Chemoresistance remains a major obstacle to successful treatment of breast cancer. Although soluble tumor necrosis factor-α (sTNF-α) has been implicated in mediating drug-resistance in human cancers, ...whether transmembrane tumor necrosis factor-α (tmTNF-α) plays a role in chemoresistance remains unclear. Here we found that over 50% of studied patients expressed tmTNF-α at high levels in breast cancer tissues and tmTNF-α expression positively correlated with resistance to anthracycline chemotherapy. Alteration of tmTNF-α expression changed the sensitivity of primary human breast cancer cells and breast cancer cell lines to doxorubicin (DOX). Overexpression of N-terminal fragment (NTF) of tmTNF-α, a mutant form with intact intracellular domain of tmTNF-α to transmit reverse signals, induced DOX-resistance. Mechanistically, the tmTNF-α/NTF-ERK-GST-π axis and tmTNF-α/NTF-NF-κB-mediated anti-apoptotic functions were required for tmTNF-α-induced DOX-resistance. In a xenograft mouse model, the combination of tmTNF-α suppression with chemotherapy significantly enhanced the efficacy of DOX. Our data indicate that tmTNF-α mediates DOX-resistance through reverse signaling and targeting tmTNF-α may be beneficial for the treatment of DOX-resistant breast cancer.
Abstract
We investigate the kinematic-chemical distribution of red-giant branch stars from the LAMOST survey crossed matched with Gaia DR2 proper motions, and present time tagging for the well-known ...ridge structures (diagonal distributions for
V
R
in the
R
,
V
ϕ
plane) in the range of Galactocentric distance
R
= 8 to 15 kpc. We detect six ridge structures, including five ridges apparent in the radial velocity distribution and three ridges apparent in the vertical velocity, the sensitive time of which to the perturbations are from young population (0–3 Gyr) to old population (9–14 Gyr). Based on an analysis of the evolution of angular momentum distribution, we find that four ridges are relatively stationary, while another is evolving with time, which is confirmed by the difference analysis at different populations and supporting that there might be two kinds of dynamical origins. Furthermore, ridge features are also vividly present in the chemical properties (Fe/H,
α
/Fe). The comparison between the north and south hemispheres of the Galaxy does show some differences and the ridge features are asymmetrical. Moreover, we find that diagonal ridge structures may affect the shape of the rotation curve, which is manifested as fluctuations and undulations on top of a smooth profile. Finally we speculate that the bar dynamics should be not enough to explain all ridge properties including the break feature in the
V
Z
–
L
Z
plane.
In order to overcome the problem of power generation in distributed energy, microgrid(MG) emerges as an alternative scheme. Compared with the ac microgrids, the dc microgrids have the advantages of ...high system efficiency, good power quality, low cost, and simple control. However, due to the complexity of the distributed generation system, the conventional droop control shows the drawbacks of low current sharing accuracy. Therefore, the improved primary control methods to enhance current sharing accuracy are systematically reviewed, such as particle swarm optimization programming, probabilistic algorithm and voltage correction factor scheme. However, it is difficult to achieve stable and coordinated operation of the dc microgrids by relying on the primary control. Hence, the various secondary control approaches, such as dynamic current sharing scheme, muti-agent system (MAS) control and virtual voltage control methods have been summarized for voltage regulation. Furthermore, the energy management system (EMS), modular-based energy router (MBER) and other coordinated control methods are reviewed to achieve power management. Besides, various control methods to compensate the effect of communication delay are summarized. Moreover, linear matrix inequality (LMI), Lyapunov-Krasovskii functional stability and Takagi-Sugeno model prediction scheme can be adopted to eliminate the influence of communication delay. In addition, due to the constant power loads (CPL) exhibit negative impedance characteristics, which may result in the output oscillation of filter. Thus, various control approaches have been reviewed to match the impedance, such as the nonlinear disturbance observer (NDO) feedforward compensation method, linear programming algorithm, hybrid potential theory and linear system analysis of polyhedral uncertainty. The merits and drawbacks of those control strategies are compared in this paper. Finally, the future research trends of hierarchical control and stability in dc microgrids and dc microgrid clusters are also presented.
