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1.
Proc Natl Acad Sci U S A ; 120(43): e2306475120, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37847733

RESUMO

Anxiety disorders are a major public health concern and current treatments are inadequate for many individuals. Anxiety is more common in women than men and this difference arises during puberty. Sex differences in physiological stress responses may contribute to this variability. During puberty, gonadal hormones shape brain structure and function, but the extent to which these changes affect stress sensitivity is unknown. We examined how pubertal androgens shape behavioral and neural responses to social stress in California mice (Peromyscus californicus), a model species for studying sex differences in stress responses. In adults, social defeat reduces social approach and increases social vigilance in females but not males. We show this sex difference is absent in juveniles, and that prepubertal castration sensitizes adult males to social defeat. Adult gonadectomy does not alter behavioral responses to defeat, indicating that gonadal hormones act during puberty to program behavioral responses to stress in adulthood. Calcium imaging in the medioventral bed nucleus of the stria terminalis (BNST) showed that social threats increased neural activity and that prepubertal castration generalized these responses to less threatening social contexts. These results support recent hypotheses that the BNST responds to immediate threats. Prepubertal treatment with the nonaromatizable androgen dihydrotestosterone acts in males and females to reduce the effects of defeat on social approach and vigilance in adults. These data indicate that activation of androgen receptors during puberty is critical for programming behavioral responses to stress in adulthood.


Assuntos
Núcleos Septais , Diferenciação Sexual , Adulto , Humanos , Masculino , Feminino , Androgênios/farmacologia , Hormônios Gonadais/farmacologia , Hormônios Gonadais/fisiologia , Puberdade
2.
Diabetologia ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037604

RESUMO

AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).

3.
Kidney Int ; 105(1): 115-131, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37914087

RESUMO

Arterial calcification is a hallmark of vascular pathology in the elderly and in individuals with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs), after attaining a senescent phenotype, are implicated in the calcifying process. However, the underlying mechanism remains to be elucidated. Here, we reveal an aberrant upregulation of transcriptional factor GATA6 in the calcified aortas of humans, mice with CKD and mice subjected to vitamin D3 injection. Knockdown of GATA6, via recombinant adeno-associated virus carrying GATA6 shRNA, inhibited the development of arterial calcification in mice with CKD. Further gain- and loss-of function experiments in vitro verified the contribution of GATA6 in osteogenic differentiation of VSMCs. Samples of human aorta exhibited a positive relationship between age and GATA6 expression and GATA6 was also elevated in the aortas of old as compared to young mice. Calcified aortas displayed senescent features with VSMCs undergoing premature senescence, blunted by GATA6 downregulation. Notably, abnormal induction of GATA6 in senescent and calcified aortas was rescued in Sirtuin 6 (SIRT6)-transgenic mice, a well-established longevity mouse model. Suppression of GATA6 accounted for the favorable effect of SIRT6 on VSMCs senescence prevention. Mechanistically, SIRT6 inhibited the transcription of GATA6 by deacetylation and increased degradation of transcription factor Nkx2.5. Moreover, GATA6 was induced by DNA damage stress during arterial calcification and subsequently impeded the Ataxia-telangiectasia mutated (ATM)-mediated DNA damage repair process, leading to accelerated VSMCs senescence and osteogenic differentiation. Thus, GATA6 is a novel regulator in VSMCs senescence. Our findings provide novel insight in arterial calcification and a potential new target for intervention.


