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Grassland vegetation is the largest terrestrial ecosystem in the Qinghai Lake Basin (QLB), and it is also the most important means of production for herders’ livelihoods. Quantifying the impact of climate change and human activities on grassland vegetation changes is an essential task for ensuring the sustainable livelihood of pastoralists. To this end, we investigated vegetation cover changes in the QLB from 2000 to 2020 using the normalized difference vegetation index (NDVI), meteorological raster data, and digital elevation and used residual analysis of multiple linear regression to evaluate the residuals of human activities. The residual analysis of partial derivatives was used to quantify the contribution of climate change and human activities to changes in vegetation cover. The results showed that: (1) The vegetation coverage of the QLB increased significantly (0.002/a, p < 0.01), with 91.38% of the area showing a greening trend, and 8.62% of the area suffering a degrading trend. The NDVI decreased substantially along the altitude gradient (−0.02/a, p < 0.01), with the highest vegetation coverage at 3600–3700 m (0.37/a). The vegetation degraded from 3200–3300 m, vegetation greening accelerated from 3300–3500 m, and vegetation greening slowed above 3500 m. (2) The contribution of climate change, temperature (T), and precipitation (P) to vegetation cover change were 1.62/a, 0.005/a, and 1.615/a, respectively. Below 3500 m, the vegetation greening was more limited by P. Above 3500 m, the vegetation greening was mainly limited by T. (3) Residual analysis showed that the contribution of human activities to vegetation cover was −1.618/a. Regarding the altitude gradient, at 3300–3500 m, human activities had the highest negative contribution to vegetation coverage (−2.389/a), and at 3200–3300 m, they had the highest positive contribution (0.389/a). In the past 21 years, the impact of human activities on vegetation coverage changed from negative to positive. Before 2009, the annual average NDVIres value was negative; after 2010, the average yearly NDVIres value turned positive. In general, the vegetation greening of the QLB depends on climate warming and humidification. The positive impact of human activities over the past decade was also essential for vegetation greening. These findings deepen our understanding of the QLB vegetation changes under climate change and human activities.

Bibliotherapy is an important part of art therapy and many publications regarding bibliotherapy have been published in the past. However, there has none about the scientometric study to systematically analyze the development and emerging research trends on bibliotherapy. Therefore, we performed a scientometric investigation to describe trends of this theme. All publications related to bibliotherapy published from 1980 to 2020 were identified and selected from Science Citation Index Expanded, Social Sciences Citation Index, and ArtsHumanities Citation Index of Web of Science Core Collection. VOSviewer was used to create collaborative network plots of countries, institutions, and authors and to perform cluster analysis of keywords. A total of 703 articles were searched, and we retrieved the 100 most cited articles published by 146 institutions from 15 countries in 57 academic journals. The United States occupied a leading position in the field of bibliotherapy and Linköping University was the most productive institution.

In the age of digitalization, travel applications (or travel apps) are indispensable tools for modern travel activities. During an app's selection and adoption phases, privacy concerns remain a sensitive issue that may demotivate users’ from continuing to use it. This study integrated both the stimulus-organism-response model (S-O-R) and psychological reaction theory (PRT) to explore the factors that influence users’ app usage experiences and behavioral responses. A self-administered questionnaire was designed and distributed to Gen Y users in mainland China. The findings of PLS-SEM analysis showed that usage intentions are predicted by the ability of travel apps to engage with users and generate favorable values. Additionally, users with low privacy concerns were shown to have a stronger intention to recommend travel apps to others. All in all, the findings from this study offer valuable insights to tourism providers and app developers.

Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer.

Soil contamination by arsenic (As) presents a high risk to public health, necessitating urgent remediation. This study sought to develop an efficient strategy for the phytoremediation of As-contaminated soil. The effects of Stevia rebaudiana Bertoni residue (SR) on the available As (A-As) concentration of soil and As extraction from the soil by Pteris vittata L. were studied by soil simulation, pot, and field experiments. The A-As concentration in the soil simulation experiment increased significantly by 84.20% after 20 days. The biomass, As concentration, and total extracted As of SR-treated P. vittata L. in the pot experiment increased significantly by 50.66%, 120.2%, and 171.2%, respectively, compared to the untreated control. The SR-treated rhizosphere soil in the pot experiment displayed a significant 21.72% decrease in total As concentration. In the one-year field experiment, treatment with SR resulted in a significant 191.1% increase in As extraction by P. vittata L. and a significant 10.26% reduction in rhizosphere soil As concentration compared to the control. This study proposes a potential mechanism for SR-mediated enhancement of P. vittata L. As extraction ability and provides a new, economic, and environmentally friendly method for As-contaminated soil remediation.

