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The major challenges for density maps estimation and accurate counting stem from the large-scale variations, serious occlusions, and perspective distortions. Existing methods generally suffer from the blurred density maps, which are caused by average convolution kernel, and the ineffective estimation across different crowd scenes. In this paper, we propose a multi-scale fusion conditional generative adversarial network (MFC-GAN) that can generate high-resolution and high-quality density maps. The fusion module of MFC-GAN is embedded in a multi-scale generator and discriminator architecture with a novel adversarial loss, which is designed to guide high-resolution density maps generation. In order to address the problem of scale variation, we further propose a bidirectional fusion module. It combines deep global semantic features and shallow local information by leveraging feature maps presented in different layers of the generator. Furthermore, in order to increase the effectiveness of the multi-scale fusion, we design a cross-attention fusion module, which weights the multi-scale fused feature and learns context-aware feature maps for generating high quality density maps. The experiments on four challenging datasets show the effectiveness, feasibility and robustness of the proposed MFC-GAN.

Breast cancer is one of the most widespread and fatal cancers in women. At present, anticancer drug-inhibiting estrogen receptor α subtype (ER α ) can greatly improve the cure rate for breast cancer patients, so the research and development of this kind of drugs are very urgent. In this paper, the problem of how to screen excellent anticancer drugs is abstracted as an optimization problem. Firstly, the graph model is used to extract low-dimensional features with strong distinguishing and describing ability according to various attributes of candidate compounds, and then, kernel functions are used to map these features to high-dimensional space. Then, the quantitative analysis model of ER α biological activity and the classification model based on ADMET properties of the support vector machine are constructed. Finally, sequential least square programming (SLSQP) is utilized to solve the ER α biological activity model. The experimental results show that for anticancer data sets, compared with principal component analysis (PCA), the error rate of the graph model constructed in this paper is reduced by 6.4%, 15%, and 7.8% on mean absolute error (MAE), mean squared error (MSE), and root mean square error (RMSE), respectively. In terms of classification prediction, compared with principal component analysis (PCA), the recall and precision rates of this method are enhanced by 19.5% and 12.41%, respectively. Finally, the optimal biological activity value (IC50_nM) 34.6 and inhibitory biological activity value (pIC50) 7.46 were obtained.

Summary Endothelial cells (ECs) exhibit phenotypic and functional tissue specificities, critical for studies in the vascular field and beyond. Thus, tissue-specific methods for isolation of highly purified ECs are necessary. Kidney, spleen, and testis ECs are relevant players in health and diseases such as chronic kidney disease, acute kidney injury, myelofibrosis, and cancer. Here, we provide tailored protocols for rapid and reproducible EC purification established for scRNA sequencing from these adult murine tissues using the combination of magnetic- and fluorescence-activated cell sorting. For complete details on the use and execution of these protocols, please refer to Kalucka et al. (2020) and Dumas et al. (2020)., Graphical abstract, Highlights • Protocols for isolation of murine endothelial cells applicable for scRNA-seq • Efficient isolation of ECs from the kidney, spleen, and testis • Combination of magnetic- and fluorescence-activated cell sorting • High purity and quality of isolated murine endothelial cells evident from scRNA-seq, Endothelial cells (ECs) exhibit phenotypic and functional tissue specificities, critical for studies in the vascular field and beyond. Thus, tissue-specific methods for isolation of highly purified ECs are necessary. Kidney, spleen, and testis ECs are relevant players in health and diseases such as chronic kidney disease, acute kidney injury, myelofibrosis, and cancer. Here, we provide tailored protocols for rapid and reproducible EC purification established for scRNA sequencing from these adult murine tissues using the combination of magnetic- and fluorescence-activated cell sorting.

