Norepinephrine regulates TNF expression via the A1AR-p38 MAPK-Relish pathway in granulocytes of oyster Crassostrea gigas.

Norepinephrine (NE) is involved in regulating cytokine expression and phagocytosis of immune cells in the innate immunity of vertebrates. In the present study, the modulation mechanism of NE on the biosynthesis of TNFs in oyster granulocytes was explored. The transcripts of CgTNF-1, CgTNF-2 and CgTNF-3 were highly expressed in granulocytes, and they were significantly up-regulated after LPS stimulation, while down-regulated after NE treatment. The phagocytic rate and apoptosis index of oyster granulocytes were also triggered by LPS stimulation and suppressed by NE treatment. The mRNA expressions of CgMAPK14 and CgRelish were significantly induced after NE treatment, and the translocation of CgRelish from cytoplasm to nucleus was observed. The concentration of intracellular Ca2+ in granulocytes was significantly up-regulated upon NE incubation, and this trend reverted after the treatment with DOX (specific antagonist for NE receptor, CgA1AR-1). No obvious significance was observed in intracellular cAMP concentrations in the PBS, NE and NE+DOX groups. Once CgA1AR-1 was blocked by DOX, the mRNA expressions of CgMAPK14 and CgRelish were significantly inhibited, and the translocation of CgRelish from cytoplasm to nucleus was also dramatically suppressed, while the mRNA expression of CgTNF-1 and the apoptosis index increased significantly to the same level with those in LPS group, respectively. These results collectively suggested that NE modulated TNF expression in oyster granulocyte through A1AR-p38 MAPK-Relish signaling pathway.

Revisiting the diagnostic and prognostic significance of high-frequency QRS analysis in cardiovascular diseases: a comprehensive review.

Cardiovascular diseases (CVDs) present a significant global public health threat, contributing to a substantial number of cases involving morbidity and mortality. Therefore, the early and accurate detection of CVDs plays an indispensable role in enhancing patient outcomes. Decades of extensive research on electrocardiography at high frequencies have yielded a wealth of knowledge regarding alterations in the QRS complex during myocardial ischemia, as well as the methodologies to assess and quantify these changes. In recent years, the analysis of high-frequency QRS (HF-QRS) components has emerged as a promising non-invasive approach for diagnosing various cardiovascular conditions. Alterations in HF-QRS amplitude and morphology have demonstrated remarkable sensitivity as diagnostic indicators for myocardial ischemia, often surpassing measures of ST-T segment changes. This comprehensive review aims to provide an intricate overview of the current advancements, challenges, and prospects associated with HF-QRS analysis in the field of CVDs.

Resolution of trans-1,2-cyclohexanedicarboxylic acid containing two carboxylic groups by forming diastereomeric salts based on feeding molar ratio control.

To investigate the thermodynamic and molecular self-assembly mechanism of trans-1,2-cyclohexane dicarboxylic acid containing two carboxylic acid groups in the chiral resolution process, (S)-phenylethylamine was used as the chiral resolving agent. Two stoichiometric salts were formed when the raw materials were fed at different molar ratios: cyclohexane dicarboxylate monophenylethylamine salt and cyclohexane dicarboxylate diphenylethylamine salt. When the molar ratio of the (S)-phenylethylamine to trans-1,2-cyclohexane dicarboxylic acid was less than 3:1, trans-(1S,2S)-cyclohexane dicarboxylic acid was obtained with 97 e.e% purity. But when the molar ratio exceeded 3:1, the product was the racemic trans-(1,2)-cyclohexane dicarboxylic acid. In addition, single crystal structures of more soluble mono-salt, less soluble mono-salt, and less soluble di-salt were obtained. The weak intermolecular interactions and the way of the molecules packing in the crystals were analyzed. The hydrogen bond was stronger in the less soluble salt than that in the more soluble salt. And a "lock-and-key" structure in the hydrophobic layers makes it more tightly packed through the van der Waals interaction, which is responsible for the stability of less soluble salts.

