Carsim-based simulation study on the performances of raised speed deceleration facilities under different profiles.

OBJECTIVE: Studying the optimal profile shape and size of deceleration facilities suitable for low-speed environment roads under different speed control intervals. METHODS: Simulation modeling of deceleration facilities with various profile shapes and sizes and for vehicles in different speed intervals was performed using the vehicle dynamics simulation software Carsim. The height jumped by a vehicle's wheels, the vertical force on the wheels, and the vertical acceleration of the vehicle were used as indicators of ride comfort and operational stability for the various deceleration facility profiles. RESULTS: stability and comfort were related to the contour of the deceleration facility. Vertical forces were positively related to vehicle jump height, but the jump heights of vehicles passing through deceleration mounds with different planes at the same speed were not significantly different with increasing height. When the vehicle is traveling slowly, the vertical impact force on the vehicle is not significantly related to the speed loss of the vehicle. CONCLUSIONS: Within the speed range of 20-60 km/h and profile heights of 3-10.5 cm, the effectiveness ratings of circular high width and parabolic were basically at level 2 and level 3, but the circular high width had a more stable jump height and was the best profile form, followed by sinusoidal and parabolic, then isosceles trapezoidal, and lastly conventional speed bumps.

Arsenic and UVR co-exposure results in unique gene expression profile identifying key co-carcinogenic mechanisms.

Changes in gene expression underlie many pathogenic endpoints including carcinogenesis. Metals, like arsenic, alter gene expression; however, the consequences of co-exposures of metals with other stressors are less understood. Although arsenic acts as a co-carcinogen by enhancing the development of UVR skin cancers, changes in gene expression in arsenic UVR co-carcinogenesis have not been investigated. We performed RNA-sequencing analysis to profile changes in gene expression distinct from arsenic or UVR exposures alone. A large number of differentially expressed genes (DEGs) were identified after arsenic exposure alone, while after UVR exposure alone fewer genes were changed. A distinct increase in the number of DEGs was identified after exposure to combined arsenic and UVR exposure that was synergistic rather than additive. In addition, a majority of these DEGs were unique from arsenic or UVR alone suggesting a distinct response to combined arsenic-UVR exposure. Globally, arsenic alone and arsenic plus UVR exposure caused a global downregulation of genes while fewer genes were upregulated. Gene Ontology analysis using the DEGs revealed cellular processes related to chromosome instability, cell cycle, cellular transformation, and signaling were targeted by combined arsenic and UVR exposure, distinct from UVR alone and arsenic alone, while others were related to epigenetic mechanisms such as the modification of histones. This result suggests the cellular functions we identified in this study may be key in understanding how arsenic enhances UVR carcinogenesis and that arsenic-enhanced gene expression changes may drive co-carcinogenesis of UVR exposure.

Arsenic is a potent co-mutagen of ultraviolet light.

Arsenic enhances the carcinogenicity of ultraviolet radiation (UVR). However, the mechanisms of arsenic-driven oncogenesis are not well understood. Here, we utilize experimental systems to investigate the carcinogenic and mutagenic properties of co-exposure to arsenic and UVR. In vitro and in vivo exposures indicate that, by itself, arsenic is not mutagenic. However, in combination with UVR, arsenic exposure has a synergistic effect leading to an accelerated mouse skin carcinogenesis and to more than 2-fold enrichment of UVR mutational burden. Notably, mutational signature ID13, previously found only in UVR-associated human skin cancers, is observed exclusively in mouse skin tumors and cell lines jointly exposed to arsenic and UVR. This signature was not observed in any model system exposed purely to arsenic or purely to UVR, making ID13, to the best of our knowledge, the first co-exposure signature to be reported using controlled experimental conditions. Analysis of existing skin cancer genomics data reveals that only a subset of cancers harbor ID13 and these exhibit an elevated UVR mutagenesis. Our results report a unique mutational signature caused by a co-exposure to two environmental carcinogens and provide comprehensive evidence that arsenic is a potent co-mutagen and co-carcinogen of UVR.

