Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Red and processed meat intake and risk of cardiovascular disease: A two-sample Mendelian randomization study.

BACKGROUND & AIMS: Previous observational studies have yielded inconsistent findings regarding associations between red/processed meat intake and the risk of cardiovascular disease (CVD). Some studies have suggested positive relationships, while others have demonstrated no significant associations. However, causal effects remain uncertain. This 2023 Mendelianrandomization (MR) study investigated the causal relationship between red and processed meat (porkmeat, mutton meat, beef meat)intake and CVD risk by analyzing summary data from the UK Biobank (exposure), CARDIoGRAMplusC4D (coronary artery disease [CAD]), MEGASTROKE (stroke), Nielsen et al. (atrial fibrillation [AF]), HERMES (heart failure [HF]), and FinnGen (cardiovascular outcomes) public databases. METHODS: Genome-wide association studies (GWAS) of red meat (pork, beef, and mutton) and processed meat were sourced from the United Kingdom (UK) Biobank. GWAS data on CVD for this study were obtained from the Gene and FinnGen consortia. The primary method employed for the two-sample MR analysis was inverse variance weighting (IVW). Sensitivity analysis was performed to assess the reliability and consistency of the results. RESULTS: Genetically predicted red and processed meat consumption did not demonstrate a causal association with any CVD outcomes when employing the IVW method. For processed meat intake, the odds ratios (ORs) (95% confidence intervals CIs) in large consortia were as follows: 0.88 (0.56-1.39) for CAD, 0.91 (0.65-1.27) for AF, 0.84 (0.58-1.21) for HF, and 1.00 (0.75-1.05) for stroke. In FinnGen, the ORs were as follows: 1.15 (0.83-1.59) for CAD, 1.25 (0.75-2.07) for AF, 1.09 (0.73-1.64) for HF, and 1.27 (0.85-1.91) for stroke. For beef intake, the ORs (95% CIs) in large consortia were as follows: 0.70 (0.28-1.73) for CAD, 0.85 (0.49-1.49) for AF, 0.80 (0.35-1.83) for HF, and 1.29 (0.85-1.95) for stroke. In FinnGen, the ORs were as follows: 2.01 (0.75-5.39) for CAD, 1.83 (0.60-5.56) for AF, 0.80 (0.30-2.13) for HF, and 1.30 (0.62-2.73) for stroke. For pork intake, the ORs (95% CIs) in large consortia were as follows: 1.25 (0.37-4.22) for CAD, 1.26 (0.73-2.15) for AF, 1.71 (0.86-3.39) for HF, and 1.15 (0.63-2.11) for stroke. In FinnGen, the ORs were as follows: 1.12 (0.43-2.88) for CAD, 0.39 (0.08-1.83) for AF, 0.62 (0.20-1.88) for HF, and 0.60 (0.21-1.65) for stroke. For mutton intake, the ORs (95% CIs) in large consortia were as follows: 0.84 (0.48-1.44) for CAD, 0.84 (0.56-1.26) for AF, 1.04 (0.65-1.67) for HF, and 1.06 (0.77-1.45) for stroke. In FinnGen, the ORs were as follows: 1.20 (0.65-2.21) for CAD, 0.92 (0.44-1.92) for AF, 0.74 (0.34-1.58) for HF, and 0.75 (0.45-1.24) for stroke. The results remained robust and consistent in both the meta-analysis and supplementary MR analysis. CONCLUSIONS: This MR study demonstrated no significant causal relationships between red/processed meat intake and the risk of the four CVD outcomes examined. Further investigation is warranted to confirm these findings.

Childhood obesity and hypertension in pregnancy: a two-sample Mendelian randomization analysis.

