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1.
Mol Cell ; 83(21): 3885-3903.e5, 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37832545

RESUMEN

The translocation of stimulator of interferon genes (STING) from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC) enables its activation. However, the mechanism underlying the regulation of STING exit from the ER remains elusive. Here, we found that STING induces the activation of transforming growth factor beta-activated kinase 1 (TAK1) prior to STING trafficking in a TAK1 binding protein 1 (TAB1)-dependent manner. Intriguingly, activated TAK1 directly mediates STING phosphorylation on serine 355, which facilitates its interaction with STING ER exit protein (STEEP) and thereby promotes its oligomerization and translocation to the ERGIC for subsequent activation. Importantly, activation of TAK1 by monophosphoryl lipid A, a TLR4 agonist, boosts cGAMP-induced antitumor immunity dependent on STING phosphorylation in a mouse allograft tumor model. Taken together, TAK1 was identified as a checkpoint for STING activation by promoting its trafficking, providing a basis for combinatory tumor immunotherapy and intervention in STING-related diseases.


Asunto(s)
Neoplasias , Animales , Ratones , Fosforilación
2.
Nature ; 595(7869): 718-723, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34082438

RESUMEN

Resistance represents a major challenge for antibody-based therapy for COVID-191-4. Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by immunoglobulin G (IgG)-based therapeutics. IgM-14 is over 230-fold more potent than its parental IgG-14 in neutralizing SARS-CoV-2. IgM-14 potently neutralizes the resistant virus raised by its corresponding IgG-14, three variants of concern-B.1.1.7 (Alpha, which first emerged in the UK), P.1 (Gamma, which first emerged in Brazil) and B.1.351 (Beta, which first emerged in South Africa)-and 21 other receptor-binding domain mutants, many of which are resistant to the IgG antibodies that have been authorized for emergency use. Although engineering IgG into IgM enhances antibody potency in general, selection of an optimal epitope is critical for identifying the most effective IgM that can overcome resistance. In mice, a single intranasal dose of IgM-14 at 0.044 mg per kg body weight confers prophylactic efficacy and a single dose at 0.4 mg per kg confers therapeutic efficacy against SARS-CoV-2. IgM-14, but not IgG-14, also confers potent therapeutic protection against the P.1 and B.1.351 variants. IgM-14 exhibits desirable pharmacokinetics and safety profiles when administered intranasally in rodents. Our results show that intranasal administration of an engineered IgM can improve efficacy, reduce resistance and simplify the prophylactic and therapeutic treatment of COVID-19.


Asunto(s)
COVID-19/prevención & control , COVID-19/virología , Inmunoglobulina M/administración & dosificación , Inmunoglobulina M/inmunología , SARS-CoV-2/clasificación , SARS-CoV-2/inmunología , Administración Intranasal , Enzima Convertidora de Angiotensina 2/antagonistas & inhibidores , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Neutralizantes/efectos adversos , Anticuerpos Neutralizantes/genética , Anticuerpos Neutralizantes/inmunología , Proteínas Reguladoras de la Apoptosis/química , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/inmunología , Proteínas Reguladoras de la Apoptosis/metabolismo , COVID-19/inmunología , Relación Dosis-Respuesta Inmunológica , Femenino , Humanos , Inmunoglobulina A/genética , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/efectos adversos , Inmunoglobulina M/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Ingeniería de Proteínas , Receptores Virales/antagonistas & inhibidores , Receptores Virales/metabolismo , SARS-CoV-2/genética , Tratamiento Farmacológico de COVID-19
3.
Proc Natl Acad Sci U S A ; 120(19): e2217887120, 2023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-37126704

