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We analyze 16-month data of 13 major halocarbons measured at a southern China coastal site in the greater Pearl River Delta (PRD). A total of 188 canister air samples were collected from August 2001 to December 2002. Overall inspection indicated that CH2Cl2, C2Cl 4, and C2HCl3 had similar temporal variations while CFC-11, CFC-12, and CFC-113 showed the same emission patterns during the sampling period. Diurnal variations of halocarbons presented different patterns during ozone episode days, mainly related to emission strength, atmospheric dispersion, and photochemical lifetimes. For further statistics and source appointment, Lagrangian backward particle release simulations were conducted to help understand the potential source regions of all samples and classify them into different categories, including local Hong Kong, inner PRD, continental China, and marine air masses. With the exception of HCFC-142b, the mixing ratios of all halocarbons in marine air were significantly lower than those in urban and regional air (p < 0.01), whereas no significant difference was found between urban Hong Kong and inner PRD regional air, reflecting the dominant impact of the greater PRD regional air on the halocarbon levels. The halocarbon levels in this region were significantly influenced by anthropogenic sources, causing the halocarbon mixing ratios in South China Sea air to be higher than the corresponding background levels, as measured by global surface networks and by airborne missions such as Transport and Chemical Evolution Over the Pacific. Interspecies correlation analysis suggests that CHCl3 is mainly used as a solvent in Hong Kong but mostly as a feedstock for HCFC-22 in the inner PRD. Furthermore, CH3Cl is often used as a refrigerant and emitted from biomass/biofuel burning in the inner PRD. A positive matrix factorization receptor model was applied to the classified halocarbon samples in the greater PRD for source profiles and apportionments. Seven major sources were identified and quantified. Emissions from solvent use were the most significant source of halocarbons (71 ± 9%), while refrigeration was the second largest contributor (18 ± 2%). By further looking at samples from the inner PRD and from urban Hong Kong separately, we found that more solvent was used in the dry cleaning industry in Hong Kong, whereas the contribution of cleaning solvent in the electronic industry was higher in the inner PRD. Besides the two common sources of solvent use and refrigeration, the contributions of biomass/biofuel burning and feedstock in chemical manufacturing was remarkable in the inner PRD but negligible in Hong Kong. These findings are of help to effectively control and phase out the emissions of halocarbons in the greater PRD region of southern China Copyright 2009 by the American Geophysical Union.

Space-borne formaldehyde (HCHO) column measurements from the Ozone Monitoring Instrument (OMI), with 13 × 24 km2 nadir footprint and daily global coverage, provide new constraints on the spatial distribution of biogenic isoprene emission from North America. OMI HCHO columns for June-August 2006 are consistent with measurements from the earlier GOME satellite sensor (1996-2001) but OMI is 2-14% lower. The spatial distribution of OMI HCHO columns follows that of isoprene emission; anthropogenic hydrocarbon emissions are undetectable except in Houston. We develop updated relationships between HCHO columns and isoprene emission from a chemical transport model (GEOS-Chem), and use these to infer top-down constraints on isoprene emissions from the OMI data. We compare the OMI-derived emissions to a state-of-science bottom-up isoprene emission inventory (MEGAN) driven by two land cover databases, and use the results to optimize the MEGAN emission factors (EFs) for broadleaf trees (the main isoprene source). The OMI-derived isoprene emissions in North America (June-August 2006) with 1° × 1° resolution are spatially consistent with MEGAN (R2 = 0.48-0.68) but are lower (by 4-25% on average). MEGAN overestimates emissions in the Ozarks and the Upper South. A better fit to OMI (R2 = 0.73) is obtained in MEGAN by using a uniform isoprene EF from broadleaf trees rather than variable EFs. Thus MEGAN may overestimate emissions in areas where it specifies particularly high EFs. Within-canopy isoprene oxidation may also lead to significant differences between the effective isoprene emission to the atmosphere seen by OMI and the actual isoprene emission determined by MEGAN. Copyright 2008 by the American Geophysical Union.

We use a continuous 6-year record (1996 - 2001) of GOME satellite measurements of formaldehyde (HCHO) columns over east and south Asia to improve regional emission estimates of reactive nonmethane volatile organic compounds (NMVOCs), including isoprene, alkenes, HCHO, and xylenes. Mean monthly HCHO observations are compared to simulated HCHO columns from the GEOS-Chem chemical transport model using state-of-science, "bottom-up" emission inventories from Streets et al. (2003a) for anthropogenic and biomass burning emissions and Guenther et al. (2006) for biogenic emissions (MEGAN). We find that wintertime GOME observations can diagnose anthropogenic reactive NMVOC emissions from China, leading to an estimate 25% higher than Streets et al. (2003a). We attribute the difference to vehicular emissions. The biomass burning source for east and south Asia is almost 5 times the estimate of Streets et al. (2003a). GOME reveals a large source from agricultural burning in the North China Plain in June missing from current inventories. This source may reflect a recent trend toward in-field burning of crop residues as the need for biofuels diminishes. Biogenic isoprene emission in east and south Asia derived from GOME is 56 ± 30 Tg yr-1, similar to 52 Tg yr-1 from MEGAN. We find, however, that MEGAN underestimates emissions in China and overestimates emissions in the tropics. The higher Chinese biogenic and biomass burning emissions revealed by GOME have important implications for ozone pollution. We find 5 to 20 ppb seasonal increases in surface ozone in GEOS-Chem for central and northern China when using GOME-derived versus bottom-up emissions. Our methodology can be adapted for other regions of the world to provide top-down constraints on NMVOC emissions where multiple emission source types overlap in space and time. Copyright 2007 by the American Geophysical Union.

We investigate how a recently suggested pathway for production of secondary organic aerosol (SOA) affects the consistency of simulated organic aerosol (OA) mass in a global three-dimensional model of oxidant-aerosol chemistry (GEOS-Chem) versus surface measurements from the interagency monitoring of protected visual environments (IMPROVE) network. Simulations in which isoprene oxidation products contribute to SOA formation, with a yield of 2.0% by mass reduce a model bias versus measured OA surface mass concentrations. The resultant increase in simulated OA mass concentrations during summer of 0.6-1.0 μg m-3 in the southeastern United States reduces the regional RMSE to 0.88 μg m-3 from 1.26 μg m-3. Spring and fall biases are also reduced, with little change in winter when isoprene emissions are negligible. © 2006 Elsevier Ltd. All rights reserved.

Quantifying isoprene emissions using satellite observations of the formaldehyde (HCHO) columns is subject to errors involving the column retrieval and the assumed relationship between HCHO columns and isoprene emissions,taken here from the GEOSCHEM chemical transport model. Here we use a 6-year (1996-2001) HCHO column data set from the Global Ozone Monitoring Experiment (GOME) satellite instrument to (1) quantify these errors, (2) evaluate GOME-derived isoprene emissions with in situ flux measurements and a process-based emission inventory (Model of Emissions of Gases and Aerosols from Nature, MEGAN), and (3) investigate the factors driving the seasonal and interannual variability of North American isoprene emissions. The error in the GOME HCHO column retrieval is estimated to be 40%. We use the Master Chemical Mechanism (MCM) to quantify the time-dependent HCHO production from isoprene, α-and β-pinenes, and methylbutenol and show that only emissions of isoprene are detectable by GOME. The time-dependent HCHO yield from isoprene oxidation calculated by MCM is 20-30% larger than in GEOS-CHEM. GOME-derived isoprene fluxes track the observed seasonal variation of in situ measurements at a Michigan forest site with a -30% bias. The seasonal variation of North American isoprene emissions during 2001 inferred from GOME is similar to MEGAN, with GOME emissions typically 25% higher (lower) at the beginning (end) of the growing season. GOME and MEGAN both show a maximum over the southeastern United States, but they differ in the precise location. The observed interannual variability of this maximum is 20-30%, depending on month. The MEGAN isoprene emission dependence on surface air temperature explains 75% of the month-to-month variability in GOME-derived isoprene emissions over the southeastern United States during May-September 1996-2001. Copyright 2006 by the American Geophysical Union.

