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1.
Environ Geochem Health ; 46(4): 136, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483758

RESUMO

Many organic contaminated sites require on-site remediation; excavation remediation processes can release many volatile organic compounds (VOCs) which are key atmospheric pollutants. It is therefore important to rapidly identify VOCs during excavation and map their risk areas for human health protection. In this study, we developed a rapid analysis and assessment method, aiming to and reveal the real-time distribution of VOCs, evaluate their human health risks by quantitative models, and design appropriate control measures. Through on-site diagonal distribution sampling and analysis, VOCs concentration showed a decreasing trend within 5 m from the excavation point and then increased after 5 m with the increase in distance from the excavation point (p < 0.05). The concentrations of VOCs near the dominant wind direction were higher than the concentrations of surrounding pollutants. In contrast with conventional solid-phase adsorption (SPA) and thermal desorption gas chromatography-mass spectrometry (TD-GC/MS) methods for determining the composition and concentration of VOCs, the rapid measurement of VOCs by photo-ionization detector (PID) fitted well with the chemical analysis and modeling assessment of cancer/non-cancer risk. The targeting area was assessed as mild-risk (PID < 10 ppm), moderate-risk (PID from 10 to 40 ppm), and heavy-risk (PID > 40 ppm) areas. Similarly, the human health risks also decreased gradually with the distance from the excavation point, with the main risk area located in the dominant wind direction. The results of rapid PID assessment were comparable to conventional risk evaluation, demonstrating its feasibility in rapidly identifying VOCs releases and assessing the human health risks. This study also suggested appropriate control measures that are important guidance for personal protection during the remediation excavation process.


Assuntos
Poluentes Atmosféricos , Poluentes Ambientais , Compostos Orgânicos Voláteis , Humanos , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Compostos Orgânicos Voláteis/análise , Cromatografia Gasosa-Espectrometria de Massas , Poluentes Ambientais/análise
2.
J Am Chem Soc ; 146(12): 8567-8575, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38489761

RESUMO

Ferroptosis as a promising method of cancer treatment heavily relies on the intracellular iron ion level. Herein, a new iron-supplement nanodrug was developed by conjugating transferrin-homing peptide T10 on the surface of cross-linked lipoic acid vesicles (T10@cLAV), which could hijack blood transferrin (Tf) and specifically deliver it to tumor cells to elevate the Fe2+ level. Meanwhile, the intracellular degradation product of cLAV, dihydrolipoic acid, could regenerate Fe2+ to further boost the ferroptosis. The results disclosed that T10@cLAV achieved tumor inhibition comparable to that of cisplatin at a dose as low as 5 mg/kg in the HeLa tumor-bearing nude mice model and caused no toxicity at the dose up to 300 mg/kg. This tactful iron-supplement strategy of hijacking blood Tf is superior to the current strategies: one is the induction of intracellular ferritin degradation, which is limited by the low content of ferritin, and the other is the delivery of iron-based materials, which easily causes adverse effects.


Assuntos
Ferroptose , Nanopartículas , Neoplasias , Camundongos , Animais , Transferrina/metabolismo , Camundongos Nus , Ferro/metabolismo , Ferritinas , Nanopartículas/química
3.
Int J Nanomedicine ; 19: 1887-1908, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414529

RESUMO

Introduction: Since intrinsic ocular barrier limits the intraocular penetration of therapeutic protein through eye drops, repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are the standard therapy for neovascular age-related macular degeneration (nAMD), which are highly invasive and may cause particular ocular complications, leading to poor patient compliance. Methods: Using Penetratin (Pen) as the ocular penetration enhancer and hyaluronic acid (HA) as the retina-targeting ligand, a dual-modified ophthalmic liposome (Penetratin hyaluronic acid-liposome/Conbercept, PenHA-Lip/Conb) eye drop was designed to non-invasively penetrate the ocular barrier and deliver anti-VEGF therapeutic agents to the targeted intraocular tissue. Results: PenHA-Lip effectively penetrates the ocular barrier and targets the retinal pigment epithelium via corneal and non-corneal pathways. After a single topical administration of conbercept-loaded PenHA-Lip (PenHA-Lip/Conb), the intraocular concentration of conbercept peaked at 18.74 ± 1.09 ng/mL at 4 h, which is 11.55-fold higher than unmodified conbercept. In a laser-induced choroidal neovascularization (CNV) mouse model, PenHA-Lip/Conb eye drops three times daily for seven days inhibited CNV formation and progression without any significant tissue toxicity and achieved an equivalent effect to a single intravitreal conbercept injection. Conclusion: PenHA-Lip efficiently and safely delivered conbercept to the posterior eye segment and may be a promising noninvasive therapeutic option for nAMD.


