RESUMEN
Plants frequently encounter wounding and have evolved an extraordinary regenerative capacity to heal the wounds. However, the wound signal that triggers regenerative responses has not been identified. Here, through characterization of a tomato mutant defective in both wound-induced defense and regeneration, we demonstrate that in tomato, a plant elicitor peptide (Pep), REGENERATION FACTOR1 (REF1), acts as a systemin-independent local wound signal that primarily regulates local defense responses and regenerative responses in response to wounding. We further identified PEPR1/2 ORTHOLOG RECEPTOR-LIKE KINASE1 (PORK1) as the receptor perceiving REF1 signal for plant regeneration. REF1-PORK1-mediated signaling promotes regeneration via activating WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1), a master regulator of wound-induced cellular reprogramming in plants. Thus, REF1-PORK1 signaling represents a conserved phytocytokine pathway to initiate, amplify, and stabilize a signaling cascade that orchestrates wound-triggered organ regeneration. Application of REF1 provides a simple method to boost the regeneration and transformation efficiency of recalcitrant crops.
Asunto(s)
Proteínas de Plantas , Regeneración , Transducción de Señal , Solanum lycopersicum , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Solanum lycopersicum/metabolismo , Regulación de la Expresión Génica de las Plantas , Péptidos/metabolismoRESUMEN
The presence of DNA in the cytoplasm is normally a sign of microbial infections and is quickly detected by cyclic GMP-AMP synthase (cGAS) to elicit anti-infection immune responses. However, chronic activation of cGAS by self-DNA leads to severe autoimmune diseases for which no effective treatment is available yet. Here we report that acetylation inhibits cGAS activation and that the enforced acetylation of cGAS by aspirin robustly suppresses self-DNA-induced autoimmunity. We find that cGAS acetylation on either Lys384, Lys394, or Lys414 contributes to keeping cGAS inactive. cGAS is deacetylated in response to DNA challenges. Importantly, we show that aspirin can directly acetylate cGAS and efficiently inhibit cGAS-mediated immune responses. Finally, we demonstrate that aspirin can effectively suppress self-DNA-induced autoimmunity in Aicardi-Goutières syndrome (AGS) patient cells and in an AGS mouse model. Thus, our study reveals that acetylation contributes to cGAS activity regulation and provides a potential therapy for treating DNA-mediated autoimmune diseases.
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ADN/inmunología , Nucleotidiltransferasas/metabolismo , Autotolerancia/inmunología , Acetilación , Secuencia de Aminoácidos , Animales , Aspirina/farmacología , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes del Sistema Nervioso/genética , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/metabolismo , Autoinmunidad , Línea Celular , ADN/genética , ADN/metabolismo , Modelos Animales de Enfermedad , Exodesoxirribonucleasas/metabolismo , Células HEK293 , Células HeLa , Humanos , Ratones , Ratones Endogámicos C57BL , Modelos Moleculares , Mutación , Malformaciones del Sistema Nervioso/genética , Malformaciones del Sistema Nervioso/inmunología , Malformaciones del Sistema Nervioso/metabolismo , Nucleotidiltransferasas/antagonistas & inhibidores , Nucleotidiltransferasas/química , Nucleotidiltransferasas/genética , Células THP-1RESUMEN
Cyclic GMP-AMP synthase (cGAS) is a key sensor responsible for cytosolic DNA detection. Here we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for DNA sensing and efficient activation of cGAS. G3BP1 enhanced DNA binding of cGAS by promoting the formation of large cGAS complexes. G3BP1 deficiency led to inefficient DNA binding by cGAS and inhibited cGAS-dependent interferon (IFN) production. The G3BP1 inhibitor epigallocatechin gallate (EGCG) disrupted existing G3BP1-cGAS complexes and inhibited DNA-triggered cGAS activation, thereby blocking DNA-induced IFN production both in vivo and in vitro. EGCG administration blunted self DNA-induced autoinflammatory responses in an Aicardi-Goutières syndrome (AGS) mouse model and reduced IFN-stimulated gene expression in cells from a patient with AGS. Thus, our study reveals that G3BP1 physically interacts with and primes cGAS for efficient activation. Furthermore, EGCG-mediated inhibition of G3BP1 provides a potential treatment for cGAS-related autoimmune diseases.
Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso/metabolismo , ADN Helicasas/metabolismo , Complejos Multiproteicos/metabolismo , Malformaciones del Sistema Nervioso/metabolismo , Nucleotidiltransferasas/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , ARN Helicasas/metabolismo , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , Animales , Autoantígenos/inmunología , Autoantígenos/metabolismo , Enfermedades Autoinmunes del Sistema Nervioso/tratamiento farmacológico , Enfermedades Autoinmunes del Sistema Nervioso/genética , Catequina/análogos & derivados , Catequina/uso terapéutico , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Citosol/inmunología , Citosol/metabolismo , ADN/inmunología , ADN/metabolismo , ADN Helicasas/antagonistas & inhibidores , ADN Helicasas/genética , Modelos Animales de Enfermedad , Exodesoxirribonucleasas/genética , Células HEK293 , Células HeLa , Humanos , Interferones/metabolismo , Ratones , Ratones Noqueados , Malformaciones del Sistema Nervioso/tratamiento farmacológico , Malformaciones del Sistema Nervioso/genética , Fármacos Neuroprotectores/uso terapéutico , Fosfoproteínas/genética , Proteínas de Unión a Poli-ADP-Ribosa/antagonistas & inhibidores , Proteínas de Unión a Poli-ADP-Ribosa/genética , Unión Proteica , ARN Helicasas/antagonistas & inhibidores , ARN Helicasas/genética , Proteínas con Motivos de Reconocimiento de ARN/antagonistas & inhibidores , Proteínas con Motivos de Reconocimiento de ARN/genéticaRESUMEN
With the improvement of single-cell measurement techniques, there is a growing awareness that individual differences exist among cells, and protein expression distribution can vary across cells in the same tissue or cell line. Pinpointing the protein subcellular locations in single cells is crucial for mapping functional specificity of proteins and studying related diseases. Currently, research about single-cell protein location is still in its infancy, and most studies and databases do not annotate proteins at the cell level. For example, in the human protein atlas database, an immunofluorescence image stained for a particular protein shows multiple cells, but the subcellular location annotation is for the whole image, ignoring intercellular difference. In this study, we used large-scale immunofluorescence images and image-level subcellular locations to develop a deep-learning-based pipeline that could accurately recognize protein localizations in single cells. The pipeline consisted of two deep learning models, i.e. an image-based model and a cell-based model. The former used a multi-instance learning framework to comprehensively model protein distribution in multiple cells in each image, and could give both image-level and cell-level predictions. The latter firstly used clustering and heuristics algorithms to assign pseudo-labels of subcellular locations to the segmented cell images, and then used the pseudo-labels to train a classification model. Finally, the image-based model was fused with the cell-based model at the decision level to obtain the final ensemble model for single-cell prediction. Our experimental results showed that the ensemble model could achieve higher accuracy and robustness on independent test sets than state-of-the-art methods.
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Aprendizaje Profundo , Humanos , Proteínas/metabolismo , Algoritmos , Línea Celular , Técnica del Anticuerpo FluorescenteRESUMEN
Many infections and stress signals can rapidly activate the NLRP3 inflammasome to elicit robust inflammatory responses. This activation requires a priming step, which is thought to be mainly for upregulating NLRP3 transcription. However, recent studies report that the NLRP3 inflammasome can be activated independently of transcription, suggesting that the priming process has unknown essential regulatory steps. Here, we report that JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation. We show that NLRP3 inflammasome activation is disrupted in NLRP3-S194A knockin mice. JNK1-mediated NLRP3 S194 phosphorylation is critical for NLRP3 deubiquitination and facilitates its self-association and the subsequent inflammasome assembly. Importantly, we demonstrate that blocking S194 phosphorylation prevents NLRP3 inflammasome activation in cryopyrin-associated periodic syndromes (CAPS). Thus, our study reveals a key priming molecular event that is a prerequisite for NLRP3 inflammasome activation. Inhibiting NLRP3 phosphorylation could be an effective treatment for NLRP3-related diseases.
