To date, mechanisms of tumour cell survival under energy stress are not well understood. Cumulative evidence is beginning to reveal that specific mitochondrial morphologies are often associated with ...energetic states and survival of cells. However, the functional roles of mitochondria in the metabolic adaptation of tumour cells to energy stress remain to be elucidated. In this study, we first investigated the changes in mitochondrial morphology induced by nutrition deprivation in tumour cells, and the underlying molecular mechanism. We then systematically explored glucose metabolism reprogramming by energy stress-induced alteration of mitochondrial morphology and its effect on tumour cell survival. Our results showed that starvation treatment resulted in a dramatic mitochondrial elongation, which was mainly mediated by DRP1
phosphorylation through protein kinase A activation and subsequent suppression of mitochondrial translocation of DRP1. We further observed that tumour cells under an energy stress condition exhibited a clear shift from glycolysis towards oxidative phosphorylation, which was reversed by the recovery of mitochondrial fission induced by forced expression of mutant DRP1
. Mechanistically, energy stress-induced mitochondrial elongation facilitated cristae formation and assembly of respiratory complexes to enhance oxidative phosphorylation, which in turn exhibited a feedback inhibitory effect on glycolysis through NAD
-dependent SIRT1 activation. In addition, our data indicated that DRP1
-mediated mitochondrial elongation under energy stress was essential for tumour cell survival both in vitro and in vivo and predicted poor prognosis of hepatocellular carcinoma patients. Overall, our study demonstrates that remodelling of mitochondrial morphology plays a critical role in tumour cell adaptation to energy stress by reprogramming glucose metabolism.
Severe deficiency of plasma ADAMTS13 activity may result in potentially fatal thrombotic thrombocytopenic purpura and relative deficiency of plasma ADAMTS13 activity may be associated with adverse ...outcomes of certain malignancies. Here, we report the role of ADAMTS13 or lack of von Willebrand factor (VWF) in reducing irradiation and melanoma‐induced thrombotic microangiopathy (TMA) and mortality in zebrafish.
Zebrafish melanoma cell line (ZMEL) was injected subcutaneously into wild‐type (wt), adamts13−/− (a13−/−), von Willebrand factor (vwf−/−), and a13−/−vwf−/− zebrafish following total body irradiation; the tumor growth, its gene expression pattern, the resulting thrombocytopenia, and the mortality were determined.
Total body irradiation at 30 Gy alone resulted in a transient thrombocytopenia in both wt and a13−/− zebrafish. However, thrombocytopenia occurred earlier and more profound in a13−/− than in wt zebrafish, which was resolved 2 weeks following irradiation alone. An inoculation of ZMEL following the irradiation resulted in more severe and persistent thrombocytopenia, as well as earlier death in a13−/− than in wt zebrafish. The vwf−/− or a13−/−vwf−/− zebrafish were protected from developing severe thrombocytopenia following the same maneuvers. RNA‐sequencing revealed significant differentially expressed genes associated with oxidation–reduction, metabolism, lipid, fatty acid and cholesterol metabolic processes, steroid synthesis, and phospholipid efflux in the melanoma explanted from a13−/− zebrafish compared with that from the wt controls.
Our results indicated that plasma ADAMTS13 or lack of VWF may offer a significant protection against the development of irradiation‐ and/or melanoma‐induced TMA. Such a microenvironment may directly affect melanoma cell phenotypes via alternation in the oxidation–reduction and lipid metabolic pathways.
Tropospheric ozone significantly damages vegetation and reduces net primary productivity (NPP). We developed a stable linear NPP response model based on accumulated ozone exposure over a threshold of ...40 parts per billion (ppb) (AOT40). We then estimated the effects of regional ozone damage on NPP for different vegetation types. The study suggests an average decrease in NPP of 24.7% due to ozone pollution in the North China Plain, similar to previous estimates ranging from 10.1% to 24.7%, with a maximum reduction exceeding 200 g C m‐2 yr‐1 and more than 50%. Vegetation types such as broadleaf forests, needleleaf forest, crops, and grasses showed significant NPP decreases of 47.1%, 37.8%, 36.7%, and 44.6%, respectively. Declining NPP also had negative impacts on several Chinese crop species. Our work highlights the need for urgent and effective action to mitigate ozone pollution's substantial detrimental effects on ecosystem health and productivity.
Plain Language Summary
Ozone pollution led to an average 25% decrease in net primary productivity in the North China Plain. This decline is consistent with previous estimates that ranged from 10% to 25%. Productivity of forest trees, crops, and grasses declined significantly, ranging from 36.7% to 47.1%. These results have implications for Chinese crops, as lower crop productivity can negatively affect crop yields. Our study highlights the urgent need for action to mitigate the detrimental effects of ozone pollution on ecosystem health and productivity.
