Interaction between Age and Obesity on Cardiomyocyte Contractile Function: Role of Leptin and Stress Signaling

OBJECTIVES: This study was designed to evaluate the interaction between aging and obesity on cardiac contractile and intracellular Ca2+ properties. METHODS: Cardiomyocytes from young (4-mo) and aging (12- and 18-mo) male lean and the leptin deficient ob/ob obese mice were treated with leptin (0.5, 1.0 and 50 nM) for 4 hrs in vitro. High fat diet (45% calorie from fat) and the leptin receptor mutant db/db obesity models at young and older age were used for comparison. Cardiomyocyte contractile and intracellular Ca2+ properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (+/- dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR(90)), intracellular Ca2+ levels and decay. O2(-) levels were measured by dihydroethidium fluorescence. RESULTS: Our results revealed reduced survival in ob/ob mice. Aging and obesity reduced PS, +/- dL/dt, intracellular Ca2+ rise, prolonged TR(90) and intracellular Ca2+ decay, enhanced O2(-) production and p(47phox) expression without an additive effect of the two, with the exception of intracellular Ca2+ rise. Western blot analysis exhibited reduced Ob-R expression and STAT-3 phosphorylation in both young and aging ob/ob mice, which was restored by leptin. Aging and obesity reduced phosphorylation of Akt, eNOS and p38 while promoting pJNK and pIkappaB. Low levels of leptin reconciled contractile, intracellular Ca2+ and cell signaling defects as well as O2(-) production and p(47phox) upregulation in young but not aging ob/ob mice. High level of leptin (50 nM) compromised contractile and intracellular Ca2+ response as well as O2(-) production and stress signaling in all groups. High fat diet-induced and db/db obesity displayed somewhat comparable aging-induced mechanical but not leptin response. CONCLUSIONS: Taken together, our data suggest that aging and obesity compromise cardiac contractile function possibly via phosphorylation of Akt, eNOS and stress signaling-associated O2(-) release

Local lung hypoxia determines epithelial fate decisions during alveolar regeneration.

After influenza infection, lineage-negative epithelial progenitors (LNEPs) exhibit a binary response to reconstitute epithelial barriers: activating a Notch-dependent ΔNp63/cytokeratin 5 (Krt5) remodelling program or differentiating into alveolar type II cells (AEC2s). Here we show that local lung hypoxia, through hypoxia-inducible factor (HIF1α), drives Notch signalling and Krt5pos basal-like cell expansion. Single-cell transcriptional profiling of human AEC2s from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C (SPC), and transdifferentiation toward a Krt5pos basal-like state. Activated murine Krt5pos LNEPs and diseased human AEC2s upregulate strikingly similar core pathways underlying migration and squamous metaplasia. While robust, HIF1α-driven metaplasia is ultimately inferior to AEC2 reconstitution in restoring normal lung function. HIF1α deletion or enhanced Wnt/β-catenin activity in Sox2pos LNEPs blocks Notch and Krt5 activation, instead promoting rapid AEC2 differentiation and migration and improving the quality of alveolar repair

Dissolved nutrient distributions in the Antarctic Cosmonaut Sea in austral summer 2021

Dissolved nutrients are essential to marine productivity and ecosystem structures in the Southern Ocean. The spatial distributions of dissolved nutrients in the Cosmonaut Sea were studied during the 37th Chinese National Antarctic Research Expedition in 2021. The relative standard deviations of the nitrate (NO3-N), nitrite (NO2-N), ammonium (NH4-N), phosphate (PO4-P), and silicate (SiO3-Si) concentrations found in duplicate samples (n=2) were 1.01%, 9.04%, 6.45%, 0.94%, and 0.67%, respectively. The mean NO3-N, NO2-N, NH4-N, PO4-P, and SiO3-Si concentrations in the mixed layer were 26.41±4.13, 0.15±0.09, 0.51±0.22, 1.73±0.23, and 41.48±6.94 μmol·L−1, respectively, and were higher than the relevant limitation concentrations. The concentrations were generally bounded horizontally by the Southern Boundary (SB) of the Antarctic Circumpolar Current, the NO3-N, NO2-N, NH4-N, and PO4-P concentrations being higher northeast than southwest of the SB but the SiO3-Si concentrations being higher southwest than northeast, indicating that the SB dominates nutrient distributions in the mixed layer. The NO3-N, NH4-N, and PO4-P concentrations gradually increased moving vertically down from the mixed layer to 200 m deep and then remained at 33.73±3.51, 0.26±0.13, and 2.28±0.10 μmol·L−1, respectively, to the bottom. The SiO3-Si concentration increased as depth increased and reached a maximum in the bottom layer. The NO2-N concentration decreased rapidly as depth increased and was ~0 μmol·L−1 at >150 m deep. Circumpolar Deep Water upwelling may cause high nutrient concentrations in shallower layers up to the 100 m layer between 62.5°S and 64°S

Muon radiography experiments on the subway overburden structure detection

Muon radiography is an innovative and non-destructive technique for internal density structure imaging, based on measuring the attenuation of cosmic-ray muons after they penetrate the target. Due to the strong penetration ability of muons, the detection range of muon radiography can reach the order of hundreds of meters or even kilometers. Using a portable muon detector composed of plastic scintillators and silicon photomultipliers, we performed a short-duration(1h) flux scanning experiment of the overburden above the platform and tunnel of the Xiaoying West Road subway station under construction. With the observation direction facing up, the detector is placed on the north side of the track and moved eastward from the platform section inside the station to the tunnel section. The scanning length is 264m and a total of 21 locations are observed. By comparing the observed and predicted values of the muon survival ratio at different locations, the experiment accurately detects the jump in thickness at the interface of the platform section and tunnel section. Furthermore, unknown anomalies caused by random placed light brick piles and side passage mouth above the observation locations are detected and confirmed later. This experiment verifies the feasibility of using natural muons to quickly detect abnormal structures of the overburden of tunnel, and shows that muon radiography has broad application prospects in tunnel safety and other similar aspects.Comment: 30 pages, 10 figure