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Inflamasomas/genética , Macrófagos/inmunología , Proteína Quinasa 8 Activada por Mitógenos/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Choque Séptico/genética , Secuencia de Aminoácidos , Animales , Enzimas Desubicuitinizantes/genética , Enzimas Desubicuitinizantes/inmunología , Escherichia coli/química , Femenino , Regulación de la Expresión Génica , Células HEK293 , Humanos , Inflamasomas/inmunología , Lipopolisacáridos/farmacología , Macrófagos/patología , Masculino , Ratones , Ratones Transgénicos , Proteína Quinasa 8 Activada por Mitógenos/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/deficiencia , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Fosforilación , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Choque Séptico/inducido químicamente , Choque Séptico/mortalidad , Choque Séptico/patología , Transducción de Señal , Análisis de SupervivenciaRESUMEN
Here, we present the second generation of our bicyclic peptide library (NTB), featuring a stereodiversified structure and a simplified construction strategy. We utilized a tandem ring-opening metathesis and ring-closing metathesis reaction (ROM-RCM) to cyclize the linear peptide library in a single step, representing the first reported instance of this reaction being applied to the preparation of macrocyclic peptides. Moreover, the resulting bicyclic peptide can be easily linearized for MS/MS sequencing with a one-step deallylation process. We employed this library to screen against the E363-R378 epitope of MYC and identified several MYC-targeting bicyclic peptides. Subsequent in vitro cell studies demonstrated that one candidate, NT-B2R, effectively suppressed MYC transcription activities and cell proliferation.
Asunto(s)
Biblioteca de Péptidos , Espectrometría de Masas en Tándem , Péptidos/farmacología , Péptidos/químicaRESUMEN
BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.
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Células Estrelladas Hepáticas , Hepatocitos , Cirrosis Hepática , Proteína de la Región Y Determinante del Sexo , Animales , Femenino , Masculino , Ratones , Tetracloruro de Carbono/toxicidad , Tetracloruro de Carbono/efectos adversos , Colestasis/genética , Colestasis/metabolismo , Colestasis/fisiopatología , Modelos Animales de Enfermedad , Células Estrelladas Hepáticas/metabolismo , Hepatocitos/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Ratones Noqueados , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Caracteres Sexuales , Proteína de la Región Y Determinante del Sexo/genética , Proteína de la Región Y Determinante del Sexo/metabolismoRESUMEN
Location proteomics seeks to provide automated high-resolution descriptions of protein location patterns within cells. Many efforts have been undertaken in location proteomics over the past decades, thereby producing plenty of automated predictors for protein subcellular localization. However, most of these predictors are trained solely from high-throughput microscopic images or protein amino acid sequences alone. Unifying heterogeneous protein data sources has yet to be exploited. In this paper, we present a pipeline called sequence, image, network-based protein subcellular locator (SIN-Locator) that constructs a multi-view description of proteins by integrating multiple data types including images of protein expression in cells or tissues, amino acid sequences and protein-protein interaction networks, to classify the patterns of protein subcellular locations. Proteins were encoded by both handcrafted features and deep learning features, and multiple combining methods were implemented. Our experimental results indicated that optimal integrations can considerately enhance the classification accuracy, and the utility of SIN-Locator has been demonstrated through applying to new released proteins in the human protein atlas. Furthermore, we also investigate the contribution of different data sources and influence of partial absence of data. This work is anticipated to provide clues for reconciliation and combination of multi-source data for protein location analysis.
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Proteínas , Proteómica , Secuencia de Aminoácidos , Diagnóstico por Imagen , Humanos , Proteínas/química , Proteómica/métodosRESUMEN
Variants in voltage-gated sodium channel (VGSC) genes are implicated in seizures, epilepsy, and neurodevelopmental disorders, constituting a significant aspect of hereditary epilepsy in the Chinese population. Through retrospective analysis utilizing next-generation sequencing (NGS), we examined the genotypes and phenotypes of VGSC-related epilepsy cases from a cohort of 691 epilepsy subjects. Our findings revealed that 5.1% of subjects harbored VGSC variants, specifically 22 with SCN1A, 9 with SCN2A, 1 with SCN8A, and 3 with SCN1B variants; no SCN3A variants were detected. Among these, 14 variants were previously reported, while 21 were newly identified. SCN1A variant carriers predominantly presented with Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures Plus (GEFS + ), featuring a heightened sensitivity to fever-induced seizures. Statistically significant disparities emerged between the SCN1A-DS and SCN1A-GEFS+ groups concerning seizure onset and genetic diagnosis age, incidence of status epilepticus, mental retardation, anti-seizure medication (ASM) responsiveness, and familial history. Notably, subjects with SCN1A variants affecting the protein's pore region experienced more frequent cluster seizures. All SCN2A variants were of de novo origin, and 88.9% of individuals with SCN2A variations exhibited cluster seizures. This research reveals a significant association between variations in VGSC-related genes and the clinical phenotype diversity of epilepsy subjects in China, emphasizing the pivotal role of NGS screening in establishing accurate disease diagnoses and guiding the selection of ASM.