Key Points
We developed a stable model to estimate ozone impact on the productivity of plants'
Ozone pollution resulted in an average decline in productivity of 25% per year in all ecosystem types in the North China Plain region
Ozone pollution led to net primary productivity declines in forest, crops, and grasses, with reductions ranging from 36.7% to 47.1%
Nanoindentation technology is an effective and convenient method for evaluating the mechanical properties of materials at micro and nano scales. Since the complete nanoindentation process is a ...typical non-linear mechanical behavior and the material deformation varies with the indentation depth, it is difficult to analytically obtain plastic parameters of constitutive models which are however important to describe the material properties in finite element simulations. In this study, nanoindentation experiments are carried out on the sintered silver nanoparticle (AgNP) which is one of the advanced die-attach materials for high-power electronic devices working in harsh environment. In order to further stabilize and enhance the thermal conductivity, different weight contents of SiC microparticles are incorporated in the AgNP paste before the sintering process. Finite element simulations are used to simulate the deformation and load resistance of materials in nanoindentation process. Plastic properties of materials are analyzed by proposing a reverse algorithm based on the measurements of nanoindentation responses. Essentially, the proposed reverse algorithm couples the dimensional analysis and trial-and-error fitting technique. The complete constitutive relationship of sintered AgNP with different SiC contents is obtained accordingly after examining the loading and unloading stages of nanoindentation responses. The influence of SiC content on the mechanical properties of sintered AgNP is also discussed by considering the material microstructure observed using a scanning electron microscopy. Finally, the uniqueness of constitutive curve from the proposed reverse algorithm is confirmed by the agreement of predicted and measured load-displacement responses using independent spherical indentations.
Background
Altered visceral sensation is common in irritable bowel syndrome (IBS) and nerve growth factor (NGF) participates in visceral pain development. Sodium butyrate (NaB) could induce colonic ...hypersensitivity via peripheral up‐regulation of NGF in animals. Enteric glial cells (EGCs) appear to be an important source of NGF. Whether butyrate could induce visceral hypersensitivity via increased EGC‐derived NGF is still unknown.
Methods
CRL‐2690 cells were used for transcriptome analyses after butyrate treatment. Rats received butyrate enemas to induce colonic hypersensitivity. Colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were used to evaluate the co‐expression of glial fibrillary acidic protein (GFAP) and NGF or growth associated protein 43 in animal model. NGF expression in rat colon was also investigated. In vitro, CRL‐2690 cells were stimulated with NaB or trichostatin A (TSA). NGF or GFAP expression was also examined.
Key Results
Transcriptome analyses showed that butyrate induced marked changes of genes expression related to neurotrophic signaling pathways. NaB‐treated rats showed increased visceral sensitivity. An improved NGF expression level was observed in NaB‐treated rats. Meanwhile, a 2.1‐fold increase in co‐expression of GFAP and NGF was also determined in rats received NaB enemas. In cultured cells, both NaB and TSA treatment could cause obvious NGF expression. Thus, butyrate might regulate EGC function via histone deacetylase inhibition.
Conclusions & Inferences
Butyrate‐EGC interplay may play a pivotal role in regulation of NGF expression and the development of colonic hypersensitivity in IBS‐like animal model.
Our study illustrated that butyrate promoted the secretion of NGF from enteric glial cells (EGCs) and contributed to visceral hypersensitivity in rats. The results clarified the potential unignorable source of NGF from EGC and highlighted the important role of EGC in pathogenesis of irritable bowel syndrome (IBS).
Immune thrombotic thrombocytopenic purpura (iTTP) is caused by severe deficiency of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. ...Despite advances in early diagnosis and management, the mortality rate of acute iTTP remains high in a large part of world where access to some of the most novel therapies is limited. To determine the role of plasma big endothelin-1 (bigET-1) or its bioactive product ET-1 as a biomarker and/or a pathogenic factor in acute iTTP, plasma levels of bigET-1 were determined using an immunoassay in patients with iTTP on admission and during remission, as well as in healthy controls; moreover, the biological effect of ET-1 in thrombus formation was determined by a microfluidic assay. We show that plasma levels of bigET-1 were dramatically increased in patients with acute iTTP on admission, which was significantly decreased during clinical response/remission; elevated admission levels of plasma bigET-1 were associated with low estimated glomerular filtration rate, the need for intensive care unit admission or intubation, and in-hospital mortality. Moreover, an addition of a bioactive product ET-1 to cultured endothelial cells in a microfluidic channel significantly accelerated the rate of thrombus formation under arterial flow. Our results demonstrate for the first time a potential role of measuring plasma bigET-1 in patients with acute iTTP in assessing the disease severity and risk of in-hospital mortality, which may help stratify patients for a more aggressive monitoring and therapeutic strategy; also, the bioactive ET-1, derived from bigET-1, may result in acute renal injury in TTP patient, likely through its vasoconstriction and prothrombotic properties.