Assuntos
Peptídeos Penetradores de Células , Neovascularização de Coroide , Degeneração Macular , Camundongos , Animais , Humanos , Lipossomos/uso terapêutico , Inibidores da Angiogênese/farmacologia , Ácido Hialurônico , Fator A de Crescimento do Endotélio Vascular , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/metabolismo , Degeneração Macular/tratamento farmacológico , Soluções Oftálmicas/uso terapêutico , Injeções Intravítreas
4.
Poult Sci ; 103(4): 103554, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401225

RESUMO

Heat stress (HS) causes oxidative damage and abnormal metabolism of muscle, thus impairing the meat quality in broilers. Selenium is an indispensable element for enhancing antioxidant systems. In our previous study, we synthesized a novel type of biogenic selenium nanoparticles synthesized with alginate oligosaccharides (SeNPs-AOS), and found that the particle size of Se is 80 nm and the Se content is 8% in the SeNPs-AOS; and dietary 5 mg/kg SeNPs-AOS has been shown to be effective against HS in broilers. However, whether SeNPs-AOS can mitigate HS-induced the impairment of thigh muscle quality in broilers is still unclear. Therefore, the purpose of this study was to investigate the protective effects of dietary SeNPs-AOS on meat quality, antioxidant capacity, and metabolomics of thigh muscle in broilers under HS. A total of 192 twenty-one-day-old Arbor Acres broilers were randomly divided into 4 groups with 6 replicates per group (8 broilers per replicate) according to a 2 × 2 experimental design: thermoneutral group (TN, broilers raised under 23±1.5°C); TN+SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (broilers raised under 33 ± 2°C for 10 h/d); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). The results showed that HS increased the freezing loss, cooking loss, and malondialdehyde (MDA) content of thigh muscle, whereas decreased the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities, as well as downregulated the mRNA expression of SOD2, CAT, GPX3, nuclear factor erythroid 2-related factor 2 (Nrf2), selenoprotein S (SELENOS), solute carrier family 7 member 11 (SLC7A11), GPX4, and ferroportin 1 (Fpn1) of thigh muscle (P < 0.05). Dietary SeNPS-AOS reduced the b* value, elevated the pH0min value and the activities of T-SOD, GSH-Px, glutathione S-transferase (GST) and the mRNA expression levels of GSTT1, GSTA3, GPX1, GPX3, ferritin heavy polypeptide-1 (FTH1), and Fpn1 of thigh muscle in broilers under HS (P < 0.05). Nontargeted metabolomics analysis identified a total of 79 metabolites with significant differences among the four groups, and the differential metabolites were mainly enriched in 8 metabolic pathways including glutathione metabolism and ferroptosis (P < 0.05). In summary, dietary 5 mg/kg SeNPs-AOS (Se content of 8%) could alleviate HS-induced impairment of meat quality by improving the oxidative damage, metabolic disorders and ferroptosis of thigh muscle in broilers challenged with HS. Suggesting that the SeNPs-AOS may be used as a novel nano-modifier for meat quality in broilers raised in thermal environment.