Assuntos
Insuficiência Renal Crônica , Sirtuínas , Calcificação Vascular , Humanos , Camundongos , Animais , Idoso , Músculo Liso Vascular , Fator de Transcrição GATA6/genética , Fator de Transcrição GATA6/metabolismo , Fator de Transcrição GATA6/farmacologia , Osteogênese , Células Cultivadas , Insuficiência Renal Crônica/patologia , Dano ao DNA , Senescência Celular/genética , Envelhecimento/genética , Sirtuínas/genética , Sirtuínas/metabolismo , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo
4.
Pharmacol Res ; 208: 107384, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39209083

RESUMO

Energy metabolism disorder, mainly exhibiting the inhibition of fatty acid degradation and lipid accumulation, is highly related with aging acceleration. However, the intervention measures are deficient. Here, we reported Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), especially EPA, exerted beneficial effects on maintaining energy metabolism and lipid homeostasis to slow organ aging. As the endogenous agonist of peroxisome proliferator-activated receptor α (PPARα), Omega-3 PUFAs significantly boosted fatty acid ß-oxidation and ATP production in multiple aged organs. Consequently, Omega-3 PUFAs effectively inhibited age-related pathological changes, preserved organ function, and retarded aging process. The beneficial effects of Omega-3 PUFAs were also testified in mfat-1 transgenic mice, which spontaneously generate abundant endogenous Omega-3 PUFAs. In conclusion, our study innovatively demonstrated Omega-3 PUFAs administration in diet slow aging through promoting energy metabolism. The supplement of Omega-3 PUFAs or fat-1 transgene provides a promising therapeutic approach to promote healthy aging in the elderly.

5.
Rapid Commun Mass Spectrom ; 38(14): e9761, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38714820

RESUMO

RATIONALE: Himalayan marmot oil (SPO) has been used for pharmaceutical purposes for centuries, but its composition is still unclear. The bioactivity of SPO highly depends on the techniques used for its processing. This study focused on the comprehensive lipidomics of SPO, especially on the ones derived from dry rendering, wet rendering, cold pressing, and ultrasound-assisted solvent extraction. METHODS: We performed lipid profiling of SPO acquired by different extraction methods using ultrahigh-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry, and 17 classes of lipids (2 BMPs, 12 LysoPCs, 9 LysoPEs, 41 PCs, 24 PEs, 23 Plasmenyl-PCs, 10 Plasmenyl-PEs, 10 MGs, 63 DGs, 187 TGs, 2 MGDGs, 3 Cer[NDS]s, 22 Cer[NS]s, 2 GlcCer[NS]s, 14 SMs, 14 CEs, and 6 AcylCarnitines) were characterized. RESULTS: Fifty-five lipids were differentially altered (VIP > 1.5, p < 0.05) between the extraction techniques, which can be used as potential biomarkers to differentiate SPO extracted by various methods. Additionally, the contents of oleic acid and arachidic acid were abundant in all samples that may suggest their medicinal values and are conducive to in-depth research. CONCLUSIONS: These findings reveal the alterations of lipid profile and free fatty acid composition in SPO obtained with different extraction methods, providing a theoretical foundation for investigating its important components as functional factors in medicines and cosmetics.


Assuntos
Lipídeos , Marmota , Espectrometria de Massas , Cromatografia Líquida de Alta Pressão/métodos , Lipídeos/química , Lipídeos/análise , Espectrometria de Massas/métodos , Óleos de Plantas/química , Óleos de Plantas/análise , Lipidômica/métodos , Fracionamento Químico/métodos
6.
Environ Sci Technol ; 58(37): 16399-16409, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39235209

RESUMO

The cyclical variations in environmental temperature generated by natural rhythms constantly impact the wastewater treatment process through the aeration system. Engineering data show that fluctuations in environmental temperature cause the reactor temperature to drop at night, resulting in increased dissolved oxygen concentration and improved effluent wastewater quality. However, the impact of natural temperature variation on wastewater treatment systems and the energy-saving potential has yet to be fully recognized. Here, we conducted a comprehensive study, using a full-scale oxic-hydrolytic and denitrification-oxic (OHO) coking wastewater treatment process as a case and developed a dynamic aeration model integrating thermodynamics and kinetics to elucidate the energy-saving mechanisms of wastewater treatment systems in response to diurnal temperature variations. Our case study results indicate that natural diurnal temperature variations can cut the energy consumption of 660,980 kWh annually (up to 30%) for the aeration unit in the OHO system. Wastewater treatment facilities located in regions with significant environmental temperature variation stand to benefit more from this energy-saving mechanism. Methods such as flow dynamic control, load shifting, and process unit editing can be fitted into the new or retrofitted wastewater treatment engineering.