A bone morphogenetic protein regulates the shell formation of Crassostrea gigas under ocean acidification.

Bone morphogenetic proteins (BMPs) are key factors controlling osteoblast differentiation, which have been proved to be involved in the hard tissue formation of marine mollusks. In the present study, a member of BMPs gene (CgBMP7) was identified from Pacific oyster Crassostrea gigas (C. gigas) with the aim to understand its possible role in the regulation of shell formation under ocean acidification (OA) conditions. The open reading frame (ORF) of CgBMP7 was of 1254 bp encoding a polypeptide of 417 amino acids. The deduced amino acid sequence of CgBMP7 was comprised of one signal peptide, one prodomain and one TGF-ß domain, which shared 21.69%-61.10% identities with those from other species. The mRNA transcript of CgBMP7 was ubiquitously expressed in all the tested tissues of adult oysters with a higher expression level in mantle, notably highest in the middle fold (MF) of the three folds of mantle. The expression level of bone morphogenetic protein type I receptor (CgBMPR1B) mRNA was also highest in the MF and up-regulated dramatically post recombinant BMP7 protein (rCgBMP7) stimulation. After the blockage of BMPR1B with inhibitor LDN193189 (LDN), the mRNA expression level and phosphorylation level of CgSmad1/5/8 in mantle were decreased, and the mRNA expression levels of CgCaM and Cgengrailed-1 were down-regulated significantly. During the oysters were exposed to acidified seawater for weeks, the expression levels of CgBMP7, CgBMPR1B and CgSmad1/5/8 in the MF decreased significantly (p < 0.01) at the 4th week, and CgCaM and Cgengrailed-1 also exhibited the same variable expression patterns as CgBMP7. In addition, the growth of shell in the treatment group (pH 7.8) was slower than that in the control group (pH 8.1). These results collectively indicated that BMP7 was able to trigger the BMPR-Smad signaling pathway and involved in controlling the formation of oyster calcified shell under OA conditions.

Molecular Design of Porous Organic Polymer-Derived Carbonaceous Electrocatalysts for Pinpointing Active Sites in Oxygen Reduction Reaction.

The widespread application of fuel cells is hampered by the sluggish kinetics of the oxygen reduction reaction (ORR), which traditionally necessitates the use of high-cost platinum group metal catalysts. The indispensability of these metal catalysts stems from their ability to overcome kinetic barriers, but their high cost and scarcity necessitate alternative strategies. In this context, porous organic polymers (POPs), which are built up from the molecular level, are emerging as promising precursors to produce carbonaceous catalysts owning to their cost-effectiveness, high electrical conductivity, abundant active sites and extensive surface area accessibility. To enhance the intrinsic ORR activity and optimize the performance of these electrocatalysts, recognizing, designing, and increasing the density of active sites are identified as three crucial steps. These steps, which form the core of our review, serve to elucidate the link between the material structure design and ORR performance evaluation, thereby providing valuable insights for ongoing research in the field. Leveraging the precision of polymer skeletons based on molecular units, POP-derived carbonaceous catalysts provide an excellent platform for in-depth exploration of the role and working mechanism for the specific active site during the ORR process. In this review, the recent advances pertaining to the synthesis techniques and electrochemical functions of various types of active sites, pinpointed from POPs, are systematically summarized, including heteroatoms, surficial substituents and edge/defects. Notably, the structure-property relationship, between these active sites and ORR performance, are discussed and emphasized, which creates guidelines to shed light on the design of high-performance ORR electrocatalysts.

Service network design for freight railway transportation: The Chinese case.

Service network design is a typical tactical planning problem faced in freight railway transportation. In this paper, we propose an integer linear programming model for the rail freight service network design problem in the context of the China railway system. The model aims to minimize the overall costs (including train costs and car costs) while satisfying a set of practical restrictions and operational requirements. Our model also considers a distinct operational feature in Chinese railway transportation practice, i.e., the tree-shaped path. A numerical experiment as well as a real-life case study from the China Railway Jinan Group (CR Jinan) is conducted to demonstrate the proposed solution approach. The real-life problem size reaches as many as 139 stations, 473 alternative train services and 562 shipments. Computational results show that our proposed approach is able to obtain quality solutions within a reasonable time frame.