Assuntos
Ferroptose , Selênio , Animais , Antioxidantes/metabolismo , Selênio/metabolismo , Galinhas/fisiologia , Coxa da Perna , Suplementos Nutricionais/análise , Músculo Esquelético , Resposta ao Choque Térmico , Superóxido Dismutase/metabolismo , Carne/análise , RNA Mensageiro/metabolismo , Ração Animal/análise
5.
J Environ Manage ; 354: 120280, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38350280

RESUMO

Coal mining is one of the human activities that has the greatest impact on the global carbon (C) cycle and biodiversity. Biochar and plant growth-promoting bacteria (PGPB) have been both used to improve coal mining degraded soils; however, it is uncertain whether the effects of biochar application on soil respiration and microbial communities are influenced by the presence or absence of PGPB and soil nitrogen (N) level in coal mining degraded soils. A pot experiment was carried out to examine whether the effects of biochar addition (0, 1, 2 and 4% of soil mass) on soil properties, soil respiration, maize growth, and microbial communities were altered by the presence or absence of PGPB (i.e. Sphingobium yanoikuyae BJ1) (0, 200 mL suspension (2 × 106 colony forming unit (CFU) mL-1)) and two soil N levels (N0 and N1 at 0 and 0.2 g kg-1 urea- N, respectively). The results showed the presence of BJ1 enhanced the maize biomass relative to the absence of BJ1, particularly in N1 soils, which was related to the discovery of Lysobacter and Nocardioides that favor plant growth in N1 soils. This indicates a conversion in soil microbial communities to beneficial ones. The application of biochar at a rate of 1% decreased the cumulative CO2 regardless of the presence or absence of BJ1; BJ1 increased the ß-glucosidase (BG) activities, and BG activities were also positively correlated with RB41 strain with high C turnover in N1 soils, which indicates that the presence of BJ1 improves the C utilization rates of RB41, decreasing soil C mineralization. Our results highlight that biochar addition provided environmental benefits in degraded coal mining soils, and the direction and magnitude of these effects are highly dependent on the presence of PGPB and the soil N level.


Assuntos
Minas de Carvão , Zea mays , Humanos , Dióxido de Carbono/metabolismo , Solo , Microbiologia do Solo , Carvão Vegetal/metabolismo , Bactérias
6.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38383724

RESUMO

Human behavior often aligns with fairness norms, either voluntarily or under external pressure, like sanctions. Prior research has identified distinct neural activation patterns associated with voluntary and sanction-based compliance or non-compliance with fairness norms. However, an investigation gap exists into potential neural connectivity patterns and sex-based differences. To address this, we conducted a study using a monetary allocation game and functional magnetic resonance imaging to examine how neural activity and connectivity differ between sexes across three norm compliance conditions: voluntary, sanction-based, and voluntary post-sanctions. Fifty-five adults (27 females) participated, revealing that punishment influenced decisions, leading to strategic calculations and reduced generosity in voluntary compliance post-sanctions. Moreover, there were sex-based differences in neural activation and connectivity across the different compliance conditions. Specifically, the connectivity between the right dorsolateral prefrontal cortex and right dorsal anterior insular appeared to mediate intuitive preferences, with variations across norm compliance conditions and sexes. These findings imply potential sex-based differences in intuitive motivation for diverse norm compliance conditions. Our insights contribute to a better understanding of the neural pathways involved in fairness norm compliance and clarify sex-based differences, offering implications for future investigations into psychiatric and neurological disorders characterized by atypical socialization and mentalizing.


Assuntos
Imageamento por Ressonância Magnética , Comportamento Social , Adulto , Feminino , Humanos , Caracteres Sexuais , Motivação , Córtex Insular
7.
Neuropharmacology ; 244: 109802, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38043643

RESUMO

Schizophrenia (SCZ) is a heterogeneous psychiatric disorder marked by impaired thinking, emotions, and behaviors. Studies have suggested a strong connection between SCZ and Alzheimer's disease (AD), however, controversies exist and the underlying mechanisms linking these two disorders remain largely unknown. Therefore, systematic studies of SCZ- and AD-related genes will provide valuable insights into the molecular features of these two diseases and their comorbidities. In this study, we obtained 331 SCZ-related genes, 650 AD-related genes, 65 shared genes between SCZ and AD. Enrichment analysis shown that these 65 shared genes were mainly involved in cognition, neural development, synaptic transmission, drug reactions, metabolic processes and immune related processes, suggesting a complex mechanism for the co-existence of SCZ and AD. In addition, we performed pathway enrichment analysis and found a total of 57 common pathways between SCZ and AD, which could be largely grouped into three modules: immune module, neurodevelopment module and cancer module. We eventually identified the potential disease-related genes whose interactions provide clues to the overlapping symptoms between SCZ and AD.