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Epilepsia , Genotipo , Canal de Sodio Activado por Voltaje NAV1.1 , Canal de Sodio Activado por Voltaje NAV1.2 , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Adulto Joven , China/epidemiología , Pueblos del Este de Asia/genética , Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/epidemiología , Epilepsia/genética , Epilepsia/epidemiología , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Canal de Sodio Activado por Voltaje NAV1.1/genética , Canal de Sodio Activado por Voltaje NAV1.2/genética , Fenotipo , Estudios Retrospectivos , Convulsiones Febriles/genética , Convulsiones Febriles/epidemiologíaRESUMEN
Preeclampsia is a gestational disease characterized by two major pathological changes-shallow trophoblast invasion and impaired spiral artery remodeling. Atrial natriuretic peptide (ANP) is a kind of peptide hormone that regulates blood pressure, while the lack of active ANP participates in preeclampsia pathogenesis. However, the underlying mechanism of how ANP modulates trophoblasts function remains unclarified. Here, we performed isobaric tags for relative and absolute quantification (iTRAQ) in ANP-treated HTR-8/SVneo cells and identified Protein Kinase 3 (PKN3) as the downstream factor of ANP, which was downregulated in preeclamptic placenta. Chromatin immunoprecipitation analysis and luciferase assays showed that NFYA was one of the transcription factors for the PKN3 promoter, which was also regulated by ANP treatment in HTR-8/SVneo cells. Transmission electron microscopy and Western Blotting in HTR-8/SVneo cells indicated that ANP inhibited autophagy via AMPK-mTORC1 signaling, while excess autophagy was observed in preeclamptic placenta. The increased expression of PKN3 and enhanced cell invasion ability in HTR-8/SVneo cells induced by ANP could be abolished by autophagy activation or transfection with PKN3 shRNA or NFYA shRNA or NPR-A shRNA via regulating the invasion-related genes and the epithelial mesenchymal transition molecules. Our results demonstrated that ANP could enhance trophoblast invasion by upregulating PKN3 via NFYA promotion through autophagy inhibition in an AMPK/mTORC1 signaling-dependent manner.
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Preeclampsia , Femenino , Humanos , Embarazo , Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia , Línea Celular , Movimiento Celular , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Placenta/metabolismo , Preeclampsia/metabolismo , ARN Interferente Pequeño/metabolismo , Trofoblastos/metabolismo , Factor Natriurético AtrialRESUMEN
Erdheim-Chester disease (ECD) is a rare histiocytosis that tends to co-exist with other myeloid malignancies. Here, we use genetic and transcriptomic sequencing to delineate a case of co-occurring BRAFV600E-mutated ECD and acute myeloid leukemia (AML), followed by AML remission and relapse. The AML relapse involved the extinction of clones with KMT2A-AFDN and FLT3-ITD, and the predominance of PTPN11-mutated subclones with distinct transcriptomic features. This case report has highlighted the screening for other myeloid malignancies at the diagnosis of ECD and the clinical significance of PTPN11-mutated AML subclones that require meticulous monitoring.
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Enfermedad de Erdheim-Chester , Leucemia Mieloide Aguda , Mutación , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Tirosina Quinasa 3 Similar a fms , Humanos , Enfermedad de Erdheim-Chester/genética , Enfermedad de Erdheim-Chester/complicaciones , Enfermedad de Erdheim-Chester/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Tirosina Quinasa 3 Similar a fms/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Masculino , Evolución Clonal/genética , Femenino , Proteínas Proto-Oncogénicas B-raf/genética , Persona de Mediana EdadRESUMEN
Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.
