China's "coal-to-gas" policy had large impact on PM1.0 distribution during 2016-2019.

Particulate matter with an aerodynamic diameter of less than 1 µm (PM1.0) can be extremely hazardous to human health, so it is imperative to accurately estimate the spatial and temporal distribution of PM1.0 and analyze the impact of related policies on it. In this study, a stacking generalization model was trained based on aerosol optical depth (AOD) data from satellite observations, combined with related data affecting aerosol concentration such as meteorological data and geographic data. Using this model, the PM1.0 concentration distribution in China during 2016-2019 was estimated, and verified by comparison with ground-based stations. The coefficient of determination (R2) of the model is 0.94, and the root-mean-square error (RMSE) is 8.49 µg/m3, mean absolute error (MAE) is 4.10 µg/m3, proving that the model has a very high performance. Based on the model, this study analyzed the PM1.0 concentration changes during the heating period (November and December) in the regions where the "coal-to-gas" policy was implemented in China, and found that the proposed "coal-to-gas" policy did reduce the PM1.0 concentration in the implemented regions. However, the lack of natural gas due to the unreasonable deployment of the policy in the early stage caused the increase of PM1.0 concentration. This study can provide a reference for the next step of urban air pollution policy development.

Endothelium-Derived Engineered Extracellular Vesicles Protect the Pulmonary Endothelial Barrier in Acute Lung Injury.

Acute lung injury (ALI) is a severe respiratory disease with a high mortality rate. The integrity of the pulmonary endothelial barrier influences the development and prognosis of ALI. Therefore, it has become an important target for ALI treatment. Extracellular vesicles (EVs) are promising nanotherapeutic agents against ALI. Herein, endothelium-derived engineered extracellular vesicles (eEVs) that deliver microRNA-125b-5p (miRNA-125b) to lung tissues exerting a protective effect on endothelial barrier integrity are reported. eEVs that are modified with lung microvascular endothelial cell-targeting peptides (LET) exhibit a prolonged retention time in lung tissues and targeted lung microvascular endothelial cells in vivo and in vitro. To improve the efficacy of the EVs, miRNA-125b is loaded into EVs. Finally, LET-EVs-miRNA-125b is constructed. The results show that compared to the EVs, miRNA-125b, and EVs-miRNA-125b, LET-EVs-miRNA-125b exhibit the most significant treatment efficacy in ALI. Moreover, LET-EVs-miRNA-125b is found to have an important protective effect on endothelial barrier integrity by inhibiting cell apoptosis, promoting angiogenesis, and protecting intercellular junctions. Sequencing analysis reveals that LET-EVs-miRNA-125b downregulates early growth response-1 (EGR1) levels, which may be a potential mechanism of action. Taken together, these findings suggest that LET-EVs-miRNA-125b can treat ALI by protecting the endothelial barrier integrity.

In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design.

Mpox virus (MPXV), the most pathogenic zoonotic orthopoxvirus, caused worldwide concern during the SARS-CoV-2 epidemic. Growing evidence suggests that the MPXV surface protein A29 could be a specific diagnostic marker for immunological detection. In this study, a fully synthetic phage display library was screened, revealing two nanobodies (A1 and H8) that specifically recognize A29. Subsequently, an in vitro affinity maturation strategy based on computer-aided design was proposed by building and docking the A29 and A1 three-dimensional structures. Ligand-receptor binding and molecular dynamics simulations were performed to predict binding modes and key residues. Three mutant antibodies were predicted using the platform, increasing the affinity by approximately 10-fold compared with the parental form. These results will facilitate the application of computers in antibody optimization and reduce the cost of antibody development; moreover, the predicted antibodies provide a reference for establishing an immunological response against MPXV.

Computational and Experimental Confirmation of the Diradical Character of para-Quinonedimethide.

