynus melanostictus serum. It was identified as serum albumin, with molecular weight of 67 kDa (DmA-serum). Different from bovine serum albumin, DmA-serum potently inhibited trypsin with similar K i values around 1.6 × 10−7 M. No inhibitory effect on thrombin, chymotrypsin, elastase and subtilisin was observed under the assay conditions. The N-terminal amino acid is EAEPHSRI. Subsequently, a protein with same N-terminal amino acid was purified from skin, termed as DmA-skin. However, DmA-skin is distinct from DmA-serum by binding of a haem b (0.5 mol/mol protein), and with low trypsin inhibitory activity. Frog albumin is distributed in frog skin and exhibited trypsin inhibitory activity, suggesting that it plays important roles in skin physiological functions, like water economy, metabolite exchange and osmoregulation, etc.

Objective To examine maternal and fetal exposure levels to four carcinogenic metals, arsenic (As), cadmium (Cd), nickel (Ni), and beryllium (Be), and to investigate their environmental influences. Methods Metal concentrations in maternal and umbilical cord blood were measured by inductively coupled plasma–mass spectrometry (ICP-MS). Environmental factors that might play a role in exposure were analyzed using Mann–Whitney nonparametric U-tests and multiple linear regression. Results The concentrations of As, Cd, and Ni in umbilical cord blood (5.41, 0.87, and 139.54 μg/L) were significantly lower than those in maternal blood (6.91, 1.93, and 165.93 μg/L). There were significant positive correlations between the maternal and cord concentrations of each carcinogen. Our results showed that: (i) exposures to potentially harmful occupational factors during pregnancy were associated with high levels of maternal As, Cd, and Ni; (ii) living close to major transportation routes (

Mosquitoes transmit a number of diseases in animals and humans, including Dengue, Chikungunya and Zika viruses that affect millions of people each year. Controlling the disease-transmitting mosquitoes has proven to be a successful strategy to reduce the viruses transmission. Polyamines are required for the life cycle of the RNA viruses, Chikungunya virus and Zika virus, and a depletion of spermidine and spermine in the host via induction of spermine N-acetyltransferase restricts their replication. Spermine N-acetyltransferase is a key catabolic enzyme in the polyamine pathway, however there is no information of the enzyme identification in any insects. Aliphatic polyamines play a fundamental role in tissue growth and development in organisms. They are acetylated by spermidine/spermine N-1-acetyl-transferase (SAT). In this study we provided a molecular and biochemical identification of SAT from Aedes aegypti mosquitoes. Screening of purified recombinant proteins against polyamines established that aaNAT5b, named previously based on sequence similarity with identified aaNAT1 in insects, is active to spermine and spermidine. A crystal structure was determined and used in molecular docking in this study. Key residues were identified to be involved in spermine binding using molecular docking and simulation. In addition, SAT transcript was down regulated by blood feeding using a real time PCR test. Based on its substrate profile and transcriptional levels after blood feeding, together with previous reports for polyamines required in arboviruses replication, SAT might be potentially used as a target to control arboviruses with human interference. National Natural Science Foundation of China [31472186] This work was supported by National Natural Science Foundation of China [Grant Number 31472186] (QH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Studies suggested that the conditioned medium of mesenchymal stem cells (MSC-CM) inhibited the increased apoptosis in various cells. However, there are no reports underlying the protection of MSC-CM against 2,5-hexanedione (HD)-induced apoptosis in neural cells. In the present study, the viability was observed in PC12 cells that received HD alone or with MSC-CM by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was estimated by Hoechst 33342 staining and flow cytometry. Mitochondrial transmembrane potential was examined by rhodamine 123. Moreover, we investigated the expression of Bax and Bcl-2, cytochrome c translocation, and caspase 3 activity by real-time polymerase chain reaction, Western blot, and immunochemistry. Nerve growth factor (NGF) was examined in MSCs and MSC-CM. Our results showed that MSC-CM promoted cell survival and reduced apoptosis in HD-exposed PC12 cells. Moreover, MSC-CM significantly reversed disturbance of Bax and Bcl-2, ameliorated disruption of mitochondrial transmembrane potential, and reduced release of cytochrome c and activity of caspase 3 in HD-exposed PC12 cells. In the meantime, NGF was detected in MSCs and MSC-CM. These findings demonstrate that MSC-CM protects against HD-induced apoptosis in PC12 cells via inhibiting mitochondrial pathway. Our results indicate that NGF in MSC-CM may be involved in the protection of MSC-CM against HD-induced apoptosis. Our study clarifies the protection of MSC-CM on HD neurotoxicity and its underlying mechanism.

Developmental processes (i.e., gestation and early childhood) in the nervous system are vulnerable to disruption by some neurotoxicants at doses that may not be toxic to mature systems. The vulnerability of the brain originates from the combination of immaturity and ongoing development. Arsenic and its metabolites easily pass to the fetuses and accumulate in nerve tissue. Epidemiological investigations and animal experiments indicate that chronic arsenic exposure can induce developmental neurotoxicity. Developmental arsenic exposure affects adversely the development of the nervous system and neurobehavior. The mechanisms involved in arsenic-induced developmental neurotoxicity are likely to include inductions of oxidative stress, apoptosis, and oxidative DNA damage, deleterious effects on neurotransmitters and neuroendocrine and cell cycle, perturbation of one-carbon metabolism, and epigenetic effects. These data suggest that developmental arsenic exposure can have long lasting effects on the nervous system well into adolescence. The effects of developmental arsenic exposure may be implicated in long-term fetal programming.