Graphical abstract A novel label-free surface plasmon resonance (SPR) aptasensor has been constructed for the detection of N-gene of SARS-CoV-2 by using thiol-modified niobium carbide MXene quantum dots (Nb2C-SH QDs) as the bioplatform for anchoring N-gene-targeted aptamer. In the presence of SARS-CoV-2 N-gene, the immobilized aptamer strands changed their conformation to specifically bind with N-gene. It thus increased the contact area or enlarged the distance between aptamer and the SPR chip, resulting in a change of the SPR signal irradiated by the laser (He-Ne) with the wavelength (λ) of 633 nm. Nb2C QDs were derived from Nb2C MXene nanosheets via a solvothermal method, followed by functionalization with octadecanethiol through a self-assembling method. Subsequently, the gold chip for SPR measurements was modified with Nb2C-SH QDs via covalent binding of the Au-S bond also by self-assembling interaction. Nb2C-SH QDs not only resulted in high bioaffinity toward aptamer but also enhanced the SPR response. Thus, the Nb2C-SH QD-based SPR aptasensor had low limit of detection (LOD) of 4.9 pg mL−1 toward N-gene within the concentration range 0.05 to 100 ng mL−1. The sensor also showed excellent selectivity in the presence of various respiratory viruses and proteins in human serum and high stability. Moreover, the Nb2C-SH QD-based SPR aptasensor displayed a vast practical application for the qualitative analysis of N-gene from different samples, including seawater, seafood, and human serum. Thus, this work can provide a deep insight into the construction of the aptasensor for detecting SARS-CoV-2 in complex environments. A novel label-free surface plasmon resonance aptasensor has been constructed to detect sensitively and selectively the N-gene of SARS-CoV-2 by using thiol-modified niobium carbide MXene quantum dots as the scaffold to anchor the N-gene-targeted aptamer. Supplementary Information The online version contains supplementary material available at 10.1007/s00604-021-04974-z.

Summary Endothelial cells (ECs) harbor distinct phenotypical and functional characteristics depending on their tissue localization and contribute to brain, eye, lung, and muscle diseases such as dementia, macular degeneration, pulmonary hypertension, and sarcopenia. To study their function, isolation of pure ECs in high quantities is crucial. Here, we describe protocols for rapid and reproducible blood vessel EC purification established for scRNA sequencing from murine tissues using mechanical and enzymatic digestion followed by magnetic and fluorescence-activated cell sorting. For complete details on the use and execution of these protocol, please refer to Kalucka et al. (2020), Rohlenova et al. (2020), and Goveia et al. (2020)., Graphical Abstract, Highlights • Protocols for isolation of murine endothelial cells designed for scRNA-seq • Rapid and efficient isolation of ECs from brain, choroid, lung, and muscle • Combination of magnetic and fluorescent activated cell sorting • High purity and quality of isolated murine endothelial cells evident from scRNA-seq, Endothelial cells (ECs) harbor distinct phenotypical and functional characteristics depending on their tissue localization and contribute to brain, eye, lung, and muscle diseases such as dementia, macular degeneration, pulmonary hypertension, and sarcopenia. To study their function, isolation of pure ECs in high quantities is crucial. Here, we describe protocols for rapid and reproducible blood vessel EC purification established for scRNA sequencing from murine tissues using mechanical and enzymatic digestion followed by magnetic and fluorescence-activated cell sorting.

The malfunction of junctional adhesion molecule C (JAM-C) has been reported to induce congenital cataract in humans and mice; however, specific characters and the mechanism of this cataract are still unclear. This study aimed to characterize abnormal lens development in Jamc knockout mice and clarify the underlying mechanism.Jamc knockout mice backcrossed onto the C57BL/6 genetic background were used for this research. Slit-lamp and darkfield images showed the cataract phenotype of Jamc-/- mice. Hematoxylin and eosin staining was performed to visualize the morphological and histological features. RNA sequencing was applied to detect differentially expressed genes. Quantitative RT-PCR, western blot, and immunofluorescence were used to determine the level of unfolded protein response (UPR)-related genes. TUNEL staining was utilized to label cell death.Jamc knockout mice exhibited nuclear cataract with abnormal lens morphology and defective degradation of nuclei and organelles in lens fiber cells. Compared with wild-type control mice, the expression level of BiP, CHOP, TRIB3, and CHAC1, genes involved in endoplasmic reticulum stress and the UPR, were highly upregulated in Jamc-/- lenses, suggesting that abnormal lens development was accompanied by UPR activation. Moreover, increased cell death was also found in Jamc-/- lenses.Congenital nuclear cataract caused by Jamc deficiency is accompanied by defective degradation of nuclei and organelles in lens fiber cells, lens structure disorder, and UPR activation, suggesting that JAM-C is required for maintaining normal lens development and that UPR activation is involved in cataract formation in Jamc-deficient lenses.

