The association between circulating APRIL levels and severity of obstructive sleep apnea in Chinese adults.

BACKGROUND: Obstructive sleep apnea (OSA) is the most common type of sleep breathing disorder and is characterized by chronic intermittent hypoxia, which could cause inflammation and nuclear factor kappa B (NF-KB)-dependent inflammatory pathways activation. Circulating APRIL (a proliferation-inducing ligand) play an important role in promoting inflammation and NF-KB-dependent inflammatory pathways activation. We explored the role of APRIL as a potential mechanism of inflammation in OSA patients. METHODS: After detailed sleep evaluated, venous blood and demographic data were collected from 155 subjects with varying severity of OSA and 52 control subjects. Plasma levels of APRIL were measured by human Magnetic Luminex assay. RESULTS: Plasma APRIL levels were significantly higher in OSA subjects compared with control subjects. Categorization of the OSA subjects into mild, moderate, and severe OSA subgroups found that plasma levels of APRIL increased with the severity of OSA. After adjusting confounding factors, found that increased plasma APRIL levels were conferred a higher odds ratio of OSA. Moreover, plasma APRIL levels were positively associated with the apnea-hypopnea index, which represents the severity of OSA. Furthermore, plasma APRIL showed higher discriminatory accuracy in predicting the presence of OSA. CONCLUSIONS: Plasma APRIL levels were significantly associated with the occurrence of OSA and its severity. APRIL could be a plasma biomarker with a positive diagnostic value for inflammation and NF-KB-dependent inflammatory pathways activation in subjects with OSA. TRIAL REGISTRATION: The project was approved by the Chinese Clinical Trial Registry (No. ChiCTRROC-17011027).

Prediction mode of more than 5 central lymph nodes metastases in clinically node-negative ipsilateral papillary thyroid carcinoma with tumor size 1 to 4 cm.

According to the 2015 American Thyroid Association guidelines, either lobectomy or total thyroidectomy was recommended for patients with papillary thyroid carcinoma (PTC) of 1 to 4 cm without extrathyroidal extension and lymph node metastasis. However, lymph node metastases showed strong association with recurrence and low survival rate, especially in PTC patients with more than 5 metastatic lymph nodes. Therefore, this study aimed to investigate the predictive factors of more than 5 central lymph nodes metastases (CLNM) in PTC patients with tumor sizes of 1 to 4 cm. A total of 382 patients with clinically node-negative (cN0) ipsilateral PTC who underwent thyroidectomy with central neck dissection between January 2012 and December 2016 were retrospectively analyzed. CLNMs of >5 were found in 54 (14.1%) patients, while CLNM was detected in 230 (60.2%) patients. Multivariate logistic regression revealed age < 45 years (P < .001), male gender (P = .013), and tumor sizes of >2 cm (P = .001) as independent predictive factors of >5 CLNMs in cN0 ipsilateral PTC patients with tumor sizes 1 to 4 cm. The prediction equation (Y = 1.694 × age + 0.807 × gender + 1.190 × tumor size - 3.530) was developed, with a sensitivity (57.4%) and a specificity (80.8%), respectively, at an optimal cut-off point of -1.685. Therefore, if the predictive value was higher than -1.685 according to the equation in cN0 ipsilateral PTC patients with tumor sizes 1 to 4 cm, then total thyroidectomy might be considered.

Nocardia mangyaensis sp. nov., a novel actinomycete isolated from crude-oil-contaminated soil.