HR3C austenitic heat resistant steel has been gradually applied as tubes to manufacture components of superheaters and reheaters in ultra-supercritical (USC) power plants. Creep tests were conducted at 650 °C under the applied stresses in the range of 150 MPa–250 MPa. Scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and X-ray diffraction (XRD) were employed to investigate the creep damage characteristics and evolution. The results show that intergranular microcracks and dense creep cavities along grain boundaries are the major features of creep damage. Different states of creep damage characteristic distribution are related to the applied stress and creep duration at high temperature. The wedge-cracking is prone to take place at the triple junctions of grain boundaries, and creep cavities are nucleated preferentially at M23C6 precipitates along grain boundaries. The nucleation and growth of creep cavities and wedge-cracks have a crystallographic orientation relationship with the neighboring austenite grains. The adjacent grains have a large difference of Schmid factor, and one of them is close to //the stress axis orientation, which has greater resistance to deformation. The Orientation Deviation (KAM) obtained from EBSD analysis implies that the creep damage is obviously affected by the stress level. Microcracks under high stress are mainly attributed to the local deformation, and dense creep cavities under low stress are dominated by time-dependent diffusion. Under the intermediate stress level, local deformation and time-dependent diffusion act together, leading to the most serious damage.

Microlens array (MLA) errors in plenoptic cameras can cause the confusion or mismatching of 4D spatio-angular information in the image space, significantly affecting the accuracy and efficiency of target reconstruction. In this paper, we present a high-accuracy correction method for light fields distorted by MLA errors. Subpixel feature points are extracted from the microlens subimages of a raw image to obtain correction matrices and perform registration of the corresponding subimages at a subpixel level. The proposed method is applied for correcting MLA errors of two different categories in light-field images, namely form errors and orientation errors. Experimental results show that the proposed method can rectify the geometric and intensity distortions of raw images accurately and improve the quality of light-field refocusing. Qualitative and quantitative comparisons between images before and after correction verify the performance of our method in terms of accuracy, stability, and adaptability.

Background Triple-negative breast cancer (TNBC) is often aggressive and associated with a poor prognosis. Due to the lack of available targeted therapies and to problems of resistance with conventional chemotherapeutic agents, finding new treatments for TNBC remains a challenge and a better therapeutic strategy is urgently required. Methods TNBC cells and xenograft mice were treated with a combination of chloroquine (CQ) and isorhamnetin (IH). Mitochondrial fission, apoptosis, and related signaling pathways were determined by flow cytometry, immunofluorescence, and related molecular biological techniques. Results The inhibition of autophagy/mitophagy by CQ selectively enhances IH-induced mitochondrial fission and apoptosis in TNBC cells but not in estrogen-dependent breast cancer cells. These events were accompanied by mitochondrial translocation of Bax and the release of cytochrome c. Mechanistically, these effects were associated with oxidative stress-mediated phosphorylation of CaMKII (Thr286) and Drp1 (S616), and subsequent mitochondrial translocation of CaMKII and Drp1. The interruption of the CaMKII pathway by genetic approaches (e.g. CaMKII mutant or siRNA) attenuated combination-mediated mitochondrial fission and apoptosis. The combination of CQ/IH was a marked inhibitor tumor growth, inducing apoptosis in the TNBC xenograft mouse model in association with the activation of CaMKII and Drp1 (S616). Conclusions Our study highlights the critical role of ROS-mediating CaMKII/Drp1 signaling in the regulation of mitochondrial fission and apoptosis induced by combination of CQ/IH. These findings also suggest that IH could potentially be further developed as a novel chemotherapeutic agent. Furthermore, a combination of IH with classic autophagy/mitophagy inhibitor could represent a novel therapeutic strategy for the treatment of TNBC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1201-4) contains supplementary material, which is available to authorized users.