The theoretical and empirical results of the capitalization effect of agricultural support policies on land rental price remain inconclusive. Based on the survey of Chinese Household Income Projects in 2007 and 2008, this paper adopts the panel data of 800 villages in 11 provinces in China to empirically analyze the impact of agricultural support policies on village-level land rental price. It shows that both output price support and agricultural subsidies have a significant positive effect on land rental price in the village. For each 1 CNY/kg increase in output price support, the land rental price in the village will rise by about 322.44 CNY/mu, while with an additional 1 CNY/mu increase in agricultural subsidies, it will increase by CNY 0.45. The stronger the social relationships in the village, the less area of land transfer for a fee and the lower the land rental price. For villages with weak social relationships or renting land to outsiders, output price support and agricultural subsidies can significantly increase the land rental price. Output price support and agricultural subsidies not only have a significant positive effect on the area of land transfer in the village but also an indirect negative effect on it by raising the price of regional land rent.

The mitogen-inducible gene 6 (MIG6) is an adaptor protein widely expressed in vascular endothelial cells. However, it remains unknown thus far whether it plays a role in angiogenesis. Here, using comprehensive in vitro and in vivo model systems, we unveil a potent anti-angiogenic effect of MIG6 in retinal development and neovascularization and the underlying molecular and cellular mechanisms. Loss of function assays using genetic deletion of Mig6 or siRNA knockdown increased angiogenesis in vivo and in vitro, while MIG6 overexpression suppressed pathological angiogenesis. Moreover, we identified the cellular target of MIG6 by revealing its direct inhibitory effect on vascular endothelial cells (ECs). Mechanistically, we found that the anti-angiogenic effect of MIG6 is fulfilled by binding to SHC1 and inhibiting its phosphorylation. Indeed, SHC1 knockdown markedly diminished the effect of MIG6 on ECs. Thus, our findings show that MIG6 is a potent endogenous inhibitor of angiogenesis that may have therapeutic value in anti-angiogenic therapy.

BACKGROUND: Renal endothelial cells from glomerular, cortical, and medullary kidney compartments are exposed to different microenvironmental conditions and support specific kidney processes. However, the heterogeneous phenotypes of these cells remain incompletely inventoried. Osmotic homeostasis is vitally important for regulating cell volume and function, and in mammals, osmotic equilibrium is regulated through the countercurrent system in the renal medulla, where water exchange through endothelium occurs against an osmotic pressure gradient. Dehydration exposes medullary renal endothelial cells to extreme hyperosmolarity, and how these cells adapt to and survive in this hypertonic milieu is unknown. METHODS: We inventoried renal endothelial cell heterogeneity by single-cell RNA sequencing >40,000 mouse renal endothelial cells, and studied transcriptome changes during osmotic adaptation upon water deprivation. We validated our findings by immunostaining and functionally by targeting oxidative phosphorylation in a hyperosmolarity model in vitro and in dehydrated mice in vivo. RESULTS: We identified 24 renal endothelial cell phenotypes (of which eight were novel), highlighting extensive heterogeneity of these cells between and within the cortex, glomeruli, and medulla. In response to dehydration and hypertonicity, medullary renal endothelial cells upregulated the expression of genes involved in the hypoxia response, glycolysis, and-surprisingly-oxidative phosphorylation. Endothelial cells increased oxygen consumption when exposed to hyperosmolarity, whereas blocking oxidative phosphorylation compromised endothelial cell viability during hyperosmotic stress and impaired urine concentration during dehydration. CONCLUSIONS: This study provides a high-resolution atlas of the renal endothelium and highlights extensive renal endothelial cell phenotypic heterogeneity, as well as a previously unrecognized role of oxidative phosphorylation in the metabolic adaptation of medullary renal endothelial cells to water deprivation. ispartof: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY vol:31 issue:1 pages:118-138 ispartof: location:United States status: published