Neuronal Zinc Transporter ZnT3 Modulates Cerebral Ischemia-Induced Blood-Brain Barrier Disruption.

Zinc plays important roles in both physiological and pathological processes in the brain. Accumulation of free zinc in ischemic tissue is recognized to contribute to blood-brain barrier (BBB) disruption following cerebral ischemia, but little is known either about the source of free zinc in microvessels or the mechanism by which free zinc mediates ischemia-induced BBB damage. We utilized cellular and animal models of ischemic stroke to determine the source of high levels of free zinc and the mechanism of free zinc-mediated BBB damage after ischemia. We report that cerebral ischemia elevated the level of extracellular fluid (ECF-Zn) of ischemic brain, leading to exacerbated BBB damage in a rat stroke model. Specifically suppressing zinc release from neurons, utilizing neuronal-specific zinc transporter 3 (ZnT3) knockout mice, markedly reduced ECF-Zn and BBB permeability after ischemia. Intriguingly, the activity of zinc-dependent metalloproteinase-2 (MMP-2) was modulated by ECF-Zn levels. Elevated ECF-Zn during ischemia directly bound to MMP-2 in extracellular fluid, increased its zinc content and augmented MMP-2 activity, leading to the degradation of tight junction protein in cerebral microvessels and BBB disruption. These findings suggest the role of neuronal ZnT3 in modulating ischemia-induced BBB disruption and reveal a novel mechanism of MMP-2 activation in BBB disruption after stroke, demonstrating ZnT3 as an effective target for stroke treatment.

Identification of Potential Biomarkers of Septic Shock Based on Pathway and Transcriptome Analyses of Immune-Related Genes.

Immunoregulation is crucial to septic shock (SS) but has not been clearly explained. Our aim was to explore potential biomarkers for SS by pathway and transcriptional analyses of immune-related genes to improve early detection. GSE57065 and GSE95233 microarray data were used to screen differentially expressed genes (DEGs) in SS. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses of DEGs were performed, and correlations between immune cell and pathway enrichment scores were analyzed. The predictive value of candidate genes was evaluated by receiver operating characteristic (ROC) curves. GSE66099, GSE4607, and GSE13904 datasets were used for external validation. Blood samples from six patients and six controls were collected for validation by qRT-PCR and western blotting. In total, 550 DEGs in SS were identified; these genes were involved in the immune response, inflammation, and infection. Immune-related pathways and levels of infiltration of CD4 + TCM, CD8 + T cells, and preadipocytes differed between SS cases and controls. Seventeen genes were identified as potential biomarkers of SS (areas under ROC curves >0.9). The downregulation of CD8A, CD247, CD3G, LCK, and HLA-DRA in SS was experimentally confirmed. We identified several immune-related biomarkers in SS that may improve early identification of disease risk.

Arsenic is a potent co-mutagen of ultraviolet light.

Environmental co-exposures are widespread and are major contributors to carcinogenic mechanisms. Two well-established environmental agents causing skin cancer are ultraviolet radiation (UVR) and arsenic. Arsenic is a known co-carcinogen that enhances UVR's carcinogenicity. However, the mechanisms of arsenic co-carcinogenesis are not well understood. In this study, we utilized primary human keratinocytes and a hairless mouse model to investigate the carcinogenic and mutagenic properties of co-exposure to arsenic and UVR. In vitro and in vivo exposures revealed that, on its own, arsenic is neither mutagenic nor carcinogenic. However, in combination with UVR, arsenic exposure has a synergistic effect leading to an accelerated mouse skin carcinogenesis as well as to more than 2-fold enrichment of UVR mutational burden. Notably, mutational signature ID13, previously found only in UVR-associated human skin cancers, was observed exclusively in mouse skin tumors and cell lines jointly exposed to arsenic and UVR. This signature was not observed in any model system exposed purely to arsenic or purely to UVR, making ID13 the first co-exposure signature to be reported using controlled experimental conditions. Analysis of existing genomics data from basal cell carcinomas and melanomas revealed that only a subset of human skin cancers harbor ID13 and, consistent with our experimental observations, these cancers exhibited an elevated UVR mutagenesis. Our results provide the first report of a unique mutational signature caused by a co-exposure to two environmental carcinogens and the first comprehensive evidence that arsenic is a potent co-mutagen and co-carcinogen of UVR. Importantly, our findings suggest that a large proportion of human skin cancers are not formed purely due to UVR exposure but rather due to a co-exposure of UVR and other co-mutagens such as arsenic.