Noninvasive photoacoustic computed tomography/ultrasound imaging to identify high-risk atherosclerotic plaques.

PURPOSE: Noninvasive detection of high-risk plaques is still challenging. In this study, we aimed to noninvasively assess αvß3-integrin expression using a customed photoacoustic (PA) computed tomography (PACT)/ultrasound (US) system in atherosclerotic lesions of varying degrees of severity and to explore its potential value for detecting high-risk plaques. METHODS: We constructed αvß3-integrin-targeted ultrasmall gold nanorods (AuNRs) with cyclo Arg-Gly-Asp (cRGD) and tested their properties. Employing C57BL/6 J (wild-type, WT) mice and apolipoprotein E gene knockout (ApoE-/-) mice fed either a chow diet or a high-fat/high-cholesterol diet (HFHCD), we established varying degrees of lesion severity. In vivo PACT/US imaging was performed to assess αvß3-integrin expression in the 4 groups by cRGD-AuNRs. Further histopathologic examination was conducted to evaluate the plaque vulnerability indicators. RESULTS: The data showed that cRGD-AuNRs exhibited excellent photothermal conversion capacity, stability, targeting ability, and biocompatibility. The immunohistochemical results indicated that αvß3-integrin was upregulated with increasing aggravation of the lesions. In vivo PACT/US imaging showed good consistency with αvß3-integrin expression. Notably, ApoE-/- mice fed a HFHCD showed an abrupt PA intensity increase compared with the other groups. The histopathologic examination verified that the atherosclerotic plaques of ApoE-/- mice fed the HFHCD developed unstable phenotypes. Correlation analysis showed that PA intensity was mainly related to inflammation and angiogenesis among all of the indicators. CONCLUSION: Our data indicated that αvß3-integrin is an effective indicator of plaque instability, and noninvasive PACT/US molecular imaging assessment of αvß3-integrin holds promise in detecting high-risk plaques.

The Association Between the Frequency of Annual Health Checks Participation and the Control of Cardiovascular Risk Factors.

Background: General health checks can help in controlling cardiovascular risk factors. However, few studies have investigated whether regular participation in annual health checks could further improve the control of cardiovascular risk factors compared with intermittent participation. Therefore, our study aimed to explore the association between the frequency of annual health check participation and the control of cardiovascular risk factors. Methods: Residents aged ≥ 65 years or having chronic diseases (hypertension or diabetes) from 37 communities of Guangzhou, Guangdong, who participated in the Basic Public Health Service project between January 2015 and December 2019, were enrolled and divided into 3 groups ("Sometimes," "Usually," and "Always") according to their frequencies of annual health check participation. Multivariable linear regression models were performed to assess the association between the frequency of annual health check participation and the control of cardiovascular risk factors. A subgroup analysis stratified by gender was also conducted. Results: In total, 9,102 participants were finally included. Significant differences were identified between groups in systolic blood pressure (SBP), diastolic blood pressure (DBP), weight, fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and serum creatinine. After fully adjusting for confounding factors, residents who always participated in the annual health check tended to have lower SBP (ß = -4.36, 95% CI: -5.46; -3.26, p < 0.001), fasting glucose (ß = -0.27, 95% CI: -0.38; -0.15, p < 0.001), and total cholesterol (ß = -0.19, 95% CI: -0.26; -0.13, p < 0.001), compared with those who attended sometimes. Furthermore, gender did not alter these associations. Conclusion: A higher frequency of annual health check participation was associated with lower SBP, fasting glucose, and total cholesterol.

Study on the influence of different production factors on PSY and its correlation.