Assuntos
Temperatura , Eliminação de Resíduos Líquidos , Águas Residuárias , Águas Residuárias/química , Coque , Purificação da Água
7.
J Nanobiotechnology ; 22(1): 554, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261890

RESUMO

BACKGROUND: Myocardial infarction (MI) is the main contributor to most cardiovascular diseases (CVDs), and the available post-treatment clinical therapeutic options are limited. The development of nanoscale drug delivery systems carrying natural small molecules provides biotherapies that could potentially offer new treatments for reactive oxygen species (ROS)-induced damage in MI. Considering the stability and reduced toxicity of gold-phenolic core-shell nanoparticles, this study aims to develop ellagic acid-functionalized gold nanoparticles (EA-AuNPs) to overcome these limitations. RESULTS: We have successfully synthesized EA-AuNPs with enhanced biocompatibility and bioactivity. These core-shell gold nanoparticles exhibit excellent ROS-scavenging activity and high dispersion. The results from a label-free imaging method on optically transparent zebrafish larvae models and micro-CT imaging in mice indicated that EA-AuNPs enable a favorable excretion-based metabolism without overburdening other organs. EA-AuNPs were subsequently applied in cellular oxidative stress models and MI mouse models. We found that they effectively inhibit the expression of apoptosis-related proteins and the elevation of cardiac enzyme activities, thereby ameliorating oxidative stress injuries in MI mice. Further investigations of oxylipin profiles indicated that EA-AuNPs might alleviate myocardial injury by inhibiting ROS-induced oxylipin level alterations, restoring the perturbed anti-inflammatory oxylipins. CONCLUSIONS: These findings collectively emphasized the protective role of EA-AuNPs in myocardial injury, which contributes to the development of innovative gold-phenolic nanoparticles and further advances their potential medical applications.


Assuntos
Ácido Elágico , Ouro , Nanopartículas Metálicas , Infarto do Miocárdio , Estresse Oxidativo , Espécies Reativas de Oxigênio , Peixe-Zebra , Animais , Ouro/química , Nanopartículas Metálicas/química , Infarto do Miocárdio/tratamento farmacológico , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Ácido Elágico/farmacologia , Ácido Elágico/química , Estresse Oxidativo/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Masculino , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Camundongos Endogâmicos C57BL
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 368-376, 2024 Mar 10.
Artigo em Zh | MEDLINE | ID: mdl-38448031

RESUMO

In recent years, mRNA drugs have shown a great potential for the treatment of genetic diseases and attracted the attention of many researchers. This article has reviewed the advance in the research of mRNA drugs for the treatment of genetic diseases over the past 30 years, including their mechanisms of action and structure design, with a focus on their advantages as alternative therapies such as high specificity, low dosage, and sustained expression. Meanwhile, challenges for the effective delivery and storage methods for the mRNA drugs are discussed, with an aim to provide guidance for subsequent researches.


Assuntos
RNA Mensageiro , Humanos , RNA Mensageiro/genética
9.
BMC Oral Health ; 24(1): 1074, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266981