Biotic resistance may influence invasion success; however, the relative roles of species richness, functional or phylogenetic distance in predicting invasion success are not fully understood. We used ...biomass fraction of Chromolaena odorata, an invasive species in tropical and subtropical areas, as a measure of ‘invasion success’ in a series of artificial communities varying in species richness. Communities were constructed using species from Mexico (native range) or China (non‐native range). We found strong evidence of biotic resistance: species richness and community biomass were negatively related with invasion success; invader biomass was greater in plant communities from China than from Mexico. Harvesting time had a greater effect on invasion success in plant communities from China than on those from Mexico. Functional and phylogenetic distances both correlated with invasion success and more functionally distant communities were more easily invaded. The effects of plant‐soil fungi and plant allelochemical interactions on invasion success were species‐specific.
Abstract
A database (TAMUdust2020) of the optical properties of irregular aerosol particles is developed for applications to radiative transfer simulations involving aerosols, particularly dust and ...volcanic ash particles. The particle shape model assumes an ensemble of irregular hexahedral geometries to mimic complex aerosol particle shapes in nature. State-of-the-art light scattering computational capabilities are employed to compute the single-scattering properties of these particles for wide ranges of values of the size parameter, the index of refraction, and the degree of sphericity. The database therefore is useful for various radiative transfer applications over a broad spectral region from ultraviolet to infrared. Overall, agreement between simulations and laboratory/in-situ measurements is achieved for the scattering phase matrix and backscattering of various dust aerosol and volcanic ash particles. Radiative transfer simulations of active and passive spaceborne sensor signals for dust plumes with various aerosol optical depths and the effective particle sizes clearly demonstrate the applicability of the database for aerosol studies. In particular, the present database includes, for the first time, robust backscattering of nonspherical particles spanning the entire range of aerosol particle sizes, which shall be useful to appropriately interpret lidar signals related to the physical properties of aerosol plumes. Furthermore, thermal infrared simulations based on in-situ measured refractive indices of dust aerosol particles manifest the effects of the regional variations of aerosol optical properties. This database includes a user-friendly interface to obtain user-customized aerosol single-scattering properties with respect to spectrally dependent complex refractive index, size, and the degree of sphericity.
Interleukin 10 (IL‐10)‐producing B cells (B10 cells) are a canonical cell fraction for regulating other activities of immune cells. Posttranscriptional modification of IL‐10 in B10 cells is not yet ...fully understood. Short‐chain fatty acids play an important role to regulate the functions of immune cells. This study aims to clarify the role of propionic acid (PA), a short‐chain fatty acid, in regulating the expression of IL‐10 in B10 cells. Blood samples were collected from patients with food allergy (FA) and healthy subjects. Serum and cellular components were prepared with the samples, and analysed by enzyme‐linked immunosorbent assay and flow cytometry, respectively. The results showed that serum PA levels were lower in FA patients. PA concentrations were negatively correlated with serum cytokine Th2 concentrations, specific IgE concentrations in serum and skin prick test results. The peripheral frequency of B10 cells and the production of IL‐10 in B cells were also associated with serum PA concentrations. Activation of B cells by CpG induced the production of IL‐10 and tristetretrprolin (TTP), in which TTP caused the spontaneous decay of IL‐10 mRNA. PA was necessary to stabilize the IL‐10 mRNA in B cells by inducing the production of granzyme B, which resulted in the degradation of the IL‐10 mRNA. Administration of PA attenuated FA response in mice by maintaining homeostasis of B10 cells. In conclusion, PA is needed to stabilize the expression of IL‐10 in B10 cells. PA administration can mitigate experimental FA by maintaining B10 cell functions.