Assuntos
Doença de Alzheimer , Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/metabolismo , Doença de Alzheimer/genética , Transmissão Sináptica , Comorbidade
8.
Sci Bull (Beijing) ; 69(4): 512-525, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38160175

RESUMO

In vaccine development, broadly or cross-type neutralizing antibodies (bnAbs or cnAbs) are frequently targeted to enhance protection. Utilizing immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization strategies. However, the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly elucidated. In this study, we discovered a cross-type neutralizing monoclonal antibody, 13H5, against human papillomavirus 6 (HPV6) and HPV11. This nAb exhibited a marked preference for HPV6, demonstrating superior binding activity to virus-like particles (VLPs) and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum (90% vs. 31%). Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex, we delineated the epitope as spanning four segments of amino acids (Phe42-Ala47, Gly172-Asp173, Glu255-Val275, and Val337-Tyr351) on the L1 surface loops. Further interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and L1. Substituting Ser341 with alanine, which is the residue type present in HPV11 L1, almost completely abolished binding activity to 13H5. By swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1 (Ser341, Thr338, and Thr339), we engineered chimeric HPV11-6HI VLPs. Remarkably, the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human primates. This approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.


Assuntos
Vacinas contra Papillomavirus , Animais , Camundongos , Anticorpos Amplamente Neutralizantes , Proteínas do Capsídeo/genética , Anticorpos Antivirais , Papillomavirus Humano 6 , Imunização , Aminoácidos
9.
Antioxidants (Basel) ; 12(12)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38136152

RESUMO

Selenium (Se) is an indispensable trace element with versatile functions in antioxidant defense in poultry. In our previous study, we synthesized a novel type of biogenic selenium nanoparticle based on alginate oligosaccharides (SeNPs-AOS), and found that the particles are sized around 80 nm with an 8% Se content, and the dietary addition of 5 mg/kg of SeNPs-AOS could effectively alleviate the deleterious effects of heat stress (HS) in broilers, but it is still unclear whether SeNPs-AOS can improve the meat quality. Therefore, the aim of this study was to evaluate the protective effects of SeNPs-AOS on breast meat quality in heat-stressed broilers, and explore the relevant mechanisms. Birds at the age of 21 days were randomly divided into four groups with six replicates per group (eight broilers per replicate) according to a 2 × 2 experimental design, using HS (33 ± 2 °C, 10 h/day vs. thermoneutral, TN, under 23 ± 1.5 °C) and SeNPs-AOS (5 mg/kg feed vs. no inclusion) as variables. The results showed that dietary SeNPs-AOS decreased the cooking loss (p < 0.05), freezing loss (p < 0.001), and shear force (p < 0.01) of breast muscle in heat-stressed broilers. The non-targeted metabolomics analysis of the breast muscle identified 78 differential metabolites between the HS and HS + SeNPs-AOS groups, mainly enriched in the arginine and proline metabolism, ß-alanine metabolism, D-arginine and D-ornithine metabolism, pantothenate, and CoA biosynthesis pathways (p < 0.05). Meanwhile, supplementation with SeNPs-AOS increased the levels of the total antioxidant capacity (T-AOC), the activities of catalase (CAT) and glutathione peroxidase (GSH-Px), and decreased the content of malondialdehyde (MDA) in the breast muscle (p < 0.05) in broilers under HS exposure. Additionally, SeNPs-AOS upregulated the mRNA expression of CAT, GPX1, GPX3, heme oxygenase-1 (HO-1), masculoaponeurotic fibrosarcoma G (MafG), MafK, selenoprotein W (SELENOW), SELENOK, ferritin heavy polypeptide-1 (FTH1), Ferroportin 1 (Fpn1), and nuclear factor erythroid 2-related factor 2 (Nrf2) (p < 0.05), while it downregulated Kelch-like ECH-associated pro-36 tein 1 (Keap1) and prostaglandin-endoperoxide Synthase 2 (PTGS2) expression (p < 0.05) in broilers under HS. These findings demonstrated that the dietary addition of SeNPs-AOS mitigated HS-induced oxidative damage and metabolite changes in the breast muscle of broilers, which may be related to the regulation of the Nrf2 signaling pathway and selenoprotein synthesis. In addition, SeNPs-AOS upregulated the breast muscle gene expression of anti-ferroptosis-related molecules in broilers under HS, suggesting that SeNPs-AOS can be used as novel Se supplements against HS in broilers.