RESUMO

BACKGROUND: There is increasing evidence that inflammation plays a key role in the pathophysiology of periodontitis (PT) and Alzheimer's disease (AD), but the roles of inflammation in linking PT and AD are not clear. Our aim is to analyze the potential molecular mechanisms between these two diseases using bioinformatics and systems biology approaches. METHODS: To elucidate the link between PT and AD, we selected shared genes (SGs) with gene-disease-association scores of ≥ 0.1 from the Disease Gene Network (DisGeNET) database, followed by extracting the hub genes. Based on these genes, we constructed gene ontology (GO) enrichment analysis, pathway enrichment analysis, protein-protein interaction (PPI) networks, transcription factors (TFs)-gene networks, microRNAs (miRNAs)-gene regulatory networks, and gene-disease association analyses. Finally, the Drug Signatures database (DSigDB) was utilized to predict candidate molecular drugs related to hub genes. RESULTS: A total of 21 common SGs between PT and AD were obtained. Cell cytokine activity, inflammatory response, and extracellular membrane were the most important enriched items in GO analysis. Interleukin-10 Signaling, LTF Danger Signal Response Pathway, and RAGE Pathway were identified as important shared pathways. IL6, IL10, IL1B, TNF, IFNG, CXCL8, CCL2, MMP9, TLR4 were identified as hub genes. Both shared pathways and hub genes are closely related to endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Importantly, glutathione, simvastatin, and dexamethasone were identified as important candidate drugs for the treatment of PT and AD. CONCLUSIONS: There is a close link between PT and AD pathogenesis, which may involve in the inflammation, ER and mitochondrial function.


Assuntos
Doença de Alzheimer , Biologia Computacional , Periodontite , Biologia de Sistemas , Humanos , Periodontite/genética , Doença de Alzheimer/genética , Redes Reguladoras de Genes/genética , Mapas de Interação de Proteínas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Ontologia Genética
10.
J Cell Mol Med ; 27(9): 1168-1178, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37002701

RESUMO

The complement system defences against pathogenic microbes and modulates immune homeostasis by interacting with the innate and adaptive immune systems. Dysregulation, impairment or inadvertent activation of complement system contributes to the pathogenesis of some autoimmune diseases and cardiovascular diseases (CVD). Vascular calcification is the pivotal pathological basis of CVD, and contributes to the high morbidity and mortality of CVD. Increasing evidences indicate that the complement system plays a key role in chronic kidney diseases, atherosclerosis, diabetes mellitus and aging-related diseases, which are closely related with vascular calcification. However, the effect of complement system on vascular calcification is still unclear. In this review, we summarize current evidences about the activation of complement system in vascular calcification. We also describe the complex network of complement system and vascular smooth muscle cells osteogenic transdifferentiation, systemic inflammation, endoplasmic reticulum stress, extracellular matrix remodelling, oxidative stress, apoptosis in vascular calcification. Hence, providing a better understanding of the potential relationship between complement system and vascular calcification, so as to provide a direction for slowing the progression of this burgeoning health concern.


Assuntos
Doenças Cardiovasculares , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , Músculo Liso Vascular/patologia , Calcificação Vascular/patologia , Osteogênese , Insuficiência Renal Crônica/patologia , Doenças Cardiovasculares/patologia , Miócitos de Músculo Liso
11.
Bioconjug Chem ; 34(3): 477-488, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36740781

RESUMO

Myocardial ischemia/reperfusion (MI/R) injury is an unresolved clinical challenge. The blockade of binding fibrinogen by glycoprotein IIb/IIIa (GPIIb-IIIa) inhibitors has become a new therapeutic approach against MI/R injury. In this study, we modified the RGD structure to combine with scutellarin and synthesized a novel peptide, scutellarin-HomoArg-Gly-Asp-Trp-NH2 (WK001). Herein, reported experimental and docking evidence indicates that WK001 provides immediate and potent platelet inhibition, with stronger inhibition of platelet aggregation than eptifibatide and scutellarin. In particular, it is administered intravenously to prevent thrombus formation and attenuate myocardial fibrosis progression in vivo. Therefore, WK001 could be developed as an antiplatelet drug to treat thrombosis-associated diseases, such as stroke and myocardial infarction.


