The Indian and Pacific Oceans surround the Maritime Continent (MC). Major modes of sea surface temperature variability in both oceans, including the Indian Ocean Dipole (IOD) and El Niño-Southern Oscillation (ENSO), can strongly affect precipitation on the MC. The prevalence of fires in the MC is closely associated with precipitation amount and terrestrial water storage in September and October. Precipitation and terrestrial water storage, which is a measurement of hydrological drought conditions, are significantly modulated by Indian Ocean Dipole (IOD) and El Niño events. We utilize long-term datasets to study the combined effects of ENSO and the IOD on MC precipitation during the past 100 years (1900-2019) and find that the reductions in MC precipitation and terrestrial water storage are more pronounced during years when El Niño and a positive phase of the IOD (pIOD) coincided. The combined negative effects are produced mainly through an enhanced reduction of upward motion over the MC. Coincident El Niño-pIOD events have occurred more frequently after 1965. However, climate models do not project a higher occurrence of coincident El Niño-pIOD events in a severely warming condition, implying that not the global warming but the natural variability might be the leading cause of this phenomenon.

Composite bimaterial lattice structures which possess both low, tailorable thermal expansion and nearly optimal stiffness have been proposed for applications which require high structural stiffness in environments which include large temperature fluctuations, such as the surfaces of high-speed aerospace vehicles. An experimental validation of the thermal properties of these lattices when they are constructed of practical materials with easily manufactured bonded joints is contained herein. Bonded lattices, comprising aluminum and titanium alloys, have been manufactured with press-fit dovetail joints and tested in a variety of thermal environments. Results for equilibrium heating, rapid transient heating and thermal cycling leading to shakedown are presented and shown to be consistent with theoretically and numerically attained results.

Background Damage to the coronary arteries during the acute phase of Kawasaki disease (KD) is linked to inflammatory cell infiltration, myointimal proliferation, and endothelial cell (EC) dysfunction. To understand the response of ECs to KD treatment, we studied the genome-wide transcriptional changes in cultured ECs incubated with KD sera before and after treatment with or without atorvastatin. Methods and Results RNA sequencing of human umbilical vein ECs incubated with pooled sera from patients with acute KD before or after treatment with intravenous immunoglobulin and infliximab revealed differentially expressed genes in interleukin-1, tumor necrosis factor-α, and inflammatory cell recruitment pathways. Subacute sera pooled from patients treated with intravenous immunoglobulin, infliximab, and atorvastatin uniquely induced expression of NOS3, Kruppel like factor (KLF2, and KLF4 (promotes EC homeostasis and angiogenesis) and ZFP36 ring finger protein (ZFP36) and suppressor of cytokine signaling 3 (SOCS3) (suppresses inflammation), and suppressed expression of TGFB2 and DKK1 (induces endothelial-mesenchymal transition) and sphingosine kinase 1 (SPHK1) and C-X-C motif chemokine ligand 8 (CXCL8) (induces inflammation). Conclusions These results suggest that atorvastatin treatment of patients with acute KD may improve EC health, reduce mediators of inflammation produced by ECs, and block KD-induced myofibroblast proliferation.

The accelerator mass spectrometry (AMS) is an effective method for the determination of the half-life of long-lived radionuclides. In this paper, we report a method for measurement of the half-life of 79Se. The number of 79Se atoms was determined from measured 79Se/Se absolute ratios with the AMS system at the China Institute of Atomic Energy and the decay rate of 79Se was determined by counting the emitted β-rays with a liquid scintillation spectrometer. The major improvements of our measurements include using the high abundance of an 79Se sample which was cooled for many years to exclude the interference of short-lived nuclides, the extraction of SeO2- molecular ions, that results in a suppression of the 79Br background by as much as about five orders of magnitude. Also, an AMS measurement of the absolute ratio of 79Se/Se was developed to avoid systematic errors. The results show that 79Se/Se is (2.35±0.12)×10-7 in the reference sample and the radioactivity of 79Se is (1.24±0.05) Bq/g, so the half-life of 79Se is (2.78±0.18)×105 a.