RESUMEN

Treatment of HIV-1ADA-infected CD34+ NSG-humanized mice with long-acting ester prodrugs of cabotegravir, lamivudine, and abacavir in combination with native rilpivirine was followed by dual CRISPR-Cas9 C-C chemokine receptor type five (CCR5) and HIV-1 proviral DNA gene editing. This led to sequential viral suppression, restoration of absolute human CD4+ T cell numbers, then elimination of replication-competent virus in 58% of infected mice. Dual CRISPR therapies enabled the excision of integrated proviral DNA in infected human cells contained within live infected animals. Highly sensitive nucleic acid nested and droplet digital PCR, RNAscope, and viral outgrowth assays affirmed viral elimination. HIV-1 was not detected in the blood, spleen, lung, kidney, liver, gut, bone marrow, and brain of virus-free animals. Progeny virus from adoptively transferred and CRISPR-treated virus-free mice was neither detected nor recovered. Residual HIV-1 DNA fragments were easily seen in untreated and viral-rebounded animals. No evidence of off-target toxicities was recorded in any of the treated animals. Importantly, the dual CRISPR therapy demonstrated statistically significant improvements in HIV-1 cure percentages compared to single treatments. Taken together, these observations underscore a pivotal role of combinatorial CRISPR gene editing in achieving the elimination of HIV-1 infection.


Asunto(s)
Infecciones por VIH , Seropositividad para VIH , Ratones , Animales , Humanos , Antirretrovirales/uso terapéutico , Edición Génica , Provirus/genética , Receptores CCR5
4.
J Am Chem Soc ; 146(12): 8206-8215, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38412246

RESUMEN

Spin-crossover (SCO) materials exhibit remarkable potential as bistable switches in molecular devices. However, the spin transition temperatures (Tc) of known compounds are unable to cover the entire ambient temperature spectrum, largely limiting their practical utility. This study reports an exemplary two-dimensional SCO solid solution system, [FeIII(H0.5LCl)2-2x(H0.5LF)2x]·H2O (H0.5LX = 5-X-2-hydroxybenzylidene-hydrazinecarbothioamide, X = F or Cl, x = 0 to 1), in which the adjacent layers are adhered via hydrogen bonding. Notably, the Tc of this system can be fine-tuned across 90 K (227-316 K) in a linear manner by modulating the fraction x of the LF ligand. Elevating x results in strengthened hydrogen bonding between adjacent layers, which leads to enhanced intermolecular interactions between adjacent SCO molecules. Single-crystal diffraction analysis and periodic density functional theory calculations revealed that such a special kind of alteration in interlayer interactions strengthens the FeIIIN2O2S2 ligand field and corresponding SCO energy barrier, consequently resulting in increased Tc. This work provides a new pathway for tuning the Tc of SCO materials through delicate manipulation of molecular interactions, which could expand the application of bistable molecular solids to a much wider temperature regime.

5.
Biochem Biophys Res Commun ; 719: 150027, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38749089

RESUMEN

Aging is a complex, degenerative process associated with various metabolic abnormalities. Ginsenosides (GS) is the main active components of Panax ginseng, which has anti-aging effects and improves metabolism. However, the anti-aging effect and the mechanism of GS in middle-aged mice has not been elucidated. In this study, GS after 3-month treatment significantly improved the grip strength, fatigue resistance, cognitive indices, and cardiac function of 15-month-old mice. Meanwhile, GS treatment reduced the fat content and obviously inhibited histone H2AX phosphorylation at Ser 139 (γ-H2AX), a marker of DNA damage in major organs, especially in the heart and liver. Further, the correlation analysis of serum metabolomics combined with aging phenotype suggested that myo-inositol (MI) upregulated by GS was positively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), the main indicators of cardiac function. More importantly, liver tissue metabolomic analysis showed that GS increased MI content by promoting the synthesis pathway from phosphatidylcholine (PC) to MI for the inhibition of liver aging. Finally, we proved that MI reduced the percentage of senescence-associated ß-galactosidase staining, γ-H2AX immunofluorescence staining, p21 expression, and the production of reactive oxygen species in H2O2-induced cardiomyocytes. These results suggest that GS can enhance multiple organ functions, especially cardiac function for promoting the healthspan of aging mice, which is mediated by the conversion of PC to MI in the liver and the increase of MI level in the serum. Our study might provide new insights into the potential mechanisms of ginsenosides for prolonging the healthspan of natural aging mice.