BACKGROUND: Finding out the key reproductive performance factors, affecting piglets weaned per sow per year (PSY) can improve the production efficiency and profitability of pig farms. The objective was to understand the actual distribution of different production factors and PSY of breeding pig farms, analyze the correlation to find the main production factors affecting PSY, and formulating a Production Efficiency Improvement Plan in practice. Data included 603 breeding pig farms from September 28, 2020 to September 26, 2021. Regression analysis was used to evaluate the relationship between PSY and key production factors, and the characteristics of total pig farms versus high performance (HP) pig farms (the production performance was in the top 10%) or top 5% pig farms were compared. Spearman's rank correlation coefficient was used to analyze the correlation between production factors and find the factors related to PSY. Non-linear support vector regression (NL-SVR) was used to analyze the personalized PSY improvement through a various change of the four key factors. RESULTS: The median distribution of 15 production factors and PSY in total pig farms were different from those of HP farms. All of data were distributed nonlinearly. Mating rate within 7 days after weaning (MR7DW), farrowing rate (FR), number of piglets born alive per litter (PBAL) and number of weaned piglets per litter (WPL) were moderately correlated with PSY, and the correlation coefficients were 0.5058, 0.4427, 0.3929 and 0.3839, respectively. When the four factors in NL-SVR changed in medium (0.5 piglet or 5%) or high level (1.0 piglet or 10%), PSY can be increased by more than 0.5. CONCLUSION: NL-SVR model can be used to analyze the impact of changes in key production factors on PSY. By taking measures to improve MR7DW, FR, PBAL and WPL, it may effectively improve the current PSY and fully develop the reproductive potential of sows.

Angiotensin-converting enzyme polymorphisms AND Alzheimer's disease susceptibility: An updated meta-analysis.

BACKGROUND: Many studies among different ethnic populations suggested that angiotensin converting enzyme (ACE) gene polymorphisms were associated with susceptibility to Alzheimer's disease (AD). However, the results remained inconclusive. In the present meta-analysis, we aimed to clarify the effect of ACE polymorphisms on AD risk using all available relevant data. METHODS: Systemic literature searches were performed using PubMed, Embase, Alzgene and China National Knowledge Infrastructure (CNKI). Relevant data were abstracted according to predefined criteria. RESULTS: Totally, 82 independent cohorts from 65 studies were included, focusing on five candidate polymorphisms. For rs1799752 polymorphism, in overall analyses, the insertion (I) allele conferred increased risk to AD compared to the deletion (D) allele (I vs. D: OR = 1.091, 95% CI = 1.007-1.181, p = 0.032); while the I carriers showed increased AD susceptibility compared with the D homozygotes (II + ID vs. DD: OR = 1.131, 95% CI = 1.008-1.270, p = 0.036). However, none of the positive results passed FDR adjustment. In subgroup analysis restricted to late-onset individuals, the associations between rs1799752 polymorphism and AD risk were identified using allelic comparison (OR = 1.154, 95% CI = 1.028-1.295, p = 0.015, FDR = 0.020), homozygotes comparison, dominant model and recessive model (II vs. ID + DD: OR = 1.272, 95% CI = 1.120-1.444, p < 0.001, FDR < 0.001). Nevertheless, no significant association could be revealed after excluding studies not in accordance with Hardy-Weinberg equilibrium (HWE). In North Europeans, but not in East Asians, the I allele demonstrated increased AD susceptibility compared to the D allele (OR = 1.096, 95% CI = 1.021-1.178, p = 0.012, FDR = 0.039). After excluding HWE-deviated cohorts, significant associations were also revealed under homozygotes comparison, additive model (ID vs. DD: OR = 1.266, 95% CI = 1.045-1.534, p = 0.016, FDR = 0.024) and dominant model (II + ID vs. DD: OR = 1.197, 95% CI = 1.062-1.350, p = 0.003, FDR = 0.018) in North Europeans. With regard to rs1800764 polymorphism, significant associations were identified particularly in subgroup of European descent under allelic comparison (T vs. C: OR = 1.063, 95% CI = 1.008-1.120, p = 0.023, FDR = 0.046), additive model and dominant model (TT + TC vs. CC: OR = 1.116, 95% CI = 1.018-1.222, p = 0.019, FDR = 0.046). But after excluding studies not satisfying HWE, all these associations disappeared. No significant associations were detected for rs4343, rs4291 and rs4309 polymorphisms in any genetic model. CONCLUSIONS: Our results suggested the significant but modest associations between rs1799752 polymorphism and risk to AD in North Europeans. While rs4343, rs4291 and rs4309 polymorphisms are unlikely to be major factors in AD development in our research.

