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Adipocyte progenitors reside in the stromal vascular fraction (SVF) of adipose tissues that are composed of fibroblasts, immune cells, and endothelial cells. It remains to be elucidated how the SVF regulates adipocyte progenitor fate determination and adipose homeostasis. Here, we report that fibroblast-specific protein-1 (FSP1)+ fibroblasts in the SVF are essential to adipose homeostasis. FSP1+ fibroblasts, devoid of adipogenic potential, are adjacent to the preadipocytes in the SVF. Ablation of FSP1+ fibroblasts in mice severely diminishes fat content of adipose depots. Activation of canonical Wnt signaling in the FSP1+ fibroblasts results in gradual loss of adipose tissues and resistance to diet-induced obesity. Alterations in the FSP1+ fibroblasts reduce platelet-derived growth factor (PDGF)-BB signaling and result in the loss of preadipocytes. Reduced PDGF-BB signaling, meanwhile, impairs the adipogenic differentiation capability of preadipocytes by regulating matrix metalloproteinase (MMP) expression, extracellular matrix remodeling, and the activation of Yes-associated protein (YAP) signaling. Thus, FSP1+ fibroblasts are an important niche essential to the maintenance of the preadipocyte pool and its adipogenic potential in adipose homeostasis.

To achieve automatic generation control coordination in the islanded smart grid environment resulted from the increasing penetration of renewable energy, a novel ecological population cooperative control (EPCC) strategy is proposed in this paper. The proposed EPCC, based on the new win-loss criterion and the time tunnel idea, can compute the win-loss criterion accurately and converge to Nash equilibrium rapidly. Moreover, based on a multiagent system stochastic consensus game (MAS-SCG) framework, a frequent information exchange between agents (AGC units) is implemented to rapidly calculate optimal power command, which achieves the optimal cooperative control of the islanded smart grid. The PDWoLF-PHC(λ), WPH strategy (wolf pack hunting), DWoLF-PHC(λ), Q(λ)-learning, and Q-learning are implemented into the islanded smart grid model for the control performance analysis. Two case studies have been done, including the modified IEEE standard two-area load frequency control power system model and the islanded smart grid model with distributed energy and microgrids. The effectiveness, stronger robustness, and better adaptability in the islanded smart grid of the proposed method are verified. Compared with five other smart ones, EPCC can improve convergence speed than that of others by nearly 33.9%–50.1% and the qualification rate of frequency assessment effectively by 2%–64% and can reduce power generation cost.

Mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) gene were recently discovered in vast majority of World Health Organization (WHO) grade II/III gliomas. This study is to understand the effects of IDH1 R132H mutation in gliomagenesis and to develop new strategies to treat glioma with IDH1 R132H mutation.Over expression of IDH1 R132H in U87MG cells was done by transfecting cells with IDH1 R132H plasmid. MTT assay, scratch repair assay and western blot were performed to study effects of IDH1 R132H mutation on cell proliferation, migration, regulating AKT-mTOR signaling pathway and cell death respectively. NADP+/NADPH and GSH quantification assays were performed to evaluate effects of IDH1 R132H mutation on the production of antioxidant NADPH and GSH.We found that over expression of IDH1 R132H mutation decreased cell proliferation consistent with previous reports; however, it increased cell migration and enhanced AKT-mTOR signaling pathway activation. Mutations in isocitrate dehydrogenase (IDH) 1 also change the function of the enzymes and cause them to produce 2-hydroxyglutarate and not produce NADPH. We tested the level of NADPH and GSH and demonstrated that IDH1 R132H mutant stable cells had significantly low NADPH and GSH level compared to control or IDH1 wild type stable cells. The reduced antioxidants (NADPH and GSH) sensitized U87MG cells with IDH R132H mutant to 5-FU treatment.Our study highlights the important role of IHD1 R132H mutant in up- regulating AKT-mTOR signaling pathway and enhancing cell migration. Furthermore, we demonstrate that IDH1 R132H mutation affects cellular redox status and sensitizes gliomas cells with IDH1 R132H mutation to 5FU treatment.