Asunto(s)
Envejecimiento , Ginsenósidos , Inositol , Metabolómica , Panax , Fosfatidilcolinas , Animales , Panax/química , Ginsenósidos/farmacología , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Fosfatidilcolinas/metabolismo , Ratones , Masculino , Inositol/farmacología , Hígado/metabolismo , Hígado/efectos de los fármacos , Ratones Endogámicos C57BL
6.
Small ; : e2402557, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38845022

RESUMEN

Perovskite materials, particularly FAPbI3, have emerged as promising candidates for solar energy conversion applications. However, these materials are plagued by well-known defects and suboptimal film quality. Enhancing crystallinity and minimizing defect density are therefore essential steps in the development of high-performance perovskite solar cells. In this study, 1H-Pyrazole-1-carboximidamide hydrochloride (PCH) is introduced into FAPbI3 perovskite films. The molecular structure of PCH features a pyrazole ring bonded to formamidine (FA). The FA moiety of PCH facilitated the incorporation of this additive into the film lattice, while the negatively charged pyrazole ring effectively passivated positively charged iodine vacancies. The presence of PCH led to the fabrication of an FAPbI3 device with improved crystallinity, a smoother surface, and reduced defect density, resulting in enhanced Voc and fill factor. A record power conversion efficiency of 24.62% is achieved, along with exceptional stability under prolonged air exposure and thermal stress. The findings highlight the efficacy of PCH as a novel additive for the development of high-performance perovskite solar cells.

7.
Small ; : e2405071, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39221666

RESUMEN

Design of hypotoxic lead-free perovskites, e.g. Bismuth(Bi)-based perovskites, is much beneficial for commercialization of perovskite X-ray detectors due to their strong radiation absorption. Nevertheless, the design principles governing the selection of A-site cations for achieving high-performance X-ray detectors remain elusive. Here, seven molecules (methylamine MA, amine NH3, dimethylbiguanide DGA, phenylethylamine PEA, 4-fluorophenethylamine p-FPEA, 1,3-propanediamine PDA, and 1,4-butanediamine BDA) and calculated their dipole moments and interaction strength with metal halide (BiI3) are selected. The first-principles calculations and related spectroscopy measurements confirm that organic molecules (DGA) with large dipole moments can have strong interactions with perovskite octahedron and improve the carrier transport between the organic and inorganic clusters. Consequently, zero-dimensional single crystal (SC) (DGA)BiI5∙H2O is synthesized. The (DGA)BiI5∙H2O SCs demonstrate an exceptional carrier mobility-lifetime product of 6.55 × 10-3 cm2 V-1, resulting in the high sensitivity of 5879.4 µCGyair -1cm-2, featuring a low detection limit (4.7 nGyair s-1) and remarkable X-ray irradiation stability even after 100 days of aging at a high electric field (100 V mm-1). Furthermore, the (DGA)BiI5∙H2O SCs for imaging, achieving a notable spatial resolution of 5.5 lp mm-1 are applied. This investigation establishes a pathway for systematically screening A-site cations to design low-dimensional SCs for high-performance X-ray detection.

8.
Appl Environ Microbiol ; 90(5): e0004624, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38563787

RESUMEN

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.


Asunto(s)
Alginatos , Microbioma Gastrointestinal , Oligosacáridos , Alginatos/metabolismo , Oligosacáridos/metabolismo , Ratones , Animales , Humanos , Colitis/microbiología , Colitis/inducido químicamente , Ratones Endogámicos C57BL , Ácidos Grasos Volátiles/metabolismo , Inflamación/metabolismo , Sulfato de Dextran , Fibras de la Dieta/metabolismo
9.
J Exp Bot ; 75(1): 168-179, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37798132

RESUMEN

Submergence is a major constraint on rice production in South and Southeast Asia. In this study, we determined that a gene of the Sub1A-binding protein family, SAB23, encodes a plant homeodomain (PHD)-type transcription factor that has a novel function of negatively regulating submergence tolerance in rice. The T-DNA insertion mutant sab23 displayed reduced plant height, delayed seed maturation, and lower percentage seed set. Importantly, this mutant also exhibited enhanced submergence tolerance. In addition, CRISPR/Cas9 knock out of SAB23 resulted in a significant reduction in the content of the gibberellin GA4 and a dramatic increase in the content of GA1 in the plants. SAB23 binds to the promoter of CYTOCHROME P450 714B2 (CYP714B2), which encodes a GA13-oxidase that catalyses the conversion of GA53 to GA19. Disruption of SAB23 function led to increased CYP714B2 transcription, and overexpression of CYP714B2 produced phenotypes similar to those of the SAB23-knockout plants. Taken together, our results reveal that SAB23 negatively regulates rice submergence tolerance by modulating CYP714B2 expression, which has significant potential for use in future breeding.


