Estimation of Short-Term Effects of Air Pollution on Stroke Hospital Admissions in Wuhan,China

Background and Objective

High concentrations of air pollutants have been linked to increased incidence of stroke in North America and Europe but not yet assessed in mainland China. The aim of this study is to evaluate the association between stroke hospitalization and short-term elevation of air pollutants in Wuhan, China.

Methods

Daily mean NO₂, SO₂ and PM₁₀ levels, temperature and humidity were obtained from 2006 through 2008. Data on stroke hospitalizations (ICD 10: I60–I69) at four hospitals in Wuhan were obtained for the same period. A time-stratified case-crossover design was performed by season (April-September and October-March) to assess effects of pollutants on stroke hospital admissions.

Results

Pollution levels were higher in October-March with averages of 136.1 µg/m³ for PM₁₀, 63.6 µg/m³ for NO₂ and 71.0 µg/m³ for SO₂ than in April-September when averages were 102.0 µg/m³, 41.7 µg/m³ and 41.7 µg/m³, respectively (p<.001). During the cold season, every 10 µg/m³ increase in NO₂ was associated with a 2.9% (95%C.I. 1.2%–4.6%) increase in stroke admissions on the same day. Every 10 ug/m³ increase in PM₁₀ daily concentration was significantly associated with an approximate 1% (95% C.I. 0.1%–1.4%) increase in stroke hospitalization. A two-pollutant model indicated that NO₂ was associated with stroke admissions when controlling for PM₁₀. During the warm season, no significant associations were noted for any of the pollutants.

Conclusions

Exposure to NO₂ is significantly associated with stroke hospitalizations during the cold season in Wuhan, China when pollution levels are 50% greater than in the warm season. Larger and multi-center studies in Chinese cities are warranted to validate our findings.     

Pseudoxanthoma Elasticum: Cardiac Findings in Patients and Abcc6-Deficient Mouse Model

Background

Pseudoxanthoma elasticum (PXE), caused by mutations in the ABCC6 gene, is a rare multiorgan disease characterized by the mineralization and fragmentation of elastic fibers in connective tissue. Cardiac complications reportedly associated with PXE are mainly based on case reports.

Methods

A cohort of 67 PXE patients was prospectively assessed. Patients underwent physical examination, electrocardiogram, transthoracic echocardiography, cardiac magnetic resonance imaging (CMR), treadmill testing, and perfusion myocardial scintigraphy (SPECT). Additionally, the hearts of a PXE mouse models (Abcc6^−/−) and wild-type controls (WT) were analyzed.

Results

Three patients had a history of proven coronary artery disease. In total, 40 patients underwent exercise treadmill tests, and 28 SPECT. The treadmill tests were all negative. SPECT showed mild perfusion abnormalities in two patients. Mean left ventricular (LV) dimension and function values were within the normal range. LV hypertrophy was found in 7 (10.4%) patients, though the hypertrophy etiology was unknown for 3 of those patients. Echocardiography revealed frequent but insignificant mitral and tricuspid valvulopathies. Mitral valve prolapse was present in 3 patients (4.5%). Two patients exhibited significant aortic stenosis (3.0%). While none of the functional and histological parameters diverged significantly between the Abcc6^−/− and WT mice groups at age of 6 and 12 months, the 24-month-old Abcc6^−/− mice developed cardiac hypertrophy without contractile dysfunction.

Conclusions

Despite sporadic cases, PXE does not appear to be associated with frequent cardiac complications. However, the development of cardiac hypertrophy in the 24-month-old Abcc6^−/− mice suggests that old PXE patients might be prone to developing late cardiopathy.     