Background Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular mechanism for lysosomal degradation of damaged cellular components. The specific degradation of nuclear components by the autophagy pathway is called nucleophagy. Most studies have focused on autophagic turnover of cytoplasmic materials, and little is known about the role of autophagy in the degradation of nuclear components. Methods Human MDA-MB-231 and MCF-7 breast cancer cell lines were used as model systems in vitro. Induction of nucleophagy by nuclear DNA leakage was determined by western blot and immunofluorescence analyses. The interaction and colocalization of LC3 and lamin A/C was determined by immunoprecipitation and immunofluorescence. The role of the SUMO E2 ligase, UBC9, on the regulation of SUMOylation of lamin A/C and nucleophagy was determined by siRNA silencing of UBC9, and analyzed by immunoprecipitation and immunofluorescence. Results DNA damage induced nuclear accumulation of UBC9 ligase which resulted in SUMOylation of lamin A/C and that SUMOylation of this protein was required for the interaction between the autophagy protein LC3 and lamin A/C, which was required for nucleophagy. Knockdown of UBC9 prevented SUMOylation of lamin A/C and LC3-lamin A/C interaction. This attenuated nucleophagy which degraded nuclear components lamin A/C and leaked nuclear DNA mediated by DNA damage. Conclusions Our findings suggest that nuclear DNA leakage activates nucleophagy through UBC9-mediated SUMOylation of lamin A/C, leading to degradation of nuclear components including lamin A/C and leaked nuclear DNA. Electronic supplementary material The online version of this article (10.1186/s13046-019-1048-8) contains supplementary material, which is available to authorized users.

Figure S1. Combined treatment with CQ/IH induces apoptosis in BT549 cells. Figure S2. Excessive accumulation of mitophagosomes contributes to apoptosis induced by combination of CQ/IH in MDA-MB-231 cells. Figure S3. Combined treatment with CQ/IH induces phosphorylation of Drp1 (Ser616) and mitochondrial translocation of Drp1 in BT549 cells. Figure S4. Combined treatment with CQ/IH induces the colocalization of Drp1 and Bax at mitochondria in MDA-MB-231 cells. Figure S5. Combined treatment with CQ/IH induces phosphorylation of CaMKII (Thr286) and mitochondrial translocation of CaMKII (Thr286) in BT549 cells. Figure S6. CaMKII mutation blocks mitochondrial fission and apoptosis induced by combination of CQ/IH. Figure S7. Knockdown of CaMKII blocks mitochondrial fission and apoptosis induced by combination of CQ/IH. Figure S8. Effects of antioxidants on CQ/IH-induced ROS generation, mitochondrial fission, apoptosis, and cell signaling proteins. (DOCX 4596 kb)

Figure S1. Nuclear DNA leakage activates nucleophagy. Figure S2. Nuclear autophagy exists in other cancer cell lines. Figure S3. LC3-lamin A/C interaction is required for nucleophagy. Figure S4. Inhibiting autophagy impairs degradation of lamin A/C. Figure S5. Lamin A/C is SUMOylated in response to DNA damage. Figure S6. UBC9 accumulates in nucleus in response to DNA damage. Figure S7. Knockdown of UBC9 attenuates SUMOylation of lamin A/C and nucleophagy mediated by DNA damage. (DOCX 6283 kb)

Background: Coronavirus disease 2019 (COVID-19) has spread almost all regions of the world and caused great loss to the whole body of mankind. Thus, numerous clinical trials were conducted to find specific medicine for COVID-19 recently. However, it remains unanswered whether they are beneficial. Objective: This study aimed to evaluate the efficiency and safety of the COVID-19 medicine. Methods: Studies were determined through searching PubMed, Embase, Cochrane Library and Medline. The clinical trials of COVID-19 medicine were involved with eligible end points containing mortality, discharge rate, rate of clinical improvement and rate of serious adverse events. The risk ratio (RR) was adopted for variables as effect magnitude with 95% confidence intervals (CI), and the random‐effects model was adopted for analysis. Results: A total of eleven RCTs and eleven Non-RCTs involving 12,796 patients were included in our study, whose intervening measures contained three major types of COVID-19 medicine, ACEI/ARB, antiviral medicine and chloroquine/hydroxychloroquine. Compared to control group, COVID-19 medicine has the obvious advantage in reducing discharge rate (RR, 1.18; 95% CI, 1.07-1.29, pConclusion: The results indicated antiviral medicine was potential drug of first choice recommended for COVID-19 treatment. Chloroquine/hydroxychloroquine therapy was not recommended for COVID-19 patients. Additionally, the ACEI/ARB could be adopted for COVID-19 treatment when combined with standard treatment.

