Most patients with triple negative breast cancer (TNBC) do not respond to anti-PD1/PDL1 immunotherapy, indicating the necessity to explore immune checkpoint targets. B7H3 is a highly glycosylated ...protein. However, the mechanisms of B7H3 glycosylation regulation and whether the sugar moiety contributes to immunosuppression are unclear. Here, we identify aberrant B7H3 glycosylation and show that N-glycosylation of B7H3 at NXT motif sites is responsible for its protein stability and immunosuppression in TNBC tumors. The fucosyltransferase FUT8 catalyzes B7H3 core fucosylation at N-glycans to maintain its high expression. Knockdown of FUT8 rescues glycosylated B7H3-mediated immunosuppressive function in TNBC cells. Abnormal B7H3 glycosylation mediated by FUT8 overexpression can be physiologically important and clinically relevant in patients with TNBC. Notably, the combination of core fucosylation inhibitor 2F-Fuc and anti-PDL1 results in enhanced therapeutic efficacy in B7H3-positive TNBC tumors. These findings suggest that targeting the FUT8-B7H3 axis might be a promising strategy for improving anti-tumor immune responses in patients with TNBC.
Using VSC-MTDC for wind farm integration is considered to be a promising solution. In order to provide a stable ac voltage control and avoid active power control conflicts, the amplitude-phase ...control strategy, rather than the active/reactive power decoupled control strategy, is generally applied for the VSC connected to wind farms. However, using such a control strategy, the flexibility of power flow control will be partly lost. As the positive and negative pole dc networks in the bipolar VSC-MTDC can operate independently, a novel hybrid control strategy is proposed in this paper. In the proposed hybrid control strategy, the amplitude-phase control and active/reactive power decoupled control can be applied to the positive and negative poles, respectively. Hence, the hybrid strategy combines the advantages of the amplitude-phase control and active/reactive power decoupled control and can be adapted to bipolar VSC-MTDC for large-scale wind farm integration. Simulation results using PSCAD show that the hybrid control strategy can provide the stable ac voltage control and active/reactive power flow control for the integration of wind farms; moreover, such a hybrid control strategy is helpful to avoid the overload of dc lines, stabilize the dc voltage, and enhance the power transfer capability.
A novel pillared-layered entangled luminescent metal-organic framework Zn
(bpdc)
(BPyTPE) (1) (BPyTPE = (E)-1,2-diphenyl-1,2-bis(4-(pyridin-4-yl)phenyl)ethene) has been designed and constructed. The ...solvent-free 1 exhibits strong blue-green emission with an excellent fluorescence quantum yield of 99% and provides a facile and reversible method to sensitively and quantitatively detect trace pesticide of 2,6-dichloro-4-nitroaniline.
Abstract
The formation mechanism of aerosol sulfate during wintertime haze events in China is still largely unknown. As companions, SO
2
and transition metals are mainly emitted from coal combustion. ...Here, we argue that the transition metal-catalyzed oxidation of SO
2
on aerosol surfaces could be the dominant sulfate formation pathway and investigate this hypothesis by integrating chamber experiments, numerical simulations and in-field observations. Our analysis shows that the contribution of the manganese-catalyzed oxidation of SO
2
on aerosol surfaces is approximately one to two orders of magnitude larger than previously known routes, and contributes 69.2% ± 5.0% of the particulate sulfur production during haze events. This formation pathway could explain the missing source of sulfate and improve the understanding of atmospheric chemistry and climate change.
PM2.5 (particulate matter ≤2.5 µm in aerodynamic diameter) refers to atmospheric particulate matter (PM) with an aerodynamic diameter of equal and less than 2.5 µm that tends to be suspended for long ...periods of time and travel over long distances in both outdoor and indoor atmospheres. PM2.5, along with the toxic compounds attached on it, may cause a wide range of disorders. The fetus is considered to be highly susceptible to a variety of toxicants including atmospheric pollutants such as PM2.5 through prenatal exposure. To better understand the relationship between maternal exposure to PM2.5 and adverse birth outcomes for reproduction and fetus development, we studied the published data on this issue including case-control studies, cohort studies and meta-analyses studies, and summarized the basic impact of ambient particulate matter on adverse birth outcomes. Research evidence indicates that PM2.5 has a potential to induce low birth weight (LBW), preterm birth (PTB), and stillbirth. A further in-depth analysis shows that oxidative stress, DNA methylation, mitochondrial DNA (mtDNA) content alteration, and endocrine disruptions may all play an important role in PM2.5 induced adverse effects to pregnant women and fetuses. In addition, PM2.5 exposure can cause male reproductive toxicity, leading to associated adverse pregnancy outcomes.