The polypropylene (PP)/polystyrene (PS)/montmorillonite (MMT) blends were prepared by an innovative eccentric rotor extruder based on continuous elongational flow. Addition of MMT nanoparticles was found to reduce the PS droplet size and improve the compatibility of PP/PS. The MMT nanoparticles had clear intercalation and/or exfoliation structures and were located mostly at the interface of PP/PS. It was found that the intercalation and exfoliation of MMT was finished under the synergy of interfacial interaction and tensile deformation so that we called the mechanism as “MMT exfoliation mechanism induced by synergy of interface and tensile deformation”. The rheological analysis showed that incorporation of MMT led to an increase in complex viscosity to an optimum level (5 wt%), after which any further increase in MMT concentration decreased the complex viscosity. Moreover, the degree of crystallinity of blends was controlled by the heterogeneous nucleation effect of MMT and the inhibition effect of PS.

Polymer/clay nanocomposites exhibit desirable performance and multifunctional properties. The ideal dispersion and exfoliation of clay layers in polymeric matrixes is a significant drawback that affects its application. In this study, a novel extruder generating a continuous elongation flow was used to fabricate the representative polypropylene (PP)/organic montmorillonite (OMMT) nanocomposites and then compare with the twin-screw extruder (TSE). Phase morphology, dynamic rheological properties, and mechanical properties were characterized by thermal gravimetric analysis, wide-angle X-ray diffraction, transmission electron microscopy, rotational rheometer and impact tests. The morphology and rheological behavior of the nanocomposites evidenced that ideal intercalation or/and exfoliation dispersion of OMMT in PP matrixes can be achieved under continuous elongation flow. Thus, the double-side exfoliation of the OMMT platelets combined with the pulling/diffusion process under an elongation flow is leading to an effective strengthening and toughening of PP better than that in the TSE.

Little is known about the metabolism of quiescent endothelial cells (QECs). Nonetheless, when dysfunctional, QECs contribute to multiple diseases. Previously, we demonstrated that proliferating endothelial cells (PECs) use fatty acid β-oxidation (FAO) for de novo dNTP synthesis. We report now that QECs are not hypometabolic, but upregulate FAO >3-fold higher than PECs, not to support biomass or energy production but to sustain the tricarboxylic acid cycle for redox homeostasis through NADPH regeneration. Hence, endothelial loss of FAO-controlling CPT1A in CPT1AΔEC mice promotes EC dysfunction (leukocyte infiltration, barrier disruption) by increasing endothelial oxidative stress, rendering CPT1AΔEC mice more susceptible to LPS and inflammatory bowel disease. Mechanistically, Notch1 orchestrates the use of FAO for redox balance in QECs. Supplementation of acetate (metabolized to acetyl-coenzyme A) restores endothelial quiescence and counters oxidative stress-mediated EC dysfunction in CPT1AΔEC mice, offering therapeutic opportunities. Thus, QECs use FAO for vasculoprotection against oxidative stress-prone exposure. ispartof: CELL METABOLISM vol:28 issue:6 pages:881-+ ispartof: location:United States status: published

In recent years, with the rapid development of Internet technology, various online car-hailing platforms (Uber, DiDi, CaoCao, etc.) have swept the world. The convenient and fast information exchange of "Internet +" greatly alleviates the information obstruction caused by the space-time deviation between passengers and drivers in the traditional taxi system, and becomes a powerful tool to improve the efficiency of the taxi market. In order to improve the utilization of resource allocation, this paper designs a model based on the vehicle's empty driving distance, and uses the Hungarian solution to obtain the shortest vehicle's empty driving distance to optimize the resource allocation problem. Then, according to the position coordinates and the travel route of the vehicle, the vehicle information of eleven times a day is calculated, and it is found that the result obtained by the algorithm is ideal；At the same time, we design the subsidy pricing model and its scheme. Finally, we make a systematic summary of the research content of this paper and look forward to the possible research directions in the future.