The objective of this work was to prepare a series of composite films (polysaccharides with LaFe0.8Cu0.2O3) for the degradation of methyl orange under ultraviolet irradiation. LaFe0.8Cu0.2O3 was prepared by a sol-gel method, and the composite films were obtained by cross-linking reactions between polysaccharides (xylan and chitosan) and LaFe0.8Cu0.2O3. Physical and chemical properties of the composite films were investigated by XRD, FTIR, SEM, and BET. Moreover, the influence of the weight ratio of polysaccharide to LaFe0.8Cu0.2O3 on the methyl orange degradation reaction was also studied. Results showed that 67% of the degradation efficiency was achieved within 480 min using chitosan/LaFe0.8Cu0.2O3 (2:1) as photocatalysts, while 58% was for xylan/LaFe0.8Cu0.2O3 (1:1). The difference was due to the variety in the structure of chitosan and xylan.

Microalgae are considered as excellent candidates for bioactive compounds, yet microalgal residues remaining after the extraction of one or two compounds are usually discarded, which is not economical. This study demonstrates the alkaline extraction of proteins from Chlorella pyrenoidosa residue after lipid and pigment extractions, and their functional properties. Single-factor experiments and response surface methodology were used to obtain the optimal conditions for protein extraction. Based on our results, a maximum protein yield of 722.70 mg/g, was obtained under the following extraction conditions: sodium hydroxide concentration 7.90%, extraction temperature 70.00 °C, extraction time 34.80 min, and microalgal residue concentration 8.20 mg/mL. The molecular weight of microalgal residue protein isolate (MRPI) was mainly distributed at the regions of 0.18−0.50 kDa, 0.50−1.50 kDa, and 1.50−5.00 kDa. The essential amino acid content was greater than the values recommended by FAO/WHO standards; a high essential amino acid index value (1.49) was another good indication that MRPI is suitable for human consumption. Moreover, MRPI exhibited excellent emulsifying properties and antioxidant activity, which suggests it may be useful as an emulsifying agent and antioxidant. These findings could improve the extraction methods of functional protein from microalgal residue and add value to microalgae-based bioactive compound production processes.

Background: The antitumor activity of CLE-10 (4-epi-isoinuviscolide), a sesquiterpene lactone compound, isolated from Carpesium abrotanoides L. has rarely been reported. The aim of this study is to investigate the antitumor activity of CLE-10 and give a greater explanation of its underlying mechanisms. Methods: The cytotoxicity of CLE-10 was evaluated using MTT assay. Autophagy was detected by the formation of mRFP-GFP-LC3 fluorescence puncta and observed using transmission electron microscopy, while flow cytometry was employed to detect apoptosis. The protein expressions were detected through Western blotting. Results: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by increasing the protein expression of LC3-II, p-ULK1, Bax, and Bad, as well as downregulating p-PI3K, p-Akt, p-mTOR, p62, LC3-I, Bcl-2, and Bcl-xl. CLE-10 that was pretreated with 3-methyladenine (3-MA) or chloroquine (CQ) weakened the upregulation of the protein expression of p-ULK1, or the downregulation of p62, p-mTOR, and decreased the level of cytotoxicity against MDA-MB-231 cells. Meanwhile, rapamycin enhanced the effect of CLE-10 on the expression of autophagy-related protein and its cytotoxicity, with the IC50 value of CLE-10 decreasing from 4.07 µM to 2.38 µM. Conclusion: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by upregulating the protein expressions of LC3-II, p-ULK1, Bax, and Bad and downregulating p-PI3K, p-Akt, p-mTOR, p62, Bcl-2, and Bcl-xl.

This paper addresses the problem of localization accuracy degradation caused by outliers of the angle of arrival (AOA). The problem of outlier detection of the AOA is converted into the detection of the estimated source position sets, which are obtained by the proposed division and greedy replacement method. The Mahalanobis distance based on robust mean and covariance matrix estimation method is then introduced to identify the outliers from the position sets. Finally, the weighted least squares method based on the reliable probabilities and distances is proposed for source localization. The simulation and experimental results show that the proposed method outperforms representative methods when unreliable AOAs are present.