10.
J Neuroinflammation ; 20(1): 264, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968698

RESUMO

BACKGROUND: Lipid metabolism has a crucial role in neural repair in neurodegenerative diseases. We recently revealed that lipogenesis-mediated interleukin-33 (IL-33) upregulation lead to blood-brain barrier (BBB) repair after ischemic stroke. However, manipulating the key enzyme fatty acid synthase (FASN) to enhance lipogenesis was very challenging. Glyceryl triacetate (GTA) was used as a donor of acetate and precursor of acetyl coenzyme A, the key substrate for de novo lipogenesis catalyzed by FASN. Therefore, we hypothesized that GTA would promote lipogenesis the peri-infarct after ischemic stroke and contribute to the BBB repair through IL-33. METHODS: Middle cerebral artery occlusion (MCAO) was performed on C57BL mice and GTA was gavage administrated (4 g/kg) on day 2 and 4 after MCAO. Lipogenesis was evaluated by assessment of the protein level of FASN, lipid droplets, and fatty acid products through liquid chromatography-mass spectrometry in the peri-infarct area on day 3 after MCAO, respectively. BBB permeability was determined by extravasation of Evans blue, IgG and dextran, and levels of tight junction proteins in the peri-infarct area on day 7 after MCAO, respectively. Infarct size and neurological defects were assessed on day 7 after MCAO. Brain atrophy on day 30 and long-term sensorimotor abilities after MCAO were analyzed as well. The inhibitor of FASN, C75 and the virus-delivered FASN shRNA were used to evaluate the role of FASN-driven lipogenesis in GTA-improved BBB repair. Finally, the therapeutic potential of recombinant IL-33 on BBB repair and neurological recovery was evaluated. RESULTS: We found that treatment with GTA increased the lipogenesis as evidenced by lipid droplets level and lauric acid content, but not the FASN protein level. Treatment with GTA increased the IL-33 level in the peri-infarct area and decreased the BBB permeability after MCAO. However, infarct size and neurological defect score were unchanged on day 7 after MCAO, while the long-term recovery of sensorimotor function and brain atrophy were improved by GTA. Inhibition of lipogenesis using C75 or FASN shRNA reversed the beneficial effect of GTA. Finally, exogenous IL-33 improved BBB repair and long-term functional recovery after stroke. CONCLUSION: Collectively, we concluded that treatment with GTA improved the BBB repair and functional recovery after ischemic stroke, probably by the enhancement of lipogenesis and IL-33 expression.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Camundongos , Animais , AVC Isquêmico/patologia , Barreira Hematoencefálica , Interleucina-33/farmacologia , Lipogênese , Camundongos Endogâmicos C57BL , Acidente Vascular Cerebral/patologia , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , RNA Interferente Pequeno/metabolismo , Atrofia/patologia , Isquemia Encefálica/metabolismo
11.
Biochem Genet ; 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37952039

RESUMO

SLC4A4 variants are the etiologies of inherited proximal renal tubular acidosis (pRTA), which results in metabolic acidosis, hypokalemia, glaucoma, band keratopathy, and cataract. This study aims to characterize SLC4A4 variant and uniparental isodisomy of chromosome 4 in a patient, and analyse the functional characterization of SLC4A4 variants. This study analyzed renal tubular acidosis disease genes by whole exome sequencing (WES). H3M2 algorithm was used to analyze the run of homozygosity region in chromosomal regions in trio-WES data. The pathogenicity analysis of variants was performed using bioinformatics tools. Additionally, protein stability was analyzed by cycloheximide chase assay. Whole-cell patch clamping was used to examine the electrophysiological properties of NBCe1-A. A novel homozygous SLC4A4 variant was identified in the patient: a missense variant c.496C > T, p. Arg166Trp (NM_003759.4). But the father was heterozygous variant carrier, and the mother did not detect the variant. The H3M2 and UPDio algorithm revealed paternal uniparental isodisomy on chromosome 4 in the patient. SIFT, Poly Phen-2, FATHMM and Mutant Taster showed that the variant might be pathogenic. The tertiary structure analysis showed that the variant could cause structural damage to NBCe1 protein. Foldx results showed that the protein stability of the variant was slightly reduced. Cycloheximide chase assay demonstrated that the variant affects protein stability. The result of electrophysiological studies showed that the variant altered Na+/HCO3- cotransport activity of protein. In conclusion, the study is the first to report a pRTA patient with Arg166Trp variant with UPiD (4) pat and analyze the function of Arg166Trp variant.