BACKGROUND: The causal relationship between childhood obesity and hypertension in pregnancy remains unclear. To examine the causal association between childhood obesity and hypertension in pregnancy, two-sample Mendelian randomization analysis was applied. METHODS: Single-nucleotide polymorphisms (SNPs) associated with childhood obesity were obtained from a published genome-wide association study (GWAS) of 13 848 European individuals. Summary-level data for hypertension in pregnancy were obtained from the FinnGen consortium (11534 cases and 162212 controls). Inverse-variance weighted analysis, weighted-median analysis, and Mendelian randomization-Egger regression were conducted in this Mendelian randomization analysis. Sensitivity analyses were conducted to confirm the accuracy and robustness of our results. RESULTS: Genetically determined childhood obesity significantly affects hypertension in pregnancy by IVW [odds ratio (OR) = 1.161, 95% confidence interval (CI) 1.086-1.039; P = 9.92 × 10 -6 ] and weighted median (OR = 1.123, 95% CI 1.038-1.214; P  = 0.004). These results were validated by multiple sensitivity analyses. CONCLUSION: A causal effect between genetically predicted childhood obesity and the risk of hypertension in pregnancy was identified. The prevention of hypertension in pregnancy should be promoted in populations with childhood obesity.

Case report: An elderly woman with recurrent syncope after pacemaker implantation.

Syncope caused by atrioventricular block may occur as a result of a cardiac vasodepressor reflex. This article reports on a case of recurrent syncope in an 80-year-old woman with high-grade atrioventricular block, documented by electrocardiographic monitoring after pacemaker implantation. Pacemaker testing revealed stable impedance and sensing but a clear increase in the ventricular capture threshold at outputs. This case is unusual because the patient's primary diagnosis was non-cardiac. However, a combination of high D-dimer, hypoxemia, and computerized tomography scan of the pulmonary artery confirmed the diagnosis of pulmonary embolism (PE). With 1 month of anticoagulant therapy, the ventricular capture threshold gradually dropped to the normal range and syncope resolved. This is the first report of an electrophysiological phenomenon detected by pacemaker testing in a patient with syncope arising from PE.

Investigation and research on elderly people's willingness to combine medical and health care and related factors in coastal cities in eastern China.

Background: The problem of global aging was becoming increasingly prominent. At present, the empty nest and miniaturization of family structure reduce the function of home-based elderly care. Methods: A questionnaire survey was conducted on 347 elderly people in multiple communities and nursing homes in eastern coastal cities of China, and 13 institutional staff members of eight nursing institutions that carried out the medical-nursing integration model were interviewed as the research objects. The survey mainly focuses on the basic characteristics of the elderly, the family support system, and the acceptance of medical care and health care. The influencing factors were screened by t test, univariate analysis and multivariate logistic regression analysis. SPSS software was used to test the reliability and validity of the questionnaire, and the Crobach's was 0.792, which can be considered that the questionnaire had good internal reliability. The classification of the questionnaire was reasonable, the reliability of the questionnaire was high, and the internal consistency of the scale was high. According to KMO and Bartlett test, KMO = 0.826, χ2 = 853.731, the degree of freedom was 36, and the P value was 0.000. Results: The proportion of male and female respondents was 48.1% and 51.9% respectively. Multivariate logistic regression analysis results showed that gender had no statistical significances on the degree of support for combine medical and health care in the elderly (P > 0.05). The results showed that gender, age, marital status, medical insurance type and old-age insurance type had little effect on the support of the combination of medical care and health care for the elderly (P > 0.05). Compared with the control group with education below primary school, the elderly with bachelor's degree or above are more willing to support the combination of medical care and health (P < 0.05). The registered residence type is more obvious than that of the urban residents (P < 0.05). Compared with the enterprise employees in the control group, the elderly who were employed as migrant workers before retirement were more willing to support the combination of medical care and health (P < 0.05). From the perspective of family monthly income, the elderly with family income ≥10,000 RMB have more obvious support for the combination of medical care and health than the elderly with family monthly income <3,000 RMB in the control group (P < 0.05). In terms of the degree of understanding, the degree of understanding and support in different degrees are significantly higher than that in the control group (P < 0.05). Conclusion: Through multivariate logistic regression analysis, education level, registered residence, pre-retirement occupation and family income are more obvious for the elderly to support medical care and health. It is necessary to increase investment in elderly activity centers, actively carry out activities.

A Case of Syncope in a Child due to the Large Segment of Myocardial Bridge.