Type IV collagens (Col IV), components of basement membrane, are essential in the maintenance of tissue integrity and proper function. Alteration of Col IV is related to developmental defects and diseases, including cancer. Col IV α chains form α1α1α2, α3α4α5 and α5α5α6 protomers that further form collagen networks. Despite knowledge on the functions of major Col IV (α1α1α2), little is known whether minor Col IV (α3α4α5 and α5α5α6) plays a role in cancer. It also remains to be elucidated whether major and minor Col IV are functionally redundant. We show that minor Col IV α5 chain is indispensable in cancer development by using α5(IV)-deficient mouse model. Ablation of α5(IV) significantly impeded the development of KrasG12D-driven lung cancer without affecting major Col IV expression. Epithelial α5(IV) supports cancer cell proliferation, while endothelial α5(IV) is essential for efficient tumor angiogenesis. α5(IV), but not α1(IV), ablation impaired expression of non-integrin collagen receptor discoidin domain receptor-1 (DDR1) and downstream ERK activation in lung cancer cells and endothelial cells. Knockdown of DDR1 in lung cancer cells and endothelial cells phenocopied the cells deficient of α5(IV). Constitutively active DDR1 or MEK1 rescued the defects of α5(IV)-ablated cells. Thus, minor Col IV α5(IV) chain supports lung cancer progression via DDR1-mediated cancer cell autonomous and non-autonomous mechanisms. Minor Col IV can not be functionally compensated by abundant major Col IV.

The detection and separation of circulating tumor cells (CTCs) are crucial in early cancer diagnosis and cancer prognosis. Filtration through a thin film is one of the size and deformability based separation methods, which can isolate rare CTCs from the peripheral blood of cancer patients regardless of their heterogeneity. In this paper, volume of fluid (VOF) multiphase flow models are employed to clarify the cells’ filtering processes. The cells may deform significantly when they enter a channel constriction, which will induce cell membrane stress and damage if the area strain is larger than the critical value. Therefore, the cellular damage criterion characterized by membrane area strain is presented in our model, i.e., the lysis limit of the lipid bilayer is taken as the critical area strain. Under this criterion, we discover that the microfilters with slit-shaped pores do less damage to cells than those with circular pores. The influence of contact angle between the microfilters and blood cells on cellular injury is also discussed. Moreover, the optimal film thickness and flux in our simulations are obtained as 0.5 μm and 0.375 mm/s, respectively. These findings will provide constructive guidance for the improvement of next generation microfilters with higher throughput and less cellular damage.

Adhesion and detachment are coordinated critical steps during cell migration. Conceptually, efficient migration requires both effective stabilization of membrane protrusions at the leading edge via nascent adhesions and their successful persistence during retraction of the trailing side via disruption of focal adhesions. As nascent adhesions are much smaller in size than focal adhesions, they are expected to exhibit a stronger adhesivity in order to achieve the coordination between cell front and back. Here, we show that Nudel knockdown by interference RNA (RNAi) resulted in cell edge shrinkage due to poor adhesions of membrane protrusions. Nudel bound to paxillin, a scaffold protein of focal contacts, and colocalized with it in areas of active membrane protrusions, presumably at nascent adhesions. The Nudel-paxillin interaction was disrupted by focal adhesion kinase (FAK) in a paxillin-binding-dependent manner. Forced localization of Nudel in all focal contacts by fusing it to paxillin markedly strengthened their adhesivity, whereas overexpression of structurally activated FAK or any paxillin-binding FAK mutant lacking the N-terminal autoinhibitory domain caused cell edge shrinkage. These results suggest a novel mechanism for selective reinforcement of nascent adhesions via interplays of Nudel and FAK with paxillin to facilitate cell migration.

In 2004, 3 and 4 strains of avian influenza virus (subtype H5N1) were isolated from waterfowl and chickens, respectively, in central People’s Republic of China. Viral replication and pathogenicity were evaluated in chickens, quails, pigeons, and mice. We analyzed the sequences of the hemagglutinin and neuraminidase genes of the isolates and found broad diversity among them.