The ground-state structure of the parent para-quinonedimethide (p-QDM) molecule is generally represented in its closed shell form, i.e., as a cyclic, nonaromatic, through-conjugated/cross-conjugated hybrid comprising four C═C bonds. Nonetheless, p-QDM has been theorized to contain a contribution from its open-shell aromatic singlet diradical form. VBSCF calculations identify an open-shell contribution of 29% to the structure, while CASPT2(16,16)/def2-TZVP and ωB97XD/aug-cc-pVTZ calculations predict that dimerization proceeds along an open-shell singlet diradical pathway with a low (77 kJ/mol) barrier toward dimerization, which occurs by way of C-C bond formation between the exocyclic methylene carbons. A similar low (98 kJ/mol) barrier exists toward the reaction between a p-QDM molecule and the radical trap TEMPO. These predictions are verified experimentally through the isolation of bis-TEMPO-trapped p-QDM, its C-C coupled dimer, and by demonstrating that a mixture of p-QDM and TEMPO can initiate the radical polymerization of n-butyl acrylate at ambient temperature. In contrast to p-QDM, tetracyanoquinone (TCNQ) neither dimerizes nor reacts with TEMPO, despite having a similar diradical character to p-QDM. This lack of reactivity is consistent with both a higher kinetic barrier and a thermodynamically unfavorable process, which is ascribed to destabilizing steric clashes and polar effects.

HMSCs exosome-derived miR-199a-5p attenuates sulfur mustard-associated oxidative stress via the CAV1/NRF2 signalling pathway.

Sulfur mustard (SM) is a blister-producing chemical warfare agent which could lead to a cascade of systemic damage, especially severe acute lung injury. Oxidative stress is considered to be vital processes for the SM toxicity mechanism. We previously proved the therapeutic effect of exosomes derived from bone marrow mesenchymal stromal cells in promoting the repair of alveolar epithelial barrier and inhibiting apoptosis. However, the key functional components in exosomes and the underlying mechanisms have not been fully elaborated. This research shed light on the function of the key components of human umbilical cord mesenchymal stem cell-derived exosomes (HMSCs-Ex). We noted that HMSCs-Ex-derived miR-199a-5p played a vital role in reducing pneumonocyte oxidative stress and apoptosis by reducing reactive oxygen species, lipid peroxidation products and increasing the activities of antioxidant enzymes in BEAS-2B cells and mouse models after exposure to SM for 24 h. Furthermore, we demonstrated that the overexpression of miR-199a-5p in HMSCs-Ex treatment induced a further decrease of Caveolin1 and the activation of the mRNA and protein level of NRF2, HO1 and NQO1, compared with HMSCs-Ex administration. In summary, miR-199a-5p was one of the key molecules in HMSCs-Ex that attenuated SM-associated oxidative stress via regulating CAV1/NRF2 signalling pathway.

MiR-146a-5p delivered by hucMSC extracellular vesicles modulates the inflammatory response to sulfur mustard-induced acute lung injury.

BACKGROUND: Sulfur mustard (SM) is a highly toxic chemical warfare agent that has caused numerous casualties during wars and conflicts in the past century. Specific antidotes or therapeutic strategies are rare due to the complicated mechanism of toxicity, which still awaits elucidation. Clinical data show that acute lung injury (ALI) is responsible for most mortality and morbidity after SM exposure. Extracellular vesicles are natural materials that participate in intercellular communication by delivering various substances and can be modified. In this study, we aim to show that extracellular vesicles derived from human umbilical cord mesenchymal stromal cells (hucMSC-EVs) could exert therapeutic effects on SM-induced ALI, and to explain the underlying mechanism of effects. METHODS: MiR-146a-5p contained in hucMSC-EVs may be involved in the process of hucMSC-EVs modulating the inflammatory response to SM-induced ALI. We utilized miR-146a-5p delivered by extracellular vesicles and further modified hucMSCs with a miR-146a-5p mimic or inhibitor to collect miR-146a-5p-overexpressing extracellular vesicles (miR-146a-5p+-EVs) or miR-146a-5p-underexpressing extracellular vesicles (miR-146a-5p--EVs), respectively. Through in vivo and in vitro experiments, we investigated the mechanism. RESULTS: The effect of miR-146a-5p+-EVs on improving the inflammatory reaction tied to SM injury was better than that of hucMSC-EVs. We demonstrated that miR-146a-5p delivered by hucMSC-EVs targeted TRAF6 to negatively regulate inflammation in SM-induced ALI models in vitro and in vivo. CONCLUSION: In summary, miR-146a-5p delivered by hucMSC-EVs targeted TRAF6, causing hucMSC-EVs to exert anti-inflammatory effects in SM-induced ALI; thus, hucMSC-EVs treatment may be a promising clinical therapeutic after SM exposure.