A Gram-stain-positive, aerobic, non-motile and mycolic-acid-containing strain, designated Y48T, was isolated from soil contaminated by crude oil located in the northern margin of the Qaidam Basin. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Y48T belongs to the genus Nocardia and is closely related to N. cummidelens DSM 44490T (99.0 % similarity), N. soli DSM 44488T (99.0 %), N. lasii 3C-HV12T (98.9 %), N. salmonicida NBRC 13393T (98.6 %), N. ignorata NBRC 108230T (98.6 %) and N. coubleae NBRC 108252T (98.6 %). The average nucleotide identity and DNA-DNA hybridization values between strain Y48T and the reference strains were 75.9-84.5 and 27.5-29.0 %, respectively, values that were below the thresholds for species delineation. Chemotaxonomic analysis indicated that the major fatty acids of strain Y48T were C16 : 0, summed feature 3 (C16 : 1ω6c/C16 : 1ω7c), C18 : 1ω9c and C18 : 0 10-methyl (TBSA). The respiratory quinone was MK-8(H4, ω-cycl). The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, two glycolipids and three unidentified lipids. The cell-wall hydrolysates contained meso-diaminopimelic acid, with ribose, arabinose, glucose and galactose as whole-cell sugars. A combination of 16S rRNA gene sequence analysis, and phenotypic and chemotaxonomic characterizations demonstrated that strain Y48T represents a novel species of the genus Nocardia, for which the name Nocardia mangyaensis sp. nov. is proposed. The type strain is Y48T (=JCM 32795T=CGMCC 4.7494T).

TNFRSF11B: A potential plasma biomarker for diagnosis of obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) was characterized by chronic intermittent hypoxia, which was an independent risk factor for endothelial dysfunction. Circulating TNFRSF11B might play an important role in promoting endothelial cells dysfunction. We explored the role of plasma TNFRSF11B as a potential mechanism of endothelial dysfunction in OSA patients. METHODS: The study population consisted of 120 patients with varying severity of OSA and 40 control subjects. Plasma TNFRSF11B levels were measured using human Magnetic Luminex assay. RESULTS: Our data showed that plasma TNFRSF11B levels were significantly higher in patients with OSA. After adjusting confounding factors, plasma TNFRSF11B levels were independently associated with the presence of OSA (Beta:0.434, 95% CI: 664.096 to 1076.247; P < 0.001) and plasma TNFRSF11B levels were positively associated with the apnea-hypopnea index (Beta:0.486, 95% CI: 0.007 to 0.017; P < 0.001). Furthermore, plasma TNFRSF11B showed higher discriminatory accuracy in predicting the presence of OSA (AUC:0.964). CONCLUSIONS: Plasma TNFRSF11B levels were significantly associated with the presence of OSA and its severity. TNFRSF11B could be a plasma biomarker with a positive diagnostic value for premature vascular endothelial dysfunction in patients with OSA.

Association between decreased serum parathyroid hormone after total thyroidectomy and persistent hypoparathyroidism.

BACKGROUND: Postoperative hypocalcemia caused by hypoparathyroidism is one of the most common morbidities of total thyroidectomy. The aim of this study was to analyze the kinetics and factors affecting PTH levels after total thyroidectomy and central neck dissection (CND). MATERIAL/METHODS: We performed a retrospective study in 438 consecutive patients who underwent total thyroidectomy between January 2007 and December 2010. No patient had a history of thyroid or neck surgery. PTH and calcium levels were recorded 1 day before the operation, during the first 5 days, and during follow-up (2 weeks and 2, 6, and 12 months). RESULTS: PTH levels declined to 41.90% of its initial value on the first day after the operation. After surgery, PTH was correlated positively with calcium and inversely with phosphate levels from postoperative day 1 to 14. Based on clinical observation, using a PTH threshold of <7 ng/L on postoperative day 1 was predictive of persistent hypoparathyroidism, with sensitivity and negative predictive value 100%, but poor specificity (70.19%). CND increased the risk of transient hypoparathyroidism compared with total thyroidectomy alone. Patients with thyroiditis had an increased risk of permanent hypoparathyroidism compared with those without thyroiditis. Iatrogenic removal of the parathyroid glands increased the risk of permanent hypoparathyroidism compared with those without iatrogenic parathyroidectomy. CONCLUSIONS: PTH declined on the first day after thyroidectomy. PTH levels <7 ng/L on the first day after surgery might be associated with persistent hypoparathyroidism. CND, thyroiditis, and iatrogenic parathyroidectomy increased the risk of hypoparathyroidism.

