| 1. |
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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Zhou, J. M., et al.
(author)
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Digoxin is associated with worse outcomes in patients with heart failure with reduced ejection fraction
- 2020
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In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 7:1, s. 139-147
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Journal article (peer-reviewed)abstract
- Aims The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline-recommended treatments in the real world in China. Methods and results Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN-HF) were enrolled to assess the all-cause mortality, HF mortality, all-cause re-hospitalization, and HF re-hospitalization associated with digoxin use. Eight hundred eighty-two eligible HFrEF patients in the CN-HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow-up of 28.6 months. Kaplan-Meier survival analysis showed that the all-cause mortality (P < 0.001) and all-cause re-hospitalization (P = 0.020) were significantly higher in digoxin group than non-digoxin group, while HF mortality (P = 0.232) and HF re-hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional-hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all-cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27-2.44; P = 0.001] and all-cause re-hospitalization (HR 1.27; 95% CI 1.03-1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all-cause mortality irrespective of rhythm or in combination with other guideline-recommended therapies. Conclusions Digoxin use is independently associated with increased risk of all-cause mortality and all-cause re-hospitalization in HFrEF patients.
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| 4. |
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| 5. |
- Chiu, Ming-Jang, et al.
(author)
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Synergistic Association between Plasma Aβ1-42 and p-tau in Alzheimer's Disease but Not in Parkinson's Disease or Frontotemporal Dementia.
- 2021
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In: ACS chemical neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 12:8
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Journal article (peer-reviewed)abstract
- Beta-amyloid (Aβ1-42) triggers the phosphorylation of tau protein in Alzheimer's disease (AD), but the relationship between phosphorylated tau (p-tau) and Aβ1-42 in the blood is not elucidated. We investigated the association in individuals with AD (n = 62, including amnesic mild cognitive impairment and dementia), Parkinson's disease (n = 30), frontotemporal dementia (n = 25), and cognitively unimpaired controls (n = 41) using immunomagnetic reduction assays to measure plasma Aβ1-42 and p-tau181 concentrations. Correlation and regression analyses were performed to examine the relation between plasma levels, demographic factors, and clinical severity. Both plasma Aβ1-42 and p-tau concentrations were significantly higher in AD and frontotemporal dementia than in the controls and Parkinson's disease. A significant positive association was found between plasma p-tau and Aβ1-42 in controls (r = 0.579, P < 0.001) and AD (r = 0.699, P < 0.001) but not in frontotemporal dementia or Parkinson's disease. Plasma p-tau was significantly associated with clinical severity in the AD in terms of scores of clinical dementia rating (r = 0.288, P = 0.025) and mini-mental state examination (r = -0.253, P = 0.049). Regression analysis showed that plasma Aβ1-42 levels explain approximately 47.7% of the plasma p-tau levels in the AD after controlling age, gender, and clinical severity. While in non-AD participants, the clinical dementia rating explained about 47.5% of the plasma p-tau levels. The disease-specific association between plasma Aβ1-42 and p-tau levels in AD implies a possible synergic effect in mechanisms involving these two pathological proteins' genesis.
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| 6. |
- Tang, R., et al.
(author)
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Increasing terrestrial ecosystem carbon release in response to autumn cooling and warming
- 2022
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In: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 12
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Journal article (peer-reviewed)abstract
- Despite overall warming, many regions in the Northern Hemisphere have been cooling in autumn. This cooling resulted in an increasing release of net CO2 2004-2018 as primary production decreased more than respiration in cooling and respiration increased more than production in warming areas. Part of the Northern Hemisphere has experienced widespread autumn cooling during the most recent decades despite overall warming, but how this contrasting temperature change has influenced the ecosystem carbon exchange remains unclear. Here, we show that autumn cooling has occurred over about half of the area north of 25 degrees N since 2004, producing a weak cooling trend over the period 2004-2018. Multiple lines of evidence suggest an increasing net CO2 release in autumn during 2004-2018. In cooling areas, the increasing autumn CO2 release is due to the larger decrease of gross primary productivity (GPP) growth than total ecosystem respiration (TER) growth suppressed by cooling. In the warming areas, TER increased more than GPP because the warming and wetting conditions are more favourable for TER growth than GPP increase. Despite the opposite temperature trends, there has been a systematic increase in ecosystem carbon release across the Northern Hemisphere middle and high latitudes.
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| 7. |
- Zhong, Ziqian, 1995, et al.