Total Syntheses of the Structures Assigned to the Marine Natural Products Orthoscuticellines A-E.

The readily prepared and vinylated ß-carboline 11 has been converted over one or two steps into compounds 1-5, the structures assigned to the recently reported marine natural products orthoscuticellines A-E. The spectral data recorded on the synthetically derived compounds are fully consistent with the assigned structures and, on making allowances for variations in the pH of the medium in which the spectra of the natural products were recorded, it is concluded that the structures assigned to orthoscuticellines A-E are most likely correct. Certainly, the calculated 13C NMR spectra of the α-, γ-, and δ-carboline isomers of compounds 1-5 suggest that orthoscuticellines A-E do incorporate the assigned ß-carboline core.

Covalent-anion-driven self-assembled cadmium/ molybdenum sulfide hybrids for efficient nitenpyram degradation.

Photocatalytic technology is an attractive and promising approach for nitenpyram degradation; however, how to ensure the carrier separation efficiency and catalytic sites exposure is still great challenges. In this study, we construct CdS@MoS2 (CM) nanohybrids with a 3D hierarchical configuration to enhance the separation and transfer efficiency of the photo-induced electron by a covalent-anion-driven self-assembly method. The vertical orientation of MoS2 ultrathin nanosheets not only provides a large specific surface area for the oxidation and reduction reactions but also enables the active edge sites of MoS2 to be maximally exposed. As a result, this structure drastically facilitates the exposure of the catalytic active region and the performance of the carrier transfer and injection into photocatalytic degradation for nitenpyram (NTP). The optimal CdS-MoS2 has an impressive and stable NTP removal efficiency with a high reaction rate constant up to 0.078 min-1, which is 3.25 times higher than that of pure cadmium sulfide. The photocatalytic degradation mechanism and degradation pathway of NTP were presented by synthesizing the results of experimental analysis and density flooding theory (DFT) calculations. In further, for the first time, the cytotoxicity and genotoxicity of NTP on moving bed biofilm reactors (MBBRs) was disclosed and a continuous photocatalytic wastewater pretreatment device based on the CM is proposed for the stable biological nitrogen removal activity of MBBRs, which can degrade more than 80% NTP per hour.

Reversing RAFT Polymerization: Near-Quantitative Monomer Generation Via a Catalyst-Free Depolymerization Approach.

The ability to reverse controlled radical polymerization and regenerate the monomer would be highly beneficial for both fundamental research and applications, yet this has remained very challenging to achieve. Herein, we report a near-quantitative (up to 92%) and catalyst-free depolymerization of various linear, bulky, cross-linked, and functional polymethacrylates made by reversible addition-fragmentation chain-transfer (RAFT) polymerization. Key to our approach is to exploit the high end-group fidelity of RAFT polymers to generate chain-end radicals at 120 °C. These radicals trigger a rapid unzipping of both conventional (e.g., poly(methyl methacrylate)) and bulky (e.g., poly(oligo(ethylene glycol) methyl ether methacrylate)) polymers. Importantly, the depolymerization product can be utilized to either reconstruct the linear polymer or create an entirely new insoluble gel that can also be subjected to depolymerization. This work expands the potential of polymers made by controlled radical polymerization, pushes the boundaries of depolymerization, offers intriguing mechanistic aspects, and enables new applications.

Diradical Generation via Relayed Proton-Coupled Electron Transfer.

Diradical generation followed by radical-radical cross-coupling is a powerful synthetic tool, but its detailed mechanism has yet to be established. Herein, we proposed and confirmed a new model named relayed proton-coupled electron transfer (relayed-PCET) for diradical generation, which could open a door for new radical-radical cross-coupling reactions. Quantum mechanics calculations were performed on a selected carbene-mediated diradical cross-coupling reaction model and a designed model, and the exact electronic structural changes during the radical processes have been observed for the first time.