This paper is to discuss the development of Deep Reinforcement Learning and the future of it from the perspective of Game Theory. The relationship and potential interaction between these two areas are also introduced, especially the optimization method. This paper discusses about the situations both under non-cooperative and cooperative game. Recently, Artificial Intelligence (AI) and Machine Learning (ML) have grasp sufficient attention from various research areas. Deep Reinforcement Learning, as one of the most promising ML methods, enlighten more researchers to devote themselves in this area. However, even such accomplishment could not belie that, for most kinds of real-life problems, DRL is still unable to provide with an optimal strategy. Because unlike the well-adjusted environment in laboratory, real life problems are not always able to be converted into mathematical problems. Under such circumstances, most of real-life problems have no nominal “optimal solution”. Game Theory provides potential solutions to covert “real issues” into “mathematical problems”, then it is easier for researchers to handle.

Ars2 is a component of the nuclear cap-binding complex (CBC) that contributes to microRNA biogenesis and is required for cellular proliferation. Little is known regarding the functional role of Ars2 in cell proliferation and leukemogenesis of acute myeloid leukemia. Here, we show that the elevated expression of Ars2 was observed in acute myeloid leukemia (AML) cell lines and bone marrow samples from AML patients and was correlated with poorer overall survival. Overexpression of Ars2 promoted cell proliferation and colony formation in AML cells, whereas depletion of Ars2 inhibited cell proliferation and colony formation. Mechanistic studies reveal that depletion of Ars2 suppressed the interaction of Ars2 with CBC and led to alterations in miRNA processing. Furthermore, Ars2 depletion reduced the levels of miR-6734-3p, resulting in upregulation of p27 and culminating in cell cycle arrest at the G1 phase. In vivo studies indicate that depletion of Ars2 significantly reduced leukemic cell burden and prolonged the survival time of the leukemia-bearing mice. These findings indicate that Ars2 may not only play a crucial role in the regulation of cell proliferation and leukemogenesis, but could also be identified as a critical therapeutic target for treatment of AML.

We investigated anthocyanin concentrations by HPLC (high-performance liquid chromatography) and expression of MYB , bHLH and UFGT gene families by quantitative real time PCR in apple skin of red cultivar ‘Starkrimson’ and non-red cultivars ‘Golden Delicious’ and ‘Granny Smith’ in response to light. Young fruits were bagged at 40 DAFB (days after full bloom), and fruits of ‘Golden Delicious’ and ‘Starkrimon’ were debagged at 120 DAFB, while fruits of ‘Granny Smith’ at 160 DAFB. In bagged fruit, anthocyanin synthesis and related genes expression were both depressed, whereas these genes expression was enhanced by light, accompanied by anthocyanin accumulation in apple skin. ‘Starkrimson’ and ‘Granny Smith’ accumulated relatively higher anthocyanin concentrations than ‘Golden Deliicous’. Transcript levels of most selected regulatory genes, including MdMYB1-1, MdMYB1-2, MdbHLH3-1 and MdbHLH33-1 , were up-regulated in apple skin of all the three cultivars, although transcript levels of these genes in ‘Starkrimson’ and ‘Granny Smith’ increased before outer layered bag removal, and increased after outer layered in ‘Golden Delicious’. However, UFGT family showed differences between red and non-red cultivars. MdUFGT2 was up-regulated only in non-red cultivars, while MdUFGT4 was up-regulated only in red skin cultivar, suggesting that UFGT is also important for anthocyanin accumulation in apple skin of different colors. Our results indicated that anthocyanin regulation in different colored apple cultivars were accomplished through different mechanisms, which will be valuable for further research of anthocyanin regulation in apple skin and for apple breeding programs that take genetic tools to improve the consistency of color in apples.