Although Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share some clinical manifestations, their cardiovascular outcomes are different, and this may be reflected at the level of the endothelial cell (EC). We performed RNA-seq on cultured ECs incubated with pre-treatment sera from KD (n = 5), MIS-C (n = 7), and healthy controls (n = 3). We conducted a weighted gene co-expression network analysis (WGCNA) using 935 transcripts differentially expressed between MIS-C and KD using relaxed filtering (unadjusted p < 0.05, >1.1-fold difference). We found seven gene modules in MIS-C, annotated as an increased TNFα/NFκB pathway, decreased EC homeostasis, anti-inflammation and immune response, translation, and glucocorticoid responsive genes and endothelial-mesenchymal transition (EndoMT). To further understand the difference in the EC response between MIS-C and KD, stringent filtering was applied to identify 41 differentially expressed genes (DEGs) between MIS-C and KD (adjusted p < 0.05, >2-fold-difference). Again, in MIS-C, NFκB pathway genes, including nine pro-survival genes, were upregulated. The expression levels were higher in the genes influencing autophagy (UBD, EBI3, and SQSTM1). Other DEGs also supported the finding by WGCNA. Compared to KD, ECs in MIS-C had increased pro-survival transcripts but reduced transcripts related to EndoMT and EC homeostasis. These differences in the EC response may influence the different cardiovascular outcomes in these two diseases.

Background

Obstructive Sleep Apnea (OSA) is a highly prevalent condition that is associated with several comorbidities including cardiovascular disease (CVD). Recent studies have revealed mixed results as to whether standard OSA therapy reverses CVD in adult patients. Thus, many advocate for earlier recognition of OSA induced CVD, as early as childhood, to prompt treatment antecedent to the onset of irreversible CVD. Here we investigated if the serum level of miR-92a, a known biomarker for CVD, can be used to identify patients with OSA in both children and adults.

Methods

Consecutive snoring patients undergoing polysomnography were recruited for determination of circulating miR-92a, in addition to inflammatory and metabolic profiles. We assessed whether circulating miR-92a was associated with OSA severity.

Results

Using two separate cohorts of adults (n=57) and children (n=13), we report a significant increase in the serum level of miR-92a in patients with severe OSA (p=0.021) and further demonstrate a significant correlation (Spearman rank correlation 0.308, p=0.010) with serum miR-92a levels and the apnea hypopnea index (AHI), a primary measure of OSA severity. Stepwise regression analysis revealed that serum miR-92a levels were independently associated with AHI (ß=0.332, p=0.003), age (ß=0.394, p=0.002) and LDL cholesterol levels (ß=0.368, p=0.004).

Conclusion

Our study is the first to establish that miR-92a is a useful biomarker for OSA severity in both children and adults. Given the canonical role of miR-92a on endothelial dysfunction, miR-92a may be useful to identify early onset CVD in OSA patients or stratify patient CVD risk to identify those that may benefit from earlier OSA treatment.

It is well documented that the rate of aging can be slowed, but it remains unclear to which extent aging-associated conditions can be reversed. How the interface of immunity and metabolism impinges upon the diabetes pandemic is largely unknown. Here, we show that NLRP3, a pattern recognition receptor, is modified by acetylation in macrophages and is deacetylated by SIRT2, an NAD⁺-dependent deacetylase and a metabolic sensor. We have developed a cell-based system that models aging-associated inflammation, a defined co-culture system that simulates the effects of inflammatory milieu on insulin resistance in metabolic tissues during aging, and aging mouse models; and demonstrate that SIRT2 and NLRP3 deacetylation prevent, and can be targeted to reverse, aging-associated inflammation and insulin resistance. These results establish the dysregulation of the acetylation switch of the NLRP3 inflammasome as an origin of aging-associated chronic inflammation and highlight the reversibility of aging-associated chronic inflammation and insulin resistance.

Rationale

Endothelial-mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell-mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD.

Objective

We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis. As well, the modulation of this process by statin therapy was studied.

Methods and results

Sera from healthy children and KD subjects were incubated with human umbilical vein endothelial cells. Cardiovascular disease-related miRNAs, CTGF, and EndoMT markers were quantified using reverse transcriptase quantitative polymerase chain reaction, ELISA, and Western blotting. Compared with healthy controls, human umbilical vein endothelial cell incubated with sera from acute KD patients had decreased miR-483, increased CTGF, and increased EndoMT markers. Bioinformatics analysis followed by functional validation demonstrated that Krüppel-like factor 4 (KLF4) transactivates miR-483, which in turn targets the 3' untranslated region of CTGF mRNA. Overexpression of KLF4 or pre-miR-483 suppressed, whereas knockdown of KLF4 or anti-miR-483 enhanced, CTGF expression in endothelial cells in vitro and in vivo. Furthermore, atorvastatin, currently being tested in a phase I/IIa clinical trial in KD children, induced KLF4-miR-483, which suppressed CTGF and EndoMT in endothelial cells.

Conclusions

KD sera suppress the KLF4-miR-483 axis in endothelial cells, leading to increased expression of CTGF and induction of EndoMT. This detrimental process in the endothelium may contribute to coronary artery abnormalities in KD patients. Statin therapy may benefit acute KD patients, in part, through the restoration of KLF4-miR-483 expression.

Clinical trial registration

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01431105.

[Figure: see text].