查看更多>>摘要：Therapeutics targeting tumor endothelial cells(TECs)have been explored for decades,with only suboptimal efficacy achieved,partly due to an insufficient understanding of the TEC heterogeneity across cancer patients.We integrated single-cell RNA-seq data of575 cancer patients from 19 solid tumor types,comprehensively charting the TEC phenotypic diversities.Our analyses uncovered underappreciated compositional and functional heterogeneity in TECs from a pan-cancer perspective.Two subsets,CXCR4+tip cells and SELE+veins,represented the prominent angiogenic and proinflammatory phenotypes of TECs,respectively.They exhibited distinct spatial organization patterns,and compared to adjacent non-tumor tissues,tumor tissue showed an increased prevalence of CXCR4+tip cells,yet with SELE+veins depleted.Such functional and spatial characteristics underlie their differential associations with the response of anti-angiogenic therapies and immunotherapies.Our integrative resources and findings open new avenues to understand and clinically intervene in the tumor vasculature.
查看更多>>摘要：It remains debatable how many genes and how various the mechanisms are behind human adaptation to extreme environments,such as high altitudes.Despite extensive studies on Tibetans,Andeans and Ethiopians,new insights are expected to be provided with careful analysis of underrepresented highlanders living in a different geographical region,such as the Tajiks,who reside on the Pamir Plateau at an average altitude exceeding 4000 meters.Moreover,genetic admixture,as we observed in the current whole-genome deep-sequencing study of Xinjiang Tajiks(XJT),offers a unique opportunity to explore how admixture may facilitate adaptation to high-altitude environments.Compared with other extensively studied highlanders,XJT showed pronounced admixture patterns:most of their ancestry are derived from West Eurasians(34.5％-48.3％)and South Asians(21.4％-40.0％),and some minor ancestry from East Asians and Siberians(3.62％-17.5％).The greater genetic diversity in XJT than in their ancestral source populations provides a genetic basis for their adaptation to high-altitude environments.The admixture gain of functional adaptive components from ancestral populations could facilitate adaptation to high-altitude environments.Specifically,admixture-facilitated adaptation was strongly associated with skin-related candidate genes that respond to UV radiation(e.g.HERC2 and BNC2)and cardiovascular-system-related genes(e.g.MPI and BEST1).Notably,no adaptive variants of genes showing outstanding natural selection signatures in the Tibetan or Andean highlanders were identified in XJT,including EPAS1 and EGLN1,indicating that a different set of genes contributed to XJT's survival on the Pamir Plateau,although some genes underlying natural selection in XJT have been previously reported in other highlanders.Our results highlight the unique genetic adaptations in XJT and propose that admixture may play a vital role in facilitating high-altitude adaptation.By introducing and elevating diversity,admixture likely induces novel genetic factors that contribute to the survival of populations in extreme environments like the highlands.
查看更多>>摘要：Resolving complex three-dimensional(3D)subcellular dynamics noninvasively in live tissues demands imaging tools that balance spatiotemporal resolution,field-of-view and phototoxicity.Image scanning microscopy(ISM),as an advancement of confocal laser scanning microscopy,provides a 2-fold 3D resolution enhancement.Nevertheless,the relatively low imaging speed has been the major obstacle for ISM to be further employed in in vivo imaging of biological tissues.Our proposed solution,multi-confocal image scanning microscopy(MC-ISM),aims to overcome the limitations of existing techniques in terms of spatiotemporal resolution balancing by optimizing pinhole diameter and pitch,eliminating out-of-focus signals,and introducing a frame reduction reconstruction algorithm.The imaging speed is increased by 16 times compared with multifocal structured illumination microscopy.We further propose a single-galvo scan,akin to the Archimedes spiral in spinning disk confocal systems,to ensure a high-speed and high-accuracy scan without the galvanometer's inertial motion.Benefitting from its high photon efficiency,MC-ISM allows continuous imaging of mitochondria dynamics in live cells for 1000 frames without apparent phototoxicity,reaching an imaging depth of 175 μm.Noteworthy,MC-ISM enables the observation of the inner membrane structure of living mitochondria in Arabidopsis hypocotyl for the first time,demonstrating its outstanding performance.