We report a child with an unusual coronary bridge crossing over the left anterior descending (LAD), circumflex (CX), and right coronary artery (RCA). The bridges range from 0.8-1.2 mm depth. The patient presented with exercise-induced syncope and myocardial infarction (MI). She exhibited no syncope after medicine and exercise control.

Prognostic Value of ß1 Adrenergic Receptor Autoantibody and Soluble Suppression of Tumorigenicity-2 in Patients With Acutely Decompensated Heart Failure.

BACKGROUND: Both ß1 adrenergic receptor autoantibody (ß1-AA) and soluble suppression of tumorigenicity-2 (sST2) take a role in the pathological remodeling of heart failure. However, limited studies investigated the correlation between the expression of ß1-AA and sST2 in patients with acutely decompensated heart failure (ADHF). OBJECTIVE: To explore the correlation between ß1-AA and sST2, and evaluate their prognostic value in patients with ADHF. METHODS: Patients who were admitted for ADHF were included. The N-terminal pro-brain natriuretic peptide (NT-proBNP), sST2, and ß1-AA in blood samples were tested at hospital admission and then followed up for assessing the outcomes. Pearson correlation analysis was used to explore the correlation between ß1-AA and sST2. The effects of ß1-AA, sST2, or the combination of them on the all-cause mortality of patients with ADHF were assessed by Multivariate Cox regression analysis. RESULTS: There were 96 patients with ADHF and 96 control populations enrolled. The ß1-AA was significantly higher in ADHF than in the control group (0.321 ± 0.06 vs. 0.229 ± 0.04, P = 0.000). Pearson correlation analysis showed that ß1-AA was positively correlated with sST2 (r = 0.593), NT-proBNP (r = 0.557), Procalcitonin (r = 0.176), and left ventricular end-diastolic diameter (r = 0.315), but negatively correlated with triglycerides (r = -0.323), and left ventricular ejection fraction (r = -0.430) (all P < 0.05) in ADHF. Patients with ADHF, complicated with both high ß1-AA and sST2, showed the highest all-cause mortality during an average of 25.5 months of follow-up. Multivariate Cox regression showed the combination of both high ß1-AA and sST2 independently correlated with the all-cause mortality after adjustment for other risk factors (hazard ratio 3.348, 95% CI 1.440 to 7.784, P = 0.005). After adding with ß1-AA and sST2, the area under the curves for the prognostic all-cause mortality could increase from 0.642 to 0.748 (P = 0.011). CONCLUSION: The ß1-AA is positively correlated with sST2 in patients with ADHF. Elevated plasma ß1-AA and sST2 level in patients with ADHF are associated with poorer prognoses.

Evolutionary analysis and functional characterization of SiBRI1 as a Brassinosteroid receptor gene in foxtail millet.

Brassinosteroids (BRs) play important roles in plant growth and development. Although BR receptors have been intensively studied in Arabidopsis, those in foxtail millet remain largely unknown. Here, we show that the BR signaling function of BRASSINOSTEROID INSENSITIVE 1 (BRI1) is conserved between Arabidopsis and foxtail millet, a new model species for C4 and Panicoideae grasses. We identified four putative BR receptor genes in the foxtail millet genome: SiBRI1, SiBRI1-LIKE RECEPTOR KINASE 1 (SiBRL1), SiBRL2 and SiBRL3. Phylogenetic analysis was used to classify the BR receptors in dicots and monocots into three branches. Analysis of their expression patterns by quantitative real-time PCR (qRT-PCR) showed that these receptors were ubiquitously expressed in leaves, stems, dark-grown seedlings, roots and non-flowering spikelets. GFP fusion experiments verified that SiBRI1 localized to the cell membrane. We also explored the SiBRI1 function in Arabidopsis through complementation experiments. Ectopic overexpression of SiBRI1 in an Arabidopsis BR receptor loss-of-function mutant, bri1-116, mostly reversed the developmental defects of the mutant. When SiBRI1 was overexpressed in foxtail millet, the plants showed a drooping leaf phenotype and root development inhibition, lateral root initiation inhibition, and the expression of BR synthesis genes was inhibited. We further identified BRI1-interacting proteins by immunoprecipitation (IP)-mass spectrometry (MS). Our results not only demonstrate that SiBRI1 plays a conserved role in BR signaling in foxtail millet but also provide insight into the molecular mechanism of SiBRI1.