Msb1 Interacts with Cdc42, Boi1, and Boi2 and May Coordinate Cdc42 and Rho1 Functions during Early Stage of Bud Development in Budding Yeast

Msb1 is not essential for growth in the budding yeast Saccharomyces cerevisiae since msb1Δ cells do not display obvious phenotypes. Genetic studies suggest that Msb1 positively regulates Cdc42 function during bud development, since high-copy MSB1 suppressed the growth defect of temperature-sensitive cdc24 and cdc42 mutants at restrictive temperature, while deletion of MSB1 showed synthetic lethality with cdc24, bem1, and bem2 mutations. However, the mechanism of how Msb1 regulates Cdc42 function remains poorly understood. Here, we show that Msb1 localizes to sites of polarized growth during bud development and interacts with Cdc42 in the cells. In addition, Msb1 interacts with Boi1 and Boi2, two scaffold proteins that also interact with Cdc42 and Bem1. These findings suggest that Msb1 may positively regulate Cdc42 function by interacting with Cdc42, Boi1, and Boi2, which may promote the efficient assembly of Cdc42, Cdc24, and other proteins into a functional complex. We also show that Msb1 interacts with Rho1 in the cells and Msb1 overproduction inhibits the growth of rho1-104 and rho1-3 but not rho1-2 cells. The growth inhibition appears to result from the down-regulation of Rho1 function in glucan synthesis, specifically during early stage of bud development. These results suggest that Msb1 may coordinate Cdc42 and Rho1 functions during early stage of bud development by promoting Cdc42 function and inhibiting Rho1 function. Msb1 overproduction also affects cell morphology, septin organization, and causes increased, aberrant deposition of 1,3-β-glucan and chitin at the mother-bud neck. However, the stimulation of glucan synthesis mainly occurs during late, but not early, stage of bud development.     

Systemic Transplantation of Human Umbilical Cord Derived Mesenchymal Stem Cells-Educated T Regulatory Cells Improved the Impaired Cognition in AβPPswe/PS1dE9 Transgenic Mice

Alzheimer’s disease (AD) is one of most prevalent dementias, which is characterized by the deposition of extracellular amyloid-beta protein (Aβ) and the formation of neurofibrillary tangles within neurons. Although stereotaxic transplantation of mesenchymal stem cells (MSCs) into the hippocampus of AD animal model as immunomodulatory cells has been suggested as a potential therapeutic approach to prevent the progress of AD, it is invasive and difficult for clinical perform. Systemic and central nervous system inflammation play an important role in pathogenesis of AD. T regulatory cells (Tregs) play a crucial role in maintaining systemic immune homeostasis, indicating that transplantation of Tregs could prevent the progress of the inflammation. In this study, we aimed to evaluate whether systemic transplantation of purified autologous Tregs from spleens of AβPPswe/PS1dE9 double-transgenic mice after MSCs from human umbilical cords (UC-MSCs) education in vitro for 3 days could improve the neuropathology and cognition deficits in AβPPswe/PS1dE9 double-transgenic mice. We observed that systemic transplantation of autologous Tregs significantly ameliorate the impaired cognition and reduced the Aβ plaque deposition and the levels of soluble Aβ, accompanied with significantly decreased levels of activated microglia and systemic inflammatory factors. In conclusion, systemic transplantation of autologous Tregs may be an effective and safe intervention to prevent the progress of AD.     

NCAM regulates the proliferation,apoptosis, autophagy,EMT, and migration of human melanoma cells via the Src/Akt/mTOR/cofilin signaling pathway

The neural cell adhesion molecule (NCAM) plays critical roles in multiple cellular processes in neural cells, mesenchymal stem cells, and various cancer cells. However, the effect and mechanism of NCAM in human melanoma cells are still unclear. In this study, we found that NCAM regulated the proliferation, apoptosis, autophagy, migration, and epithelial-to-mesenchymal transition of human melanoma cells by determining the biological behavior of NCAM knockdown A375 and M102 human melanoma cells. Further studies revealed that NCAM knockdown impaired the organization of actin cytoskeleton and reduced the phosphorylation of cofilin, an actin-cleaving protein. When cells were transfected with cofilin S3A (dephosphorylated cofilin), biological behavior similar to that of NCAM knockdown cells was observed. Research on the underlying molecular mechanism showed that NCAM knockdown suppressed activation of the Src/Akt/mTOR pathway. Specific inhibitors of Src and PI3K/Akt were employed to further verify the relationship between Src/Akt/mTOR signaling and cofilin, and the results showed that the phosphorylation level of cofilin decreased following inhibition of the Src/Akt/mTOR pathway. These results indicated that NCAM may regulate the proliferation, apoptosis, autophagy, migration, and epithelial-to-mesenchymal transition of human melanoma cells via the Src/Akt/mTOR/cofilin pathway-mediated dynamics of actin cytoskeleton.     