Assuntos
Traumatismo por Reperfusão Miocárdica , Humanos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Glicoproteínas da Membrana de Plaquetas , Oligopeptídeos
12.
Mol Pharm ; 20(8): 3987-4006, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37503854

RESUMO

Ototoxic drugs such as aminoglycoside antibiotics and cisplatin (CDDP) can cause sensorineural hearing loss (SNHL), which is closely related to oxidative stress and the acidification of the inner ear microenvironment. Effective treatment of SNHL often requires multifaceted approach due to the complex pathology, and drug combination therapy is expected to be at the forefront of modern hearing loss treatment. Here, space-station-like composite nanoparticles (CCC@mPP NPs) with pH/oxidation dual responsiveness and multidrug simultaneous delivery capability were constructed and then loaded with various drugs including panax notoginseng saponins (PNS), tanshinone IIA (TSIIA), and ammonia borane (AB) to provide robust protection against SNHL. Molecular dynamics simulation revealed that carboxymethyl chitosan/calcium carbonate-chitosan (CCC) NPs and monomethoxy poly(ethylene glycol)-PLGA (mPP) NPs can rendezvous and dock primarily by hydrogen bonding, and electrostatic forces may be involved. Moreover, CCC@mPP NPs crossed the round window membrane (RWM) and entered the inner ear through endocytosis and paracellular pathway. The docking state was basically maintained during this process, which created favorable conditions for multidrug delivery. This nanosystem was highly sensitive to pH and reactive oxygen species (ROS) changes, as evidenced by the restricted release of payload at alkaline condition (pH 7.4) without ROS, while significantly promoting the release in acidic condition (pH 5.0 and 6.0) with ROS. TSIIA/PNS/AB-loaded CCC@mPP NPs almost completely preserved the hair cells and remained the hearing threshold shift within normal limits in aminoglycoside- or CDDP-treated guinea pigs. Further experiments demonstrated that the protective mechanisms of TSIIA/PNS/AB-loaded CCC@mPP NPs involved direct and indirect scavenging of excessive ROS, and reduced release of pro-inflammatory cytokines. Both in vitro and in vivo experiments showed the high biocompatibility of the composite NPs, even after long-term administration. Collectively, this work suggests that composite NPs is an ideal multi-drug-delivery vehicle and open new avenues for inner ear disease therapies.


Assuntos
Quitosana , Perda Auditiva Neurossensorial , Nanopartículas , Animais , Cobaias , Ácido Láctico/química , Quitosana/química , Hidrogênio , Medicina Tradicional Chinesa , Espécies Reativas de Oxigênio , Perda Auditiva Neurossensorial/tratamento farmacológico , Cisplatino , Nanopartículas/química , Aminoglicosídeos
13.
J Chem Inf Model ; 63(20): 6169-6176, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37820365

RESUMO

Target identification and bioactivity prediction are critical steps in the drug discovery process. Here we introduce CODD-Pred (COmprehensive Drug Design Predictor), an online web server with well-curated data sets from the GOSTAR database, which is designed with a dual purpose of predicting potential protein drug targets and computing bioactivity values of small molecules. We first designed a double molecular graph perception (DMGP) framework for target prediction based on a large library of 646 498 small molecules interacting with 640 human targets. The framework achieved a top-5 accuracy of over 80% for hitting at least one target on both external validation sets. Additionally, its performance on the external validation set comprising 200 molecules surpassed that of four existing target prediction servers. Second, we collected 56 targets closely related to the occurrence and development of cancer, metabolic diseases, and inflammatory immune diseases and developed a multi-model self-validation activity prediction (MSAP) framework that enables accurate bioactivity quantification predictions for small-molecule ligands of these 56 targets. CODD-Pred is a handy tool for rapid evaluation and optimization of small molecules with specific target activity. CODD-Pred is freely accessible at http://codd.iddd.group/.