查看更多>>摘要：More intense fire weather due to climate change is implicated as a key driver of recent extreme wildfire events.As fuel stock,the role of vegetation and its phenology changes in wildfire dynamics,however is not fully appreciated.Using long-term satellite-based burned areas and photosynthesis observations,we reveal that an earlier peak photosynthesis timing(PPT)potentially acts to escalate subsequent wildfires,with an increase in the global average burned fraction of 0.021％(～2.20 Mha)for every additional day of PPT advancement.Satellite observations and Earth System modeling consistently show that this fire escalation is likely due to intensified drought conditions and increased fuel availability associated with the climate feedback arising from earlier PPT.Current fire-enabled dynamic global vegetation models can reproduce the observed negative correlation between PPT and burned area but underestimate the strength of the relationship notably.Given the continued PPT advancement owing to climate change,the bioclimatic effects of vegetation phenology change suggest a potentially pervasive upward pressure on future wildfires.
查看更多>>摘要：War-related urban destruction is a significant global concern,impacting national security,social stability,people's survival and economic development.The effects of urban geomorphology and complex geological contexts during conflicts,characterized by different levels of structural damage,are not yet fully understood globally.Here we report how integrating deep learning with data from the independently developed LuoJia3-01 satellite enables near real-time detection of explosions and assessment of different building damage levels in the Israel-Palestine conflict.We found that the damage continually increased from 17 October 2023 to 2 March 2024.We found 3747 missile craters with precision positions and sizes,and timing on vital infrastructure across five governorates in the Gaza Strip on 2 March 2024,providing accurate estimates of potential unexploded ordnance locations and assisting in demining and chemical decontamination.Our findings reveal a significant increase in damage to residential and educational structures,accounting for 58.4％of the total-15.4％destroyed,18.7％severely damaged,11.8％moderately damaged and 12.5％slightly damaged-which exacerbates the housing crisis and potential population displacement.Additionally,there is a 34.1％decline in the cultivated area of agricultural land,posing a risk to food security.The LuoJia3-01 satellite data are crucial for impartial conflict monitoring,and our innovative methodology offers a cost-effective,scalable approach to assess future conflicts in various global contexts.These first-time findings highlight the urgent need for an immediate ceasefire to prevent further damage and support the release of hostages and subsequent reconstruction efforts.
查看更多>>摘要：The mechanism that causes the rapid uplift and active magmatism of the Hoh-Xil Basin in the northern Tibetan Plateau and hence the outward growth of the proto-plateau is highly debated,more specifically,over the relationship between deep dynamics and surface uplift.Until recently the Hoh-Xil Basin remained uncovered by seismic networks due to inaccessibility.Here,based on linear seismic arrays across the Hoh-Xil Basin,we present a three-dimensional S-wave velocity(Vs)model of the crust and uppermost mantle structure beneath the Tibetan Plateau from ambient noise tomography.This model exhibits a widespread partially molten crust in the northern Tibetan Plateau but only isolated pockets in the south manifested as low-Vs anomalies in the middle crust.The spatial correlation of the widespread low-Vs anomalies with strong uppermost mantle low-Vs anomalies and young exposed magmatic rocks in the Hoh-Xil Basin suggests that the plateau grew through lithospheric mantle removal and its driven magmatism.
查看更多>>摘要：In the past decade,China has motivated proactive emission control measures that have successfully reduced emissions of many air pollutants.For atmospheric mercury,which is a globally transported neurotoxin,much less is known about the long-term changes in its concentrations and anthropogenic emissions in China.In this study,over a decade of continuous observations at four Chinese sites show that gaseous elemental mercury(GEM)concentrations continuously increased until the early 2010s,followed by significant declines at rates of 1.8％-6.1％yr-1 until 2022.The GEM decline from 2013 to 2022(by 38.6％±12.7％)coincided with the decreasing concentrations of criteria air pollutants in China and were larger than those observed elsewhere in the northern hemisphere(5.7％-14.2％).The co-benefits of emission control measures contributed to the reduced anthropogenic Hg emissions and led to the GEM decline in China.We estimated that anthropogenic GEM emissions in China were reduced by 38％-50％(116-151 tons)from 2013 to 2022 using the machine-learning and relationship models.