Abstract
Organismal aging is driven by interconnected molecular changes encompassing internal and extracellular factors. Combinational analysis of high-throughput ‘multi-omics’ datasets (gathering ...information from genomics, epigenomics, transcriptomics, proteomics, metabolomics and pharmacogenomics), at either populational or single-cell levels, can provide a multi-dimensional, integrated profile of the heterogeneous aging process with unprecedented throughput and detail. These new strategies allow for the exploration of the molecular profile and regulatory status of gene expression during aging, and in turn, facilitate the development of new aging interventions. With a continually growing volume of valuable aging-related data, it is necessary to establish an open and integrated database to support a wide spectrum of aging research. The Aging Atlas database aims to provide a wide range of life science researchers with valuable resources that allow access to a large-scale of gene expression and regulation datasets created by various high-throughput omics technologies. The current implementation includes five modules: transcriptomics (RNA-seq), single-cell transcriptomics (scRNA-seq), epigenomics (ChIP-seq), proteomics (protein–protein interaction), and pharmacogenomics (geroprotective compounds). Aging Atlas provides user-friendly functionalities to explore age-related changes in gene expression, as well as raw data download services. Aging Atlas is freely available at https://bigd.big.ac.cn/aging/index.
A novel bi-graded honeycomb was proposed by introducing both in-plane and out-of-plane thickness gradients into a regular honeycomb. The graded honeycombs were additively manufactured by fused ...deposition modeling (FDM) with polylactic acid (PLA) and then tested for axial crushing. Numerical simulation models were constructed through LS-DYNA and validated using experiment results. Based on the super folding element (SFE) method, theoretical models of the proposed bi-graded honeycombs were derived and the accuracy for crushing response was validated against the numerical results. Finally, an active learning based multi-objective optimization algorithm was used to seek the optimal design. The results showed that the bi-graded design for honeycomb structures could improve energy absorption capacity and decrease the peak crushing force in the Pareto frontier manner. The specific energy absorption of the optimal bi-graded honeycomb could be 45.6% higher than that of the regular honeycomb while the peak crushing force was controlled at the same level.
•A bi-graded honeycomb was proposed by introducing two direction thickness gradients.•Test specimens were additively manufactured and tested for quasi-static crushing.•Theoretical models of the proposed bi-graded honeycomb were built.•Optimal design was derived by an active learning based multi-objective optimization.
Diabetic kidney disease (DKD) is a serious complication of hyperglycemia. Currently, there is no effective therapeutic intervention for DKD. In this study, we sought to provide a set of gene profile ...in diabetic kidneys. We identified 338 genes altered in diabetes-induced DKD glomeruli, and PLK2 exhibited the most dramatic change. Gene set enrichment analysis (GSEA) indicated multiple signaling pathways are involved DKD pathogenesis. Here, we investigated whether PLK2 contributes to podocyte dysfunction, a characteristic change in the development of DKD. High D-glucose (HDG) significantly increased PLK2 expression in mouse podocytes. Suppressing PLK2 attenuated HDG-induced apoptosis and inflammatory responses both in vitro and in vivo. NAC, an antioxidant reagent, rescued HDG and PLK2 overexpression-induced kidney injuries. In summary, we demonstrated that silencing PLK2 attenuates HDG-induced podocyte apoptosis and inflammation, which may serve as a future therapeutic target in DKD.
Henoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP.
PubMed, ...Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD).
Thirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61-1.19); age > 10 y (3.13, 1.39-7.07); male gender (1.36, 1.07-1.74); abdominal pain (1.94,1.24-3.04); gastrointestinal bleeding (1.86, 1.30-2.65); severe bowel angina (3.38, 1.17-9.80); persistent purpura (4.02, 1.22-13.25); relapse (4.70, 2.42-9.14); WBC > 15 × 109/L (2.42, 1.39-4.22); platelets > 500 × 109/L (2.98, 1.22-7.25); elevated antistreptolysin O (ASO) (2.17, 1.29-3.64); and decreased complement component 3 (C3) (3.13, 1.62-6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01-1.96).
The following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early stages of HSP. However, the results should be interpreted cautiously due to the limitations of the studies.
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