Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment

IntroductionThe ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer’s disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment.MethodsFourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann–Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers.ResultsRegarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers.ConclusionAPOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD

Monitoring the Surface Elevation Changes of a Monsoon Temperate Glacier with Repeated UAV Surveys, Mainri Mountains, China

Due to the deep valleys, steep mountains and the influence of the Indian monsoon on the Mainri Mountains (Yunnan Province, China), it is difficult to estimate glacier change from microwave and optical remote sensing. To bridge the gap between low-quality space-borne remote sensing and scarce in situ measurements, airborne remote sensing, such as unmanned aerial vehicles (UAVs), may provide a remarkable opportunity to monitor glacier change with high-quality tools. To determine monsoon temperate glacier change, three UAV surveys were conducted on the Melang Glacier in the Mainri Mountains in November 2019, April 2020 and November 2020. Then, glacier surface elevation changes were estimated from UAV orthophotos and DSMs. High accumulation and high ablation (+10.5 m and −13.5 m) were observed in the accumulation period and ablation period, with a mean surface elevation change of −3.0 m in the surveyed glacier area from November 2019 to November 2020. The avalanche, debris cover, ice cliffs and proglacial lake resulted in a heterogeneous pattern of glacier surface elevation changes. Given that the glacier is more sensitive to temperature, the Melang Glacier may have experienced a substantial recession and mass loss in the past few decades. This study provides a more appropriate approach for monitoring the changes in a temperate glacier in the Mainri Mountains

Correlation between Heart fatty acid binding protein and severe COVID-19: A case-control study

BACKGROUND: Heart-fatty acid binding protein (HFABP) has been recognized as a highly heart-specific marker. However, it is currently unknown that its HFABP is also closely related to the severity of COVID-19. METHODS: We retrospectively screened 46 patients who met our inclusion criteria within 4 weeks. They were tested for HFABP after the diagnosis of COVID-19, and monitored for HFABP during their hospital stay. We tracked the patients during their hospital stay to determine if they had severe COVID-19 or mild-to-severe transition features. We calculated the chi-square test values found for HFABP to predict the correlation between HFABP levels and the severity of the COVID-19. RESULTS: Of these 46 cases, 16 cases with confirmed COVID-19 were tested for HFABP> 7 ng / mL upon admission; among them, 14 cases were diagnosed with severe COVID-19 within the hospitalization. The Odds ratio of the measured HFABP elevation was 6.81(95% confidence interval [CI] 5.23–8.40), and 3 patients with severe COVID-19 progressed in 5 patients with mild HFABP> 7 ng/mL. CONCLUSION: These data indicate that the elevation of HFABP is closely related to the severity of COVID-19 in the patients, and the elevated HFABP may cause rapid development of patients with mild COVID-19 into severe COVID-19. But serum HFABP negative maybe make patients with mild COVID-19 safer, the current data show no effect on the all-cause mortality

Monitoring the Surface Elevation Changes of a Monsoon Temperate Glacier with Repeated UAV Surveys, Mainri Mountains, China

Due to the deep valleys, steep mountains and the influence of the Indian monsoon on the Mainri Mountains (Yunnan Province, China), it is difficult to estimate glacier change from microwave and optical remote sensing. To bridge the gap between low-quality space-borne remote sensing and scarce in situ measurements, airborne remote sensing, such as unmanned aerial vehicles (UAVs), may provide a remarkable opportunity to monitor glacier change with high-quality tools. To determine monsoon temperate glacier change, three UAV surveys were conducted on the Melang Glacier in the Mainri Mountains in November 2019, April 2020 and November 2020. Then, glacier surface elevation changes were estimated from UAV orthophotos and DSMs. High accumulation and high ablation (+10.5 m and −13.5 m) were observed in the accumulation period and ablation period, with a mean surface elevation change of −3.0 m in the surveyed glacier area from November 2019 to November 2020. The avalanche, debris cover, ice cliffs and proglacial lake resulted in a heterogeneous pattern of glacier surface elevation changes. Given that the glacier is more sensitive to temperature, the Melang Glacier may have experienced a substantial recession and mass loss in the past few decades. This study provides a more appropriate approach for monitoring the changes in a temperate glacier in the Mainri Mountains

FBXW7 alleviates hyperglycemia-induced endothelial oxidative stress injury via ROS and PARP inhibition

Diabetic retinopathy (DR) and other diabetic vascular complications are the leading cause of death and disability in patients with suboptimum glycemic control. In the pathogenesis of diabetic vascular diseases, hyperglycemia-induced oxidative stress, DNA damage, and poly-ADP-ribose-polymerase (PARP) hyperactivation play important roles in endothelial cell impairment. Adipose differentiation-related protein FBXW7 was reported to regulate PGC-1α stability and mitochondrial homeostasis. Here, we investigated the role and mechanism of FBXW7 in repairing endothelial oxidative stress injuries under hyperglycemic conditions. FBXW7 promoted the hampered activity of homologous recombination and non-homologues end joining pathway for repairing DNA double-strand breaks damage, an initiating factor for PARP hyperactivation and diabetic vascular complications. The abundant mobilization of DNA damage repair mediated by FBXW7 suppressed PARP activation, leading to downregulation of PARP expression and activity in both human endothelial cells and diabetic rat retinas. This provided a new method for PARP inhibition, superior to PARP inhibitors for treating diabetic vascular complication. Furthermore, FBXW7 rescued downregulated NAD+ levels and ameliorated mitochondrial dysfunction, thereby reducing superoxide production under hyperglycemic conditions. These effects reversed oxidative injury and vascular leakage in diabetic rat retina, providing a potential future treatment strategy

Enhancement of glycolysis-dependent DNA repair regulated by FOXO1 knockdown via PFKFB3 attenuates hyperglycemia-induced endothelial oxidative stress injury

The accumulation of DNA damage induced by oxidative stress is a crucial pathogenic factor of endothelial loss in diabetic vascular complications, but it is still unknown whether aberrant glucose metabolism leads to defective DNA repair and accounts for hyperglycemia-induced endothelial oxidative stress injury. Here, we showed that Foxo1 knockdown alleviated diabetes-associated retinal DNA damage and vascular dysfunction. Mechanistically, FOXO1 knockdown avoided persistent DNA damage and cellular senescence under high glucose in endothelial cells by promoting DNA repair mediated by the MRN (MRE11-RAD50-NBS1 complex)-ATM pathway in response to oxidative stress injury. Moreover, FOXO1 knockdown mediated robust DNA repair by restoring glycolysis capacity under high glucose. During this process, the key glycolytic enzyme PFKFB3 was stimulated and, in addition to its promoting effect on glycolysis, directly participated in DNA repair. Under genotoxic stress, PFKFB3 relocated into oxidative stress-induced DNA damage sites and promoted DNA repair by interaction with the MRN-ATM pathway. Our study proposed that defective glycolysis-dependent DNA repair is present in diabetic endothelial cells and contributes to hyperglycemia-induced vascular dysfunction, which could provide novel therapeutic targets for diabetic vascular complications