Assuntos
Computadores , Proteínas , Humanos , Proteínas/química , Desenho de Fármacos , Descoberta de Drogas , Bases de Dados Factuais
14.
Phys Chem Chem Phys ; 25(5): 4062-4069, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36651102

RESUMO

The reaction of Criegee intermediates with nitric acid (HNO3) plays an important role for removal of Criegee intermediates as well as in oxidation of atmospheric HNO3 because of its fast reaction rate. Theoretical prediction suggests that the product branching ratios of the reaction of the simplest Criegee intermediate CH2OO with HNO3 are strongly pressure dependent and the CH2OO may be catalytically converted to OH and HCO radicals by HNO3. The direct quantification of HOx radicals formed from this reaction is hence crucial to evaluate its atmospheric implications. By employing mid-infrared multifunctional dual-comb spectrometers, the kinetics and product yields of the reaction CH2OO + HNO3 are investigated. A pressure independent rate coefficient of (1.9 ± 0.2) × 10-10 cm3 molecule-1 s-1 is obtained under a total pressure of 6.3-58.6 Torr at 296 K. The product branching ratios are derived by simultaneous determination of CH2OO, formaldehyde (CH2O), OH and HO2 radicals. At the total pressure of 12.5 Torr, the yield for the formation of NO2 + CH2O + HO2 is 36% and only 3.2% for OH + CH2(O)NO3, whereas the main remainder may be thermalized nitrooxymethyl hydroperoxide (NMHP, NO3CH2OOH). Additionally, the fractional yields of both the OH and HO2 product channels are decreased by a factor of roughly 2 from 12 to 60 Torr, indicating that there is almost no catalytic conversion of CH2OO to the OH radicals in the presence of HNO3.

15.
J Chem Phys ; 159(18)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37962448

RESUMO

Absolute line strengths of several transitions in the ν1 fundamental band of the hydroxyl radical (OH) have been measured by simultaneous determination of hydrogen peroxide (H2O2) and OH upon laser photolysis of H2O2. Based on the well-known quantum yield for the generation of OH radicals in the 248-nm photolysis of H2O2, the line strength of the OH radicals can be accurately derived by adopting the line strength of the well-characterized transitions of H2O2 and analyzing the difference absorbance time traces of H2O2 and OH obtained upon laser photolysis. Employing a synchronized two-color dual-comb spectrometer, we measured high-resolution time-resolved absorption spectra of H2O2 near 7.9 µm and the OH radical near 2.9 µm, simultaneously, under varied conditions. In addition to the studies of the line strengths of the selected H2O2 and OH transitions, the kinetics of the reaction between OH and H2O2 were investigated. A pressure-independent rate coefficient kOH+H2O2 was determined to be [1.97 (+0.10/-0.15)] × 10-12 cm3 molecule-1 s-1 at 296 K and compared with other experimental results. By carefully analyzing both high-resolution spectra and temporal absorbance profiles of H2O2 and OH, the uncertainty of the obtained OH line strengths can be achieved down to <10% in this work. Moreover, the proposed two-color time-resolved dual-comb spectroscopy provides a new approach for directly determining the line strengths of transient free radicals and holds promise for investigations on their self-reaction kinetics as well as radical-radical reactions.

16.
Int J Mol Sci ; 24(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36835141

RESUMO

Organic peroxy radicals (RO2) as key intermediates in tropospheric chemistry exert a controlling influence on the cycling of atmospheric reactive radicals and the production of secondary pollutants, such as ozone and secondary organic aerosols (SOA). Herein, we present a comprehensive study of the self-reaction of ethyl peroxy radicals (C2H5O2) by using advanced vacuum ultraviolet (VUV) photoionization mass spectrometry in combination with theoretical calculations. A VUV discharge lamp in Hefei and synchrotron radiation at the Swiss Light Source (SLS) are employed as the photoionization light sources, combined with a microwave discharge fast flow reactor in Hefei and a laser photolysis reactor at the SLS. The dimeric product, C2H5OOC2H5, as well as other products, CH3CHO, C2H5OH and C2H5O, formed from the self-reaction of C2H5O2 are clearly observed in the photoionization mass spectra. Two kinds of kinetic experiments have been performed in Hefei by either changing the reaction time or the initial concentration of C2H5O2 radicals to confirm the origins of the products and to validate the reaction mechanisms. Based on the fitting of the kinetic data with the theoretically calculated results and the peak area ratios in the photoionization mass spectra, a branching ratio of 10 ± 5% for the pathway leading to the dimeric product C2H5OOC2H5 is measured. In addition, the adiabatic ionization energy (AIE) of C2H5OOC2H5 is determined at 8.75 ± 0.05 eV in the photoionization spectrum with the aid of Franck-Condon calculations and its structure is revealed here for the first time. The potential energy surface of the C2H5O2 self-reaction has also been theoretically calculated with a high-level of theory to understand the reaction processes in detail. This study provides a new insight into the direct measurement of the elusive dimeric product ROOR and demonstrates its non-negligible branching ratio in the self-reaction of small RO2 radicals.