An important policy cornerstone for China to reduce poverty includes China&rsquo, s goal of achieving complete poverty alleviation in its state-owned forest farms by 2020. This study describes and documents the poverty reduction effect in impoverished Chinese state-owned forest farms. Based on a sample of 4855 state-owned forest farms in 31 provinces in China from 2008 to 2017, this paper uses the difference-in-difference method to study the dynamic process of poverty reduction by policies for impoverished state-owned forest farms. The results show that the implementation of the policy significantly promoted the economic development of impoverished state-owned forest farms and caused the treatment group to increase by approximately 10.6% over the control group. Moreover, the establishment of a list of impoverished state-owned forest farms had an indirect impact on the economic performance of forest farms, through channels such as infrastructure poverty alleviation, human capital investment, and per capita income of forest farm employees. Additionally, the effects of the policy on non-impoverished counties were stronger than that on impoverished counties, and impoverished state-owned forest farms may not appear in impoverished counties. The degree of financial dependence of the local government had a significant positive impact on the economic development of impoverished state-owned forest farms. The effects of the policy on different forest farms were heterogeneous. Our study provides recommendations for the future development of impoverished Chinese state-owned forest farms and for the improvement of poverty alleviation efficiency.

The heterogeneity of endothelial cells (ECs) across tissues remains incompletely inventoried. We constructed an atlas of >32,000 single-EC transcriptomes from 11 mouse tissues and identified 78 EC subclusters, including Aqp7+ intestinal capillaries and angiogenic ECs in healthy tissues. ECs from brain/testis, liver/spleen, small intestine/colon, and skeletal muscle/heart pairwise expressed partially overlapping marker genes. Arterial, venous, and lymphatic ECs shared more markers in more tissues than did heterogeneous capillary ECs. ECs from different vascular beds (arteries, capillaries, veins, lymphatics) exhibited transcriptome similarity across tissues, but the tissue (rather than the vessel) type contributed to the EC heterogeneity. Metabolic transcriptome analysis revealed a similar tissue-grouping phenomenon of ECs and heterogeneous metabolic gene signatures in ECs between tissues and between vascular beds within a single tissue in a tissue-type-dependent pattern. The EC atlas taxonomy enabled identification of EC subclusters in public scRNA-seq datasets and provides a powerful discovery tool and resource value. ispartof: CELL vol:180 issue:4 pages:764-+ ispartof: location:United States status: published

Glutamine synthetase, encoded by the gene GLUL, is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation. ispartof: NATURE vol:561 issue:7721 pages:63-+ ispartof: location:England status: published

PBS/nano-CaCO3 composites with various nano-CaCO3 weight fractions were prepared by melt blending. The thermal behavior, dynamic mechanical properties and rheological properties of the composites were investigated. DSC measurements revealed that the nano-CaCO3 particles had little influence on the crystallization and melting behavior of PBS. Thermogravimetric analysis showed that the introduction of nano-CaCO3 tended to improve the thermal stability of PBS. Dynamic mechanical analysis showed that the G′ and G″ of the PBS/nano-CaCO3 composites were improved significantly when the nano-CaCO3 content was not more than 3wt%, while the G′ and G″ were mainly decided by the PBS matrix when the nano-CaCO3 content exceeded 3wt%. Rheological results showed that G′