High-Resolution Image Analysis Reveals a Decrease in Lens Thickness and Cone Density in a Cohort of Young Myopic Patients.

Purpose: To study the association between axial length (AL) and the thickness of the lens, retina, choroid, and cone density with swept-source optical coherence tomography (SS-OCT) and an adaptive optics (AO) fundus camera. Design: A prospective cross-sectional study. Methods: This study included 136 eyes in 68 subjects. SS-OCT was used to quantify the thickness of the lens, ganglion cell complex (GCC) layer, inner nuclear layer (INL), outer retinal layer (ORL), and choroid layer. Adaptive optics was used to quantify spatial features of the cone photoreceptors, including density, spacing, regularity, and dispersion. The associations among the AL and the thickness of lens, retina, choroid, and cone features were evaluated with linear regression. Results: With the severity of myopia, the increased AL was associated with thinning of the lens (P < 0.001, 95% CI: -100.42 to -49.76). The thickness of the ORL and choroid decreased significantly (all P < 0.001), whereas the thickness of the GCC and INL decreased only in the outer ring (both P < 0.01). There was a significant correlation between the cone density/spacing and AL (both P < 0.001). Although cone density was reduced from 25,160/mm2 to 19,134/mm2 in the inner region and from 17,458/mm2 to 13,896/mm2 in the outer region, the best-corrected visual acuity (BCVA) was 20/20 or greater. Conclusions: We found that the lens thickness (LT), ORL, and cone density decreased in myopia. While decreasing cone density and ORL thickness should be related to axial elongation, decreasing of LT might imply intrinsic physical accommodation. These results provide further morphological changes of myopia.

A single-CRD C-type lectin (CgCLec-3) with novel DIN motif exhibits versatile immune functions in Crassostrea gigas.

C-type lectins (CTLs), as important pattern recognition receptors (PRRs), are a superfamily of Ca2+-dependent carbohydrate-recognition proteins which participate in nonself-recognition and eliminating pathogens. In the present study, a novel CTL (designated as CgCLec-3) was identified from the Pacific oyster Crassostrea gigas. There was only one carbohydrate-recognition domain (CRD) of 151 amino acid residues within the deduced amino acid sequence of CgCLec-3. The deduced amino acid sequence of CgCLec-3 CRD shared low homology with the CRDs of other CTLs in oyster with the identities ranging from 12% to 22%. A novel DIN motif was found in Ca2+-binding site 2 of CgCLec-3. The relative expression level of CgCLec-3 in hemocytes was up-regulated significantly after the stimulations of bacteria and Pathogen Associated Molecular Patterns (PAMPs). Immunohistochemistry assay showed that CgCLec-3 protein was mainly distributed in gill and mantle, less in gonad, and could not be detected in adductor muscle and hepatopancreas. The recombinant protein (rCgCLec-3) could bind lipopolysaccharide (LPS), mannose (MAN) and peptidoglycan (PGN), but not poly (I:C). rCgCLec-3 exihibited strong binding ability to Vibrio anguillarum and V. splendidus, moderate binding activities to Escherichia coli, Pichia pastoris and Yarrowia lipolytica, weak binding affinity to Staphylococcus aureus and Micrococcus luteus. rCgCLec-3 could agglutinate microorganisms, in a Ca2+-dependent manner and its activity to agglutinate V. splendidus was remarkably higher than that to agglutinate E. coli, S. aureus and P. pastoris. The phagocytic activity of oyster hemocytes was significantly enhanced after incubation with rCgCLec-3. rCgCLec-3 also exhibited antibacterial activity against E. coli and S. aureus. The results clearly suggested that CgCLec-3 in Pacific oyster C. gigas not only served as a PRR involved in the PAMPs recognition and microbes binding, but also functioned as an immune effector participating in the clearance of invaders.