Recently, long term arsenic exposure was considered to be associated with an increased risk of diabetes mellitus. While a relation of cause-and-effect between apoptosis of pancreatic β-cells and arsenic exposure, the precise mechanisms of these events remains unclear. The aim of this study was to explore arsenic-induced pancreatic β-cell apoptosis and the mechanisms of through the possible link between lysosomal and the mitochondrial apoptotic pathway. After exposure to 10 μM of arsenic, the reactive oxygen species (ROS) level was significantly increased at 12 h, while the mitochondrial membrane potential was reduced at 24 h and the lysosomal membrane integrity was disrupted at 48 h. A significant increase in protein expression for cytochrome c was also observed using Western blot analysis after exposure to arsenic for 48 h. To further demonstrate that arsenic reduced the lysosomal membrane integrity, cells pretreated with NH4 Cl and exposed to arsenic harbored a lower fluorescence increase than cells that were only exposed to arsenic. In addition, apoptosis was mesured using Hoechst 33342/PI dual staining by microscopy and annexin V-FITC/propidium iodide dual staining by flow cytometry. The results show an increased uptake of the arsenic dose and the cells changed from dark blue to light blue, karyopyknosis, nuclear chromatin condensation, side set or fracture, and a correlation was found between the number of apoptotic cells and arsenic dose. The result of present study suggest that arsenic may induce pancreatic β-cell apoptosis through activation of the lysosome-mitochondrial pathway.

Arsenic (As) is a neurotoxin induces dysfunction of learning and memory. Research has indicated that cerebellum may be involved in arsenic-induced impairment of learning and memory. However, the molecular mechanisms that underlie these effects remain unclear. This study screened for the differentially expressed genes related to the long-term potentiation and long-term depression (LTP and LTD) at the cerebellar postsynaptic density (PSD) of mice following exposure to arsenic, and we provide evidence of the mechanism by which arsenic adversely affects the functions of learning and memory. Here, SPF mice were exposed to 1ppm, 2ppm and 4ppm As2O3 for 60 days. The ultrastructure of the synapses in cerebella of these mice was observed via transmission electron microscopy. The cerebellum global gene expression of mice exposed to 4ppm As2O3 was determined through GeneChip analysis. We used the web tool DAVID to analyze the Gene Ontology (GO) and KEGG pathways that were significantly enriched among the differentially expressed genes. Our observations of synaptic ultrastructure showed that the thickness of the cerebellar PSD was reduced in mice exposed to arsenic. Go analysis revealed the PSD as a significantly altered cellular component. KEGG pathway analysis showed that LTP and LTD were affected by arsenic with highest statistical significance, and 20 differentially expressed genes were associated with them. Among these differentially expressed genes, significant decreases in the mRNA expressions of CaMKII, Gria1, Gria2, Grin1, Itpr1, Grm1 and PLCβ4 related to the LTP and LTD were found at the PSD of mouse cerebellum exposed to arsenic. The downregulation of these genes was further confirmed via real-time reverse transcription PCR or Western blot at 1ppm, 2ppm and 4ppm As2O3. Our results indicate that the 7 genes with in cerebellar PSDs may be involved in arsenic-induced neurotoxicity, including impairment of learning and memory.

Background: Manganese (Mn) is an essential element and a potential toxicant for developing organism. Deficiency and excess of it were both deleterious to fetal growth in experimental animals. However, literature on relationship between Mn status and birth outcome in humans is sparse. Methods: Mn concentrations were measured in mother whole blood (MWB) and umbilical cord blood (UCB) in 125 pairs of mother–infant; birth size was examined and relationship between them was analysed. Potentially environmental factors influencing Mn loads in maternal and fetal organisms were investigated through epidemiological method. Results: Mn level in UCB was significantly higher than that in MWB (mean value: 54.98 vs. 78.75 µg/L), and a significant positive correlation was shown between them. There was a quadratic curvilinear (inverted U-shaped curve) relationship between MWB Mn and birth size, and between UCB Mn and birth size. Both univariate analysis and multiple linear regression analysis showed that exposure to harmful occupational factors during gestation remarkably increased maternal and fetal Mn levels. Living close to major transportation routes (

For optimizing the cutting process of Radix Isatidis, the influence of cutting process on the whole chemical constituents was studied by comparing the difference of HPLC fingerprints of Radix Isatidis from various sources before and after cutting.L9(3(4)) orthogonal table were designed with three factors: The amount of solvent, soaking time and thickness of pieces. According to the amount of water-soluble extraction, orthogonal design was applied to processing; Fingerprints of acetoacetate extraction from 9 batches of Radix Isatidis from various sources before and after cutting were established with a High Performance Liquid Chromatography method based on a Agilent Zorbax SB-C18 column (4.6 mm x 250 mm, 5 microm) with gradient elution solvent system composed of acetonitrile-water solution; the detection wave length was set at 238 nm; sample injection was 10 microL. The fingerprints were compared with similarity evaluation software published by the Committee of China Codex.The best process of cutting was following: the amount of solvent was 0.6 times of amount of Radix Isatidis, soaked for 24 h and the thickness of piece was 2 mm.The obvious difference is displayed by the comparing of HPLC fingerprints. It is indicated that the constituents in polarity medium lost a lot after cutting process.

A series of 3-aminocarbonyl-2-oxazolidinethione derivatives containing a substituted pyridine ring were designed and synthesized. The structures of all of the title compounds were characterized by 1H NMR, 13C NMR, IR, and HRMS. Their agricultural bioactivities were evaluated, and some of these compounds exhibited good herbicidal activities against Echinochloa crusgalli, Sorghum vulgare, Digitaria sanguinalis, Eclipta prostrasta, Cucumis sativus, and Brassica campestris, which were associated mainly with their steric properties and lipophilicities based on the structure−activity relationship discussion. Keywords: 2-Oxazolidinethiones; pyridine ring; herbicidal activity