Influencing Factors of Outpatients' Satisfaction in China a Cross-Sectional Study of 16 Public Tertiary Hospitals.

PURPOSE: This study aimed to analyze the status of patient satisfaction in outpatients of tertiary hospitals and the factors affecting patient satisfaction, in order to provide a scientific basis for improving patient satisfaction. METHODS: A total of 6480 surveys of outpatients were conducted by a cross-sectional study in 16 tertiary hospitals in the Zhejiang province of China. The main contents of the survey were the basic characteristics of patients. Statistical description, single-factor analysis and binary logistic regression analysis were used to screen influencing factors. RESULTS: Results of this study showed that the total satisfaction score of outpatients was 87.13±13.47, and higher scored factors in the survey factors were nursing level, the convenience of registration and convenience of appointment diagnosis and treatment. The factors with lower scores were treatment effect, environmental sanitation and comfort and other staffs' attitudes. Hospital managers should pay attention to the improvement of treatment level, environmental sanitation and comfort and other staffs' attitudes. CONCLUSION: In the process of serving outpatients, doctors should pay more attention to patients who are male, 31-45 years old or over 60 years old, permanent residents, from public institutions, possessed postgraduate education, without medical insurance, and who visiting paediatrics and Chinese medicine hospitals.

Myocardial fibrosis combined with NT-proBNP improves the accuracy of survival prediction in ADHF patients.

BACKGROUND: Soluble suppression of tumorigenesis-2 (sST2), Procollagen Type III N-Terminal Peptid (PIIINP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been verified their role in predicting survival in acutely decompensated heart failure (ADHF). However, whether their combination could improve more specific and sensitive prognostic information than NT-proBNP alone remains unclear. METHODS: This was a prospective study, in which 217 ADHF patients at admission were enrolled from November 2018 and August 2019 (mean age 66.18 years ± 13.60, 63.98% male). The blood samples were collected to measure the concentrations of NT-proBNP, sST2 and PIIINP in the first 24 h of hospitalizations. All-cause mortality was registered for all patients after they were discharge over a median period of 339 days. RESULTS: In univariate Cox analysis, the three biomarkers were predictive of short-term mortality of ADHF patients. After adjusted for some clinical variables including age, admission systolic blood pressure, peripheral edema on admission, history of chronic obstructive pulmonary disease, admission sodium < 135 mmol/L, admission hemoglobin, NT-proBNP, sST2 and PIIINP was significantly associated with the poor outcome (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14-1.53, P < 0.01; HR 1.21, 95% CI 1.03-1.43, P = 0.020; HR 1.40, 95% CI 1.08-1.81, P = 0.011). After added with Log2 PIIINP, but not Log2 sST2, the area under the curves (AUC) in the model of clinical variables and Log2 NT-proBNP could increase from 0.79 to 0.85 (95% CI 0.0071-0.10, P = 0.024). Furthermore, compared with the model of clinical variables, Log2 NT-proBNP, the improvement in the prognostic model of clinical variables, Log2 NT-proBNP and Log2 PIIINP had statistical significance [net reclassification improvement (NRI) 0.31, P = 0.018; integrated discrimination improvement (IDI) 0.068, P < 0.01]. CONCLUSIONS: NT-proBNP, sST2 and PIIINP are independent prognostic factors for all-cause mortality in ADHF patients. Furthermore, the combination of NT-proBNP and PIIINP may provide incremental prognostic value over NT-proBNP in the survival of ADHF patients.

BSR-Seq analysis provides insights into the cold stress response of Actinidia arguta F1 populations.