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ADN Helicasas , Nucleotidiltransferasas , Proteínas de Unión a Poli-ADP-Ribosa , ARN Helicasas , Proteínas con Motivos de Reconocimiento de ARN , ADN/metabolismo , ADN Helicasas/genética , ADN Helicasas/metabolismo , Nucleotidiltransferasas/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , ARN Helicasas/genética , ARN Helicasas/metabolismo , Proteínas con Motivos de Reconocimiento de ARN/genética , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , Gránulos de EstrésRESUMEN
The urea-assisted water splitting not only enables a reduction in energy consumption during hydrogen production but also addresses the issue of environmental pollution caused by urea. Doping heterogeneous atoms in Ni-based electrocatalysts is considered an efficient means for regulating the electronic structure of Ni sites in catalytic processes. However, the current methodologies for synthesizing heteroatom-doped Ni-based electrocatalysts exhibit certain limitations, including intricate experimental procedures, prolonged reaction durations, and low product yield. Herein, Fe-doped NiO electrocatalysts were successfully synthesized using a rapid and facile solution combustion method, enabling the synthesis of 1.1107 g within a mere 5 min. The incorporation of iron atoms facilitates the modulation of the electronic environment around Ni atoms, generating a substantial decrease in the Gibbs free energy of intermediate species for the Fe-NiO catalyst. This modification promotes efficient cleavage of C-N bonds and consequently enhances the catalytic performance of UOR. Benefiting from the tunability of the electronic environment around the active sites and its efficient electron transfer, Fe-NiO electrocatalysts only needs 1.334 V to achieve 50 mA cm-2 during UOR. Moreover, Fe-NiO catalysts were integrated into a dual electrode urea electrolytic system, requiring only 1.43 V of cell voltage at 10 mA cm-2.
RESUMEN
Different morphologies and sizes of α-Fe2O3 were prepared by a coprecipitation method using polyvinylpyrrolidone as a dispersant. In the preparation process, homogeneous and dispersed nanoscale FeOOH particles were first obtained by the coprecipitation method, and then the FeOOH particles were calcined at high temperature to form α-Fe2O3. The growth and aggregation of the α-Fe2O3 particles at different calcination temperatures resulted in α-Fe2O3 powders with diversiform morphologies (nanoscale microsphere, pinecone ellipsoidal, polyhedral, and quasi-spherical structures). By analyzing the SEM images, it was inferred that the polyhedral structure of α-Fe2O3 particles was formed by the accumulation of rhomboid sheet structures and high-temperature growth. In terms of the magnetic properties, the samples belonged to the class of canted antiferromagnetic materials, and the morphology, particle size, and crystallite size of the α-Fe2O3 particles were important factors affecting the coercivity. Among these, when the calcination temperature was increased from 700 °C to 800 °C, the growth rate of the particle size was significantly faster than that of the crystallite size, and the coercivity increased substantially from 1411 Oe to 2688 Oe.
RESUMEN
The persistent O3 pollution in the Beijing-Tianjin-Hebei (BTH) region remains unresolved, largely due to limited comprehension of O3-precursor relationship and photochemistry drivers. In this work, intraday O3 sensitivity evolution from VOC-limited (volatile organic compound) regime in the forenoon to transition regime in the late afternoon was inferred by relative incremental reactivity (RIR) in summer 2019 at Xianghe, a suburban site in BTH region, suggesting that VOC-focused control policy could combine with stringent afternoon NOx control. Then detailed impacts of VOC subgroups on O3 formation were further comprehensively quantified by parametric OH reactivity (KOH), O3 formation potential (OFP), as well as RIR weighted value and O3 formation path tracing (OFPT) approach based on photochemical box model. O3 episode days corresponded to stronger O3 formation, depicted by higher KOH (10.4 s-1), OFP (331.7 µg m-3), RIR weighted value (1.2), and F(O3)-OFPT (15.5 ppbv h-1). High proportions of isoprene and OVOCs (oxygenated VOCs) to the total KOH and the OFPT method were demonstrated whereas results of OFP and RIR-weighted presented extra great impacts of aromatics on O3 formation. The OFPT approach captured the process that has already happened and included final O3 response to the original VOC, thus reliable for replicating VOC impacts. The comparison results of the four methods showed similarities when utilizing KOH and OFPT methods, which reveals that the potential applicability of simple KOH for contingency VOC control and more complex OFPT method for detailed VOC- and source-oriented control during policy-making. To investigate propulsion of VOC-involved O3 photochemistry, atmospheric oxidation capacity (AOC) was quantified by two atmospheric oxidation indexes (AOI). Both AOIp_G (7.0 × 107 molec cm-3 s-1, potential AOC calculated by oxidation reaction rates) and AOIe_G (8.5 µmol m-3, estimated AOC given redox electron transfer for oxidation products) were stronger on O3 episode days, indicating that AOC promoted the radical cycling initiated from VOC oxidation and subsequent O3 production. Result-oriented AOIe_G reasonably characterized actual AOC inferred by good linear correlation between AOIe_G and O3 concentrations compared to process-oriented AOIp_G. Therefore, with continuous NOx abatement, AOIe_G should be considered to represent actual AOC, also O3-inducing ability.