大熊猫精液和包皮菌群组成及潜在致病菌调查

[目的] 大熊猫是我国国家一级保护动物,其种群面临着传染病和栖息地破碎化等持续威胁,其中生殖系统的细菌感染和菌群失衡会影响大熊猫生殖健康,严重者可导致流产,是引起大熊猫繁殖障碍的原因之一。本研究对精液与包皮分泌物样本的菌群组成情况及分离培养潜在致病菌开展研究。[方法] 通过采集13份大熊猫包皮分泌物和12份精液样本,采用16S rRNA扩增子测序技术、细菌培养及PCR鉴定的方法,确定样本中的细菌种类。[结果] 菌群组成分析结果显示,在门水平上,厚壁菌门（Firmicutes）的细菌丰度在大熊猫包皮与精液中均为最高;在属水平上,不同时期的雄性大熊猫包皮的菌群可能会发生改变,棒状杆菌属（Corynebacterium）和Dolosicoccus是Ⅰ期包皮样本中最丰富的微生物菌群,相对丰度分别为15.45%和12.40%;链球菌属（Streptococcus）和埃希氏菌属（Escherichia）是Ⅱ期包皮样本中最丰富的微生物菌群,相对分度分别为37.94%和9.68%;拟杆菌属（Bacteroides）和普雷沃氏菌属（Prevotella）是精液样本中最丰富的微生物菌群,相对丰度分别为14.40%和12.88%。菌群多样性分析结果显示,精液样品高于Ⅰ期包皮样品和Ⅱ期包皮样品,Ⅰ期包皮样品和Ⅱ期包皮样品之间无显著差异。通过细菌分离培养得到肺炎克雷伯菌（Klebsiella pneumonia）在内的多种潜在性致病菌。[结论] 本研究分析了大熊猫精液和不同时期包皮分泌物的菌群组成,其优势菌属存在差异,大熊猫包皮与精液中存在潜在性致病菌,这可能对大熊猫的生殖系统健康带来威胁,其致病性有待进一步研究。     

Demonstration of CRISPR/Cas9/sgRNA-mediated targeted gene modification in Arabidopsis,tobacco, sorghum and rice

The type II CRISPR/Cas system from Streptococcus pyogenes and its simplified derivative, the Cas9/single guide RNA (sgRNA) system, have emerged as potent new tools for targeted gene knockout in bacteria, yeast, fruit fly, zebrafish and human cells. Here, we describe adaptations of these systems leading to successful expression of the Cas9/sgRNA system in two dicot plant species, Arabidopsis and tobacco, and two monocot crop species, rice and sorghum. Agrobacterium tumefaciens was used for delivery of genes encoding Cas9, sgRNA and a non-fuctional, mutant green fluorescence protein (GFP) to Arabidopsis and tobacco. The mutant GFP gene contained target sites in its 5′ coding regions that were successfully cleaved by a CAS9/sgRNA complex that, along with error-prone DNA repair, resulted in creation of functional GFP genes. DNA sequencing confirmed Cas9/sgRNA-mediated mutagenesis at the target site. Rice protoplast cells transformed with Cas9/sgRNA constructs targeting the promoter region of the bacterial blight susceptibility genes, OsSWEET14 and OsSWEET11, were confirmed by DNA sequencing to contain mutated DNA sequences at the target sites. Successful demonstration of the Cas9/sgRNA system in model plant and crop species bodes well for its near-term use as a facile and powerful means of plant genetic engineering for scientific and agricultural applications.     