•Maternal exposure to PM2.5 increased the risk of adverse birth outcomes.•Oxidative stress, DNA and mtDNA, and endocrine might be the mechanisms.•In addition, PM2.5 exposure could also cause reproductive toxicity in males.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Rice grain filling rate contributes largely to grain productivity and accumulation of nutrients. MicroRNAs (miRNAs) are key regulators of development and physiology in plants and become a ...novel key target for engineering grain size and crop yield. However, there is little studies, so far, showing the miRNA regulation of grain filling and rice yield, in consequence. Here, we show that suppressed expression of rice miR1432 (STTM1432) significantly improves grain weight by enhancing grain filling rate and leads to an increase in overall grain yield up to 17.14% in a field trial. Molecular analysis identified rice Acyl‐CoA thioesterase (OsACOT), which is conserved with ACOT13 in other species, as a major target of miR1432 by cleavage. Moreover, overexpression of miR1432‐resistant form of OsACOT (OXmACOT) resembled the STTM1432 plants, that is, a large margin of an increase in grain weight up to 46.69% through improving the grain filling rate. Further study indicated that OsACOT was involved in biosynthesis of medium‐chain fatty acids. In addition, RNA‐seq based transcriptomic analyses of transgenic plants with altered expression of miR1432 demonstrated that downstream genes of miR1432‐regulated network are involved in fatty acid metabolism and phytohormones biosynthesis and also overlap with the enrichment analysis of co‐expressed genes of OsACOT, which is consistent with the increased levels of auxin and abscisic acid in STTM1432 and OXmACOT plants. Overall, miR1432‐OsACOT module plays an important role in grain filling in rice, illustrating its capacity for engineering yield improvement in crops.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Cascading commutation failure (CF) caused by the reactive power interaction between HVDC is one of the new forms of cascading failures in multi-infeed HVDC systems. However, the concept and mechanism ...of cascading CF have not been explained clearly, and few studies have been devoted to control strategy for cascading CF mitigation considering reactive power interaction. In this paper, the cascading CF is defined and novel coordinated control strategy for cascading CF mitigation is proposed. Firstly, the mechanism of cascading CF in multi-infeed HVDC systems is analyzed. Then influence degree of HVDC on the power system stability is evaluated considering both active power impact and reactive power interaction, based on which novel coordinated commutation failure prevention as well as voltage dependent dc current order limiter is developed to mitigate cascading CF. Simulation results based on CIGRE HVDC benchmark model in PSCAD/EMTDC verify the effectiveness and advancement of proposed strategy on cascading CF mitigation.
Objective
To investigate the natural history of persistent pulmonary pure ground-glass nodules (pGGNs) with deep learning–assisted nodule segmentation.
Methods
Between January 2007 and October 2018, ...110 pGGNs from 110 patients with 573 follow-up CT scans were included in this retrospective study. pGGN automatic segmentation was performed on initial and all follow-up CT scans using the Dr. Wise system based on convolution neural networks. Subsequently, pGGN diameter, density, volume, mass, volume doubling time (VDT), and mass doubling time (MDT) were calculated automatically. Enrolled pGGNs were categorized into growth, 52 (47.3%), and non-growth, 58 (52.7%), groups according to volume growth. Kaplan-Meier analyses with the log-rank test and Cox proportional hazards regression analysis were conducted to analyze the cumulative percentages of pGGN growth and identify risk factors for growth.
Results
The mean follow-up period of the enrolled pGGNs was 48.7 ± 23.8 months. The median VDT of the 52 pGGNs having grown was 1448 (range, 339–8640) days, and their median MDT was 1332 (range, 290–38,912) days. The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all
p
< 0.001). The growth pattern of pGGNs may conform to the exponential model. Lobulated sign (
p
= 0.044), initial mean diameter (
p
< 0.001), volume (
p
= 0.003), and mass (
p
= 0.023) predicted pGGN growth.
Conclusions
Persistent pGGNs showed an indolent course. Deep learning can assist in accurately elucidating the natural history of pGGNs. pGGNs with lobulated sign and larger initial diameter, volume, and mass are more likely to grow.
Key Points
• The pure ground-glass nodule (pGGN) segmentation accuracy of the Dr. Wise system based on convolution neural networks (CNNs) was 96.5% (573/594).
•
The median volume doubling time (VDT) of 52 pure ground-glass nodules (pGGNs) having grown was 1448 days (range, 339–8640 days), and their median mass doubling time (MDT) was 1332 days (range, 290–38,912 days). The mean time to growth in volume was 854 ± 675 days (range, 116–2856 days).
•
The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p values < 0.001). The growth pattern of pure ground-glass nodules may conform to exponential model.
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