12.
BMC Psychol ; 11(1): 402, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37986096

RESUMO

INTRODUCTION: The objective of this research was to investigate the effect of person-job fit on occupational commitment among Chinese kindergarten teachers, and to identify strategies for improving the occupational commitment of this professional group. METHODS: A survey was conducted among kindergarten teachers utilizing the Occupational Commitment Scale, Person-job Fit Scale, Occupational Well-being Scale, and Perceived Organizational Support Scale, resulting in the acquisition of 1539 valid data. RESULTS: A significant positive correlation was observed between person-job fit and occupational commitment, with occupational well-being serving as a partial mediator in this association. Additionally, the direct effect of person-job fit on occupational commitment was moderated by perceived organizational support. Specifically, a significant positive correlation between person-job fit and occupational commitment was evident when the scores of perceived organizational support were below 0.21, whereas a significant negative correlation was observed when the scores of perceived organizational support were above 1.67. CONCLUSIONS: In order to enhance the degree of occupational commitment among kindergarten teachers, it is imperative to pay attention to their person-job fit, perceived organizational support, and occupational well-being.


Assuntos
Povo Asiático , Satisfação no Emprego , Professores Escolares , Humanos , Inquéritos e Questionários
13.
ACS Nano ; 17(23): 23430-23441, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38011322

RESUMO

The mechanisms of action (MoA) have been proposed to further reduce the O2 dependence of photodynamic therapy (PDT) significantly. However, the triplet states of traditional photosensitizers are relatively short and also are easily deactivated by the quenching of H2O or O2. This is not conducive for the electron transfer in the photocatalytic process and poses a great obstacle to establish the MoA. Therefore, we selected and synthesized a zirconium(IV) complex (Zr(MesPDPPh)2) reported by Milsmann to address this issue. The specific symmetric and intact geometry endowed Zr(MesPDPPh)2 NPs with long-lived triplet excited state (τ = 350 µs), desired sensitized ability, and improved anti-interfering performance on O2, which was matched with the requirements of photoredox catalyst significantly. The results showed that while PDT (I) and PDT (II) could be achieved simultaneously by leveraging Zr(MesPDPPh)2 NPs, it also could be served as a rare example of thermally activated delayed fluorescence (TADF)-based photoredox catalyst to implement the MoA of PDT. It involved the oxidation of NADH and the establishment of catalytic cycle collaborating by O2 and cytochrome c (cyt c) in normoxia and hypoxia, respectively. As a result, the oxygen-free PDT and tumor-growth inhibition was realized.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Fluorescência , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias/tratamento farmacológico
15.
Ecotoxicol Environ Saf ; 266: 115579, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37856979