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Contaminantes Atmosféricos , Ozono , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , Ozono/análisis , Compuestos Orgánicos Volátiles/análisis , Monitoreo del Ambiente , China , Oxidación-ReducciónRESUMEN
OBJECTIVE: The aim of this retrospective study was to investigate the short-term and long-term efficacy of high-intensity focused ultrasound (HIFU) therapy for abdominal wall endometriosis (AWE) and explore its potential influencing factors. MATERIALS AND METHODS: A total of 80 patients with AWE who underwent HIFU therapy were retrospectively analyzed. Follow-ups were also conducted to evaluate the changes in lesion size and pain relief. Multivariate logistic regression analysis was applied to investigate factors influencing HIFU therapy for AWE. RESULTS: Among the 80 patients with AWE who received HIFU therapy, the effective rates were 76.3%, 80.5%, and 90.5% after 3, 12 and 24 months of follow-up, respectively. Multivariate logistic regression analysis revealed that the AWE lesion diameter and sonication intensity had statistically significant effects on the 3-month and 12-month efficacy of HIFU therapy for AWE, while age, BMI, disease duration, average sonication power and grey-scale changes did not have statistically significant effects. Four patients with AWE experienced recurrence after HIFU therapy, for a three-year cumulative recurrence rate of 6.3%. Furthermore, ten patients required reintervention after treatment, for a five-year cumulative reintervention rate of 13.9%. CONCLUSIONS: This study further confirmed the safety and effectiveness of HIFU therapy for AWE. Factors such as AWE lesion diameter and sonication intensity have been identified as key influencers affecting the short-term and long-term efficacy of HIFU therapy for AWE. The first two years following HIFU therapy constitute crucial periods for observation, and judiciously extending follow-up intervals during this timeframe is advised.
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Pared Abdominal , Endometriosis , Tratamiento con Ondas de Choque Extracorpóreas , Ultrasonido Enfocado de Alta Intensidad de Ablación , Femenino , Humanos , Endometriosis/diagnóstico por imagen , Endometriosis/terapia , Estudios Retrospectivos , Ultrasonido Enfocado de Alta Intensidad de Ablación/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: The present study aimed to investigate whether the mitochondrial KATP channel contributes to angiotensin II (Ang II)-induced vascular dysfunction, the development of hypertension, and atherosclerosis. METHODS AND RESULTS: ApoE (-/-) mice fed a high-fat diet were chronically infused with Ang II for eight weeks and concomitantly treated with losartan (ARB), apocynin, or 5-hydroxy decanoate (5-HD), or 3-methyladenine (3-MA). Systolic blood pressure was measured, and pathological changes of aortic or liver tissue were observed. Nitric oxide (NO), superoxide dismutase 2 (SOD2) levels and vasorelaxation rate were measured, and protein and mRNA expressions were examined by western blot and RT-PCR. Ang II-induced development of hypertension was suppressed not only by ARB, and apocynin but also by 5-HD or 3-MA. Ang II infusion decreased aortic NO production and relaxation, as well as SOD2 activity in liver, which were improved by all treatments. In addition, Ang II-induced activation of autophagy was suppressed by 5-HD in aortic tissue, furthermore, Ang II increases the atherosclerotic index in plasma and exacerbates the development of atherosclerosis by increases of fat deposition in the aorta and liver. Lipid metabolism-related mRNA expressions (LXR-α, LDLR, SRBI, Acca, and FASN) were changed by Ang II. Similarly, not only ARB, and apocynin, but also 5-HD and 3-MA suppressed Ang II-induced these changes. CONCLUSIONS: Our present findings evidence that mitochondrial KATP channel-mediated autophagy contributes to Ang II-induced vascular dysfunction, development of hypertension, and atherosclerosis.