Polylactide/TiO2 nanocomposites with different contents of nanoscale TiO2 were prepared by melt blending with a vane extruder in this work. SEM and TEM microphotographs indicate that the nanoparticles were well dispersed in the polymer matrix under the elongational flow field of the vane extruder. Crystallization and melting behavior were examined with DSC. The results show that TiO2 nanoparticles have an inhibition for the cold crystallization process of PLA to some extent and the cold crystallization temperature of nanocomposites shifted to a maximum value at about 106 °C with low TiO2 loadings (0.5 wt% or 1 wt%). Dynamic rheological measurements and TGA results show that the introduction of TiO2 has significantly improved the thermal stability. The toughness, surface wettability and UV resistance of the composites were also investigated in detail.

Ternary blends of PLA/PBS/CSW with different weight fractions were prepared using a vane extruder. The mechanical properties, morphology, crystallization behavior and thermal stability of the blends were investigated. For the PLA/CSW blend, the tensile strength decreased, the flexural strength and modulus increased compared with pure PLA. For PBS, the addition of CSW had little influence on the mechanical properties. For the ternary blends PLA/PBS/CSW, the tensile strength, flexural strength and modulus decreased compared with pure PLA, while the elongation at break and the impact strength increased significantly. The brittle-ductile transition of the blends took place when the PBS weight fraction reaching 30 wt%. As a soft component in the blends, PBS was beneficial to improve the tensile ductility and the toughness of PLA. SEM measurements reveal that PLA/PBS/CSW blends were immiscible. When the weight fraction of PBS was 50 wt%, significant phase separation was observed, and CSW had preferential location in the PBS phase of the blend. DSC measurement and POM observation reveal that CSW had a heterogeneous nucleation effect on PLA and PBS matrix. The addition of PBS improved the crystallization of PLA and the thermal resistance of the PLA/PBS/CSW blends significantly.

Polylactic acid (PLA)/organo-montmorillonite (OMMT) nanocomposites toughened with thermoplastic polyurethane (TPU) were prepared by melt-compounding on a novel vane extruder (VE), which generates global dynamic elongational flow. In this work, the mechanical properties of the PLA/TPU/OMMT nanocomposites were evaluated by tensile, flexural, and tensile tests. The wide-angle X-ray diffraction and transmission electron microscopy results show that PLA/TPU/OMMT nanocomposites had clear intercalation and/or exfoliation structures. Moreover, the particles morphology of nanocomposites with the addition of TPU was investigated using high-resolution scanning electronic microscopy. The results indicate that the spherical TPU particles dispersed in the PLA matrix, and the uniformity decreased with increasing TPU content (≤30%). Interestingly, there existed abundant filaments among amount of TPU droplets in composites with 30 and 40 wt% TPU. Furthermore, the thermal properties of the nanocomposites were examined with differential scanning calorimeter and dynamic mechanical analysis. The elongation at break and impact strength of the PLA/OMMT nanocomposites were increased significantly after addition of TPU. Specially, Elongation at break increased by 30 times, and notched impact strength improved 15 times when TPU loading was 40 wt%, compared with the neat PLA. Overall, the modified PLA nanocomposites can have greater application as a biodegradable material with enhanced mechanical properties. POLYM. ENG. SCI., 54:2292–2300, 2014. © 2013 Society of Plastics Engineers

Thermoplastic polyurethane (TPU) polypropylene (PP) blends of different weight ratios were prepared with a self-made vane extruder (VE), which generates global dynamic elongational flow, and a traditional twin-screw extruder (TSE), which generates shear flow. The mechanical properties, phase morphology, thermal behavior, and spherulite size of the blends were investigated to compare the different processing techniques. Samples prepared with a VE had superior mechanical properties than the samples prepared with a TSE. Scanning emission micrographs show that the fiber morphology of the TPU/PP blends (