Sedum alfredii Hance has been identified as a new zinc (Zn) hyperaccumulating plant species. In this study, the effects of cadmium (Cd) supply levels (control, 12.5, 25, 50, 100, 200, 400, 800 μmol ...Cd L-1) on the growth and cadmium accumulation and Zn supply on Cd accumulation in S. alfredii Hance were studied. The results showed that no reduction in shoot and root dry matter yields were noted when the plants were grown at Cd supply levels up to 200 μmol L-1 in nutrient solution. Slight stimulation on shoot growth was noted at relatively low Cd levels (25 to 100 μmol L-1). Cadmium concentrations in leaves and stems increased with increasing Cd supply levels, and reached a maximum of approximately 9000 and 6500 mg kg-1 (DW) at 400 μmol Cd L-1, respectively. Root Cd concentration increased sharply only at relatively high Cd levels. Cadmium distribution in different parts of the plant was in the order: leaf > stem >> root. The amount of Cd accumulated in the shoots reached 2.9 and 3.2 mg plant-1 at external Cd levels of 200 and 400 μmol L-1, respectively. The shoot/root Cd ratios were greater than 2 and more than 95% of the total Cd taken up by S. alfredii was translocated to the shoots at the external Cd levels ≤200 μmol L-1. The concentrations of P, Ca, Mg, B, Fe, Mn, Cu, and in the shoots and roots were influenced differentially by Cd treatments. High Zn supply (500 μmol L-1) enhanced Cd concentrations in the leaves and stems at the Cd levels ≤100 μmol L-1, and root Cd concentration at the Cd levels ≤50 μmol L-1. These results indicate that S. alfredii has an extraordinary ability to tolerate and hyperaccumulate Cd and this is the first report of the new Cd hyperaccumulator S. alfredii Hance. The finding of Cd/Zn hyperaccumulation in S. alfredii Hance provides an important plant material for understanding the mechanisms of Cd/Zn co-hyperaccumulation and for phytoremediation of the heavy metal contaminated soils.
Urbanization imposes complicated and heterogeneous impacts on ecosystems. With the purpose of reflecting the comprehensive influence of urbanization on the ecosystem, we choose the ecological ...footprint to represent the ecosystem's integrated change and distinguish low-income, middle-income and high-income countries to reflect the nonlinear impact. This paper uses both static and dynamic STIRPAT (Stochastic Impacts by Regression on Population, Affluence and Technology) models to analyze 72 countries at different income levels during the 1980–2008 period. The results show that the overall ecological elasticity of urbanization at the global level is negative. Specifically, results suggest urbanization, associated to increased income, to have eco-friendly potential in terms of decreased ecological footprint. To explain such results, this paper answers two questions: Why does urbanization show ecological protection effects? Why does a more pronounced protection effect seem associated to increased income levels? Improved market mechanism, increased resource use efficiency as well as increased environmental awareness in urban areas associated to increased income levels are likely to support an eco-friendly urbanization process. Burden-shift to low-income countries also needs to be taken into account, in order to avoid policies that increase wellbeing locally at the expenses of far-away areas.
•Ecological effects of urbanization are estimated.•Ecological footprint is used to represent the integrated change related to energy and land use.•Static and dynamic STIRPAT models are employed for regression.•The reasons for the ecological protection effect of urbanization are analyzed.•The heterogeneity of urban structure and function across income levels is discussed.
The effects of different nozzle structures on the performance of a steam ejector have been investigated numerically with the computational fluid dynamics (CFD) technique. The performance of the steam ...ejectors with five different nozzle structures, namely, conical, elliptical, square, rectangular and cross-shaped nozzles, have been compared under the same conditions. It is found that, compared with the CFD results of the ejector equipped with the conical nozzle, the entrainment ratio (ER) and critical back pressure (CBP) of the rectangular nozzle is 7.1% and 21.3% lower respectively; the ER and CBP of the elliptical nozzle is 7.9% and 21.3% lower respectively; the square nozzle has improved the ER by 2.0% and decreased the CBP by 2.1%; the ER and CBP of the ejector utilizing cross-shaped nozzle is 9.1% higher and 6.4% respectively lower. Based on the simulation results of the streamwise vortex and spanwise vortex distributions in the mixing chamber and the internal energy variations along the streamwise distance, the characteristics of the mixing process and the main factors accounting for the ejector performance change are clarified. The ER increase can be achieved by efficient mixing due to the interactions between the streamwise vortex and the spanwise vortex. The streamwise vortex helps to deform and rupture the spanwise vortex which has greater strength. Collides of the vortices to the mixing chamber wall at early stage would increase mechanical energy loss and reduce “effective area” for secondary flow to pass through, resulting in great decrease of the ER and CBP. This scenario should be avoided in the design of nozzles.
► We study the effects of five kinds of nozzle shapes on the ejector performance. ► The elliptical and rectangular nozzles decrease the ejector performance. ► The cross-shaped and square nozzles improve the entrainment ratio of the ejector. ► We clarify the mixing process by vortex distribution and internal energy variation. ► The causes of the ejector performance variations are studied qualitatively.