Arsenic and cancer: Evidence and mechanisms.

Arsenic is a potent carcinogen and poses a significant health concern worldwide. Exposure occurs through ingestion of drinking water and contaminated foods and through inhalation due to pollution. Epidemiological evidence shows arsenic induces cancers of the skin, lung, liver, and bladder among other tissues. While studies in animal and cell culture models support arsenic as a carcinogen, the mechanisms of arsenic carcinogenesis are not fully understood. Arsenic carcinogenesis is a complex process due its ability to be metabolized and because of the many cellular pathways it targets in the cell. Arsenic metabolism and the multiple forms of arsenic play distinct roles in its toxicity and contribute differently to carcinogenic endpoints, and thus must be considered. Arsenic generates reactive oxygen species increasing oxidative stress and damaging DNA and other macromolecules. Concurrently, arsenic inhibits DNA repair, modifies epigenetic regulation of gene expression, and targets protein function due its ability to replace zinc in select proteins. While these mechanisms contribute to arsenic carcinogenesis, there remain significant gaps in understanding the complex nature of arsenic cancers. In the future improving models available for arsenic cancer research and the use of arsenic induced human tumors will bridge some of these gaps in understanding arsenic driven cancers.

Arsenite Methyltransferase Is an Important Mediator of Hematotoxicity Induced by Arsenic in Drinking Water.

Chronic arsenic exposures via the consumption of contaminated drinking water are clearly associated with many deleterious health outcomes, including anemia. Following exposure, trivalent inorganic arsenic (AsIII) is methylated through a series of arsenic (+III oxidation state) methyltransferase (As3MT)-dependent reactions, resulting in the production of several intermediates with greater toxicity than the parent inorganic arsenicals. The extent to which inorganic vs. methylated arsenicals contribute to AsIII-induced hematotoxicity remains unknown. In this study, the contribution of As3MT-dependent biotransformation to the development of anemia was evaluated in male As3mt-knockout (KO) and wild-type, C57BL/6J, mice following 60-day drinking water exposures to 1 mg/L (ppm) AsIII. The evaluation of hematological indicators of anemia revealed significant reductions in red blood cell counts, hemoglobin levels, and hematocrit in AsIII-exposed wild-type mice as compared to unexposed controls. No such changes in the blood of As3mt-KO mice were detected. Compared with unexposed controls, the percentages of mature RBCs in the bone marrow and spleen (measured by flow cytometry) were significantly reduced in the bone marrow of AsIII-exposed wild-type, but not As3mt-KO mice. This was accompanied by increased levels of mature RBCS in the spleen and elevated levels of circulating erythropoietin in the serum of AsIII-exposed wild-type, but not As3mt-KO mice. Taken together, the findings from the present study suggest that As3MT-dependent biotransformation has an essential role in mediating the hematotoxicity of AsIII following drinking water exposures.

Study of instability mechanisms of trucks turning right at long downhill T-junctions based on Trucksim simulation.

The aim of this study was to investigate the influence of road factors on the safety speed threshold of a lorry turning right around a corner at a the bottom of a long downhill T-junction. Trucksim simulation software was chosen to construct a model for investigating the turning instability mechanism. A three-axle truck was chosen as the simulation vehicle and road adhesion coefficients of 0.2-0.75, road super-elevations of -2-8%, turning radii of 20-100 m, and vehicle overcharge of 0-100% selected for tuning. Simulation experiments were carried out for different bending conditions, investigating the effects of each influencing factor on the destabilization speed threshold using the control variable method. The vehicle's lateral load transfer rate and lateral acceleration were indicators for determining whether a truck was unstable. The results showed that: a) the turning radius had the most significant influence on the speed threshold for cornering instability; b) the road surface adhesion coefficient and vehicle overweight had secondary effects; and c) the road height had a general influence.