MicroRNA-210-3p Targets RGMA to Enhance the Angiogenic Functions of Endothelial Progenitor Cells Under Hypoxic Conditions.

Endothelial progenitor cells (EPCs) are multipotential stem cells considered to have immense clinical value for revascularization. However, the clinical application of EPCs has been hampered by their clinical potency in ischemic anoxic environments. This study aimed to explore the effect of microRNA-210 (miR-210) on EPCs under oxygen-glucose deprivation (OGD) conditions. We generated a model of EPCs cultured under OGD conditions to simulate ischemia and explore the expression of miR-210 in vitro. With longer exposure to hypoxia, we found that miR-210-3p expression was highly upregulated in OGD groups compared to that in controls from 4 to 24 h, but not miR-210-5p. We then transfected a miR-210-3p mimic and inhibitor into EPCs, and after 24 h, we exposed them to OGD conditions for 4 h to simulate ischemia. We detected miR-210 by real-time polymerase chain reaction (RT-PCR) and tested the proliferation, migration, and tube formation of normal EPCs and OGD-treated EPCs by CCK-8, transwell chamber, and Matrigel assays, respectively. The direct targets of miR-210-3p were predicted using miRWalk. Compared to that in normal EPCs, higher miR-210-3p expression was found in OGD-treated EPCs (p < 0.05). Moreover, upregulation of miR-210-3p was found to promote proliferation, migration, and tube formation in EPCs under normal and OGD conditions (p < 0.05), whereas down-regulation inhibited these abilities in OGD-treated EPCs (p < 0.05). Repulsive guidance molecule A (RGMA), a negative regulator of angiogenesis, was predicted to be a target of miR-210-3p. Accordingly, upregulation of miR-210-3p was found to inhibit its expression at the protein level in OGD-treated EPCs, whereas downregulation of miR-210-3p inhibited its expression (p < 0.05). A dual-luciferase reporter system confirmed that RGMA is a direct target of miR-210-3p. MicroRNA-210-3p overexpression enhances the angiogenic properties of OGD-treated EPCs by inhibiting RGMA.

Comparison Study of ASCO and TOAST Classification System in Chinese Minor Stroke Patients.

BACKGROUND: Precise subtype classification based on underlying pathophysiology is important to prevent recurrent attack in minor stroke patients. A newly developed Atherosclerosis, Small vessel disease, Cardiac source, Others (ASCO) phenotypic classification system aims to characterize patients using different grades of evidence for stroke subtypes. However, this system has not been specifically applied to minor stroke population. In our study, the impact of using the newer ASCO criteria on minor stroke etiologies was investigated, and compared with that of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. METHODS: Consecutive patients with minor ischemic stroke (NIHSS ≤3) were assessed and subtyped by the ASCO and TOAST systems. Stroke etiologies were presented and compared. The McNemar test and k statistic were used to analyze the difference and concordance between the 2 algorithms, respectively. RESULTS: A total of 604 first-ever minor stroke patients were analyzed in the present study. Using TOAST classification, large artery atherosclerosis was the most frequent subtype (281, 46.5%), followed by small artery occlusion category (165, 27.3%). When ASCO was applied, 37 different profiles of stroke etiologies were identified. Using grade 1 of evidence, atherosclerosis (A1) was the most frequent subtype (308, 51.0%), followed by small vessel disease (S1, 178, 29.5%). Under consideration of grades 1 and 2, 239 (39.6%) patients were classified into more than 1 category. The ASCO system revealed determined etiologies in 104 of the 137 patients classified to cause undetermined subtype by TOAST classification. Good to very good accordance was observed between ASCO grade 1 and TOAST schemes across etiologic subtypes (κ = 0.719-0.832) except cause undetermined category (κ = 0.470). CONCLUSION: Application of ASCO decreased the proportion of patients assigned to cause undermined category compared to TOAST system. Comprehensive characteristics of ASCO system might be helpful in the personalized therapy or secondary prevention for individual patients in the future.