Ambient fine particulate matter (PM 2.5 ) can catalyze the generation of reactive oxygen species in vivo, causing hazardous effects on human health. Molecular-level analysis of major oxidative potential (OP) active species is still limited. In this study, we used non-targeted high-resolution mass spectrometry to analyze the water-soluble organic components of ambient PM 2.5 samples in winter and summer. Chemical components and back trajectory analysis revealed significant impacts of biomass burning and ship emissions on PM 2.5 in winter and summer, respectively. Significance Analysis of the Microarray method and correlation analyses were combined to identify OP (OP DTT and OP OH ) active species in characteristic organic compounds emitted from ship and biomass combustion emissions and to explore possible mechanisms. The results showed that the characteristic compounds emitted from ship were mainly organic amine compounds and contained more sulfur-containing components, while the characteristic compounds emitted from biomass burning were mainly oxygen-containing aromatic compounds of CHO and CHON groups. The high toxicity of summer PM 2.5 might derive from reduced organic nitrogen compounds (C 6 H 14 N 2 O 3 S, C 6 H 12 N 2 O 3 S, C 10 H 9 N 3 O, C 6 H 9 N 5 O 3 S, and C 6 H 14 N 4 O) emission from ship sources. These reduced organic nitrogen compounds can form complexes with metals, affecting their solubility and reactivity in aerosols. Phenolic hydroxyl compounds were the main contributors to the PM 2.5 OP from biomass burning in winter. Semiquinone radicals produced by oxidation of phenolic compounds can further promote the generation of reactive oxygen species through Fenton-like reactions. Our studies based on ambient PM 2.5 samples further deepened the understanding of the molecular level of organic compounds emitted from ships and biomass burning, and their association with OP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Vertical mixing within the planetary boundary layer (PBL) is crucial for determining surface-level pollutant concentrations. However, standard PBL schemes in chemical transport models (CTMs) often fail to adequately define the upper bounds of vertical mixing, particularly at night. This limitation frequently results in overestimated nocturnal concentrations of pollutants near the surface. To address this issue, we propose a parameterization of mixed layer height (MLH) derived from the Yonsei University (YSU) PBL scheme and thoroughly evaluate it by comparing simulations with various observations. We utilized the Weather Research and Forecasting model coupled with GEOS-Chem (WRF-GC) to simulate gas and aerosol distributions over South Korea during the Satellite Integrated Joint Monitoring of Air Quality (SIJAQ) campaign in 2021. The WRF-GC simulations incorporating the MLH parameterization improved the excessive titration of O 3 and the overproduction of HNO 3 and NO 3 - in the model. Consequently, the model performances in gaseous and aerosol simulations showed a better agreement with observations, with changes in normalized mean biases (NMBs) of NO X (from 50 % to -27 %), O 3 (from -49 % to -28 %), NO 3 - (from 126 % to 91 %), NH 4 + (from 113 % to 85 %), BC (from 322 % to 135 %), and PM 2.5 (from 58 % to 28 %)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Light sheet microscopy is a powerful technique for high-speed three-dimensional imaging of subcellular dynamics and large biological specimens. However, it often generates datasets ranging from hundreds of gigabytes to petabytes in size for a single experiment. Conventional computational tools process such images far slower than the time to acquire them and often fail outright due to memory limitations. To address these challenges, we present PetaKit5D, a scalable software solution for efficient petabyte-scale light sheet image processing. This software incorporates a suite of commonly used processing tools that are optimized for memory and performance. Notable advancements include rapid image readers and writers, fast and memory-efficient geometric transformations, high-performance Richardson-Lucy deconvolution and scalable Zarr-based stitching. These features outperform state-of-the-art methods by over one order of magnitude, enabling the processing of petabyte-scale image data at the full teravoxel rates of modern imaging cameras. The software opens new avenues for biological discoveries through large-scale imaging experiments., Competing Interests: Competing interests: A.K. and M.N. are employees of NVIDIA. The use of the NVIDIA IndeX software platform can be licensed free of charge for educational and noncommercial research. The scientists and engineers at NVIDIA align the development of the NVIDIA IndeX solution to the requirements in various fields of scientific visualization including those that arise from the needs of the Advanced Bioimaging Center at the University of California, Berkeley. The other authors declare no competing interests., (© 2024. The Author(s).)

The recognized importance of ambient fine particulate matter (PM 2.5 ), ozone (O 3 ), and nitrogen dioxide (NO 2 ) on human health has prompted the world to enact increasingly strict regulations on anthropogenic nitrogen oxides (NO x ) emissions. However, the health concerns from soil NO x , potentially driven by fertilizer input but conventionally categorized as natural sources, remain less studied. Here, we emphasize the underappreciated roles of soil NO x emissions on health burden attributable to short-term PM 2.5 , O 3 , and NO 2 exposure. Globally, we quantify acute health effects using machine-learning-based daily exposure estimates and identify influences of soil NO x emissions based on chemical transport model simulations. We find that 72.3% of the globe is affected by soil NO x emissions, whose contributions to short-term PM 2.5 , O 3 , and NO 2 pollution lead to 13.9 (95% Confidence Interval [CI]: 9.1-18.8), 26.0 (18.2-34.2), and 13.9 (10.3-17.5) thousand premature mortality, respectively, in 2019. With distinct variations in regions, seasons, and pollutants, soil NO x -originated air pollution poses a global health concern, particularly for developing regions and intensively agricultural areas. In response to the intensive fertilizer use, South Asia, Southern Sub-Saharan Africa, and Central Europe witness the largest soil NO x -related health burden of up to 1.6 (95% CI: 1.1-2.1) mortality per 100k population. The overall health risk peaks in May, with O 3 pollution typically dominating the soil NO x -attributable health burden during warm seasons and NO 2 or PM 2.5 during cold months. Our study highlights the necessity of dynamically adapted agricultural strategies for health-oriented multi-pollutant control, among which the improved use of synthetic fertilizers deserves priority under the ever-changing climate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Leveraging the rich structural information provided by AlphaFold, we used integrated experimental approaches to characterize the HerA-DUF4297 (DUF) anti-phage defense system, in which DUF is of unknown function. To infer the function of DUF, we performed structure-guided genomic analysis and found that DUF homologs are universally present in bacterial immune defense systems. One notable homolog of DUF is Cap4, a universal effector with nuclease activity in CBASS, the most prevalent anti-phage system in bacteria. To test the inferred nuclease function of DUF, we performed biochemical experiments and discovered that the DUF only exhibits activity against DNA substrates when it is bound by HerA. To understand how HerA activates DUF, we determined the structures of DUF and the HerA-DUF complex. DUF forms large oligomeric assemblies with or without HerA, suggesting that oligomerization per se is not sufficient for DUF activation. Instead, DUF activation requires dramatic topological rearrangements that propagate from HerA to the entire HerA-DUF complex, leading to reorganization of DUF for effective DNA cleavage. We further validated these structural insights by structure- guided mutagenesis. Together, these findings reveal dramatic topological rearrangements throughout the HerA-DUF complex, challenge the long-standing dogma that protein oligomerization alone activates immune signaling, and may inform the activation mechanism of CBASS.