RESUMO

In the background of climate warming, the demand for improving soil quality and carbon (C) sequestration is increasing. The application of biochar to soil has been considered as a method for mitigating climate change and enhancing soil fertility. However, it is uncertain whether the effects of biochar application on C-mineralization and N transformation are influenced by the presence or absence of plant growth-promoting bacteria (PGPB) and soil nitrogen (N) level. An incubation study was conducted to investigate whether the effects of biochar application (0 %, 1 %, 2 % and 4 % of soil mass) on soil respiration, N status, and microbial attributes were altered by the presence or absence of PGPB (i.e., Sphingobium yanoikuyae BJ1) under two soil N levels (N0 and N1 soils as created by the addition of 0 and 0.2 g kg-1 urea- N, respectively). The results showed that biochar, BJ1 strain and their interactive effects on cumulative CO2 emissions were not significant in N0 soils, while the effects of biochar on the cumulative CO2 emissions were dependent on the presence or absence of BJ1 in N1 soils. In N1 soils, applying biochar at 2 % and 4 % increased the cumulative CO2 emissions by 141.0 % and 166.9 %, respectively, when BJ1 was absent. However, applying biochar did not affect CO2 emissions when BJ1 was present. In addition, the presence of BJ1 generally increased ammonium contents in N0 soils, but decreased nitrate contents in N1 soils relative to the absence of BJ1, which indicates that the combination of biochar and BJ1 is beneficial to play the N fixation function of BJ1 in N0 soils. Our results highlight that biochar addition influences not only soil C mineralization but also soil available N, and the direction and magnitude of these effects are highly dependent on the presence of PGPB and the soil N level.


Assuntos
Carbono , Solo , Nitrogênio/análise , Dióxido de Carbono/análise , Carvão Vegetal/farmacologia , Bactérias
16.
Front Bioeng Biotechnol ; 11: 1261563, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818237

RESUMO

Daqu is a spontaneous, solid-state cereal fermentation product used for saccharification and as a starter culture for Chinese Baijiu production. Bacillus and Acinetobacter, two dominant microbial genera in Daqu, produce enzymes and organic acids that influence the Daqu quality. However, there are no rapid analytical methods for detecting Bacillus and Acinetobacter. We designed primers specific to the genera Bacillus and Acinetobacter to perform genetic comparisons using the 16 S rRNA. After amplification of polymerase chain reaction using specific primers, high-throughput sequencing was performed to detect strains of Bacillus and Acinetobacter. The results showed that the effective amplification rates for Bacillus and Acinetobacter in Daqu were 86.92% and 79.75%, respectively. Thus, we have devised and assessed a method to accurately identify the species associated with Bacillus and Acinetobacter in Daqu, which can also hold significance for bacterial typing and identification.

17.
Heliyon ; 9(9): e20369, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809939

RESUMO

In the field of early childhood education, research has increasingly paid attention to male kindergarten teachers as research subjects. The shortage of male professionals in this field, coupled with the persistent issue of high turnover rates, presents significant challenges to the preschool education sector. Elevating the retention rate of male kindergarten teachers stands as a vital concern, with occupational commitment emerging as a pivotal factor influencing retention. This study endeavors to construct a moderated mediation model to unveil the potential pathways through which perceived organizational support, occupational well-being, and person-job fit impact occupational commitment. This study administered a questionnaire that included person-job fit, perceived organizational support, occupational well-being, and occupational commitment scales. The study collected 402 valid responses from male kindergarten teachers. The findings reveal several key insights: perceived organizational support has a positive direct influence on occupational commitment; occupational well-being acts as a mediator in the relationship between perceived organizational support and occupational commitment; and person-job fit plays a moderating role, negatively impacting the predictive effect of occupational well-being on occupational commitment. Consequently, perceived organizational support can exert both a direct influence on occupational commitment and an indirect impact, mediated by occupational well-being, with person-job fit moderating the latter pathway. These results contribute to the quantitative literature surrounding male kindergarten teachers, offering valuable insights. Moreover, they furnish policymakers in preschool education and kindergarten management with effective strategies to bolster the occupational commitment of male kindergarten teachers, ultimately addressing the pressing issue of teacher turnover in this field.

18.
Int J Biol Macromol ; 252: 126450, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37634779

RESUMO

The estrogen receptor-positive (ER+) breast cancers constitute more than 50 % of breast cancers, seriously threatening the health of women. Unfortunately, the detection and targeted therapy of ER+ breast cancers remain a challenge. Here, a novel nucleic acid aptamer S1-4 was developed to specifically target ER+ breast cancer MCF-7 cells by using Cell-SELEX and nucleic acid truncation strategies. The affinity dissociation constant of the binding of aptamer S1-4 to MCF-7 cells was 97.6 ± 7.5 nM in vitro. Compared with HER2+ breast cells SK-BR-3 and triple-negative breast cancer cells MDA-MB-231, MCF-7 cells were selectively recognized and targeted by aptamer S1-4. Fluorescence tracing in vivo results also indicated that aptamer S1-4 selectively targeted the cell membrane of tumor tissues in MCF-7- but not in SK-BR3 or MDB-MA-231-bearing mice. This selectively developed novel aptamer probe S1-4 with high affinity could be used for the diagnosis and treatment of ER+ breast cancers.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias da Mama , Ácidos Nucleicos , Humanos , Feminino , Animais , Camundongos , Neoplasias da Mama/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Receptores de Estrogênio/genética , Células MCF-7 , Linhagem Celular Tumoral
19.
Biomed Pharmacother ; 165: 115085, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37392656