BH9, a New Comprehensive Benchmark Data Set for Barrier Heights and Reaction Energies: Assessment of Density Functional Approximations and Basis Set Incompleteness Potentials.

The calculation of accurate reaction energies and barrier heights is essential in computational studies of reaction mechanisms and thermochemistry. To assess methods regarding their ability to predict these two properties, high-quality benchmark sets are required that comprise a reasonably large and diverse set of organic reactions. Due to the time-consuming nature of both locating transition states and computing accurate reference energies for reactions involving large molecules, previous benchmark sets have been limited in scope, the number of reactions considered, and the size of the reactant and product molecules. Recent advances in coupled-cluster theory, in particular local correlation methods like DLPNO-CCSD(T), now allow the calculation of reaction energies and barrier heights for relatively large systems. In this work, we present a comprehensive and diverse benchmark set of barrier heights and reaction energies based on DLPNO-CCSD(T)/CBS called BH9. BH9 comprises 449 chemical reactions belonging to nine types common in organic chemistry and biochemistry. We examine the accuracy of DLPNO-CCSD(T) vis-a-vis canonical CCSD(T) for a subset of BH9 and conclude that, although there is a penalty in using the DLPNO approximation, the reference data are accurate enough to serve as a benchmark for density functional theory (DFT) methods. We then present two applications of the BH9 set. First, we examine the performance of several density functional approximations commonly used in thermochemical and mechanistic studies. Second, we assess our basis set incompleteness potentials regarding their ability to mitigate basis set incompleteness errors. The number of data points, the diversity of the reactions considered, and the relatively large size of the reactant molecules make BH9 the most comprehensive thermochemical benchmark set to date and a useful tool for the development and assessment of computational methods.

Electrostatic effects in N-heterocyclic carbene catalysis: revealing the nature of catalysed decarboxylation.

Quantum chemistry is used to investigate the nature of protonated N-heterocyclic carbene (NHC·H+) catalysed decarboxylation recently reported by Zhang et al. (ACS Catal., 2021, 11, 3443-3454). Our results show that there are strong electrostatic effects within the NHC·H+ catalysed decarboxylation, and these dominate hydrogen bonding. At the same time, energy decomposition analyses and comparison between the original NHC·H+ catalyst and a truncated form reveal that stabilizing dispersion interactions are also critical, as is induction. We also show that the electrostatic effects and their associated catalytic effects can be further enhanced using charged functional groups.

Structure-function relationships in aryl diazirines reveal optimal design features to maximize C-H insertion.

Diazirine reagents allow for the ready generation of carbenes upon photochemical, thermal, or electrical stimulation. Because carbenes formed in this way can undergo rapid insertion into any nearby C-H, O-H or N-H bond, molecules that encode diazirine functions have emerged as privileged tools in applications ranging from biological target identification and proteomics through to polymer crosslinking and adhesion. Here we use a combination of experimental and computational methods to complete the first comprehensive survey of diazirine structure-function relationships, with a particular focus on thermal activation methods. We reveal a striking ability to vary the activation energy and activation temperature of aryl diazirines through the rational manipulation of electronic properties. Significantly, we show that electron-rich diazirines have greatly enhanced efficacy toward C-H insertion, under both thermal and photochemical activation conditions. We expect these results to lead to significant improvements in diazirine-based chemical probes and polymer crosslinkers.

Flexible polyfluorinated bis-diazirines as molecular adhesives.

Motivated by a desire to develop flexible covalent adhesives that afford some of the same malleability in the adhesive layer as traditional polymer-based adhesives, we designed and synthesized two flexible, highly fluorinated bis-diazirines. Both molecules are shown to function as effective crosslinkers for polymer materials, and to act as strong adhesives when painted between two polymer objects of low surface energy, prior to thermal activation. Data obtained from lap-shear experiments suggests that greater molecular flexibility is correlated with improved mechanical compliance in the adhesive layer.

BMSC-derived exosomes ameliorate sulfur mustard-induced acute lung injury by regulating the GPRC5A-YAP axis.