This work focused on the study of crystallization behavior and thermal stability of degradable poly(butylene succinate) (PBS) and poly(propylene carbonate) (PPC) blends prepared by vane extruder based on elongation force field, which is novel equipment for polymer processing. Dicumyl peroxide (DCP) was applied in this work as compatibilizer for PBS/PPC blend. Crystallization behavior and melting behavior of the blends were investigated by differential scanning calorimetry (DSC) testing. Thermal stability of the blends was studied by thermogravimetric (TG) testing. Furthermore, the melt flow indices (MFI) of the blends were examined by a MFI instrument. The results showed that the crystallization temperature of PBS decreased with the addition of PPC and DCP. The glass transition temperature of PPC increased and the melting temperature of the blend increased with the addition of PPC and DCP, which indicated that the entanglement between the molecular chains of PBS and PPC was enhanced. Thermogravimetric ana...

Poly (lactic acid) (PLA)/Poly (propylene carbonate) (PPC) blends were prepared by vane extruder which is a type of novel polymer processing extruder based on elongation force field. Scanning electron microscope (SEM), differential scanning calorimetry (DSC) and thermogravimetric (TG) were used respectively to analyze the compatibility, the melting behavior and thermal stability properties of PLA/PPC blends affected by the different content of PPC. The results showed that with the increase of the PPC content, the glass transition temperature of PLA was reduced, and the glass transition temperature of PPC was increased, which indicated that PLA and PPC had partial compatibility. The cold crystallization temperature of PLA increased with the increase of the PPC content, which showed that PPC hindered the cold crystallization process of PLA. The addition of PPC had little impact on the melting process of PLA, and the melting temperature of PLA was almost kept the same value. Thermogravimetric analysis showed that the thermal stability of PPC was worse than that of PLA, the addition of PPC reduced the thermal stability of PLA.

The role of fatty acid synthesis in endothelial cells (ECs) remains incompletely characterized. We report that fatty acid synthase knockdown (FASNKD) in ECs impedes vessel sprouting by reducing proliferation. Endothelial loss of FASN impaired angiogenesis in vivo, while FASN blockade reduced pathological ocular neovascularization, at >10-fold lower doses than used for anti-cancer treatment. Impaired angiogenesis was not due to energy stress, redox imbalance, or palmitate depletion. Rather, FASNKD elevated malonyl-CoA levels, causing malonylation (a post-translational modification) of mTOR at lysine 1218 (K1218). mTOR K-1218 malonylation impaired mTOR complex 1 (mTORC1) kinase activity, thereby reducing phosphorylation of downstream targets (p70S6K/4EBP1). Silencing acetyl-CoA carboxylase 1 (an enzyme producing malonyl-CoA) normalized malonyl-CoA levels and reactivated mTOR in FASNKD ECs. Mutagenesis unveiled the importance of mTOR K1218 malonylation for angiogenesis. This study unveils a novel role of FASN in metabolite signaling that contributes to explaining the anti-angiogenic effect of FASN blockade. ispartof: CELL METABOLISM vol:28 issue:6 pages:866-+ ispartof: location:United States status: published

The role of phosphoglycerate dehydrogenase (PHGDH), a key enzyme of the serine synthesis pathway (SSP), in endothelial cells (ECs) remains poorly characterized. We report that mouse neonates with EC-specific PHGDH deficiency suffer lethal vascular defects within days of gene inactivation, due to reduced EC proliferation and survival. In addition to nucleotide synthesis impairment, PHGDH knockdown (PHGDHKD) caused oxidative stress, due not only to decreased glutathione and NADPH synthesis but also to mitochondrial dysfunction. Electron transport chain (ETC) enzyme activities were compromised upon PHGDHKD because of insufficient heme production due to cellular serine depletion, not observed in other cell types. As a result of heme depletion, elevated reactive oxygen species levels caused EC demise. Supplementation of hemin in PHGDHKD ECs restored ETC function and rescued the apoptosis and angiogenesis defects. These data argue that ECs die upon PHGDH inhibition, even without external serine deprivation, illustrating an unusual importance of serine synthesis for ECs. ispartof: CELL METABOLISM vol:28 issue:4 pages:573-587 ispartof: location:United States status: published