Asunto(s)
Oryza , Factores de Transcripción , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fitomejoramiento , Sistema Enzimático del Citocromo P-450/metabolismo , Mutación
10.
BMC Cancer ; 24(1): 124, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267866

RESUMEN

HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.


Asunto(s)
Biosimilares Farmacéuticos , Linfoma de Células B Grandes Difuso , Humanos , Biosimilares Farmacéuticos/efectos adversos , Rituximab/efectos adversos , Estudios de Seguimiento , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Ciclofosfamida/efectos adversos , Doxorrubicina , Prednisona/efectos adversos
11.
Ann Hematol ; 103(8): 3061-3069, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38805037

RESUMEN

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .


Asunto(s)
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/mortalidad , Linfoma de Células T Periférico/tratamiento farmacológico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Aminopiridinas/uso terapéutico , Benzamidas/uso terapéutico , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , China/epidemiología , Trasplante Autólogo , Anciano , Tasa de Supervivencia , Adulto Joven , Quimioterapia de Mantención , Autoinjertos , Inducción de Remisión , Adolescente
12.
EMBO Rep ; 23(6): e53932, 2022 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-35403787

RESUMEN

Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases.


Asunto(s)
Enfermedades Autoinmunes , Neoplasias , Animales , Enfermedades Autoinmunes/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Neoplasias/metabolismo , Piperazinas/farmacología , Piridinas/farmacología , Piridinas/uso terapéutico
13.
J Org Chem ; 89(7): 4349-4365, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38497642

RESUMEN

The 5-fluoroalkyl-1,2,3-triazoles, serving as a pivotal element in medicinal chemistry, hold substantial research significance. In this work, we developed a furan dearomatization reaction for the synthesis of various 5-fluoroalkyl-1,2,3-triazoles, which contains -CF3, -CF2H, -CF2CF3, -CF2CF2CF3, -CF2CO2Et, and -C6F5. This methodology relies on the intermolecular [3 + 2] cycloaddition/furan ring-opening triggered by α-fluoroalkyl furfuryl cation with azides to stereoselectively synthesize a series of (E)-fluoroalkyl enone triazoles. The reaction proceeds without metal participation, exhibits excellent substrate tolerance, and has excellent synthetic utility.

14.
Inorg Chem ; 63(37): 17298-17304, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39238210

RESUMEN

Adsorptive ethylene separation from the C2H2/C2H4/C2H6/CO2 four-component gas mixture provides a low-energy input solution for industrial ethylene purification, yet it is still a great challenge. Herein, we report a facile scaled-up synthesis of a stable ultramicroporous coordination network of Zn-CO3-datz (Hdatz = 3,5-diamine-1,2,4-triazole), which enables selective adsorption of C2H2, C2H4 and CO2 over C2H4, thanks to its specific pore environment supported by GCMC simulation of gas adsorption sites. Dynamic breakthrough experiments exhibited efficient one-step production of polymer-grade (≥99.95%) C2H4 from the quaternary C2H4/C2H2/C2H6/CO2 (1/1/1/1) mixture, with excellent C2H4 productivity of 0.12 mol kg-1 at 298 K. Moreover, it can be easily synthesized in kilogram scale with an affordable and low-cost ligand, rendering its further potential industrial applications.