(author)
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Disentangling the effects of vapor pressure deficit on northern terrestrial vegetation productivity
- 2023
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In: Science Advances. - 2375-2548. ; 9:32
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Journal article (peer-reviewed)abstract
- The impact of atmospheric vapor pressure deficit (VPD) on plant photosynthesis has long been acknowledged, but large interactions with air temperature (T) and soil moisture (SM) still hinder a complete understanding of the influence of VPD on vegetation production across various climate zones. Here, we found a diverging response of productivity to VPD in the Northern Hemisphere by excluding interactive effects of VPD with T and SM. The interactions between VPD and T/SM not only offset the potential positive impact of warming on vegetation productivity but also amplifies the negative effect of soil drying. Notably, for high-latitude ecosystems, there occurs a pronounced shift in vegetation productivity's response to VPD during the growing season when VPD surpasses a threshold of 3.5 to 4.0 hectopascals. These results yield previously unknown insights into the role of VPD in terrestrial ecosystems and enhance our comprehension of the terrestrial carbon cycle's response to global warming.
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| 8. |
- Cao, J., et al.
(author)
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Prognostic value of N-terminal B-type natriuretic peptide on all-cause mortality in heart failure patients with preserved ejection fraction
- 2019
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In: Chinese Journal of Cardiology. Zhonghua xin xue guan bing za zhi. - 0253-3758. ; 47:11, s. 875-881
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Journal article (peer-reviewed)abstract
- Objective: To investigate the prognostic value of N-terminal B-type natriuretic peptide (NT-proBNP) on all-cause mortality in heart failure patients with preserved ejection fraction (HFpEF) at real world scenarios. Methods: Patients who met the diagnostic criteria of HFpEF in the China National Heart Failure Registration Study (CN-HF) were divided into death and survival groups. The demographic data, physical examination, results of the first echocardiography, laboratory results at admission, complications, drug use and clinical outcomes were obtained from CN-HF. The univariate Cox proportional hazard model was used to screen the variates that might predict prognosis, and then the covariates with statistical significance were included in the multivariate Cox regression model to analyze the predictive value of baseline NT-proBNP on all-cause death. Spearman correlation analysis was used to evaluate the relationship between NT-proBNP and estimated glomerular filtration rate (eGFR), so as to further explore the predictive value of the interaction between renal dysfunction and NT-proBNP on death. Since NT-proBNP did not obey the binary normal distribution, it was expressed by the natural logarithm of NT-proBNP (LnNT-proBNP). Results: A total of 1 846 HFpEF patients were enrolled in this study, with an average age of 71.5 years, 1 017 males(55.1%), median NT-proBNP 860 ng/L, and median eGFR 73.9 ml·min-1·1.73m-2. After a median follow-up of 34 months, 213 (11.5%) patients died. Patients in the death group were older, with higher NYHA classification Ⅲ-Ⅳ ratio, longer hospital stay, higher serum potassium and NT-proBNP level, prevalence of complications of diabetes mellitus, arrhythmia and atrial fibrillation, use of angiotensin receptor antagonist(ARB), mineralocorticoid receptor antagonists (MRA), diuretic and digoxin was significantly higher in death group than in survival group. Body mass index (BMI), diastolic blood pressure, left ventricular ejection fraction (LVEF), hemoglobin, serum cholesterol(TC), serum triglycerides (TG) and eGFR, and use of angiotensin converting enzyme inhibitors (ACEI), statins and aspirin were lower in death group than in survival group. Univariate Cox regression analysis showed that NT-proBNP was a predictor of all-cause death in HFpEF patients (HR=2.522, 95%CI 2.040-3.119, P<0.001). Multivariate Cox regression analysis showed that the elevated NT-proBNP remains as the independent predictor of all-cause death in patients with HFpEF (HR=1.230, 95%CI 1.049-1.442, P=0.011) after adjusting for age, BMI, diastolic blood pressure, LVEF, hemoglobin, serum potassium, serum sodium, TC, serum high-density lipoprotein cholesterol (HDL-C), TG, eGFR, atrial fibrillation, as well as the treatment of ACEI/ARB, MRA, diuretics and digoxin. Spearman correlation analysis showed that LnNT-proBNP was negatively correlated with eGFR (r=-0.361, P<0.001), but there was no interaction between NT-proBNP and renal dysfunction in predicting death in HFpEF patients (P>0.05). Conclusion: The elevated level of NT-proBNP at admission is an independent predictor of all-cause mortality in HFpEF patients. 