The ancient role for GATA2/3 transcription factor homolog in the hemocyte production of oyster.

Hemocytes, the cellular component of invertebrate hemolymph, are essential for invertebrate immunity, but the hematopoiesis and regulation mechanism are still largely unknown. In the present study, a conserved hematopoietic transcription factor Cg-GATA2/3 was identified in Pacific oyster Crassotrea gigas, which was evolutionarily close to the vertebrate GATA1/2/3. Cg-GATA2/3 was mainly distributed in the immune organs, such as gill, hemocytes, and mantle. After Cg-GATA2/3 was interferenced by dsRNA, the mRNA expressions of hemocytes specific gene (EcSOD) and hematopoietic transcription factor (C-Myb) were all significant down-regulated, and the hemocyte renewal rates also decreased both in hemolymph and gill. During the larval developmental stages, the mRNA transcripts of Cg-GATA2/3 increased immediately after fertilization and kept a high level during blastula and early trochophore larvae stage (4-10 hpf, hours post fertilization), then decreased sharply in early D-veliger larvae stage (15 hpf). Whole-mount immunofluorescence assay further revealed that the abundant immunoreactivity of Cg-GATA2/3 was distributed in the whole body of blastula and gastrula embryos, while specialized gradually to a ring structure around the dorsal region in trochophore larvae. In the D-veliger and umbo larvae, scattered positive signals appeared in the specific sinus structure on the dorsal side and velum region. These results demonstrated that Cg-GATA2/3 was a hematopoietic lineage-specific transcription factor to regulate the hemocyte production, and it could also be used as hematopoietic specific marker to trace potential developmental events of hematopoiesis during ontogenesis of oyster.

Hemiballism-hemichorea induced by ketotic hyperglycemia: case report with PET study and review of the literature.

Hemiballism-hemichorea (HB-HC) is commonly used to describe the basal ganglion dysfunction in non-ketotic hyperglycemic elderly patients. Here we report two elderly female patients with acute onset of involuntary movements induced by hyperglycemia with positive urine ketones. We described the computed tomography and magnetic resonance imaging findings in these two patients, which is similar to that of non-ketotic hyperglycemic HB-HC patients. FDG-PET was performed and the glucose metabolism in the corresponding lesion in these two patients was contradictory with each other. We tried to clarify the underlying mechanisms of HB-HC and explain the contradictory neuroradiological findings in FDG-PET as being performed at different clinical stages.

Restless legs syndrome in Chinese elderly people of an urban suburb in Shanghai: a community-based survey.

OBJECTIVE: The aim of the study is to investigate the prevalence rate of restless legs syndrome (RLS) in elderly Chinese people over 50 years of age in an urban suburb of Shanghai by a community-based study. METHODS: A 3-step survey was adopted including two telephone-based interviews and one face-to-face interview. We used questions based on four diagnostic criteria for RLS to perform the first telephone interview. The second telephone interview was performed by a sleep specialist to rule out the 'mimics' and secondary RLS. The final face-to-face interview was performed in the clinic for confirmation and examination. RESULTS: There were 2609 inhabitants in the Wuli Bridge suburb of Shanghai who responded to the first telephone interview (men 68.55±10.13 years of age and women 65.34±10.52 years of age, mean±SD). Eighteen people were finally diagnosed with RLS. In this sample, the overall prevalence rate of RLS was about 0.69% (95% confidence interval (CI): 0.41-1.09). CONCLUSION: Our study provided the first data about the prevalence rate of RLS in an urban suburb of Shanghai from mainland China, which is consistent with the low prevalence rate reported in other Asian countries.