Assuntos
Ozônio , Vácuo , Espectrometria de Massas/métodos , Fotólise
17.
J Environ Manage ; 340: 117981, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37167082

RESUMO

Aquatic macrophytes debris decomposition could release pollutants and nutrients into the water of constructed wetlands (CWs), but their role in nitrogen removal and transformation remains poorly understood. The present study investigated the effects of plant-self debris on nitrogen removal and microbial communities in mesocosm CWs planted with Myriophyllum aquaticum. During the 68-day operation, the plant debris addition did not change the mean removal efficiency of ammonium (NH4+-N) and total nitrogen (TN) of CWs but showed significant differences over the operation time. The NH4+-N and organic nitrogen released from the plant debris decomposition affected the nitrogen removal. The plant debris decreased the effluent nitrate concentration and N2O emission fluxes of the CWs with the increased abundance of denitrifying bacterial genera, indicating that plant debris decomposition increased the denitrification activities via dissolved organic carbon release. High-throughput sequencing indicated that the plant debris altered the distribution and composition of the microbial community in the sediments. Proteobacteria was the dominant phylum (28-52%), and the relative abundance of denitrifying bacteria genera was significantly higher in the sediments with debris addition (37-40%) than in the non-addition (6.6-7.7%). The present study provided new insights into the role of macrophytes in pollutant removal and the plant management strategy of CWs.


Assuntos
Compostos de Amônio , Microbiota , Nitrogênio , Desnitrificação , Áreas Alagadas , Bactérias , Eliminação de Resíduos Líquidos
18.
Pak J Med Sci ; 39(2): 444-449, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950412

RESUMO

Objective: To evaluate the clinical efficacy of a chemotherapy regimen combined with levofloxacin in patients with pulmonary tuberculosis complicated with Type-2 diabetes. Methods: Total 80 patients with pulmonary tuberculosis complicated with Type-2 diabetes admitted to Baoding People's Hospital from January, 2019 to January, 2022 were randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. Patients in the control group were given the conventional 2HRZE/10HRE regimen, while those in the experimental group were given the chemotherapy regimen 2HRZEL/6HRE combined with levofloxacin. Sixty four slice spiral CT was used for chest plain scan before and after treatment, respectively, to evaluate the absorption of lesions based on the range of lung lesions; Venous blood was drawn to detect the changes of oxidative stress indicators, the incidence of adverse drug reactions and the negative conversion rate of sputum tuberculosis bacteria in the two groups. Results: After treatment, the efficacy of the experimental group was 90%, which was significantly higher than that of the control group (67.5%), with a statistically significant difference (p=0.01). After treatment, CD3+, CD4+, CD4+/CD8+ and other indicators in the experimental group were significantly higher than those in the control group, with a statistically significant difference (CD3+, p=0.01; CD4+, p=0.01; CD4+/CD8+, p=0.00), while CD8+ did not change significantly (p=0.92); The incidence of adverse reactions was 52.5% in the experimental group and 47.5% in the control group, with no statistically significant difference (p=0.66); The negative conversion rate of patients in the experimental group was significantly higher than that in the control group at one month, three months and six months after treatment, with a statistically significant difference (p<0.05). Conclusion: Chemotherapy combined with levofloxacin is a safe and effective regimen for patients' pulmonary tuberculosis complicated with Type-2 diabetes, boasting a variety of benefits such as improved clinical efficacy, ameliorated cellular immune status, a high negative conversion rate of sputum tuberculosis bacteria, and no significant increase in adverse reactions.