Planktonic microorganisms have been recognized as important components in biogeochemical cycling in lakes. However, research into the impact of phyllosphere microorganisms, particularly those involved in carbon cycling, on CO2 fluxes in macrophyte-dominated lakes within the context of global environmental changes remains scarce. Here, by employing high-throughput sequencing techniques, we experimentally tested how nutrient enrichment, top-down effects of fish and increases in dissolved organic carbon (DOC) affect CO2 exchange flux at the water-air interface by altering the community structure and functioning of phyllosphere bacteria on macrophytes. We found that our mesocosm ecosystems exhibited a net absorption of CO2, but nutrient enrichment significantly decreased the absorption ability. Mantel tests and multiple regression modeling also showed that eutrophication-associated parameters (total nitrogen, total phosphorus and ammonium nitrogen), pH, and extinction coefficient were the key drivers influencing abundance of phyllosphere functional microorganisms. In addition, these experimental treatments significantly altered the composition, diversity and co-occurrence networks of carbon cycling-associated phyllosphere microorganisms, which impacted the CO2 flux. Structural equation models and linear regression further showed that the Shannon Index of phyllosphere functional microorganisms related to carbon cycling (rather than plant volume inhabited - PVI) had a significant positive impact on CO2 fixation. This means that environmental changes—especially eutrophication—may hinder carbon sequestration by decreasing the diversity of phyllosphere microorganisms rather than reducing the abundance of submerged macrophytes. This study increases our understanding of carbon cycling processes in aquatic environments from a management perspective by emphasizing the importance of protecting the diversity of phyllosphere microorganisms in macrophyte-dominated lakes. [ABSTRACT FROM AUTHOR]

Higher-order topological phases in non-Hermitian photonics revolutionize the understanding of wave propagation and modulation, which lead to hierarchical states in open systems. However, intrinsic insulating properties endorsed by the lattice symmetry of photonic crystals fundamentally confine the robust transport only at explicit system boundaries, letting alone the flexible reconfiguration in hierarchical states at arbitrary positions. Here, we report a dynamic topological platform for creating the reconfigurable hierarchical bound states in heat transport systems and observe the robust and nonlocalized higher-order states in both the real-and imaginary-valued bands. Our experiments showcase that the hierarchical features of zero-dimension corner and nontrivial edge modes occur at tailored positions within the system bulk states instead of the explicit system boundaries. Our findings uncover the mechanism of non-localized hierarchical non-trivial topological states and offer distinct paradigms for diffusive transport field management. [ABSTRACT FROM AUTHOR]

The topological physics has sparked intensive investigations into topological lattices in photonic, acoustic, and mechanical systems, powering counterintuitive effects otherwise inaccessible with usual settings. Following the success of these endeavors in classical wave dynamics, there has been a growing interest in establishing their topological counterparts in diffusion. Here, we propose an additional real-space dimension in diffusion, and the system eigenvalues are transformed from "imaginary" to "real." By judiciously tailoring the effective Hamiltonian with coupling networks, localized and delocalized topological modes are realized in heat transfer. Simulations and experiments in active thermal lattices validate the effectiveness of the proposed theoretical strategy. This approach can be applied to establish various topological lattices in diffusion systems, offering insights into engineering topologically protected edge states in dynamic diffusive scenarios. [ABSTRACT FROM AUTHOR]

Instrumented indentation combined with the classic Oliver-Pharr method has been widely utilized to measure elastic modulus of various materials. However, the elastic modulus measured by instrumented spherical indentation (ISI) is not as accurate as that measured by instrumented sharp indentation, especially at large indentation depth. In this work, the effect of the maximum indentation depth on measurement of elastic modulus by ISI was deeply investigated through finite element simulations and experiments. It was found that errors in measured elastic moduli increase significantly due to the inaccurate estimation of contact radius and excessive increase in initial unloading stiffness as maximum indentation depth increases. A correction function was then proposed to correct the measured elastic modulus. After correction, the errors were effectively reduced to within ±5 % for most cases. This work contributes to discovery of the error source in the measurement of elastic modulus by ISI, thereby improving the measurement accuracy. [ABSTRACT FROM AUTHOR]