Sulfur mustard (SM) is a highly toxic chemical warfare agent that causes acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). There are no effective therapeutic treatments or antidotes available currently to counteract its toxic effects. Our previous study shows that bone marrow-derived mesenchymal stromal cells (BMSCs) could exert therapeutic effects against SM-induced lung injury. In this study, we explored the therapeutic potential of BMSC-derived exosomes (BMSC-Exs) against ALI and the underlying mechanisms. ALI was induced in mice by injection of SM (30 mg/kg, sc) at their medial and dorsal surfaces. BMSC-Exs (20 µg/kg in 200 µL PBS, iv) were injected for a 5-day period after SM exposure. We showed that BMSC-Exs administration caused a protective effect against pulmonary edema. Using a lung epithelial cell barrier model, BMSC-Exs (10, 20, 40 µg) dose-dependently inhibited SM-induced cell apoptosis and promoted the recovery of epithelial barrier function by facilitating the expression and relocalization of junction proteins (E-cadherin, claudin-1, occludin, and ZO-1). We further demonstrated that BMSC-Exs protected against apoptosis and promoted the restoration of barrier function against SM through upregulating G protein-coupled receptor family C group 5 type A (GPRC5A), a retinoic acid target gene predominately expressed in the epithelial cells of the lung. Knockdown of GPRC5A reduced the antiapoptotic and barrier regeneration abilities of BMSC-Exs and diminished their therapeutic effects in vitro and in vivo. BMSC-Exs-caused upregulation of GPRC5A promoted the expression of Bcl-2 and junction proteins via regulating the YAP pathway. In summary, BMSC-Exs treatment exerts protective effects against SM-induced ALI by promoting alveolar epithelial barrier repair and may be an alternative approach to stem cell-based therapy.

Two birds with one stone: The detection of nerve agents and AChE activity with an ICT-ESIPT-based fluorescence sensor.

Nerve agents are among the world's deadliest poisons, and the target enzyme is acetylcholinesterase (AChE). To better diagnosis nerve agent poisonings, a reliable diagnostic method for both nerve agents and AChE is desirable. Herein, we synthesized a series of fluorescent sensors for both real nerve agents and acetylcholinesterase activity detection. Among these sensors, HBQ-AE exhibited a fast response rate (within 10 s for nerve agent and 8 min for AChE), good sensitivity (the limit of detection is 6 nM and 0.2 U/mL) and a high off/on contrast. To the best of our knowledge, HBQ-AE is the first fluorescence sensor for nerve agents and AChE activity detection. The fluorescent change of HBQ-AE from nonfluorescence to blue fluorescence (nerve agent) or orange fluorescence (AChE) by excitation at 365 nm can be easily observed with the naked eye. HBQ-AE was successfully applied to image nerve agents and AChE activity in living cells. Moreover, HBQ-AE is the vital member to construct a test paper that can be employed to detect and diagnose chemical warfare agents.

Response of major air pollutants to COVID-19 lockdowns in China.

COVID-19 suddenly struck Wuhan at the end of 2019 and soon spread to the whole country and the rest of world in 2020. To mitigate the pandemic, China authority has taken unprecedentedly strict measures across the country. That provides a precious window to study how the air quality response to quick decline of anthropogenic emissions in terms of national scale, which would be critical basis to make atmospheric governance policies in the future. In this work, we utilized observations from both remote sensing and in-situ measurements to investigate impacts of COVID-19 lockdown on different air pollutions in different regions of China. It is witnessed that the PM2.5 concentrations exhibited distinct trends in different regions, despite of plunges of NO2 concentrations over the whole country. The steady HCHO concentration in urban area provides sufficient fuels for generations of tropospheric O3, leading to high concentrations of O3, especially when there is not enough NO to consume O3 via the titration effect. Moreover, the SO2 concentration kept steady at a low level regardless of cities. As a conclusion, the COVID-19 lockdown indeed helped reduce NO2 concentration. However, the atmospheric quality in urban areas of China has not improved overall due to lockdown measures. It underscores the significance of comprehensive control of atmospheric pollutants in cleaning air. Reducing VOCs (volatile organic compounds) concentrations in urban areas would be a critical mission for better air quality in the future.

Research Progress in Rare Earth-Doped Perovskite Manganite Oxide Nanostructures.