The nocturnal boundary layer (NBL) significantly influences the dispersion and fate of atmospheric species at night. Subtropical forests are crucial in carbon and water exchange between the biosphere and the atmosphere. However, the NBL characteristics and their impact on atmospheric species over these forests remain unknown. This study conducted vertical measurements of atmospheric species such as O 3 and volatile organic compounds (VOCs), along with meteorological variables, over a national forest reserve in Southern China. Results reveal that the NBL height ranged from 180 to 300 m in the summer and from 80 to 160 m in the winter. The vertical distribution of chemical species varied by time and season, with greater concentration gradients observed in the summer. Over 90% of VOCs above the NBL were anthropogenic, while biogenic VOCs were mainly found within the NBL. Higher O 3 concentration and VOC product-to-reactant ratios were observed in the residual layer, suggesting enhanced oxidation levels. This unique vertical distribution of atmospheric species at night is driven by factors, such as emission, deposition, turbulence, and atmospheric chemistry, potentially affecting ecosystem functions. Results from this study highlight the importance of incorporating NBL dynamics into atmospheric models to better understand the evolution of chemical species and their ecological effects over forests.

Carcinogenic nitrosamines have been widely studied due to their risk to human health. However, the universality and evolutionary processes of their generation, particularly concerning their secondary sources, remain unclear at present. We demonstrated through laboratory flow tube experiments that corresponding nitrosamines were generated from heterogeneous reactions of nitrous acid (HONO) with five structurally diverse amines commonly found indoors, including diphenylamine (DPhA), dibenzylamine (DBzA), dioctylamine (DOtA), N -(1,3-dimethylbutyl)- N '-phenyl- p -phenylenediamine (6PPD), and N -phenyl-1-naphthylamine (PANA). The heterogeneous reaction rate constants of DBzA and DOtA with HONO (∼70 ppb) were 1.21 × 10 -3 and 2.13 × 10 -3 min -1 at 30% relative humidity (RH), resulting in a lifetime of 13.8 and 7.8 h. As compared to higher RH (∼80%), more nitrosamines were produced from the reaction of HONO with surface-sorbed DBzA, DOtA, 6PPD, and PANA at lower RH (30%), with product yields ranging from <0.1% to 0.5%. Furthermore, we observed the formation of nitroso-6PPDs and nitro-6PPDs during room air exposure of 6PPD in a genuine indoor environment, in addition to various other transformation products indicative of reactions of 6PPD with HONO, NOx, and ozone indoors. This study confirmed the universality of the heterogeneous reaction of surface-sorbed amine with HONO as a source of nitrosamines indoors.

Human cytomegalovirus (CMV) causes serious developmental disabilities in newborns infected in utero following oral acquisition by the mother. Thus, neutralizing antibodies in maternal saliva have potential to prevent maternal infection and, consequently, fetal transmission and disease. Based on standard cell culture models, CMV entry mediators (and hence neutralizing targets) are cell type-dependent: entry into fibroblasts requires glycoprotein B (gB) and a trimeric complex (TC) of glycoproteins H, L, and O, whereas endothelial and epithelial cell entry additionally requires a pentameric complex (PC) of glycoproteins H and L with UL128, UL130, and UL131A. However, as the mediators of mucosal cell entry and the potential impact of cellular differentiation remained unclear, the present studies utilized mutant viruses, neutralizing antibodies, and soluble TC-receptor to determine the entry mediators required for infection of mucocutaneus cell lines and primary tonsil epithelial cells. Entry into undifferentiated cells was largely PC-dependent, but PC-independent entry could be induced by differentiation. TC-independent entry was also observed and varied by cell line and differentiation. Infection of primary tonsil cells from some donors was entirely TC-independent. In contrast, an antibody to gB or disruption of virion attachment using heparin blocked entry into all cells. These findings indicate that CMV entry into the spectrum of cell types encountered in vivo is likely to be more complex than has been suggested by standard cell culture models and may be influenced by the relative abundance of virion envelope glycoprotein complexes as well as by cell type, tissue of origin, and state of differentiation., Competing Interests: Declaration of competing interest Lawrence M. Kauvar is employed by and owns stock in Trellis Bioscience Inc., which provided TRL345 for this study. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Horizontal gene transfer is a key driver of bacterial evolution, but it also presents severe risks to bacteria by introducing invasive mobile genetic elements. To counter these threats, bacteria have developed various defense systems, including prokaryotic Argonautes (pAgos) and the DNA defense module DdmDE system. Through biochemical analysis, structural determination, and in vivo plasmid clearance assays, we elucidate the assembly and activation mechanisms of DdmDE, which eliminates small, multicopy plasmids. We demonstrate that DdmE, a pAgo-like protein, acts as a catalytically inactive, DNA-guided, DNA-targeting defense module. In the presence of guide DNA, DdmE targets plasmids and recruits a dimeric DdmD, which contains nuclease and helicase domains. Upon binding to DNA substrates, DdmD transitions from an autoinhibited dimer to an active monomer, which then translocates along and cleaves the plasmids. Together, our findings reveal the intricate mechanisms underlying DdmDE-mediated plasmid clearance, offering fundamental insights into bacterial defense systems against plasmid invasions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ultrafine particles (UFPs) dominate the atmospheric particles in number concentration, impacting human health and climate change. However, existing studies primarily rely on mass-based approaches, leading to a restricted understanding of the number-based and chemically resolved health effects of atmospheric UFPs. In this study, we utilized a high-mass-resolution single-particle aerosol mass spectrometer to investigate the online chemical composition and number size distribution of ultrafine, fine, and coarse particles during the summertime in urban Shenzhen, China. Human respiratory deposition dose assessments of particles with varying chemical compositions were further conducted by a respiratory deposition model. The results showed that during our observation, particles containing elemental carbon (EC) were the dominant components in UFPs (0.05-0.1 μm). Compared to fine and coarse particles, UFPs can deposit more deeply into the respiratory tract with a daily dose of ∼2.08 ± 0.67 billion particles. Among the deposited UFPs, EC-cluster particles constituted ∼85.7% in number fraction, accounting for a daily number dose of ∼1.78 billion particles, which poses a greater impact on human health. Simultaneously, we found discrepancies in the chemically resolved particle depositions among number-, surface area-, and mass-based approaches, emphasizing the importance of an appropriate metric for particle health-risk evaluation.