Serum autoantibodies and exploratory molecular pathways in rural miners: A pilot study.

Introduction: The Southwestern United States (SWUS) has an extensive history of coal and metal mining, including uranium (U) mining. Lung diseases, including but not limited to, lung cancer and pulmonary fibrosis, have been studied extensively in miners due to occupational, dust-related exposures. However, high-throughput autoimmune biomarkers are largely understudied in miners, despite the fact that ore miners, such as U-miners, are at an increased risk for the development of autoimmune diseases such as systemic sclerosis and systemic lupus erythematosus (SLE). Additionally, there are current gaps in knowledge regarding which signaling pathways may play a role in occupational exposure-associated autoimmunity. Methods: Most current and former miners in the SWUS live close to their previous workplaces, in remote areas, with limited access to healthcare. In this pilot study, by leveraging a mobile clinical platform for patient care and clinical outreach, we recruited 44 miners who self-identified as either U (n = 10) or non-U miners (n = 34) and received health screenings. Serum IgG and IgM autoantibodies against 128 antigens were assessed using a high-throughput molecular technique, as a preliminary health screening opportunity. Results: Even when adjusting for age as a covariate, there was a significant (p < 0.05) association between self-reported U-mining exposure and biomarkers including IgM alpha-actinin, histones H2B, and H4, myeloperoxidase (MPO) and myelin basic protein. However, adjusting for age did not result in significant associations for IgG autoantibody production in U-miners. Bioinformatic pathway analysis revealed several altered signaling pathways between IgM and IgG autoantibodies among both U and non-U miners. Conclusions: Further research is warranted regarding the mechanistic connection between U-exposure and autoantibody development, especially regarding histone-related alterations and IgM autoantibody production.

Distribution of polycyclic aromatic hydrocarbons in indoor/outdoor window films and the indoor film/air partition of northeastern Chinese college dormitories.

Indoor window films can represent short-term air pollution conditions of indoor environment through rapidly capturing organic contaminants as effective passive air samplers. To investigate the temporal variation, influence factors of polycyclic aromatic hydrocarbons (PAHs) in indoor window films, and the exchange behavior with gas phase in college dormitories, 42 pairs window films of interior and exterior window surfaces and corresponding indoor gas phase and dust samples were collected monthly in six selected dormitories, Harbin, China, from August to December 2019 and September 2020. The average concentration of ∑16PAHs in indoor window films (398 ng/m2) was significantly (p < 0.01) lower than that in outdoors (652 ng/m2). In addition, the median indoor/outdoor ∑16PAHs concentration ratio was close to 0.5, showing that outdoor air acted as a major PAH source to indoor environment. The 5-ring PAHs were mostly dominant in window films whereas the 3-ring PAHs contributed mostly in gas phase. 3-ring PAHs and 4-ring PAHs were both important contributors for dormitory dust. Window films showed stable temporal variation, i.e. PAH concentrations in heating months were higher than those in non-heating months. The atmospheric O3 concentration was the main influence factor of PAHs in indoor window films. PAHs with low molecular weight in indoor window films rapidly reached film/air equilibrium phase within in dozens of hours. The large deviation in the slope of the log KF-A versus log KOA regression line from that in reported equilibrium formula might be the difference between the window film composition and octanol.

Particulate arsenic trioxide induces higher DNA damage and reactive oxygen species than soluble arsenite in lung epithelial cells.

Environmental arsenic exposure is associated with lung cancer. Arsenic is the first substance known to cause lung cancer by two distinct routes, ingestion and inhalation, in the forms of soluble arsenite and particulate arsenic trioxide, respectively. In comparison to significant progresses in research on mechanisms for lung carcinogenesis of arsenic ingestion, inhalation arsenic exposure route in particulate form and its lung carcinogenic mechanisms are relatively under-investigated. Fundamentally, it remains unclear whether particulate arsenic exposure is in a dissolved form and whether particulate exposure yields higher damage. Utilizing dynamic laser scattering, particulate arsenic trioxide exposure in cellular system was confirmed to be in particulate form instead of dissolved form. Using immunofluorescence, particulate arsenic trioxide was demonstrated to generate dramatically higher oxidative DNA damage and strand break, as well as significantly higher superoxide, in lung epithelial cell lines such as BEAS-2B, HSAEC1-KT, and SAE, comparing to soluble arsenite exposure at similar or lower concentration. This study demonstrated that particulate arsenic trioxide exposure yields higher damage in lung epithelial cells, and indicated that inhalation route of particulate arsenic exposure plays an important role in lung carcinogenesis.