19.
Anal Chem ; 94(15): 5752-5759, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35377143

RESUMO

Criegee intermediates, derived from ozonolysis of alkenes and recognized as key species in the production of nonphotolytic free radicals, play a crucial role in atmospheric chemistry. Here, we present a spectrometer based on synchronized two-color time-resolved dual-comb spectroscopy, enabling simultaneous spectral acquisitions in two molecular fingerprint regions near 2.9 and 7.8 µm. Upon flash photolysis of CH2I2/O2/N2 gas mixtures, multiple reaction species, involving the simplest Criegee intermediates (CH2OO), formaldehyde (CH2O), hydroxyl (OH) and hydroperoxy (HO2) radicals are simultaneously detected with microsecond time resolution. The concentration of each molecule can be determined based on high-resolution rovibrational absorption spectroscopy. With quantitative detection and simulation of temporal concentration profiles of the targeted molecules at various conditions, the underlying reaction mechanisms and pathways related to the formation of the HOx radicals, which can be generated from decomposition of initially energized and vibrationally excited Criegee intermediates, are explored. This approach capable of achieving multispectral measurements with simultaneously high spectral and temporal resolutions opens up the opportunities for quantification of transient intermediates and products, thus, enabling elucidation of complex reaction mechanisms.


Assuntos
Alcenos , Radical Hidroxila , Alcenos/química , Formaldeído , Radicais Livres , Análise Espectral
20.
Mol Genet Genomics ; 297(1): 75-85, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34786636

RESUMO

Brassica juncea is one of a unique vegetable in China, its tumorous stem can be processed into pickle or as fresh vegetable. For a long time, early-bolting as a main factor affects yield and quality of B. juncea, which happens about 15% all year round. As plant specific blue light receptors, FKF1/LKP2 involved in photoperiod flowering. To analyze the expression levels of BjuFKF1/BjuLKP2 and screen their interaction proteins in B. juncea, qRT-PCR and yeast two hybrid assays were recruited. qRT-PCR assays found that the expression levels of BjuFKF1 and BjuLKP2 were up-regulated expressed under both white and blue light. When under different light, BjuFKF1 was significantly increased at vegetative growth stage, but decreased in flowers under blue light. For BjuLKP2, its expression levels did not show significant changes under different light treatment. To investigate interaction proteins, BjuFKF1 and BjuLKP2 were used as bait proteins, and nine potential proteins were screened from yeast library. Yeast two hybrid assays was recruited to further verify their interaction, the results showed that both BjuFKF1 and BjuLKP2 interacted with BjuCOL, BjuCOL3, BjuCOL5, BjuAP2, BjuAP2-1 and BjuSKP1f, only BjuLKP2 interacted with BjuSVP-1 and BjuCDF1 in vivo. In this study, BjuFKF1 and BjuLKP2 were up-regulated expressed under both white and blue light. Yeast two hybrid results verified that BjuFKF1 and BjuLKP2 interacted with six and eight of those nine proteins in vivo, respectively. All of those results will provided reference genes to study BjuFKF1/BjuLKP2 regulated flowering pathway in B. juncea.


Assuntos
Proteínas CLOCK , Flores/genética , Mostardeira , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Flores/crescimento & desenvolvimento , Flores/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Mostardeira/genética , Mostardeira/crescimento & desenvolvimento , Mostardeira/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mapas de Interação de Proteínas/fisiologia , Fatores de Tempo
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