15.
Environ Sci Technol ; 58(19): 8326-8335, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38696616

RESUMEN

China, especially the densely populated North China region, experienced severe haze events in the past decade that concerned the public. Although the most extreme cases have been largely eliminated through recent mitigation measures, severe outdoor air pollution persists and its environmental impact needs to be understood. Severe indoor pollution draws less public attention due to the short visible distance indoors, but its public health impacts cannot be ignored. Herein, we assess the trends and impacts of severe outdoor and indoor air pollution in North China from 2014 to 2021. Our results demonstrate the uneven contribution of severe hazy days to ambient and exposure concentrations of particulate matter with an aerodynamic diameter <2.5 (PM2.5). Although severe indoor pollution contributes to indoor PM2.5 concentrations (23%) to a similar extent as severe haze contributes to ambient PM2.5 concentrations (21%), the former's contribution to premature deaths was significantly higher. Furthermore, residential emissions contributed more in the higher PM2.5 concentration range both indoors and outdoors. Notably, severe haze had greater health impacts on urban residents, while severe indoor pollution was more impactful in rural areas. Our findings suggest that, besides reducing severe haze, mitigating severe indoor pollution is an important aspect of combating air pollution, especially toward improving public health.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Monitoreo del Ambiente , Material Particulado , China , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire , Humanos
16.
Environ Sci Technol ; 58(37): 16517-16524, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39231580

RESUMEN

Aerosol acidity (or pH) is one central parameter in determining the health, climate, and ecological effects of aerosols. While it is traditionally assumed that the long-term aerosol pH levels are determined by the relative abundances of atmospheric alkaline to acidic substances (referred to as RC/A hereinafter), we observed contrasting pH─RC/A trends at different sites globally, i.e., rising alkali-to-acid ratios in the atmosphere may unexpectedly lead to increased aerosol acidity. Here, we examined this apparently counterintuitive phenomenon using the multiphase buffer theory. We show that the aerosol water content (AWC) set a pH "baseline" as the peak buffer pH, while the RC/A and particle-phase chemical compositions determine the deviation of pH from this baseline within the buffer ranges. Therefore, contrasting long-term pH trends may emerge when RC/A increases while the AWC or nitrate fraction decreases, or vice versa. Our results provided a theoretical framework for a quantitative understanding of the response of aerosol pH to variations in SO2, NOx versus NH3, and dust emissions, offering broad applications in studies on aerosol pH and the associated environmental and health effects.


Asunto(s)
Aerosoles , Atmósfera , Atmósfera/química , Concentración de Iones de Hidrógeno , Álcalis/química , Ácidos/química , Contaminantes Atmosféricos/análisis
17.
Environ Sci Technol ; 58(22): 9548-9558, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38778038

RESUMEN

Agricultural applications of nanotechnologies necessitate addressing safety concerns associated with nanopesticides, yet research has not adequately elucidated potential environmental risks between nanopesticides and their conventional counterparts. To address this gap, we investigated the risk of nanopesticides by comparing the ecotoxicity of nanoencapsulated imidacloprid (nano-IMI) with its active ingredient to nontarget freshwater organisms (embryonic Danio rerio, Daphnia magna, and Chironomus kiinensis). Nano-IMI elicited approximately 5 times higher toxicity than IMI to zebrafish embryos with and without chorion, while no significant difference was observed between the two invertebrates. Toxicokinetics further explained the differential toxicity patterns of the two IMI analogues. One-compartmental two-phase toxicokinetic modeling showed that nano-IMI exhibited significantly slower elimination and subsequently higher bioaccumulation potential than IMI in zebrafish embryos (dechorinated), while no disparity in toxicokinetics was observed between nano-IMI and IMI in D. magna and C. kiinensis. A two-compartmental toxicokinetic model successfully simulated the slow elimination of IMI from C. kiinensis and confirmed that both analogues of IMI reached toxicologically relevant targets at similar levels. Although nanopesticides exhibit comparable or elevated toxicity, future work is of utmost importance to properly understand the life cycle risks from production to end-of-life exposures, which helps establish optimal management measures before their widespread applications.