Arsenic impairs the lineage commitment of hematopoietic progenitor cells through the attenuation of GATA-2 DNA binding activity.

Arsenic exposure produces significant hematotoxicity in vitro and in vivo. Our previous work shows that arsenic (in the form of arsenite, AsIII) interacts with the zinc finger domains of GATA-1, inhibiting the function of this critical transcription factor, and resulting in the suppression of erythropoiesis. In addition to GATA-1, GATA-2 also plays a key role in the regulation of hematopoiesis. GATA-1 and GATA-2 have similar zinc finger domains (C4-type) that are structurally favorable for AsIII interactions. Taking this into consideration, we hypothesized that early stages of hematopoietic differentiation that are dependent on the function of GATA-2 may also be disrupted by AsIII exposure. We found that in vitro AsIII exposures disrupt the erythromegakaryocytic lineage commitment and differentiation of erythropoietin-stimulated primary mouse bone marrow hematopoietic progenitor cells (HPCs), producing an aberrant accumulation of cells in early stages of hematopoiesis and subsequent reduction of committed erythro-megakaryocyte progenitor cells. Arsenic significantly accumulated in the GATA-2 protein, causing the loss of zinc, and disruption of GATA-2 function, as measured by chromatin immunoprecipitation and the expression of GATA-2 responsive genes. Our results show that the attenuation of GATA-2 function is an important mechanism contributing to the aberrant lineage commitment and differentiation of early HPCs. Collectively, findings from the present study suggest that the AsIII-induced disruption of erythro-megakaryopoiesis may contribute to the onset and/or exacerbation of hematological disorders, such as anemia.

Genetic diversity and population structure of 93 rice cultivars (lines) (Oryza sativa Xian group) in Qinba in China by 3 types of genetic markers.

BACKGROUND: The Qinba region is the transition region between Indica and Japonica varieties in China. It has a long history of Indica rice planting of more than 7000 years and is also a planting area for fine-quality Indica rice. The aims of this study are to explore different genetic markers applied to the analysis population structure, genetic diversity, selection and optimization of molecular markers of Indica rice, thus providing more information for the protection and utilization on germplasm resources of Indica rice. METHODS: Fifteen phenotypic traits, a core set of 48 SSR markers which originated protocol for identification of rice varieties-SSR marker method in agricultural industry standard of the People's Republic of China (Ministry of Agriculture of the PRC, NY/T1433-2014, Protocol for identification of rice varieties-SSR marker method, 2014), and SNPs data obtained by genotyping-by-sequencing (GBS, NlaIII and MseI digestion, referred to as SNPs-NlaIII and SNPs-MseI, respectively) for this panel of 93 samples using the Illumina HiSeq2000 sequencing platform, were employed to explore the genetic diversity and population structure of 93 samples. RESULTS: The average of coefficient of variation (CV) and diversity index (He) were 29.72% and 1.83 ranging from 3.07% to 137.43%, and from 1.45 to 2.03, respectively. The correlation coefficient between 15 phenotypic traits ranged from 0.984 to -0.604. The first four PCs accounted for 70.693% phenotypic variation based on phenotypic analysis. A total of 379 alleles were obtained using SSR markers, encompassing an average of 8.0 alleles per primer. Polymorphic bands (PPB) and polymorphism information content (PIC) was 88.65% and 0.77, respectively. The Mantel test showed that the correlation between the genetic distance matrix based on SNPs-NlaIII and SNPs-MseI was the largest (R2=0.88), and that based on 15 phenotypic traits and SSR was the smallest (R2=0.09). The 93 samples could be clustered into two subgroups by 3 types of genetic markers. Molecular variance analysis revealed that the genetic variation was 2% among populations and 98% within populations (the Nm was 0.16), Tajima's D value was 1.66, the FST between the two populations was 0.61 based on 72,824 SNPs. CONCLUSIONS: The population genetic variation explained by SNPs was larger than that explained by SSRs. The gene flow of 93 samples used in this study was larger than that of naturally self-pollinated crops, which may be caused by long-term breeding selection of Indica rice in the Qinba region. The genetic structure of the 93 samples was simple and lacked rare alleles.