Dark aqueous-phase reactions involving the nitrosation and nitration of aromatic organic compounds play a significant role in the production of light-absorbing organic carbon in the atmosphere. This process constitutes a crucial aspect of tropospheric chemistry and has attracted growing research interest, particularly in understanding the mechanisms governing nighttime reactions between phenols and nitrogen oxides. In this study, we present new findings concerning the rapid dark reactions between phenols containing electron-donating groups and inorganic nitrite in acidic aqueous solutions with pH levels <3.5. This reaction generates a substantial amount of nitroso- and nitro-substituted phenolic compounds, known for their light-absorbing properties and toxicity. In experiments utilizing various substituted phenols, we demonstrate that their reaction rates with nitrite depend on the electron cloud density of the benzene ring, indicative of an electrophilic substitution reaction mechanism. Control experiments and theoretical calculations indicate that the nitrosonium ion (NO + ) is the reactive nitrogen species responsible for undergoing electrophilic reactions with phenolate anions, leading to the formation of nitroso-substituted phenolic compounds. These compounds then undergo partial oxidation to form nitro-substituted phenols through reactions with nitrous acid (HONO) or other oxidants like oxygen. Our findings unveil a novel mechanism for swift atmospheric nitrosation and nitration reactions that occur within acidic cloud droplets or aerosol water, providing valuable insights into the rapid nocturnal formation of nitrogen-containing organic compounds with significant implications for climate dynamics and human health., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Ozone pollution is profoundly modulated by meteorological features such as temperature, air pressure, wind, and humidity. While many studies have developed empirical models to elucidate the effects of meteorology on ozone variability, they predominantly focus on local weather conditions, overlooking the influences from high-altitude and broader regional meteorological patterns. Here, we employ convolutional neural networks (CNNs), a technique typically applied to image recognition, to investigate the influence of three-dimensional spatial variations in meteorological fields on the daily, seasonal, and interannual dynamics of ozone in Shenzhen, a major coastal urban center in China. Our optimized CNNs model, covering a 13° × 13° spatial domain, effectively explains over 70% of daily ozone variability, outperforming alternative empirical approaches by 7 to 62%. Model interpretations reveal the crucial roles of 2-m temperature and humidity as primary drivers, contributing 16% and 15% to daily ozone fluctuations, respectively. Regional wind fields account for up to 40% of ozone changes during the episodes. CNNs successfully replicate observed ozone temporal patterns, attributing -5-6 μg·m -3 of interannual ozone variability to weather anomalies. Our interpretable CNNs framework enables quantitative attribution of historical ozone fluctuations to nonlinear meteorological effects across spatiotemporal scales, offering vital process-based insights for managing megacity air quality amidst changing climate regimes.

As one of the most prevalent anti-phage defense systems in prokaryotes, Gabija consists of a Gabija protein A (GajA) and a Gabija protein B (GajB). The assembly and function of the Gabija system remain unclear. Here we present cryo-EM structures of Bacillus cereus GajA and GajAB complex, revealing tetrameric and octameric assemblies, respectively. In the center of the complex, GajA assembles into a tetramer, which recruits two sets of GajB dimer at opposite sides of the complex, resulting in a 4:4 GajAB supramolecular complex for anti-phage defense. Further biochemical analysis showed that GajA alone is sufficient to cut double-stranded DNA and plasmid DNA, which can be inhibited by ATP. Unexpectedly, the GajAB displays enhanced activity for plasmid DNA, suggesting a role of substrate selection by GajB. Together, our study defines a framework for understanding anti-phage immune defense by the GajAB complex., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Short-term exposure to particles with aerodynamic diameters less than 2.5 μm (PM 2.5 ) and ozone (O 3 ) are important risk factors for human health. Despite the awareness of reducing attributable health burden, region-specific and source-specific strategies remain less explored due to the gap between precursor emissions and health effects. In this study, we isolate the health burden of individual sector sources of PM 2.5 and O 3 precursors, nitrogen oxides (NO x ) and volatile organic compounds (VOCs), across the globe. Specifically, we estimate mortalities attributable to short-term exposure using machine-learning-based daily exposure estimates and quantify sectoral impacts using chemical transport model simulations. Globally, short-term exposure to PM 2.5 and O 3 result in 713.5 (95% Confidence Interval: 598.8-843.3) thousand and 496.3 (371.3-646.1) thousand mortalities in 2019, respectively, of which 12.5% are contributed by fuel-related NO x emissions from transportation, energy, and industry. Sectoral impacts from anthropogenic NO x and VOC emissions on health burden vary significantly among seasons and regions, requiring a target shift from transportation in winter to industry in summer for East Asia, for instance. Emission control and health management are additionally complicated by unregulated natural influences during climatic events. Fire-sourced NO x and VOC emissions, respectively, contribute to 8.5 (95% CI: 6.2-11.7) thousand and 4.8 (3.6-5.9) thousand PM 2.5 and O 3 mortalities, particularly for tropics with high vulnerability to climate change. Additionally, biogenic VOC emissions during heatwaves contribute to 1.8 (95% CI: 1.5-2.2) thousand O 3 -introduced mortalities, posing challenges in urban planning for high-income regions, where biogenic contributions to health burden during heatwaves are 13% of anthropogenic contributions annually. Our study provides important implications for temporally dynamic and sector-targeted emission control and health management strategies, which are of urgency under the projection of continuously increasing energy consumption and changing climate.

Immune cells have intensely physical lifestyles characterized by structural plasticity and force exertion. To investigate whether specific immune functions require stereotyped mechanical outputs, we used super-resolution traction force microscopy to compare the immune synapses formed by cytotoxic T cells with contacts formed by other T cell subsets and by macrophages. T cell synapses were globally compressive, which was fundamentally different from the pulling and pinching associated with macrophage phagocytosis. Spectral decomposition of force exertion patterns from each cell type linked cytotoxicity to compressive strength, local protrusiveness, and the induction of complex, asymmetric topography. These features were validated as cytotoxic drivers by genetic disruption of cytoskeletal regulators, live imaging of synaptic secretion, and in silico analysis of interfacial distortion. Synapse architecture and force exertion were sensitive to target stiffness and size, suggesting that the mechanical potentiation of killing is biophysically adaptive. We conclude that cellular cytotoxicity and, by implication, other effector responses are supported by specialized patterns of efferent force.

Tropospheric nitrogen dioxide (NO 2 ) poses a serious threat to the environmental quality and public health. Satellite NO 2 observations have been continuously used to monitor NO 2 variations and improve model performances. However, the accuracy of satellite NO 2 retrieval depends on the knowledge of aerosol optical properties, in particular for urban agglomerations accompanied by significant changes in aerosol characteristics. In this study, we investigate the impacts of aerosol composition on tropospheric NO 2 retrieval for an 18 year global data set from Global Ozone Monitoring Experiment (GOME)-series satellite sensors. With a focus on cloud-free scenes dominated by the presence of aerosols, individual aerosol composition affects the uncertainties of tropospheric NO 2 columns through impacts on the aerosol loading amount, relative vertical distribution of aerosol and NO 2 , aerosol absorption properties, and surface albedo determination. Among aerosol compositions, secondary inorganic aerosol mostly dominates the NO 2 uncertainty by up to 43.5% in urban agglomerations, while organic aerosols contribute significantly to the NO 2 uncertainty by -8.9 to 37.3% during biomass burning seasons. The possible contrary influences from different aerosol species highlight the importance and complexity of aerosol correction on tropospheric NO 2 retrieval and indicate the need for a full picture of aerosol properties. This is of particular importance for interpreting seasonal variations or long-term trends of tropospheric NO 2 columns as well as for mitigating ozone and fine particulate matter pollution.