查看更多>>摘要：Biomass burning(BB)is a major source of trace gases and particles in the atmosphere,influencing air quality,radiative balance,and climate.Previous studies have mainly focused on the BB emissions of carbon and nitrogen species with less attention on chlorine.Reactive chlorine chemistry has significant effects on atmospheric chemistry and air quality.However,quantitative information on chlorine emissions from BB,particularly the long-term trend and associated atmospheric impacts,is limited both on regional and global scales.Here,we report a long-term(2001-2018)high-resolution BB emission inventory for the major chlorine-containing compounds(HCl,chloride,and CH3C1)in Asia based on satellite observations.We estimate an average of730 Gg yr-1 chlorine emitted from BB activity in Asia,with China contributing the largest share at 24.2％(177 Gg yr-1),followed by Myanmar at 18.7％and India at 18.3％.Distinct seasonal patterns and significant spatial and interannual variability are observed,mainly driven by human-mediated changes in agricultural activity.By incorporating the newly developed chlorine emission inventory into a global chemistry-climate model(CAM-Chem),we find that the BB-chlorine emissions lead to elevated levels of HCl and CH3Cl(monthly average up to 2062 and 1421 parts per trillion by volume(pptv),respectively),subsequently resulting in noticeable changes in oxidants(up to 3.1％in O3 and 17％in OH radicals).The results demonstrate that BB is not only a significant source of air pollutants but also of oxidants,suggesting a larger role of BB emissions in the atmospheric chemistry and oxidation process than previously appreciated.In light of the projected increase in BB activity toward the end of the century and the extensive control of anthropogenic emissions worldwide,the contribution of BB emissions may become fundamental to air quality composition in the future.
查看更多>>摘要：Single-cluster catalysts(SCCs)representing structurally well-defined metal clusters anchored on support tend to exhibit tunable catalytic performance for complex redox reactions in heterogeneous catalysis.Here we report a theoretical study on an SCC of Ru3@Mo2CO2 MXene for N2-to-NH3 thermal conversion.Our results show that Ru3@Mo2CO2 can effectively activate N2 and promotes its conversion to NH3 through an association mechanism,in which the rate-determining step of NH2*+H*→ NH3*has a low energy barrier of 1.29 eV.Notably,with the assistance of Mo2CO2 support,the positively charged Ru3 cluster active site can effectively adsorb and activate N2,leading to 0.74|e|charge transfer from Ru3@Mo2CO2 to the adsorbed N2.The supported Ru3 also acts as an electron reservoir to regulate the charge transfer for various intermediate steps of ammonia synthesis.Microkinetic analysis shows that the turnover frequency of the N2-to-NH3 conversion on Ru3@Mo2CO2 is as high as 1.45 × 10-2 s-1 site-1 at a selected thermodynamic condition of 48 bar and 700 K,the performance of which even surpasses that of the Ru B5 site and Fe3/θ-Al2O3(010)reported before.Our work provides a theoretical understanding of the high stability and catalytic mechanism of Ru3@Mo2CO2 and guidance for further designing and fabricating MXene-based metal SCCs for ammonia synthesis under mild conditions.
查看更多>>摘要：This study reports the successful design and synthesis of two novel polymerized nonfused ring electron acceptors,P-2BTh and P-2BTh-F,derived from the high-performance nonfused ring electron acceptor,2BTh-2F.Prepared via Stille polymerization,these polymers feature thiophene and fluorinated thiophene asπ-bridge units.Notably,P-2BTh-F,with difluorothiophene as the π-bridge,exhibits a more planar backbone and red-shifted absorption spectrum compared with P-2BTh.When employed in organic solar cells(OSCs)with PBDB-T as the donor material,P-2BTh-F-based devices demonstrate an outstanding power conversion efficiency(PCE)of over 11％,exceeding the 8.7％achieved by P-2BTh-based devices.Furthermore,all-polymer solar cells utilizing PBDB-T:P-2BTh-F exhibit superior storage stability.Additionally,P-2BTh-F was explored as a functional additive in a high-performance binary system,enhancing stability while maintaining comparable PCE(19.45％).This strategy offers a cost-effective approach for fabricating highly efficient and stable binary and ternary organic solar cells,opening new horizons for cost-effective and durable solar cell development.
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