Antibiotic resistance of Helicobacter pylori isolated from children in Chongqing, China.

The resistance of Helicobacter pylori (H. pylori) to antibiotics has been increasing worldwide and varies across different geographic areas and times. Limited studies reported the prevalence of antibiotic resistance and its related gene mutations in children in Chongqing, a city located in southwest China. We collected 112 H. pylori strains isolated from gastric biopsies of 156 children at Children's Hospital of Chongqing Medical University and calculated resistance rates of these strains to six antibiotics. The A2143G and A2142G mutations in 23S rRNA gene, which are related to clarithromycin resistance, and Asn87 and Asp91 mutations in gyrA gene, which are related to levofloxacin resistance, were investigated in 102 strains. The resistance rates to clarithromycin, metronidazole, and levofloxacin were 47.3% (53/112), 88.4% (99/112), and 18.8% (21/112), respectively. No resistance to amoxicillin, tetracycline, and furazolidone was observed. Dual and triple resistance percentages were 37.5% (42/112) and 10.7% (12/112), respectively. The detection rate of A2143G mutation in 23S rRNA gene was 83.3% (40/48). The detection rates of mutations of Asn87 and Asp91 in gyrA gene were 52.6% (10/19) and 36.8% (7/19), respectively. Conclusion: The prevalence of H. pylori resistance to clarithromycin, metronidazole, and levofloxacin was high in children in Chongqing, China. The A2143G mutation was detected in most clarithromycin-resistant strains, and Asn87 and Asp91 of gyrA mutation points were common in levofloxacin-resistant strains. In clinical practice, anti-H. pylori therapy should be individualized based on a susceptibility test.  What is Known: • The resistance of H. pylori to antibiotics changes with the geographic areas and that in Asia the resistance rate is high. • Mutation plays a vital role in antibiotics resistance of H. pylori. What is New: • High resistance rates to single and multiple antibiotics in children of Chongqing, a city located in southwest China, were observed. • Molecular assays showed good conformance with susceptibility test results to direct antibiotic resistance of H. pylori.

Arsenite exposure inhibits the erythroid differentiation of human hematopoietic progenitor CD34+ cells and causes decreased levels of hemoglobin.

Arsenic exposure poses numerous threats to human health. Our previous work in mice has shown that arsenic causes anemia by inhibiting erythropoiesis. However, the impacts of arsenic exposure on human erythropoiesis remain largely unclear. We report here that low-dose arsenic exposure inhibits the erythroid differentiation of human hematopoietic progenitor cells (HPCs). The impacts of arsenic (in the form of arsenite; As3+) on red blood cell (RBC) development was evaluated using a long-term culture of normal human bone marrow CD34+-HPCs stimulated in vitro to undergo erythropoiesis. Over the time course studied, we analyzed the expression of the cell surface antigens CD34, CD71 and CD235a, which are markers commonly used to monitor the progression of HPCs through the stages of erythropoiesis. Simultaneously, we measured hemoglobin content, which is an important criterion used clinically for diagnosing anemia. As compared to control, low-dose As3+ exposure (100 nM and 500 nM) inhibited the expansion of CD34+-HPCs over the time course investigated; decreased the number of committed erythroid progenitors (BFU-E and CFU-E) and erythroblast differentiation in the subsequent stages; and caused a reduction of hemoglobin content. These findings demonstrate that low-dose arsenic exposure impairs human erythropoiesis, likely by combined effects on various stages of RBC formation.