Asunto(s)
Agua Dulce , Toxicocinética , Pez Cebra , Animales , Agua Dulce/química , Contaminantes Químicos del Agua/toxicidad , Daphnia/efectos de los fármacos , Neonicotinoides/toxicidad
18.
Environ Sci Technol ; 58(18): 7904-7915, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38661303

RESUMEN

Nitrogen dioxide (NO2) hydrolysis in deliquesced aerosol particles forms nitrous acid and nitrate and thus impacts air quality, climate, and the nitrogen cycle. Traditionally, it is considered to proceed far too slowly in the atmosphere. However, the significance of this process is highly uncertain because kinetic studies have only been made in dilute aqueous solutions but not under high ionic strength conditions of the aerosol particles. Here, we use laboratory experiments, air quality models, and field measurements to examine the effect of the ionic strength on the reaction kinetics of NO2 hydrolysis. We find that high ionic strengths (I) enhance the reaction rate constants (kI) by more than an order of magnitude compared to that at infinite dilution (kI=0), yielding log10(kI/kI=0) = 0.04I or rate enhancement factor = 100.04I. A state-of-the-art air quality model shows that the enhanced NO2 hydrolysis reduces the negative bias in the simulated concentrations of nitrous acid by 28% on average when compared to field observations over the North China Plain. Rapid NO2 hydrolysis also enhances the levels of nitrous acid in other polluted regions such as North India and further promotes atmospheric oxidation capacity. This study highlights the need to evaluate various reaction kinetics of atmospheric aerosols with high ionic strengths.


Asunto(s)
Aerosoles , Aerosoles/química , Hidrólisis , Concentración Osmolar , Dióxido de Nitrógeno/química , Cinética , Atmósfera/química , Contaminantes Atmosféricos/química
19.
Environ Sci Technol ; 58(21): 9227-9235, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38751196

RESUMEN

Severe ozone (O3) pollution has been a major air quality issue and affects environmental sustainability in China. Conventional mitigation strategies focusing on reducing volatile organic compounds and nitrogen oxides (NOx) remain complex and challenging. Here, through field flux measurements and laboratory simulations, we observe substantial nitrous acid (HONO) emissions (FHONO) enhanced by nitrogen fertilizer application at an agricultural site. The observed FHONO significantly improves model performance in predicting atmospheric HONO and leads to regional O3 increases by 37%. We also demonstrate the significant potential of nitrification inhibitors in reducing emissions of reactive nitrogen, including HONO and NOx, by as much as 90%, as well as greenhouse gases like nitrous oxide by up to 60%. Our findings introduce a feasible concept for mitigating O3 pollution: reducing soil HONO emissions. Hence, this study has important implications for policy decisions related to the control of O3 pollution and climate change.


Asunto(s)
Ácido Nitroso , Ozono , Suelo , Ácido Nitroso/química , Suelo/química , Contaminación del Aire/prevención & control , Contaminantes Atmosféricos , China , Cambio Climático , Óxido Nitroso
20.
Phys Chem Chem Phys ; 26(7): 6099-6106, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38299603

RESUMEN

Helicenes are promising candidates for circularly polarized luminescence (CPL) materials, although the performance is poor due to the unsatisfactory dissymmetric factor (glum) and fluorescence quantum efficiency (ΦF). Herein, the influence of heteroatoms (C, Si, Ge, O, S and Se) on the electronic structures and chiroptical properties of [7]helicene derivatives is systematically investigated using density functional theory (DFT) and time-dependent DFT calculations combined with the thermal vibration correlation function theory. The results reveal that the non-radiative energy consumption processes for helicene systems are closely related to the variation of bond length upon electronic excitation. Moreover, by introducing five-membered rings and heteroatoms, the dipole-forbidden S1 → S0 emission of [7]helicene changes to dipole-allowed transition due to the rearrangement of occupied orbitals and lifting of the nearly degenerate orbitals, resulting in an enhancement of ΦF. As the heteroatomic radius increases, ΦF decreases while the glum increases. Compared with the derivatives containing aromatic five-membered rings ([7]H-O, [7]H-S, and [7]H-Se), the non-aromatic counterparts ([7]H-C, [7]H-Si, and [7]H-Ge) exhibit a balance in ΦF and glum values. The present study helps to clarify the relationship between structures and chiroptical properties and offers a feasible strategy for the future design of helicene-based CPL materials.

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