The demand for maritime transport is derived primarily from the needs of industrial processes. Therefore, the boom and bust in the shipping market are typically motivated by the global economic situation. Under such an unpredictable and uncertain circumstance, for striving for a competitive position in market, explicit strategies are very significant to liner shipping companies. This paper investigates trends in liner shipping industry and analyzes the industrial structure by five forces analysis. By means of five forces analysis, competitive rivalry and barging power of buyers show a relatively strong force in liner shipping industry. At last, seven competitive strategies are proposed for liner shipping companies by taking into account of critical forces and trend in liner shipping industry.

BACKGROUND AND PURPOSE Ursolic acid (UA) has been extensively used as an anti-leukaemic agent in traditional Chinese medicine. In the present study, we investigated the ability of UA to induce apoptosis in human leukaemia cells in relation to its effects on caspase activation, Mcl-1 down-regulation and perturbations in stress-induced signalling pathways such as PKB and JNK. EXPERIMENTAL APPROACH Leukaemia cells were treated with UA after which apoptosis, caspase activation, PKB and JNK signalling pathways were evaluated. The anti-tumour activity of UA was evaluated using xenograft mouse model. KEY RESULTS UA induced apoptosis in human leukaemia cells in a dose- and time-dependent manner; this was associated with caspase activation, down-regulation of Mcl-1 and inactivation of PKB accompanied by activation of JNK. Enforced activation of PKB by a constitutively active PKB construct prevented UA-mediated JNK activation, Mcl-1 down-regulation, caspase activation and apoptosis. Conversely, UA lethality was potentiated by the PI3-kinase inhibitor LY294002. Interruption of the JNK pathway by pharmacological or genetic (e.g. siRNA) attenuated UA-induced apoptosis. Furthermore, UA-mediated inhibition of tumour growth in vivo was associated with induction of apoptosis, inactivation of PKB as well as activation of JNK. CONCLUSIONS AND IMPLICATIONS Collectively, these findings suggest a hierarchical model of UA-induced apoptosis in human leukaemia cells in which UA induces PKB inactivation, leading to JNK activation and culminating in Mcl-1 down-regulation, caspase activation and apoptosis. These findings indicate that interruption of PKB/JNK pathways may represent a novel therapeutic strategy in haematological malignancies.

Global climate and environmental changes are endangering global water resources; and several approaches have been tested to manage and reduce the pressure on these decreasing resources. This study uses the case study of Xi’an City in China to test reasonable and effective methods to address water resource shortages. The study generated a framework combining ecosystem services and water resource management. Seven ecosystem indicators were classified as supply services, regulating services, or cultural services. Index values for each indicator were calculated, and based on questionnaire results, each index’s weight was calculated. Using the Likert method, we calculated ecosystem service supplies in every region of the city. We found that the ecosystem’s service capability is closely related to water resources, providing a method for managing water resources. Using Xi’an City as an example, we apply the ecosystem services concept to water resources management, providing a method for decision makers.

Ursolic acid (UA) has been extensively used as an anti-leukaemic agent in traditional Chinese medicine. In the present study, we investigated the ability of UA to induce apoptosis in human leukaemia cells in relation to its effects on caspase activation, Mcl-1 down-regulation and perturbations in stress-induced signalling pathways such as PKB and JNK.Leukaemia cells were treated with UA after which apoptosis, caspase activation, PKB and JNK signalling pathways were evaluated. The anti-tumour activity of UA was evaluated using xenograft mouse model.UA induced apoptosis in human leukaemia cells in a dose- and time-dependent manner; this was associated with caspase activation, down-regulation of Mcl-1 and inactivation of PKB accompanied by activation of JNK. Enforced activation of PKB by a constitutively active PKB construct prevented UA-mediated JNK activation, Mcl-1 down-regulation, caspase activation and apoptosis. Conversely, UA lethality was potentiated by the PI3-kinase inhibitor LY294002. Interruption of the JNK pathway by pharmacological or genetic (e.g. siRNA) attenuated UA-induced apoptosis. Furthermore, UA-mediated inhibition of tumour growth in vivo was associated with induction of apoptosis, inactivation of PKB as well as activation of JNK.Collectively, these findings suggest a hierarchical model of UA-induced apoptosis in human leukaemia cells in which UA induces PKB inactivation, leading to JNK activation and culminating in Mcl-1 down-regulation, caspase activation and apoptosis. These findings indicate that interruption of PKB/JNK pathways may represent a novel therapeutic strategy in haematological malignancies.