Autophagy is an evolutionarily conserved process used by the cell to degrade cytoplasmic contents for quality control, survival for temporal energy crisis, and catabolism and recycling. Rapidly ...increasing evidence has revealed an important pathogenic role of altered activity of the autophagosome-lysosome pathway (ALP) in cardiac hypertrophy and heart failure. Although an early study suggested that cardiac autophagy is increased and that this increase is maladaptive to the heart subject to pressure overload, more recent reports have overwhelmingly supported that myocardial ALP insufficiency results from chronic pressure overload and contributes to maladaptive cardiac remodeling and heart failure. This review examines multiple lines of preclinical evidence derived from recent studies regarding the role of autophagic dysfunction in pressure-overloaded hearts, attempts to reconcile the discrepancies, and proposes that resuming or improving ALP flux through coordinated enhancement of both the formation and the removal of autophagosomes would benefit the treatment of cardiac hypertrophy and heart failure resulting from chronic pressure overload.
Abstract In the cell, the proteasome and lysosomes represent the most important proteolytic machineries, responsible for the protein degradation in the ubiquitin–proteasome system (UPS) and ...autophagy, respectively. Both the UPS and autophagy are essential to protein quality and quantity control. Alterations in cardiac proteasomal and lysosomal degradation are remarkably associated with most heart disease in humans and are implicated in the pathogenesis of congestive heart failure. Studies carried out in animal models and in cell culture have begun to establish both sufficiency and, in some cases, the necessity of proteasomal functional insufficiency or lysosomal insufficiency as a major pathogenic factor in the heart. This review article highlights some recent advances in the research into proteasome and lysosome protein degradation in relation to cardiac pathology and examines the emerging evidence for enhancing degradative capacities of the proteasome and/or lysosome as a new therapeutic strategy for heart disease. This article is part of a Special Issue entitled “Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy”.
The Eucalyptus spp. is fast-growing and is usually harvested at a young age, which enables efficient and sufficient timber supply. However, its negative impact on soil fertility incurs wide debates. ...Therefore it is necessary to study on the growing traits of eucalytpus to provide scientific guidance on its plantation management and associated policy-making. In this study, we collected the sample plot data from 9 National Forest Inventories (NFIs) during 1973-2018, China Forest-Land Database Map in 2003 and 2016, as well as climate and elevation data and analyzed how the spatial distribution of eucalyptus plantations in China changes with time. We quantitatively characterized and evaluated the productivity, carbon accumulation capacity, and abandonment rate of eucalyptus plantations. Statistical models on how eucalyptus productivity and abandonment rate change with time are established to evaluate the soil fertility and feasibility for growing eucalyptus plantations and predict the temporal productivity variation. The results show that regions with annual mean temperature of 19-21 °C, annual precipitation of 1400-1600 mm, and elevation of 0-300 m above sea level is most suitable for the growth of eucalyptus. The annual mean productivity of eucalyptus plantations ranges from 4.14-8.57 m
hm
a
. Higher productivity (9.32-10.88 m
hm
a
) could be reached in newly cultivated lands. Based on data from the 9th inventory (2014-2018), the mean carbon fixation of eucalyptus is 5.29 t hm
a
, which is 2.95 and 2.18 times greater than Pinus massoniana Lamb. and Cunninghamia lanceolata Lamb. Its plantations area accounts for 6.85% of total plantations in China, but it contributes to more than 17.96% of total annual cut from plantations. In Guangdong and Guangxi provinces, areas of eucalyptus plantations are 30.32% and 34.91% of the total plantation area in each province respectively, but eucalyptus plantations contribute to 66.29% and 49.97% of harvested timber stock volume Eucalyptus pla consumes soil fertility significantly. The cumulative abandonment rate (based on area) is about 25%, 50%, and 75% after 5, 10, and 20 years of growing eucalyptus, respectively. The soil fertility decreases significantly after 50 years of growing eucalyptus continuously. In such case, it is difficult to restore the soil fertility. It is suggested that with improved management measures such as proper crop rotation rotating crops properly, it is possible for the abandoned plantations to be reused for growing eucalyptus. Currently the rates of replanting eucalyptus are still below 20% and 30% after 20 and 50 years of without growing eucalyptus, respectively. Although the proportion of eucalyptus area replanted to its abandoned area is now less than 20% in 20 years and less than 30% in 50 years, there is potential to keep increasing the replanting rate. We argue that developing eucalyptus plantations could contribute to global timber supply, help to protect natural forests, increase global carbon storage and fixation, and help to slow down global warming. In conclusion, we should not stop growing eucalyptus despite its high consumption of soil fertility.
Proteotoxicity refers to the detrimental effects of damaged/misfolded proteins on the cell. Cardiac muscle is particularly susceptible to proteotoxicity because sustained and severe proteotoxic ...stress leads to cell death and the cardiac muscle has very limited self-renewal capacity. The ubiquitin–proteasome system (UPS) and the autophagic-lysosomal pathway (ALP) are two major pathways responsible for degradation of most cellular proteins. Alterations of UPS and ALP functions are associated with the accumulation of proteotoxic species in the heart, a key pathological feature of common forms of heart disease including idiopathic, ischemic, and pressure-overloaded cardiomyopathies and a large subset of congestive heart failure. Emerging evidence suggests that proteasome inhibition or impairment activates autophagy and conversely, acute ALP inhibition may sometimes increase intrinsic proteasome peptidase activities but chronic ALP inhibition hinders UPS performance in ubiquitinated protein degradation. The exact molecular basis on which the two degradative pathways interact remains largely undefined. Here we review current understanding of the roles of the UPS and autophagy in the control of cardiac proteotoxicity, with a specific focus on the crosstalk between the two pathways. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
•The ubiquitin–proteasome system degrades protein molecules one by one.•Macroautophagy degrades misfolded proteins in aggregates.•Proteasome impairment activates autophagy for compensation.•Inhibition of autophagy may hinder the performance of the 26S proteasome.•Molecular basis for the interplay between autophagy and the UPS remains unclear.