RESUMO

Long periods of sleep deprivation (SD) have serious effects on health. While the α2 adrenoceptor agonist dexmedetomidine (DEX) can improve sleep quality for patients who have insomnia, the effect of DEX on cognition and mechanisms after SD remains elusive. C57BL/6 mice were subjected to 20 h SD daily for seven days. DEX (100 µg/kg) was administered intravenously twice daily (at 1:00 p.m. and 3:00 p.m.) during seven days of SD. We found that systemic administration of DEX attenuated cognitive deficits by performing the Y maze and novel object recognition tests and increased DCX+, SOX2+, Ki67+, and BrdU+NeuN+/NeuN+ cell numbers in the dentate gyrus (DG) region of SD mice by using immunofluorescence, western blotting, and BrdU staining. DEX did not reverse the decrease in DCX+, SOX2+, or Ki67+ cell numbers in SD mice after administration of the α2A-adrenoceptor antagonist BRL-44408. Furthermore, the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) expression was upregulated in SD+DEX mice compared with SD mice. Luminex analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of neuroinflammation, including IL-1α, IL-2, CCL5, and CXCL1. Our results suggested that DEX alleviated the impaired learning and memory of SD mice potentially by inducing hippocampal neurogenesis via the VEGF-VEGFR2 signaling pathway and by suppressing neuroinflammation, and α2A adrenoceptors are required for the neurogenic effects of DEX after SD. This novel mechanism may add to our knowledge of DEX in the clinical treatment of impaired memory caused by SD.


Assuntos
Dexmedetomidina , Camundongos , Animais , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Doenças Neuroinflamatórias , Privação do Sono/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Bromodesoxiuridina/farmacologia , Antígeno Ki-67/metabolismo , Camundongos Endogâmicos C57BL , Hipocampo , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Transdução de Sinais , Neurogênese
20.
Adv Healthc Mater ; 12(22): e2203144, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37141264

RESUMO

By conjugating a chemotherapeutic candidate drug 4ß-NH-(5-aminoindazole)-podophyllotoxin (ßIZP) and an immunosuppressive protein galectin-1 targeted aptamer AP74, a chemo-immunotherapy molecule (AP74-ßIZP) is developed against liver cancer. AP74-ßIZP can target galectin-1 and enrich the tumor microenvironment to improve the tumor inhibition ratio by 6.3%, higher than that of ßIZP in a HepG2 xenograft model. In safety evaluation, ßIZP cannot be released from AP74-ßIZP in normal tissues with low glutathione level. Therefore, the degrees of organs injury and myelosuppression after the treatment with AP74-ßIZP are lower than those with ßIZP. After 21 d treatment at a drug dose of 5 mg kg-1 , AP74-ßIZP does not cause weight loss in mice, while the weight is significantly reduced by 24% and 14% from oxaliplatin and ßIZP, respectively. In immune synergy, AP74-IZP enhances CD4/CD8 cell infiltration to promote the expression of cell factor (i.e., IL-2, TNF-α, and IFN-γ), which further improves the antitumor activity. The tumor inhibition ratio of AP74-ßIZP is 70.2%, which is higher than that of AP74 (35.2%) and ßIZP (48.8%). Because of the dual effects of chemotherapy and immunotherapy, AP74-ßIZP exhibits superior activity and lower toxicity. The approach developed in this work could be applicable to other chemotherapy drugs.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Podofilotoxina/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Galectina 1 , Neoplasias Hepáticas/tratamento farmacológico , Imunoterapia , Microambiente Tumoral
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