Glial Cells Activation Potentially Contributes to the Upregulation of Stromal Cell-Derived Factor-1α After Optic Nerve Crush in Rats

Stromal cell-derived factor-1α (SDF-1α) plays an important role after injury. However, little is known regarding its temporal and spatial expression patterns or how it interacts with glial cells after optic nerve crush injury. We characterized the temporal and spatial expression pattern of SDF-1α in the retina and optic nerve following optic nerve crush and demonstrated that SDF-1α is localized to the glial cells that are distributed in the retina and optic nerve. CXCR4, the receptor for SDF-1α, is expressed along the ganglion cell layer (GCL). The relative expression levels of Sdf-1α mRNA and SDF-1α protein in the retina and optic nerve 1, 2, 3, 5, 7, 10 and 14 days after injury were determined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay, respectively, and the Cxcr4 mRNA expression was determined using real-time PCR. Immunofluorescence and immunohistochemical approaches were used to detect the localization of SDF-1α and CXCR4 after injury. The upregulation of Sdf-1α and Cxcr4 mRNA was detected as early as day one after injury in the retina and day two in the optic nerve, the expression peaks 5–7 days after injury. The expression of Sdf-1α and Cxcr4 mRNA was maintained for at least 14 days after the optic nerve crush injury. Furthermore, SDF-1α-positive zones were distributed locally in the reactive glial cells, which suggested potential autocrine stimulation. CXCR4 was mainly expressed in the GCL, which was also adjacent to the the glial cells. These findings suggest that following optic nerve crush, the levels of endogenous SDF-1α and CXCR4 increase in the retina and optic nerve, where activated glial cells may act as a source of increased SDF-1α protein.     

Sedum plumbizincicola X.H. Guo et S.B. Zhou ex L.H. Wu (Crassulaceae): a new species from Zhejiang Province, China

Sedum plumbizincicola X.H. Guo et S.B. Zhou ex L.H. Wu (Crassulaceae), a new species restricted to lead–zinc mining areas in Zhejiang Province, China, is described and illustrated. This taxon belongs to sect. Sedum (H. Ohba) S.H. Fu based on the adaxially gibbous carpels and follicles. It superficially resembles S. alfredii Hance and three other Sedum species found in the same area, but differs from these other taxa in bearing 4-merous flowers. Differences in geographical distribution, growth habit, phenology, macromorphology, leaf and stem anatomy, as well as seed micromorphology among S. plumbizincicola, S. alfredii and other related taxa in the genus Sedum are also reported. nrDNA internal transcribed spacers (ITS) sequences from seven populations of S. plumbizincicola support the recognition of this as a taxonomic entity distinct from S. alfredii.     

Bifunctional oligo(ethylene glycol) decorated surfaces which permit covalent protein immobilization and resist protein adsorption

In this article, surface coatings derived from homo-bifunctional tri(ethylene glycol) (EG₃) and hexa(ethylene glycol) (EG₆) molecules which have two terminal aldehyde groups are reported. These homo-bifunctional molecules can be used to functionalize amine-terminated surfaces through crosslinking one aldehyde group to surface amine groups, while leaving the other aldehyde group available for covalent immobilization of proteins. Best of all, after reducing remaining aldehyde groups on the surface with a reducing agent, sodium borohydride, the surface becomes oligo(ethylene glycol) (OEG)-terminated. The OEG-terminated surface can resist nonspecific protein adsorption, a feature that is often required for many biosensors and biomedical devices. Although some mixed self-assembled monolayers formed from two different organothiols also permit covalent protein immobilization and resist nonspecific protein adsorption, the procedure reported herein requires only one type of homo-bifunctional molecule and can be applied to both silicon and gold surfaces.