BACKGROUND: Freezing injury, which is an important abiotic stress in horticultural crops, influences the growth and development and the production area of kiwifruit (Actinidia Lind1). Among Actinidia species, Actinidia arguta has excellent cold resistance, but knowledge relevant to molecular mechanisms is still limited. Understanding the mechanism underlying cold resistance in kiwifruit is important for breeding cold resistance. RESULTS: In our study, a population resulting from the cross of A. arguta 'Ruby-3' × 'Kuilv' male was generated for kiwifruit hardiness study, and 20 cold-tolerant and 20 cold-sensitive populations were selected from 492 populations according to their LT50. Then, we performed bulked segregant RNA-seq combined with single-molecule real-time sequencing to identify differentially expressed genes that provide cold hardiness. We found that the content of soluble sucrose and the activity of ß-amylase were higher in the cold-tolerant population than in the cold-sensitive population. Upon - 30 °C low-temperature treatment, 126 differentially expressed genes were identify; the expression of 59 genes was up-regulated and that of 67 genes was down-regulated between the tolerant and sensitive pools, respectively. KEGG pathway analysis showed that the DEGs were primarily related to starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism. Ten major key enzyme-encoding genes and two regulatory genes were up-regulated in the tolerant pool, and regulatory genes of the CBF pathway were found to be differentially expressed. In particular, a 14-3-3 gene was down-regulated and an EBF gene was up-regulated. To validate the BSR-Seq results, 24 DEGs were assessed via qRT-PCR, and the results were consistent with those obtained by BSR-Seq. CONCLUSION: Our research provides valuable insights into the mechanism related to cold resistance in Actinidia and identified potential genes that are important for cold resistance in kiwifruit.

The structure, functional evolution, and evolutionary trajectories of the H+-PPase gene family in plants.

BACKGROUND: The H+-PPase (pyrophosphatase) gene family is an important class of proton transporters that play key roles in plant development and stress resistance. Although the physiological and biochemical functions of H+-PPases are well characterized, the structural evolution and functional differentiation of this gene family remain unclear. RESULTS: We identified 124 H+-PPase members from 27 plant species using complete genomic data obtained from algae to angiosperms. We found that all analyzed plants carried H+-PPase genes, and members were not limited to the two main types (type I and II). Differentiation of this gene family occurred early in evolutionary history, probably prior to the emergence of algae. The type I and II H+-PPase genes were retained during the subsequent evolution of higher plants, and their copy numbers increased rapidly in some angiosperms following whole-genome duplication (WGD) events, with obvious expression pattern differentiation among the new copies. We found significant functional divergence between type I and II H+-PPase genes, with both showing evidence for positive selection pressure. We classified angiosperm type I H+-PPases into subtypes Ia and non-Ia, which probably differentiated at an early stage of angiosperm evolution. Compared with non-Ia subtype, the Ia subtype appears to confer some advantage in angiosperms, as it is highly conserved and abundantly expressed, but shows no evidence for positive selection. CONCLUSIONS: We hypothesized that there were many types of H+-PPase genes in the plant ancestral genome, and that different plant groups retained different types of these genes. In the early stages of angiosperm evolution, the type I H+-PPase genes differentiated into various subtypes. In addition, the expression pattern varied not only among genes of different types or subtypes, but also among copies of the same subtype. Based on the expression patterns and copy numbers of H+-PPase genes in higher plants, we propose two possible evolutionary trajectories for this gene family.

[Cloning and expression of SmDXS2 gene in Swertia mussotii].

1-deoxy-D-xylulose-5-phosphate synthase2(DXS2) is the first key enzyme of the MEP pathway,which plays an important role in terpene biosynthesis of plants. According to the data of Swertia mussotii transcriptome, DXS2 gene(Gen Bank number MH535905) was cloned and named as Sm DXS2. The bioinformatics results showed that Sm DXS2 has no intron,with a 2 145 bp open reading frame encoding a polypeptide of 714 amino acids. They are belonging to 20 kinds of amino acids,and the most abundant amino acids include Ala,Gly and Trp. The predicted protein molecular weight was 76. 91 k Da and its theoretical isoelectric point(p I) was6. 5,which belonging to a hydrophilic protein. α-Helix and loop were the major motifs of predicted secondary structure of DXS2. The three function domains are TPP＿superfamily,Transket＿pyr＿ superfamily and Transketolase＿C superfamily,respectively. The Sm DXS2 protein shared high identity with other DXS2 proteins of plants. Phylogenetic analysis showed that Sm DXS2 protein is grouped with the gentian DXS2 protein. The recombinant protein of Sm DXS2 gene in Escherichia coli was approximately 92. 00 k Da(containing sumo-His tag protein 13 k Da),which was consistent with the anticipated size.This work will provide a foundation for further functional research of Sm DXS2 protein and increasing the product of iridoid compound by genetic engineering in S. mussotii.