In this paper, the sufficient and necessary conditions for complete convergence and the Kolmogorov strong law of large numbers for weighted sums of m-extended negatively dependent random variables ...are presented. Some applications of the main results are also provided, including the weak and strong consistency of the least squares estimator in multiple linear regression models, strong consistency of conditional Value-at-risk estimator, and the asymptotics of the quasi-renewal counting process. Finally, some numerical simulations are carried out to confirm the theoretical results.
Recommender systems have been widely applied to several domains and applications to assist decision making by recommending items tailored to user preferences. One of the popular recommendation ...algorithms is the model-based approach which optimizes a specific objective to improve the recommendation performance. These traditional recommendation models usually deal with a single objective, such as minimizing the prediction errors or maximizing the ranking quality of the recommendations. In recent years, there is an emerging demand for multi-objective recommender systems in which multiple objectives are considered and the recommendations can be optimized by the multi-objective optimization. For example, a recommendation model may be built by optimizing multiple metrics, such as accuracy, novelty and diversity of the recommendations. The multi-objective optimization methodologies have been well developed and applied to the area of recommender systems. In this article, we provide a comprehensive literature review of the multi-objective recommender systems. Particularly, we identify the circumstances in which a multi-objective recommender system could be useful, summarize the methodologies and evaluation approaches in these systems, point out existing challenges or weaknesses, finally provide the guidelines and suggestions for the development of multi-objective recommender systems.
Wisdom campus is a high-level stage of digital campus construction and needs to be improved in addressing the issues of information silos and legacy systems. Based on the SERVICE ORIENTED ...ARCHITECTURE-based vocational schools wisdom campus overall architecture model contains reusable services and well-defined, standards-compliant interface, through services to achieve different platforms, different languages on the exchange between the system can be targeted at vocational colleges to provide business processes, To provide fast and flexible changes. The model of "platform + application + service" proposed by the model and service-oriented thinking can better solve the problem of information silos and legacy systems and provide an effective method for upgrading the Informatization level of vocational colleges.
•Lake warming has constituted a particular challenge for restoration of eutrophic lakes.•Changes of internal loadings are mainly responsible for the seasonal changes of nutrients in the lake.•Lake ...warming would result in more significant seasonal fluctuations in internal loadings.•Adaptions in the existing mitigation strategies of eutrophic lake are necessary in a warming world.
Lake warming induced by climate change has constituted a particular challenge for the restoration of eutrophic lakes. However, a quantitative analysis about impacts of lake warming on the internal nutrient cycling in eutrophic lakes is limited. In this study, monthly nutrient monitoring data set in 2015-2016 in eutrophic Lake Chaohu, China, revealed a regular seasonal pattern of nutrient concentration. A process-based water quality model was established to quantify contributions from internal loadings on seasonal nutrient variations and predict responses under climate change scenarios. Results indicated that internal nutrient loading was responsible for the intra-annual variations of nutrient concentrations in the lake, and the internal loadings fluctuated much more between different seasons than the external nutrient inputs. We predicted that lake warming might probably result in stronger seasonal fluctuations of internal loading and create conditions beneficial for longer duration of cyanobacteria blooms in the year. Evidence derived from this study could help water managers to rethink the existing mitigation strategies in the restoration of eutrophic lakes and emphasize the potential interactions among lake warming, eutrophication and internal nutrient cycling in the future.
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Insufficient lysosomal removal of autophagic cargoes in cardiomyocytes has been suggested as a main cause for the impairment of the autophagic-lysosomal pathway (ALP) in many forms of heart disease ...including cardiac proteinopathy and may play an important pathogenic role; however, the molecular basis and the correcting strategy for the cardiac ALP insufficiency require further investigation. The present study was sought to determine whether myocardial expression and activity of TFEB, the recently identified ALP master regulator, are impaired in a cardiac proteinopathy mouse model and to determine the effect of genetic manipulation of TFEB expression on autophagy and proteotoxicity in a cardiomyocyte model of proteinopathy. We found that increased myocardial TFEB mRNA levels and a TFEB protein isoform switch were associated with marked decreases in the mRNA levels of representative TFEB target genes and increased mTORC1 activation, in mice with cardiac transgenic expression of a missense (R120G) mutant αB-crystallin (CryABR120G), a well-established model of cardiac proteinopathy. Using neonatal rat ventricular cardiomyocyte cultures, we demonstrated that downregulation of TFEB decreased autophagic flux in cardiomyocytes both at baseline and during CryABR120G overexpression and increased CryABR120G protein aggregates. Conversely, forced TFEB overexpression increased autophagic flux and remarkably attenuated the CryABR120G overexpression-induced accumulation of ubiquitinated proteins, caspase 3 cleavage, LDH leakage, and decreases in cell viability. Moreover, these protective effects of TFEB were dramatically diminished by inhibiting autophagy. We conclude that myocardial TFEB signaling is impaired in cardiac proteinopathy and forced TFEB overexpression protects against proteotoxicity in cardiomyocytes through improving ALP activity.
•Myocardial TFEB signaling is suppressed in CryABR120G-based proteinopathy.•TFEB knockdown suppresses autophagic flux in cultured cardiomyocytes.•TFEB overexpression elevates autophagic flux in cultured cardiomyocytes.•TFEB facilitates autophagic removal of a bona fide misfolded protein.•Protection of TFEB against cardiac proteotoxicity depends on autophagy.
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