[Attenuation of cardiac ischemia/reperfusion injury by transient low hydroperoxide pretreatment in rat].

OBJECTIVE: To investigate how transient low dose of hydroperoxide pretreatment prevents cardiac ischemia/reperfusion injury. METHODS: SD rats were divided into 4 groups: sham operation (Sham), standard ischemia/reperfusion (I/R), ischemic preconditioning (IPC) and IR preceded by low H2O2 treatment. Cardiac function and injury parameter were compared among groups. RESULTS: IPC protected reperfusion injury and improved cardiac function. Low H2O2 treatment played a role in cardioprotection similar to IPC. Low H2O2 was indeed generated in the early phase of simulated ischemia and attenuated cytochrome c release induced by high Ca2+ in isolated mitochondria. CONCLUSION: Low H2O2 plays a critical role in cardioprotection probably by inhibiting mitochondrial permeability transition.

Arabidopsis sucrose transporter SUT4 interacts with cytochrome b5-2 to regulate seed germination in response to sucrose and glucose.

It remains unknown whether a sucrose transporter mediates sugar signaling. Here, we report that the Arabidopsis (Arabidopsis thaliana) sucrose transporter SUT4 interacts with five members of the Arabidopsis cytochrome b5 (Cyb5) family, and sucrose represses the interaction between SUT4 and a Cyb5 member Cyb5-2/A. We observed that down-regulation of SUT4 and three cytochrome b5 members (Cyb5-2, Cyb5-4, and Cyb5-6) confers the sucrose- and glucose-insensitive phenotypes in the sucrose/glucose-induced inhibition of seed germination. The sut4 cyb5-2 double mutant displays slightly stronger sucrose/glucose-insensitive phenotypes than either the sut4 or cyb5-2 single mutant. We showed that the SUT4/Cyb5-2-mediated signaling in the sucrose/glucose-induced inhibition of seed germination does not require ABA or the currently known ABI2/ABI4/ABI5-mediated signaling pathway(s). These data provide evidence that the sucrose transporter SUT4 interacts with Cyb5 to positively mediate sucrose and glucose signaling in the sucrose/glucose-induced inhibition of seed germination.

Identification of an important site for function of the type 2C protein phosphatase ABI2 in abscisic acid signalling in Arabidopsis.

It is known that the clade A protein phosphatase 2Cs (PP2Cs), including ABI1 and ABI2 and other PP2C members, are key players that function directly downstream of the PYR/PYL/RCAR abscisic acid (ABA) receptors. Here, identification of a crucial site for function of ABI2 protein phosphatase in ABA signalling is reported. It was observed that a calcium-dependent protein kinase (CDPK) phosphorylation site-like motif (CPL) in the ABI2 molecule is required for the interactions of ABI2 with the two members of the ABA receptors PYL5 and PYL9 and with a downstream protein kinase SnRK2.6, and for the catalytic activity of ABI2 in vitro, as well as for the response of ABI2 to the ABA receptors PYL5/PYL9 in relation to the ABA receptor-induced inhibition of the ABI2 phosphatase activity. Further, genetic evidence was provided to demonstrate that this CPL is required for the function of ABI2 to mediate ABA signalling. These data reveal that this CPL is an important site necessary for both the phosphatase activity of ABI2 and the functional interaction between ABI2 and PYL5/9 ABA receptors, providing new information to understand primary events of ABA signal transduction.

The Arabidopsis Ca(2+) -dependent protein kinase CPK12 negatively regulates abscisic acid signaling in seed germination and post-germination growth.