[NSD3 suppresses LPS-triggered TNF-α production via promoting the dimethylation of histone H3K36 in macrophages].

Objective To investigate the role of nuclear receptor-binding SET domain protein 3 (NSD3) in lipopolysaccharide (LPS)-triggered tumor necrosis factor α (TNF-α) production in macrophages and the underlying epigenetic mechanism. Methods The experiment used murine peritoneal macrophages and RAW264.7 cells as cell models. The mRNA and protein level of NSD3 were detected by real-time quantitative PCR and Western blot analysis in mouse peritoneal macrophages stimulated with LPS (100 ng/mL). ELISA was used to detect the production of TNF-α in NSD3-overexpressing RAW264.7 cells or NSD3-silencing peritoneal macrophages. Western blot analysis was performed to test the activation of LPS-triggered NF-κBp65 in NSD3-silencing macrophages. Luciferase assay was used to assess NF-κBp65-mediated transcriptional activation of TNF-α gene. ChIP assay was used to detect the recruitment of H3K36 methylation to TNF-α gene promoter. Results LPS inhibited the expression of NSD3 in the macrophages. Over-expression of NSD3 suppressed LPS-triggered TNF-α production, and silencing NSD3 promoted LPS-triggered TNF-α production. However, NSD3 had no effect on the activation of LPS-triggered NF-κBp65. NSD3 enhanced NF-κBp65-mediated transcriptional activation of TNF-α gene. NSD3 enhanced the dimethylation of H3K36 of TNF-α gene promoter. Conclusion NSD3 can promote the dimethylation of H3K36 of TNF-α gene promoter and suppress TNF-α transcription and production.

Predictive Value of Circulating Tumor Cells for Evaluating Short- and Long-Term Efficacy of Chemotherapy for Breast Cancer.

BACKGROUND The present study investigated the role of circulating tumor cells (CTCs) counts in predicting the short- and long-term efficacy of chemotherapy for breast cancer (BC). MATERIAL AND METHODS Peripheral venous blood was extracted from 187 BC patients. CTCs were measured by flow cytometry. Spearman's correlation analysis was performed to examine the correlation between the efficacy of chemotherapy and CTC counts. A receiver operating characteristic (ROC) curve was plotted to estimate the predictive value of CTC counts. The Kaplan-Meier method was employed to calculate disease-free survival (DFS) and overall survival (OS). Cox regression analysis was used to determine risk factors for prognosis of BC. RESULTS Complete response (CR) + partial response (PR) was achieved by 65.8% of BC patients. After chemotherapy, CTC counts were decreased in both the CR + PR and SD + PD groups. Spearman's correlation analysis indicated that CTC counts before chemotherapy were positively correlated with clinical response to chemotherapy (r=0.45, P<0.05). For predicting clinical response to chemotherapy, CTC counts yielded an area under the curve (AUC) of 0.958, with sensitivity reaching 96.9% and specificity reaching 85.4%. The Kaplan-Meier method and Cox regression analysis indicated that tumor node metastasis (TNM) staging, lymph node metastasis (LNM), ki-67, endocrine therapy, and CTC counts were risk factors for prognosis of BC. CONCLUSIONS These findings indicate that BC patients with CTCs ³8 exhibited poor response to chemotherapy and poor OS. CTC counts can serve as an indicator in predicting short- and long-term efficacy of chemotherapy for BC.