Isobaric Tags for Relative and Absolute Quantitation-Based Quantitative Serum Proteomics Analysis in Ischemic Stroke Patients With Hemorrhagic Transformation.

Hemorrhagic transformation (HT), which occurs with or without reperfusion treatments (thrombolysis and/or thrombectomy), deteriorates the outcomes of ischemic stroke patients. It is essential to find clinically reliable biomarkers that can predict HT. In this study, we screened for potential serum biomarkers from an existing blood bank and database with 243 suspected acute ischemic stroke (AIS) patients. A total of 37 patients were enrolled, who were diagnosed as AIS without receiving reperfusion treatment. They were divided into two groups based on whether they were accompanied with HT or not (five HT and 32 non-HT). Serum samples were labeled by isobaric tags for relative and absolute quantitation (iTRAQ) and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and compared under NCBInr database. A total of 647 proteins in sera samples were captured, and the levels of 17 proteins (12 upregulated and five downregulated) were significantly different. These differentially expressed proteins were further categorized with Gene Ontology functional classification annotation and Kyoto Encyclopedia of Genes and Genomes metabolic pathway analysis into biological processes. Further protein-protein interaction analysis using String database discovered that, among the differentially expressed proteins, 10 pairs of proteins were found to have crosstalk connections, which may have direct (physical) and indirect (functional) interactions for the development of HT. Our findings suggest that these differentially expressed proteins could serve as potential biomarkers for predicting HT after ischemic stroke.

Prevalence and molecular spectrum of α- and ß-globin gene mutations in Hainan, China.

This study investigated prenatal diagnosis of α-thalassemia and ß-thalassemia in 3049 families in 18 regions of Hainan Province. Molecular diagnosis was performed in 3049 couples with thalassemia in Hainan Province. Genomic DNA was extracted from peripheral blood of the couples and villus, amniotic fluid, or cord blood of fetuses. DNA-based diagnosis was performed using polymerase chain reaction. The most commonly detected mutation for α-thalassemia was- SEA/αα (31.53%), followed by - α4.2/αα (11.15%) and - α3.7/αα (11.02%). The most common mutation for ß-thalassemia was CD41/42 (30.27%), followed by - 28 (2.56%). Prevalence was highest in the coastal regions and lowest in the Wenchang, Lingao, and Ding'an regions. We also found that the most common gene mutations in Han people and other minority groups were not homogeneous. Prenatal diagnosis showed 556 normal fetuses, 116 with α-thalassemia hydrops, and 134 with ß-thalassemia major. Our findings provide important information for clinical genetic counseling regarding prenatal diagnosis for thalassemia major in Hainan Province.

Arsenite and monomethylarsonous acid disrupt erythropoiesis through combined effects on differentiation and survival pathways in early erythroid progenitors.

Strong epidemiological evidence demonstrates an association between chronic arsenic exposure and anemia. We recently found that As+3 impairs erythropoiesis by disrupting the function of GATA-1; however the downstream pathways impacted by the loss of GATA-1 function have not been evaluated. Additionally, our previous findings indicate that the predominant arsenical in the bone marrow of mice exposed to As+3 in their drinking water for 30 days was MMA+3, but the impacts of this arsenical on erythorpoisis also remain largely unknown. The goal of this study was to address these critical knowledge gaps by evaluating the comparative effects of arsenite (As+3) and the As+3 metabolite, monomethyarsonous acid (MMA+3) on two critical regulatory pathways that control the differentiation and survival of early erythroid progenitor cells. We found that 500 nM As+3 and 100 and 500 nM MMA+3 suppress erythropoiesis by impairing the differentiation of early stage erythroid progenitors. The suppression of early erythroid progenitor cell development was attributed to combined effects on differentiation and survival pathways mediated by disruption of GATA-1 and STAT5. Our results show that As+3 primarily disrupted GATA-1 function; whereas, MMA+3 suppressed both GATA-1 and STAT5 activity. Collectively, these findings provide novel mechanistic insights into arsenic-induced dyserythropoiesis and suggest that MMA+3 may be more toxic than As+3 to early developing erythroid cells.