Perovskite manganites exhibit a broad range of structural, electronic, and magnetic properties, which are widely investigated since the discovery of the colossal magnetoresistance effect in 1994. As compared to the parent perovskite manganite oxides, rare earth-doped perovskite manganite oxides with a chemical composition of LnxA1-xMnO3 (where Ln represents rare earth metal elements such as La, Pr, Nd, A is divalent alkaline earth metal elements such as Ca, Sr, Ba) exhibit much diverse electrical properties due to that the rare earth doping leads to a change of valence states of manganese which plays a core role in the transport properties. There is not only the technological importance but also the need to understand the fundamental mechanisms behind the unusual magnetic and transport properties that attract enormous attention. Nowadays, with the rapid development of electronic devices toward integration and miniaturization, the feature sizes of the microelectronic devices based on rare earth-doped perovskite manganite are down-scaled into nanoscale dimensions. At nanoscale, various finite size effects in rare earth-doped perovskite manganite oxide nanostructures will lead to more interesting novel properties of this system. In recent years, much progress has been achieved on the rare earth-doped perovskite manganite oxide nanostructures after considerable experimental and theoretical efforts. This paper gives an overview of the state of art in the studies on the fabrication, structural characterization, physical properties, and functional applications of rare earth-doped perovskite manganite oxide nanostructures. Our review first starts with the short introduction of the research histories and the remarkable discoveries in the rare earth-doped perovskite manganites. In the second part, different methods for fabricating rare earth-doped perovskite manganite oxide nanostructures are summarized. Next, structural characterization and multifunctional properties of the rare earth-doped perovskite manganite oxide nanostructures are in-depth reviewed. In the following, potential applications of rare earth-doped perovskite manganite oxide nanostructures in the fields of magnetic memory devices and magnetic sensors, spintronic devices, solid oxide fuel cells, magnetic refrigeration, biomedicine, and catalysts are highlighted. Finally, this review concludes with some perspectives and challenges for the future researches of rare earth-doped perovskite manganite oxide nanostructures.

Structural Characterizations and Dielectric Properties of Sphere- and Rod-Like PbTiO3 Powders Synthesized via Molten Salt Synthesis.

By reaction of PbC2O4 and TiO2 in the eutectic NaCl-KCl salts, both sphere- and rod-like PbTiO3 (PTO) powders were synthesized via molten salt synthesis (MSS) and template MSS methods, respectively. X-ray diffraction patterns reveal that all the PTO powders crystallize in a tetragonal phase structure. Increasing the molar ratio of PbC2O4:TiO2:NaCl:KCl from 1:1:10:10 to 1:1:60:60 in the MSS process has little effect on the sphere-like morphology of the PTO powders synthesized at 950 °C for 5 h. Large-scale polycrystalline rod-like PTO powders with diameters of 480 nm-1.50 µm and lengths up to 10 µm were synthesized at 800 °C for 5 h by template MSS method, where the rod-like anatase TiO2 precursors were used as templates and the molar ratio of PbC2O4:TiO2:NaCl:KCl was equal to 1:1:60:60. X-ray energy dispersive spectroscopy spectra reveal that all the PTO powders are composed of Pb, Ti, and O elements, and the measured Pb:Ti atomic ratios are close to 1:1. In the template MSS process, the molten salt content plays an important role in forming the rod-like PTO powders. Under low molten salt content, the rod-like PTO powders cannot be synthesized even if the rod-like TiO2 templates are used. In addition, prolonging the reaction time suppressed the formation of rod-like PTO powders but promoted the formation of sphere-like PTO nanoparticles. The dielectric properties the sphere- and rod-like PTO powders were comparatively investigated. At room temperature, the dielectric constant and dielectric loss of the spherical PTO powders synthesized by MSS method with the molar ratio of PbC2O4:TiO2:NaCl:KCl equal to 1:1:30:30 were ~ 340 and 0.06 (measured at 106 Hz), respectively. The corresponding values for the rod-like PTO powders synthesized by template MSS method with the molar ratio of PbC2O4:TiO2:NaCl:KCl equal to 1:1:60:60 were 140 and 0.08, respectively. The present results demonstrate the sphere-like PTO powders have better dielectric properties, which have promising applications in the fields of multilayer capacitors and resonators.