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns has revoked all authorized immunotherapeutics. Rapid viral evolution has also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative to understand how Omicron evolves into different subvariants and causes immune escape as this could help reevaluate the current intervention strategies mostly implemented in the clinics as emergency measures to counter the pandemic and, importantly, develop new solutions. Here, we provide a review focusing on the major events of Omicron viral evolution, including the features of spike mutation that lead to immune evasion against monoclonal antibody (mAb) therapy and vaccination, and suggest alternative durable options such as the ACE2-based experimental therapies superior to mAbs to address this unprecedented evolution of Omicron virus. In addition, this type of unique ACE2-based virus-trapping molecules can counter all zoonotic SARS coronaviruses, either from unknown animal hosts or from established wild-life reservoirs of SARS-CoV-2, and even seasonal alpha coronavirus NL63 that depends on human ACE2 for infection.

Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects and the most common opportunistic infection that causes life-threatening diseases post-transplantation; however, an effective vaccine remains elusive. V160 is a live-attenuated replication defective HCMV vaccine that showed a 42.4% efficacy against primary HCMV infection among seronegative women in a phase 2b clinical trial. Here, we integrated the multicolor flow cytometry, longitudinal T cell receptor (TCR) sequencing, and single-cell RNA/TCR sequencing approaches to characterize the magnitude, phenotype, and functional quality of human T cell responses to V160. We demonstrated that V160 de novo induces IE-1 and pp65 specific durable polyfunctional effector CD8 T cells that are comparable to those induced by natural HCMV infection. We identified a variety of V160-responsive T cell clones which exhibit distinctive "transient" and "durable" expansion kinetics, and revealed a transcriptional signature that marks durable CD8 T cells post-vaccination. Our study enhances the understanding of human T-cell immune responses to V160 vaccination., (© 2024. The Author(s).)

The evaporative emissions of anthropogenic volatile organic compounds (AVOCs) are sensitive to ambient temperature. This sensitivity forms an air pollution-meteorology connection that has not been assessed on a regional scale. We parametrized the temperature dependence of evaporative AVOC fluxes in a regional air quality model and evaluated the impacts on surface ozone in the Beijing-Tianjin-Hebei (BTH) area of China during the summer of 2017. The temperature dependency of AVOC emissions drove an enhanced simulated ozone-temperature sensitivity of 1.0 to 1.8 μg m -3 K -1 , comparable to the simulated ozone-temperature sensitivity driven by the temperature dependency of biogenic VOC emissions (1.7 to 2.4 μg m -3 K -1 ). Ozone enhancements driven by temperature-induced AVOC increases were localized to their point of emission and were relatively more important in urban areas than in rural regions. The inclusion of the temperature-dependent AVOC emissions in our model improved the simulated ozone-temperature sensitivities on days of ozone exceedance. Our results demonstrated the importance of temperature-dependent AVOC emissions on surface ozone pollution and its heretofore unrepresented role in air pollution-meteorology interactions.

Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Food consumption contributes to the degradation of air quality in regions where food is produced, creating a contrast between the health burden caused by a specific population through its food consumption and that faced by this same population as a consequence of food production activities. Here we explore this inequality within China's food system by linking air-pollution-related health burden from production to consumption, at high levels of spatial and sectorial granularity. We find that low-income groups bear a 70% higher air-pollution-related health burden from food production than from food consumption, while high-income groups benefit from a 29% lower health burden relative to their food consumption. This discrepancy largely stems from a concentration of low-income residents in food production areas, exposed to higher emissions from agriculture. Comprehensive interventions targeting both production and consumption sides can effectively reduce health damages and concurrently mitigate associated inequalities, while singular interventions exhibit limited efficacy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Escherichia coli Septu system, an anti-phage defense system, comprises two components: PtuA and PtuB. PtuA contains an ATPase domain, while PtuB is predicted to function as a nuclease. Here we show that PtuA and PtuB form a stable complex with a 6:2 stoichiometry. Cryo-electron microscopy structure of PtuAB reveals a distinctive horseshoe-like configuration. PtuA adopts a hexameric arrangement, organized as an asymmetric trimer of dimers, contrasting the ring-like structure by other ATPases. Notably, the three pairs of PtuA dimers assume distinct conformations and fulfill unique roles in recruiting PtuB. Our functional assays have further illuminated the importance of the oligomeric assembly of PtuAB in anti-phage defense. Moreover, we have uncovered that ATP molecules can directly bind to PtuA and inhibit the activities of PtuAB. Together, the assembly and function of the Septu system shed light on understanding other ATPase-containing systems in bacterial immunity., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Antioxidants are typically seen as agents that mitigate environmental health risks due to their ability to scavenge free radicals. However, our research presents a paradox where these molecules, particularly those within lung fluid, act as prooxidants in the presence of airborne particulate matter (PM 2.5 ), thus enhancing PM 2.5 oxidative potential (OP). In our study, we examined a range of antioxidants found in the respiratory system (e.g., vitamin C, glutathione (GSH), and N-acetylcysteine (NAC)), in plasma (vitamin A, vitamin E, and β-carotene), and in food (tert-butylhydroquinone (TBHQ)). We aimed to explore antioxidants' prooxidant and antioxidant interactions with PM 2.5 and the resulting OP and cytotoxicity. We employed OH generation assays and electron paramagnetic resonance assays to assess the pro-oxidative and anti-oxidative effects of antioxidants. Additionally, we assessed cytotoxicity interaction using a Chinese hamster ovary cell cytotoxicity assay. Our findings revealed that, in the presence of PM 2.5 , all antioxidants except vitamin E significantly increased the PM 2.5 OP by generating more OH radicals (OH generation rate: 0.16-24.67 pmol·min -1 ·m -3 ). However, it's noteworthy that these generated OH radicals were at least partially neutralized by the antioxidants themselves. Among the pro-oxidative antioxidants, vitamin A, β-carotene, and TBHQ showed the least ability to quench these radicals, consistent with their observed impact in enhancing PM 2.5 cytotoxicity (PM 2.5 LC 50 reduced to 91.2 %, 88.8 %, and 75.1 % of PM 2.5 's original level, respectively). Notably, vitamin A and TBHQ-enhanced PM 2.5 OP were strongly associated with the presence of metals and organic compounds, particularly with copper (Cu) contributing significantly (35 %) to TBHQ's pro-oxidative effect. Our study underscores the potential health risks associated with the interaction between antioxidants and ambient pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Water-soluble organic molecules (WSOMs) in inhaled PM 2.5 can readily translocate from the lungs into the blood circulation, facilitating their distribution to and health effects on distant organs and tissues in the human body. Human serum albumin (HSA), the most abundant protein carrier in the blood, readily binds exogenous substances to form non-covalent adducts and subsequently transports them throughout the circulatory system, thereby indicating their internal exposure. The direct internal exposure of WSOMs in PM 2.5 needs to be understood. In this study, the non-covalent HSA-WSOM adductome was developed as a dosimeter to evaluate the internal exposure potential of WSOMs in urban PM 2.5 . The WSOM composition was acquired from non-target high-resolution mass spectrometry analysis coupled with multiple ionizations. The binding level of HSA-WSOM non-covalent adducts was obtained from surface plasma resonance. Machine learning combined WSOM composition and the binding level of HSA-WSOM non-covalent adducts to screen bindable (also internalizable) WSOMs. The concentration of WSOM ranged from 4 to 13 μg/m 3 during our observation period. Of the 17,513 mass spectral features detected, 9,484 contributed to the non-covalent adductome and possessed the internal exposure potential. 102 major contributors accounted for 90.6 % of the HSA-WSOM binding level. The fraction of internalizable WSOMs in PM 2.5 varied from 11.9 % to 61.3 %, averaging 26.2 %. WSOMs that have internal exposure potential were primarily lignin-like and lipid-like substances. The HSA-WSOMs non-covalent adductome represents direct internal exposure potential, which can provide crucial insights into the molecular diagnosis of PM 2.5 exposure and precise assessments of PM 2.5 health effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