• Ca(2+) -dependent protein kinase (CDPK) is believed to be involved in abscisic acid (ABA) signaling, and several members of the Arabidopsis CDPK superfamily have been identified as positive ABA signaling regulators, but it remains unknown if CDPK negatively regulates ABA signaling. • Here, we investigated the function of an Arabidopsis (Arabidopsis thaliana) CDPK, CPK12, in ABA signaling pathway. • We generated Arabidopsis CPK12-RNAi lines, and observed that downregulation of CPK12 resulted in ABA hypersensitivity in seed germination and post-germination growth, and altered expression of a set of ABA-responsive genes. Expression assay showed that CPK12 was ubiquitously expressed and localized to both cytosol and nucleus. Biochemical assays showed that CPK12 interacted with, phosphorylated and stimulated a type 2C protein phosphatase ABI2, and phosphorylated two ABA-responsive transcription factors (ABF1 and ABF4) in vitro. • Our findings show that the Arabidopsis CPK12 is a negative ABA-signaling regulator in seed germination and post-germination growth, suggesting that different members of the CDPK family may constitute a regulation loop by functioning positively and negatively in ABA signal transduction.

The Mg-chelatase H subunit of Arabidopsis antagonizes a group of WRKY transcription repressors to relieve ABA-responsive genes of inhibition.

The phytohormone abscisic acid (ABA) plays a vital role in plant development and response to environmental challenges, but the complex networks of ABA signaling pathways are poorly understood. We previously reported that a chloroplast protein, the magnesium-protoporphyrin IX chelatase H subunit (CHLH/ABAR), functions as a receptor for ABA in Arabidopsis thaliana. Here, we report that ABAR spans the chloroplast envelope and that the cytosolic C terminus of ABAR interacts with a group of WRKY transcription factors (WRKY40, WRKY18, and WRKY60) that function as negative regulators of ABA signaling in seed germination and postgermination growth. WRKY40, a central negative regulator, inhibits expression of ABA-responsive genes, such as ABI5. In response to a high level of ABA signal that recruits WRKY40 from the nucleus to the cytosol and promotes ABAR-WRKY40 interaction, ABAR relieves the ABI5 gene of inhibition by repressing WRKY40 expression. These findings describe a unique ABA signaling pathway from the early signaling events to downstream gene expression.

The magnesium-chelatase H subunit binds abscisic acid and functions in abscisic acid signaling: new evidence in Arabidopsis.

Using a newly developed abscisic acid (ABA)-affinity chromatography technique, we showed that the magnesium-chelatase H subunit ABAR/CHLH (for putative abscisic acid receptor/chelatase H subunit) specifically binds ABA through the C-terminal half but not the N-terminal half. A set of potential agonists/antagonists to ABA, including 2-trans,4-trans-ABA, gibberellin, cytokinin-like regulator 6-benzylaminopurine, auxin indole-3-acetic acid, auxin-like substance naphthalene acetic acid, and jasmonic acid methyl ester, did not bind ABAR/CHLH. A C-terminal C370 truncated ABAR with 369 amino acid residues (631-999) was shown to bind ABA, which may be a core of the ABA-binding domain in the C-terminal half. Consistently, expression of the ABAR/CHLH C-terminal half truncated proteins fused with green fluorescent protein (GFP) in wild-type plants conferred ABA hypersensitivity in all major ABA responses, including seed germination, postgermination growth, and stomatal movement, and the expression of the same truncated proteins fused with GFP in an ABA-insensitive cch mutant of the ABAR/CHLH gene restored the ABA sensitivity of the mutant in all of the ABA responses. However, the effect of expression of the ABAR N-terminal half fused with GFP in the wild-type plants was limited to seedling growth, and the restoring effect of the ABA sensitivity of the cch mutant was limited to seed germination. In addition, we identified two new mutant alleles of ABAR/CHLH from the mutant pool in the Arabidopsis Biological Resource Center via Arabidopsis (Arabidopsis thaliana) Targeting-Induced Local Lesions in Genomes. The abar-2 mutant has a point mutation resulting in the N-terminal Leu-348-->Phe, and the abar-3 mutant has a point mutation resulting in the N-terminal Ser-183-->Phe. The two mutants show altered ABA-related phenotypes in seed germination and postgermination growth but not in stomatal movement. These findings support the idea that ABAR/CHLH is an ABA receptor and reveal that the C-terminal half of ABAR/CHLH plays a central role in ABA signaling, which is consistent with its ABA-binding ability, but the N-terminal half is also functionally required, likely through a regulatory action on the C-terminal half.