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Angiotensina II , Aterosclerosis , Autofagia , Hipertensión , Óxido Nítrico , Superóxido Dismutasa , Animales , Autofagia/efectos de los fármacos , Masculino , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Hipertensión/fisiopatología , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/patología , Óxido Nítrico/metabolismo , Aterosclerosis/inducido químicamente , Aterosclerosis/patología , Aterosclerosis/metabolismo , Aterosclerosis/genética , Aterosclerosis/fisiopatología , Ratones Noqueados para ApoE , Ratones Endogámicos C57BL , Aorta/efectos de los fármacos , Aorta/patología , Aorta/metabolismo , Aorta/fisiopatología , Presión Sanguínea/efectos de los fármacos , Ratones , Modelos Animales de Enfermedad , Hígado/metabolismo , Hígado/patología , Hígado/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Dieta Alta en Grasa , Canales de PotasioRESUMEN
BACKGROUND: Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia. METHODS: Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8-15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0-1 mm (central fovea), 1-3 mm (parafovea), 3-6 mm (perifovea), and 6-9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants. RESULTS: The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0-6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P < 0.001). CONCLUSIONS: In UMA children, CCT and blood flow may be related to myopia progression. A robust correlation between CT and CVV in the 0-6-mm macular region and reduced CT and diminished blood flow indicated an association with myopia.
Asunto(s)
Anisometropía , Longitud Axial del Ojo , Coroides , Miopía , Flujo Sanguíneo Regional , Tomografía de Coherencia Óptica , Humanos , Coroides/irrigación sanguínea , Coroides/patología , Coroides/diagnóstico por imagen , Niño , Adolescente , Masculino , Femenino , Anisometropía/fisiopatología , Miopía/fisiopatología , Tomografía de Coherencia Óptica/métodos , Longitud Axial del Ojo/patología , Flujo Sanguíneo Regional/fisiología , Refracción Ocular/fisiología , Angiografía con Fluoresceína/métodosRESUMEN
BACKGROUND: The prevalence of self-injury and suicide is higher than the general population of people living with HIV/AIDS (PLWHA). However, the results reported in existing studies are highly variable in China. The purpose of this systematic review and meta-analysis was to synthesize the currently available high-quality evidence to explore the prevalence and influence factors of self-injury and suicide among PLWHA in China. METHOD: We retrieve literature written in Chinese and English through databases such as PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, WanFang Database, and CQVIP from inception to 1 September 2022. Sata 16.0 software was used for analysis. RESULTS: A total of 28 studies were included with a sample size of 1,433,971 and had a satisfactory quality score of ≥ 5. The prevalence among PLWHA in China were 30% for suicidal ideation (SI), 5% for suicide attempt (SA), 8% for suicide plan (SP), 7% for attempted suicide (AS), and 3 for completed suicide. High stigma (OR = 2.94, 95%CI: 1.90 - 4.57), depression (OR, 3.17; 95%CI, 2.20 - 4.57), anxiety (OR, 3.06; 95%CI, 2.23 - 4.20), low self-esteem (OR, 3.82, 95%CI, 2.22 - 6.57), high HIV related stress (OR, 2.53; 95%CI, 1.36 - 4.72), and unemployment (OR, 2.50; 95%CI, 1.51 - 4.15) are risk factors for SI; high social support (OR, 0.61; 95%CI, 0.44 - 0.84) and spouse infected with HIV (OR, 0.39; 95%CI, 0.21 - 0.74) are protective factors for SI; depression (OR, 1.62; 95%CI, 1.24 - 2.13), high aggression (OR, 4.66; 95%CI, 2.59 - 8.39), and more negative life events (OR, 2.51; 95%CI, 1.47 - 4.29) are risk factors for AS; high level of education (OR, 1.31; 95%CI, 1.21 - 1.43) is risk factor for CS. CONCLUSION: Figures indicate that approximately one-third of PLWHA had suicidal ideation, and three out of 1,000 completed suicide in China. Positive events are protective factors for self-injury and suicide among PLWHA, while negative events are risk factors. This suggests that psychosocial support and risk assessment should be integrated into the care of PLWHA.