China's industrial restructuring and pollution controls have altered the contributions of individual sources to varying air quality over the past decade. We used the GEOS-Chem adjoint model and investigated the changing sensitivities of PM 2.5 and ozone (O 3 ) to multiple species and sources from 2010 to 2020 in the central Yangtze River Delta (YRDC), the largest economic region in China. Controlling primary particles and SO 2 from industrial and residential sectors dominated PM 2.5 decline, and reducing CO from multiple sources and ≥C 3 alkenes from vehicles restrained O 3 . The chemical regime of O 3 formation became less VOC-limited, attributable to continuous NO X abatement for specific sources, including power plants, industrial combustion, cement production, and off-road traffic. Regional transport was found to be increasingly influential on PM 2.5 . To further improve air quality, management of agricultural activities to reduce NH 3 is essential for alleviating PM 2.5 pollution, while controlling aromatics, alkenes, and alkanes from industry and gasoline vehicles is effective for O 3 . Reducing the level of NO X from nearby industrial combustion and transportation is helpful for both species. Our findings reveal the complexity of coordinating control of PM 2.5 and O 3 pollution in a fast-developing region and support science-based policymaking for other regions with similar air pollution problems.

Argonaute proteins (Agos) represent a highly conserved family of proteins prevalent in all domains of life and have been implicated in various biological processes. Based on the domain architecture, Agos can be divided into long Agos and short Agos. While long Agos have been extensively studied over the past two decades, short Agos, found exclusively in prokaryotes, have recently gained attention for their roles in prokaryotic immune defence against mobile genetic elements, such as plasmids and phages. Notable functional and structural studies provide invaluable insights into the underlying molecular mechanisms of representative short Ago systems. Despite the diverse domain arrangements, short Agos generally form heterodimeric complexes with their associated effector proteins, activating the effector's enzymatic activities upon target detection. The activation of effector proteins in the short Ago systems leads to bacterial cell death, a mechanism of sacrificing individuals to protect the community.

SIR2-HerA, a bacterial two-protein anti-phage defense system, induces bacterial death by depleting NAD + upon phage infection. Biochemical reconstitution of SIR2, HerA, and the SIR2-HerA complex reveals a dynamic assembly process. Unlike other ATPases, HerA can form various oligomers, ranging from dimers to nonamers. When assembled with SIR2, HerA forms a hexamer and converts SIR2 from a nuclease to an NAD + hydrolase, representing an unexpected regulatory mechanism mediated by protein assembly. Furthermore, high concentrations of ATP can inhibit NAD + hydrolysis by the SIR2-HerA complex. Cryo-EM structures of the SIR2-HerA complex reveal a giant supramolecular assembly up to 1 MDa, with SIR2 as a dodecamer and HerA as a hexamer, crucial for anti-phage defense. Unexpectedly, the HerA hexamer resembles a spiral staircase and exhibits helicase activities toward dual-forked DNA. Together, we reveal the supramolecular assembly of SIR2-HerA as a unique mechanism for switching enzymatic activities and bolstering anti-phage defense strategies., Competing Interests: Declaration of interests All authors declare they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The chemical industry is a significant source of nonmethane volatile organic compounds (NMVOCs), pivotal precursors to ambient ozone (O 3 ), and secondary organic aerosol (SOA). Despite their importance, precise estimation of these emissions remains challenging, impeding the implementation of NMVOC controls. Here, we present the first comprehensive plant-level assessment of NMVOC emissions from the chemical industry in China, encompassing 3461 plants, 127 products, and 50 NMVOC compounds from 2010 to 2019. Our findings revealed that the chemical industry in China emitted a total of 3105 (interquartile range: 1179-8113) Gg of NMVOCs in 2019, with a few specific products accounting for the majority of the emissions. Generally, plants engaged in chemical fibers production or situated in eastern China pose a greater risk to public health due to their higher formation potentials of O 3 and SOA or their proximity to residential areas or both. We demonstrated that targeting these high-risk plants for emission reduction could enhance health benefits by 7-37% per unit of emission reduction on average compared to the current situation. Consequently, this study provides essential insights for developing effective plant-specific NMVOC control strategies within China's chemical industry.

During asexual growth and replication cycles inside red blood cells, the malaria parasite Plasmodium falciparum primarily relies on glycolysis for energy supply, as its single mitochondrion performs little or no oxidative phosphorylation. Post merozoite invasion of a host red blood cell, the ring stage lasts approximately 20 hours and was traditionally thought to be metabolically quiescent. However, recent studies have shown that the ring stage is active in several energy-costly processes, including gene transcription, protein translation, protein export, and movement inside the host cell. It has remained unclear whether a low glycolytic flux alone can meet the energy demand of the ring stage over a long period post invasion. Here, we demonstrate that the metabolic by-product pyrophosphate (PPi) is a critical energy source for the development of the ring stage and its transition to the trophozoite stage. During early phases of the asexual development, the parasite utilizes Plasmodium falciparum vacuolar pyrophosphatase 1 (PfVP1), an ancient pyrophosphate-driven proton pump, to export protons across the parasite plasma membrane. Conditional deletion of PfVP1 leads to a delayed ring stage that lasts nearly 48 hours and a complete blockage of the ring-to-trophozoite transition before the onset of parasite death. This developmental arrest can be partially rescued by an orthologous vacuolar pyrophosphatase from Arabidopsis thaliana, but not by the soluble pyrophosphatase from Saccharomyces cerevisiae, which lacks proton pumping activities. Since proton-pumping pyrophosphatases have been evolutionarily lost in human hosts, the essentiality of PfVP1 suggests its potential as an antimalarial drug target. A drug target of the ring stage is highly desired, as current antimalarials have limited efficacy against this stage., Competing Interests: The authors declare no competing interests., (Copyright: © 2023 Solebo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.