目的： 探讨入院基线N末端B型利钠肽原（NT-proBNP）对射血分数保留的心力衰竭（HFpEF）患者全因死亡的预测价值。 方法： 入选中国住院患者心力衰竭注册研究（CN-HF）中符合HFpEF诊断标准的患者，根据随访期间是否死亡分为死亡组和存活组。从CN-HF中获得研究对象的人口学信息、入院时体格检查信息、入院首次超声心动图检查结果、实验室检查结果、合并症情况、用药情况和临床结局等资料。通过单因素Cox回归模型对可能预测预后的变量进行筛选，将单因素分析中与全因死亡有统计学意义的协变量纳入多因素Cox回归模型，进而分析基线NT-proBNP对全因死亡的预测价值。采用Spearman相关分析分析NT-proBNP与估算的肾小球滤过率（eGFR）的关系，并进一步探讨肾功能不全与NT-proBNP预测全因死亡的交互作用。鉴于NT-proBNP不服从二元正态分布，本研究中NT-proBNP作连续变量分析时均取自然对数（LnNT-proBNP）。 结果： 共1 846例患者纳入本研究，平均年龄71.5岁，男性1 017例（55.1%），NT-proBNP中位数860 ng/L，eGFR中位数73.9 ml·min-1·1.73m-2。本研究中位随访时间34（24~42）个月，随访期间全因死亡213例（11.5%）被纳入死亡组，存活1 633例（88.5%）被纳入存活组。与存活组比较，死亡组患者年龄较大，纽约心脏协会（NYHA）心功能Ⅲ~Ⅳ级者比例较高，住院时间较长，血钾、NT-proBNP较高，合并糖尿病、心律失常、心房颤动者较多，服用血管紧张Ⅱ受体阻滞剂（ARB）、盐皮质激素受体拮抗剂（MRA）、利尿剂和地高辛者较多（P均<0.05）。与存活组比较，死亡组患者体重指数（BMI）、舒张压、左心室射血分数（LVEF）较低，血红蛋白、血清总胆固醇（TC）、血清甘油三酯（TG）、eGFR较低，服用血管紧张素转化酶抑制剂（ACEI）、他汀类药物和阿司匹林者较少（P均<0.05）。单因素Cox回归分析结果显示NT-proBNP是HFpEF患者全因死亡的预测因素（HR=2.522，95%CI 2.040~3.119，P<0.001）。多因素Cox回归分析结果显示，校正了年龄、BMI、舒张压、LVEF、血红蛋白、血钾、血钠、TC、高密度脂蛋白胆固醇、TG、eGFR、心房颤动以及ACEI/ARB、MRA、利尿剂、地高辛使用情况后，NT-proBNP仍是HFpEF患者全因死亡的独立预测因素（HR=1.230，95%CI 1.049~1.442，P=0.011）。Spearman相关分析结果显示，LnNT-proBNP与eGFR呈负相关（r=-0.361，P<0.001）。而校正了混杂因素后，多因素Cox回归分析结果显示肾功能不全与NT-proBNP预测HFpEF患者全因死亡无交互作用（P>0.05）。 结论： 入院基线NT-proBNP是HFpEF患者全因死亡的独立预测因素。.
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| 9. |
- Jin, X., et al.
(author)
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Outcomes of patients with anemia and renal dysfunction in hospitalized heart failure with preserved ejection fraction (from the CN-HF registry)
- 2019
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In: IJC Heart and Vasculature. - : Elsevier BV. - 2352-9067. ; 25
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Journal article (peer-reviewed)abstract
- Background: Although a large number of studies on heart failure with reduced ejection fraction (HFrEF) have found that anemia and renal dysfunction (RD) independently predicted poor outcomes, there are still few reports on patients with heart failure with preserved ejection fraction (HFpEF). Methods: Clinical data of HFpEF patients registered in the China National Heart Failure Registration Study (CN-HF) were evaluated and the clinical features of patients with or without anemia/RD were compared to explore the impact of anemia and RD on all-cause mortality and all-cause re-hospitalization. Results: 1604 patients with HFpEF were enrolled, the prevalence of anemia was 51.0%. Although anemia was associated with increased risk of all-cause mortality and all-cause re-hospitalization in univariate COX regression (p < 0.05), multivariate COX model confirmed that anemia was not independently associated with all-cause mortality [hazard ratio (HR) 1.14, 95% confidence interval (CI) 0.85–1.52, p = 0.386] and all-cause re-hospitalization (HR 1.13, 95% CI 0.96–1.33, p = 0.152). Similarly, RD was not an independent predictor of all-cause mortality (HR 1.18, 95% CI 0.88–1.57, p = 0.269) and all-cause re-hospitalization (HR 0.94, 95% CI 0.79–1.12, p = 0.488) as assessed in the adjusted COX regression model. The interaction between RD and anemia on end-points events was also not statistically significant. However, anemia was associated with increased all-cause re-hospitalization in patients with New York Heart Association (NYHA) class III-IV. Conclusions: In patients with HFpEF from CN-HF registry, anemia was common, but was not an independent predictor of all-cause mortality and all-cause re-hospitalization, except for the all-cause re-hospitalization in patients with NYHA class III-IV. Clinical Trial Registration: http://www.clinicaltrials.gov/ct2/home; ID: NCT02079428. © 2019 The Authors
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| 10. |
- Klaric, Lucija, et al.
(author)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Other publication (other academic/artistic)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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