Association of ß1-Adrenergic, M2-Muscarinic Receptor Autoantibody with Occurrence and Development of Nonvalvular Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and is independently associated with increased risk of stroke and death. Although the exact mechanisms of AF are not completely elucidated, a large number of evidences demonstrate that autoimmunity may play an important role in the initiation, the progression, and the maintenance of AF. In this study, we aimed to compare anti-ß1-adrenergic receptor autoantibody (anti-ß1-R) and anti-M2-muscarinic receptor autoantibody (anti-M2-R) levels between nonvalvular AF patients and healthy control subjects. METHODS: The levels of serum anti-ß1-R, antinuclear antibodies, and anti-M2-R were measured in both groups by enzyme-linked immunosorbent assay (ELISA). High-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 concentration were measured, respectively, by immunoturbidimetry and chemiluminescence. RESULTS: Anti-ß1-R and anti-M2-R levels were significantly higher in patients with nonvalvular AF than in healthy controls (anti-ß1-R 221.11 [132.38-291.69] ng/mL vs 198.14 [125.70-278.40] ng/mL, P < 0.01; anti-M2-R 271.81 [144.99-378.20] ng/mL vs 235.01 [121.53-358.99] ng/mL, P < 0.01). Compared with the control group, the serum levels of IL-6 and hs-CRP were higher in the nonvalvular AF group (IL-6 19.65 ± 5.6 pg/mL vs 6.79 ± 1.09 pg/mL, hs-CRP 6.03 ± 1.35 mg/L vs 2.73 ± 0.63 mg/L, P < 0.05). Antinuclear antibody (ANA) levels were similar between two groups (ANA 10.55 [1.86-271.8] U/mL vs 10.49 [1.303-161.7] U/mL, P > 0.05). The baseline value of serum anti-ß1-R (odds ratio [OR]: 13.176, P < 0.001), anti-M2-R (OR: 4.41, P < 0.001), IL-6 (OR: 6.126, P < 0.05) levels, and left atrial diameter (OR: 5.781, P < 0.05) were independent predictors of nonvalvular AF by multivariable analyses. CONCLUSION: We found a significant association between circulating serum anti-ß1-R, anti-M2-R, IL-6 levels, and nonvalvular AF. We presume that the autoimmunity and inflammation might take part in electrical remodeling and structural remodeling of left atrium.

ASF1a enhances antiviral immune response by associating with CBP to mediate acetylation of H3K56 at the Ifnb promoter.

ASF1a (anti-silencing function 1a), an evolutionarily conserved protein and a histone chaperone, is required for a variety of chromatin-mediated cellular processes. However, the function of ASF1a in innate immune response remains unclear. Here, we find that ASF1a is induced in Vesicular Stomatitis Virus (VSV)-infected macrophages in a manner that is dependent on IRF3 signal. ASF1a promotes VSV-triggered IFN-ß production. Moreover, acetylation of H3K56 increases at the ifnb promoter after VSV infection, which is dependent on ASF1a. Furthermore, we find ASF1a-mediated H3K56ac is dependent on the acetyltransferases activity of CREB binding protein (CBP) and the association between ASF1a and CBP. Therefore, our work provides a new insight into the antiviral mechanism that histone chaperone ASF1a-mediated H3K56ac modification promotes IFN-ß production.

Cotton S-adenosylmethionine decarboxylase-mediated spermine biosynthesis is required for salicylic acid- and leucine-correlated signaling in the defense response to Verticillium dahliae.

MAIN CONCLUSION: Cotton S-adenosylmethionine decarboxylase-, rather than spermine synthase-, mediated spermine biosynthesis is required for salicylic acid- and leucine-correlated signaling in the defense response to Verticillium dahliae. Spermine (Spm) signaling is correlated with plant resistance to the fungal pathogen Verticillium dahliae. We identified genes for key rate-limiting enzymes in the biosynthesis of Spm, namely S-adenosylmethionine decarboxylase (GhSAMDC) and Spm synthase (GhSPMS). These were found by screening suppression subtractive hybridization and cDNA libraries of cotton (Gossypium) species tolerant to Verticillium wilt. Both were induced early and strongly by inoculation with V. dahliae and application of plant hormones. Silencing of GhSPMS or GhSAMDC in cotton leaves led to a significant accumulation of upstream substrates and, ultimately, enhanced plant susceptibility to Verticillium infection. Exogenous supplementation of Spm to the silenced cotton plants improved resistance. When compared with the wild type (WT), constitutive expression of GhSAMDC in Arabidopsis thaliana was associated with greater Verticillium wilt resistance and higher accumulations of Spm, salicylic acid, and leucine during the infection period. By contrast, transgenic Arabidopsis plants that over-expressed GhSPMS were unexpectedly more susceptible than the WT to V. dahliae and they also had impaired levels of putrescine (Put) and salicylic acid (SA). The susceptibility exhibited in GhSPMS-overexpressing Arabidopsis plants was partially reversed by the exogenous supply of Put or SA. In addition, the responsiveness of those two transgenic Arabidopsis lines to V. dahliae was associated with an alteration in transcripts of genes involved in plant resistance to epidermal penetrations and amino acid signaling. Together, these results suggest that GhSAMDC-, rather than GhSPMS-, mediated spermine biosynthesis contributes to plant resistance against V. dahliae through SA- and leucine-correlated signaling.