2-methoxyestradiol attenuates autophagy activation after global ischemia.

BACKGROUND: Hypoxia inducible factor 1 (HIF-1) is a key transcriptional factor activated during cerebral ischemia, which regulates a great number of downstream genes, including those associated with cell death. In the present study, we aimed to test the hypothesis that post-ischemic HIF-1α up-regulation might promote autophagy activation; thereby, HIF-1α inhibitor 2ME2 might prevent neurons from ischemic injury through inhibiting autophagy. METHODS: Global ischemia was induced using the four-vessel occlusion model (4-VO) in Sprague-Dawley rats (male, 250-280g). 2-Methoxyestradiol (2ME2, 5mg/kg, i.p.) was administrated to down-regulate HIF-1α expression. Post-ischemic beclin-1 and LC3 protein expression was determined at different time points through Western blot assay. Neuronal injury was determined by cresyl violet staining and TUNEL staining in coronal histological sections. RESULTS: The expression of beclin-1 and the ratio of LC3-II/LC3-I increased significantly at 12 and 24 h after ischemia. 2ME2 could remarkably inhibit the up-regulation of beclin-1 and the increase of LC3-II/LC3-I ratio during reperfusion. Moreover, 2ME2 and 3-MA exhibited powerful protective effects against ischemic/reperfusion induced neuronal injury. CONCLUSIONS: This study confirmed that autophagy participated in post-ischemic neuronal injury. 2ME2, a HIF-1α inhibitor, might significantly decrease autophagy activation after cerebral ischemia and relieve post-ischemic neuronal injury. Our findings demonstrate that autophagy could be a potential target for neuronal protection after cerebral ischemia.

Starvation triggers Abeta42 generation from human umbilical vascular endothelial cells.

Cerebral amyloid angiopathy is a common feature in Alzheimer's disease (AD), which is characterized by amyloid deposit around brain vessels including capillaries. The origin of the amyloid protein of CAA remains controversial. In our work, we provide data to show that primary umbilical vein endothelial cells (HUVEC) harbor APP processing secretases and can produce Abeta(42) under starvation. Starvation can increase the secretion of Abeta(42) by altering the expression of beta-secretases (BACE1) and gamma-secretases (APH and PEN2). This process is regulated by macroautophagy. Suppression of macroautophagy induction by 3MA further increased the level of Abeta(42) produced under starvation in HUVECs. These results suggest that starvation-induced Abeta(42) secretion might contribute to the formation of CAA and hence vascular degeneration in AD.

Apolipoprotein E promoter polymorphisms and risk of Alzheimer's disease: evidence from meta-analysis.

Apolipoprotein E (APOE) promoter polymorphisms have long been linked to Alzheimer disease (AD) susceptibility, although the established data remains controversial. Using meta-analysis, our study aimed to clarify the nature of the genetic risks contributed by the three polymorphisms for developing AD. Medline, Embase, and Alzgene search identified 40 studies with 9,662 cases and 9.696 controls. Both -491A/T polymorphism (AA vs AT + TT: OR = 1.49, 95% CI=1.29-1.72) and -219T/G polymorphism (TT vs TG + GG: OR=1.30, 95% CI=1.10-1.55) showed a significant association with AD susceptibility; however, significant association was not identified in the analysis for -427T/C polymorphism (TT vs TC + CC: OR =1.03, 95% CI= 0.82-1.30). Among the APOE epsilon 4} carriers, the -491A homozygotes were at higher risk to develop AD compared with the -491T carriers (OR=1.42, 95% CI =1.15-1.76). For subjects carrying the -491AA genotype, the presence of the APOE epsilon4 allele increased the risk of AD 4.37-fold (95% CI=3.43-5.56). Subgroup analysis restricted to the late-onset or the Caucasian individuals revealed a similar association as that identified without restriction regarding -491A/T polymorphism. Our results confirm a significant but modest association between APOE promoter -491A/T and -219T/G polymorphisms and AD susceptibility.