Maritime trade and associated emissions are dynamic in nature. Although shipping emissions contribute significantly to air quality and climate change, their trade-governed dynamics remain less explored due to the lack of observational evidence. Here, we use satellite measurements to capture the redistribution of shipping nitrogen oxides (NO x ) emissions from Shanghai port, the world's busiest port, during a natural experiment posted by the localized COVID-19 lockdown in 2022. Viewing the ports as nodes in a network linked by ship journeys, we quantify a lockdown-induced - 42% reduction in shipping NO x emissions for Shanghai port. We further identify an emission transfer to its neighboring connected ports, confirmed by comprehensive vessel activity observations. Our study highlights the socioeconomic drivers of shipping emissions, which may add additional layers of complexity to air quality management., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

In early 2020, two unique events perturbed ship emissions of pollutants around Southern China, proffering insights into the impacts of ship emissions on regional air quality: the decline of ship activities due to COVID-19 and the global enforcement of low-sulfur (<0.5%) fuel oil for ships. In January and February 2020, estimated ship emissions of NO x , SO 2 , and primary PM 2.5 over Southern China dropped by 19, 71, and 58%, respectively, relative to the same period in 2019. The decline of ship NO x emissions was mostly over the coastal waters and inland waterways of Southern China due to reduced ship activities. The decline of ship SO 2 and primary PM 2.5 emissions was most pronounced outside the Chinese Domestic Emission Control Area due to the switch to low-sulfur fuel oil there. Ship emission reductions in early 2020 drove 16 to 18% decreases in surface NO 2 levels but 3.8 to 4.9% increases in surface ozone over Southern China. We estimated that ship emissions contributed 40% of surface NO 2 concentrations over Guangdong in winter. Our results indicated that future abatements of ship emissions should be implemented synergistically with reductions of land-borne anthropogenic emissions of nonmethane volatile organic compounds to effectively alleviate regional ozone pollution.

The iron and steel industry (ISI) is important for socio-economic progress but emits greenhouse gases and air pollutants detrimental to climate and human health. Understanding its historical emission trends and drivers is crucial for future warming and pollution interventions. Here, we offer an exhaustive analysis of global ISI emissions over the past 60 years, forecasting up to 2050. We evaluate emissions of carbon dioxide and conventional and unconventional air pollutants, including heavy metals and polychlorinated dibenzodioxins and dibenzofurans. Based on this newly established inventory, we dissect the determinants of past emission trends and future trajectories. Results show varied trends for different pollutants. Specifically, PM 2.5 emissions decreased consistently during the period 1970 to 2000, attributed to adoption of advanced production technologies. Conversely, NO x and SO 2 began declining recently due to stringent controls in major contributors such as China, a trend expected to persist. Currently, end-of-pipe abatement technologies are key to PM 2.5 reduction, whereas process modifications are central to CO 2 mitigation. Projections suggest that by 2050, developing nations (excluding China) will contribute 52-54% of global ISI PM 2.5 emissions, a rise from 29% in 2019. Long-term emission curtailment will necessitate the innovation and widespread adoption of new production and abatement technologies in emerging economies worldwide.

OSCA/TMEM63s form mechanically activated (MA) ion channels in plants and animals, respectively. OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins form homodimers with two pores. Here, we uncover an unanticipated monomeric configuration of TMEM63 proteins. Structures of TMEM63A and TMEM63B (referred to as TMEM63s) revealed a single highly restricted pore. Functional analyses demonstrated that TMEM63s are bona fide mechanosensitive ion channels, characterized by small conductance and high thresholds. TMEM63s possess evolutionary variations in the intracellular linker IL2, which mediates dimerization in OSCAs. Replacement of OSCA1.2 IL2 with TMEM63A IL2 or mutations to key variable residues resulted in monomeric OSCA1.2 and MA currents with significantly higher thresholds. Structural analyses revealed substantial conformational differences in the mechano-sensing domain IL2 and gating helix TM6 between TMEM63s and OSCA1.2. Our studies reveal that mechanosensitivity in OSCA/TMEM63 channels is affected by oligomerization and suggest gating mechanisms that may be shared by OSCA/TMEM63, TMEM16, and TMC channels., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Atmospheric deposition of particulate organic nitrogen (ON p ) is a significant process in the global nitrogen cycle and may be pivotally important for N-limited ecosystems. However, past models largely overlooked the spatial and chemical inhomogeneity of atmospheric ON p and were thus deficient in assessing global ON p impacts. We constructed a comprehensive global model of atmospheric gaseous and particulate organic nitrogen (ON), including the latest knowledge on emissions and secondary formations. Using this model, we simulated global atmospheric ON p abundances consistent with observations. Our estimated global atmospheric ON deposition was 26 Tg N yr -1 , predominantly in the form of ON p (23 Tg N yr -1 ) and mostly from wildfires (37%), oceans (22%) and aqueous productions (17%). Globally, ON p contributed as much as 40% to 80% of the total N deposition downwind of biomass-burning regions. Atmospheric ON p deposition thus constituted the dominant external N supply to the N-limited boreal forests, tundras and the Arctic Ocean, and its importance may be amplified in a future warming climate., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Although eukaryotic and long prokaryotic Argonaute proteins (pAgos) cleave nucleic acids, some short pAgos lack nuclease activity and hydrolyse NAD(P) + to induce bacterial cell death 1 . Here we present a hierarchical activation pathway for SPARTA, a short pAgo consisting of an Argonaute (Ago) protein and TIR-APAZ, an associated protein 2 . SPARTA progresses through distinct oligomeric forms, including a monomeric apo state, a monomeric RNA-DNA-bound state, two dimeric RNA-DNA-bound states and a tetrameric RNA-DNA-bound active state. These snapshots together identify oligomerization as a mechanistic principle of SPARTA activation. The RNA-DNA-binding channel of apo inactive SPARTA is occupied by an auto-inhibitory motif in TIR-APAZ. After the binding of RNA-DNA, SPARTA transitions from a monomer to a symmetric dimer and then an asymmetric dimer, in which two TIR domains interact through charge and shape complementarity. Next, two dimers assemble into a tetramer with a central TIR cluster responsible for hydrolysing NAD(P) + . In addition, we observe unique features of interactions between SPARTA and RNA-DNA, including competition between the DNA 3' end and the auto-inhibitory motif, interactions between the RNA G2 nucleotide and Ago, and splaying of the RNA-DNA duplex by two loops exclusive to short pAgos. Together, our findings provide a mechanistic basis for the activation of short pAgos, a large section of the Ago superfamily., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

As the main anthropogenic source in open seas and coastal areas, ship emissions impact the climate, air quality, and human health. The latest marine fuel regulation with a sulfur content limit of 0.5% went into effect globally on January 1, 2020. Investigations of ship emissions after fuel switching are necessary. In this study, online field measurements at an urban coastal site and modeling simulations were conducted to detect the impact of ship emissions on air quality in the Greater Bay Area (GBA) in China under new fuel regulation. By utilizing a high mass-resolution single particle mass spectrometer, the vanadium(V) signal was critically identified and was taken as a robust indicator for ship-emitted particles (with relative peak area > 0.1). The considerable number fractions of high-V particles (up to 30-40% during ship plumes) indicated that heavy fuel oils via simple desulfurization or blending processes with low-sulfur fuels were extensively used in the GBA to meet the global 0.5% sulfur cap. Our results showed that ship-emitted particulate matter and NO x contributed up to 21.4% and 39.5% to the ambient, respectively, in the summertime, significantly affecting the air quality in the GBA. The sea-land breeze circulation also played an important role in the transport pattern of ship-emitted pollutants in the GBA.

The Holliday junction (HJ) is a DNA intermediate of homologous recombination, involved in many fundamental physiological processes. RuvB, an ATPase motor protein, drives branch migration of the Holliday junction with a mechanism that had yet to be elucidated. Here we report two cryo-EM structures of RuvB, providing a comprehensive understanding of HJ branch migration. RuvB assembles into a spiral staircase, ring-like hexamer, encircling dsDNA. Four protomers of RuvB contact the DNA backbone with a translocation step size of 2 nucleotides. The variation of nucleotide-binding states in RuvB supports a sequential model for ATP hydrolysis and nucleotide recycling, which occur at separate, singular positions. RuvB's asymmetric assembly also explains the 6:4 stoichiometry between the RuvB/RuvA complex, which coordinates HJ migration in bacteria. Taken together, we provide a mechanistic understanding of HJ branch migration facilitated by RuvB, which may be universally shared by prokaryotic and eukaryotic organisms., (© 2023. The Author(s).)