Influence of autoantibodies against AT1 receptor and AGTR1 polymorphisms on candesartan-based antihypertensive regimen: results from the study of optimal treatment in hypertensive patients with anti-AT1-receptor autoantibodies trial.

The autoantibodies against angiotensin AT1 receptors (AT1-AAs) in patients with essential hypertension exhibited an agonistic action like angiotensin II and maintained high blood pressure (BP). Angiotensin II receptor gene (AGTR1) polymorphisms were associated with BP response to RAS inhibition in the hypertensive population. Furthermore, the BP response to AT1 receptor blockers varied significantly among individuals with hypertension. We hypothesized that the polymorphisms of the AGTR1 and AT1-AAs might affect antihypertensive response to AT1 receptor blockers based in patients with primary hypertension. Patients who received a candesartan-based regimen came from the SOT-AT1 study (Study of Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor Autoantibodies). The established enzyme-labeled immunosorbent assay was used to detect AT1-AAs in the sera of the patients. Genotype 3 single nucleotide polymorphisms in AGTR1 gene was used by DNA sequencing. The correlations among AT1-AAs, AGTR1 gene polymorphisms or haplotypes, and the antihypertensive effect candesartan-based were analyzed using SPSS. The percentage of systolic BP reduction that was candesartan-based was greater in AT1-AA positive groups than in AT1-AA negative ones (21 ± 8 vs. 18 ± 9; P = .001). Meanwhile, systolic BP reduction that was candesartan-based was more significant in the group of rs5186 AC genotypes than AA homozygotes after adjusting for other confounding factors (37.55 ± 13.7 vs. 32.47 ± 17.27 mm Hg; adjusted P = .028). Furthermore, haplotypes (GCC) and (AAC) had impacts on the antihypertensive effect of candesartan therapy. The AT1-AAs, AGTR1 gene polymorphisms and haplotypes solely or jointly have influences on candesartan-based antihypertensive response in patients with primary hypertension.

The combination of L-4F and simvastatin stimulate cholesterol efflux and related proteins expressions to reduce atherosclerotic lesions in apoE knockout mice.

BACKGROUND: Both L-4F, one apolipoprotein A-1 mimetic peptide, and statins can reduce progression of atherosclerosis by different mechanisms. The combination of the two drugs can cause lesion regression by rendering HDL anti-inflammatory. We postulated that combination of L-4F and simvastatin may stimulate cholesterol efflux and related proteins expressions to alleviate atherosclerosis. METHODS: Thirty male wild-type (W-T) C57 BL/6 mice and apo E(-/-) mice were divided into five groups: W-T group, atherosclerosis (AS) group, simvastatin group, L-4F group and the combination of simvastatin and L-4F group. After 16 weeks, serum lipids, atherosclerotic lesion areas, cholesterol efflux and the expressions of related proteins including ABCA1, SR-BI, ABCG1, LXRα and PPARγ were evaluated. RESULTS: The aortic atherosclerotic lesion areas were reduced more significantly by combination of both drugs than single agent, and cholesterol efflux was promoted more in combination group than simvastatin and L-4F group. Besides, the combination group promoted expressions of cholesterol efflux related proteins. CONCLUSIONS: The combination of L-4F and simvastatin reduced atherosclerotic lesions, which stimulates cholesterol efflux by promoting the expressions of related proteins. In addition, these results help us further understand that the regression of the atherosclerosis would be assessed by reduction in LDL-C with increase of cholesterol efflux.