The short-term reduction of air pollutant emissions is an important emergency control measure for avoiding air pollution exceedances in Chinese cities. However, the impacts of short-term emission reductions on the air qualities in southern Chinese cities in spring has not been fully explored. We analyzed the changes in air quality in Shenzhen, Guangdong before, during, and after a city-wide lockdown associated with COVID-19 control during March 14 to 20, 2022. Stable weather conditions prevailed before and during the lockdown, such that local air pollution was strongly affected by local emissions. In-situ measurements and WRF-GC simulations over the Pearl River Delta (PRD) both showed that, due to reductions in traffic emissions during the lockdown, the concentrations of nitrogen dioxide (NO 2 ), respirable particulate matter (PM 10 ), and fine particulate matters (PM 2.5 ) in Shenzhen decreased by (-26±9.5)%, (-28±6.4)%, and (-20±8.2)%, respectively. However, surface ozone (O 3 ) concentration did not change significantly[(-1.0±6.5)%]. TROPOMI satellite observations of formaldehyde and nitrogen dioxide column concentrations indicated that the ozone photochemistry in the PRD in spring 2022 was mainly controlled by the volatile organic compound (VOCs) concentrations and was not sensitive to the reduction in nitrogen oxide (NO x ) concentrations. Reduction in NO x may even have increased O 3, because the titration of O 3 by NO x was weakened. Due to the small spatial-temporal extent of emission reductions, the air quality effects caused by this short-term urban-scale lockdown were weaker than the air quality effects across China during the widespread COVID-19 lockdown in 2020. Future air quality management in South China cities should consider the impacts of NO x emission reduction on ozone and focus on the co-reduction scenarios of NO x and VOCs.

Retinal Müller glia function as injury-induced stem-like cells in zebrafish but not mammals. However, insights gleaned from zebrafish have been applied to stimulate nascent regenerative responses in the mammalian retina. For instance, microglia/macrophages regulate Müller glia stem cell activity in the chick, zebrafish, and mouse. We previously showed that post-injury immunosuppression by the glucocorticoid dexamethasone accelerated retinal regeneration kinetics in zebrafish. Similarly, microglia ablation enhances regenerative outcomes in the mouse retina. Targeted immunomodulation of microglia reactivity may therefore enhance the regenerative potential of Müller glia for therapeutic purposes. Here, we investigated potential mechanisms by which post-injury dexamethasone accelerates retinal regeneration kinetics, and the effects of dendrimer-based targeting of dexamethasone to reactive microglia. Intravital time-lapse imaging revealed that post-injury dexamethasone inhibited microglia reactivity. The dendrimer-conjugated formulation: (1) decreased dexamethasone-associated systemic toxicity, (2) targeted dexamethasone to reactive microglia, and (3) improved the regeneration enhancing effects of immunosuppression by increasing stem/progenitor proliferation rates. Lastly, we show that the gene rnf2 is required for the enhanced regeneration effect of D-Dex. These data support the use of dendrimer-based targeting of reactive immune cells to reduce toxicity and enhance the regeneration promoting effects of immunosuppressants in the retina., (© 2023. The Author(s).)

The ability to optically image cellular transmembrane voltages at millisecond-timescale resolutions can offer unprecedented insight into the function of living brains in behaving animals. Here, we present a point mutation that increases the sensitivity of Ace2 opsin-based voltage indicators. We use the mutation to develop Voltron2, an improved chemigeneic voltage indicator that has a 65% higher sensitivity to single APs and 3-fold higher sensitivity to subthreshold potentials than Voltron. Voltron2 retained the sub-millisecond kinetics and photostability of its predecessor, although with lower baseline fluorescence. In multiple in vitro and in vivo comparisons with its predecessor across multiple species, we found Voltron2 to be more sensitive to APs and subthreshold fluctuations. Finally, we used Voltron2 to study and evaluate the possible mechanisms of interneuron synchronization in the mouse hippocampus. Overall, we have discovered a generalizable mutation that significantly increases the sensitivity of Ace2 rhodopsin-based sensors, improving their voltage reporting capability., Competing Interests: Declaration of interests A.S.A., L.D.L., and E.R.S. have filed for a patent on the chemigenetic voltage indicators. I.K. and C.R.F. are co-inventors on a patent describing pipette cleaning that is licensed by Sensapex. M.C. and L.C. have performed consulting services for Sensapex., (Copyright © 2023 Elsevier Inc. All rights reserved.)

To create a functional neural circuit, neurons develop a molecular identity to discriminate self from non-self. The invertebrate Dscam family and vertebrate Pcdh family are implicated in determining synaptic specificity. Recently identified in Chelicerata, a shortened Dscam (sDscam) has been shown to resemble the isoform-generating characters of both Dscam and Pcdh and represent an evolutionary transition. Here we presented the molecular details of sDscam self-recognition via both trans and cis interactions using X-ray crystallographic data and functional assays. Based on our results, we proposed a molecular zipper model for the assemblies of sDscam to mediate cell-cell recognition. In this model, sDscam utilized FNIII domain to form side-by-side interactions with neighboring molecules in the same cell while established hand-in-hand interactions via Ig1 domain with molecules from another cell around. Together, our study provided a framework for understanding the assembly, recognition, and evolution of sDscam., (© 2023. The Author(s).)

Exosome is an excellent vesicle for in vivo delivery of therapeutics, including RNAi and chemical drugs. The extremely high efficiency in cancer regression can partly be attributed to its fusion mechanism in delivering therapeutics to cytosol without endosome trapping. However, being composed of a lipid-bilayer membrane without specific recognition capacity for aimed-cells, the entry into nonspecific cells can lead to potential side-effects and toxicity. Applying engineering approaches for targeting-capacity to deliver therapeutics to specific cells is desirable. Techniques with chemical modification in vitro and genetic engineering in cells have been reported to decorate exosomes with targeting ligands. RNA nanoparticles have been used to harbor tumor-specific ligands displayed on exosome surface. The negative charge reduces nonspecific binding to vital cells with negatively charged lipid-membrane due to the electrostatic repulsion, thus lowering the side-effect and toxicity. In this review, we focus on the uniqueness of RNA nanoparticles for exosome surface display of chemical ligands, small peptides or RNA aptamers, for specific cancer targeting to deliver anticancer therapeutics, highlighting recent advances in targeted delivery of siRNA and miRNA that overcomes the previous RNAi delivery roadblocks. Proper understanding of exosome engineering with RNA nanotechnology promises efficient therapies for a wide range of cancer subtypes., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

How does wiring specificity of neural maps emerge during development? Formation of the adult Drosophila olfactory glomerular map begins with the patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon- and adaptive optical lattice light-sheet microscope-based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps., Competing Interests: KW, TL, TF, GL, CL, SK, QX, DL, SU, EB, LL No competing interests declared, (© 2023, Wong et al.)