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1.
Small ; : e2309583, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446095

RESUMO

Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, characterized by aggressiveness and high recurrence rate. As monotherapy provides limited benefit to TNBC patients, combination therapy emerges as a promising treatment approach. Gambogic acid (GA) is an exceedingly promising anticancer agent. Nonetheless, its application potential is hampered by low drug loading efficiency and associated toxic side effects. To overcome these limitations, using mesoporous polydopamine (MPDA) endowed with photothermal conversion capabilities is considered as a delivery vehicle for GA. Meanwhile, GA can inhibit the activity of heat shock protein 90 (HSP90) to enhance the photothermal effect. Herein, GA-loaded MPDA nanoparticles (GA@MPDA NPs) are developed with a high drug loading rate of 75.96% and remarkable photothermal conversion performance. GA@MPDA NPs combined with photothermal treatment (PTT) significantly inhibit the tumor growth, and effectively trigger the immunogenic cell death (ICD), which thereby increase the number of activated effector T cells (CD8+ T cells and CD4+ T cells) in the tumor, and hoist the level of immune-inflammatory cytokines (IFN-γ, IL-6, and TNF-α). The above results suggest that the combination of GA@MPDA NPs with PTT expected to activate the antitumor immune response, thus potentially enhancing the clinical therapeutic effect on TNBC.

2.
Small ; 19(49): e2304370, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37587781

RESUMO

Reprogramming the immunologically "cold" environment of solid tumors is currently becoming the mainstream strategy to elicit powerful and systemic anticancer immunity. Here, a facile and biomimetic nano-immunnoactivator (CuS/Z@M4T1 ) is detailed by engineering a Zn2+ -bonded zeolitic imidazolate framework-8 (ZIF-8) with CuS nanodots (NDs) and cancer cell membrane for amplified near-infrared-II (NIR-II) photothermal immunotherapy via Zn2+ metabolic modulation. Taking advantage of the NIR-II photothermal effect of CuS NDs and the acidic responsiveness of ZIF-8, CuS/Z@M4T1 rapidly causes intracellular Zn2+ pool overload and disturbs the metabolic flux of 4T1 cells, which effectively hamper the production of heat shock proteins and relieve the resistance of photothermal therapy (PTT). Thus, amplified immunogenic cell death is evoked and initiates the immune cascade both in vivo and in vitro as demonstrated by dendritic cells maturation and T-cell infiltration. Further combination with antiprogrammed death 1 (aPD-1) achieves escalated antitumor efficacy which eliminates the primary, distant tumor and avidly inhibits lung metastasis due to cooperation of enhanced photothermal stimulation and empowerment of cytotoxic T lymphocytes by aPD-1. Collectively, this work provides the first report of using the intrinsic modulation property of meta-organometallic ZIF-8 for enhanced cancer photoimmunotherapy together with aPD-1, thereby inspiring a novel combined paradigm of ion-rich nanomaterials for cancer treatment.


Assuntos
Nanopartículas , Neoplasias , Humanos , Adjuvantes Imunológicos , Biomimética , Fototerapia , Neoplasias/terapia , Imunoterapia , Linhagem Celular Tumoral
3.
Mol Plant Microbe Interact ; 35(3): 257-273, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34931906

RESUMO

The lipopolysaccharides (LPS) of gram-negative bacteria trigger a nitrosative and oxidative burst in both animals and plants during pathogen invasion. Liberibacter crescens strain BT-1 is a surrogate for functional genomic studies of the uncultured pathogenic 'Candidatus Liberibacter' spp. that are associated with severe diseases such as citrus greening and potato zebra chip. Structural determination of L. crescens LPS revealed the presence of a very long chain fatty acid modification. L. crescens LPS pretreatment suppressed growth of Xanthomonas perforans on nonhost tobacco (Nicotiana benthamiana) and X. citri subsp. citri on host orange (Citrus sinensis), confirming bioactivity of L. crescens LPS in activation of systemic acquired resistance (SAR). L. crescens LPS elicited a rapid burst of nitric oxide (NO) in suspension cultured tobacco cells. Pharmacological inhibitor assays confirmed that arginine-utilizing NO synthase (NOS) activity was the primary source of NO generation elicited by L. crescens LPS. LPS treatment also resulted in biological markers of NO-mediated SAR activation, including an increase in the glutathione pool, callose deposition, and activation of the salicylic acid and azelaic acid (AzA) signaling networks. Transient expression of 'Ca. L. asiaticus' bacterioferritin comigratory protein (BCP) peroxiredoxin in tobacco compromised AzA signaling, a prerequisite for LPS-triggered SAR. Western blot analyses revealed that 'Ca. L. asiaticus' BCP peroxiredoxin prevented peroxynitrite-mediated tyrosine nitration in tobacco. 'Ca. L. asiaticus' BCP peroxiredoxin (i) attenuates NO-mediated SAR signaling and (ii) scavenges peroxynitrite radicals, which would facilitate repetitive cycles of 'Ca. L. asiaticus' acquisition and transmission by fecund psyllids throughout the limited flush period in citrus.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Citrus , Rhizobiaceae , Proteínas de Bactérias , Citrus/microbiologia , Grupo dos Citocromos b , Ferritinas , Liberibacter , Lipopolissacarídeos/metabolismo , Estresse Nitrosativo , Peroxirredoxinas/metabolismo , Doenças das Plantas/microbiologia , Rhizobiaceae/metabolismo
4.
Chem Rec ; 21(4): 781-796, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33634962

RESUMO

Polydopamine (PDA) has attracted much attention recently due to its strong adhesion capability to most substrates. After combining with organic (such as organic metal framework, micelles, hydrogel, polypeptide copolymer) or inorganic nanomaterials (such as gold, silicon, carbon), polydopamine-based nanoparticles (PDA NPs) exhibit the merging of characteristics. Until now, the preparation methods, polymerization mechanism, and photothermal therapy (PTT) or chemotherapy (CT) applications of PDA NPs have been reported detailly. Since the PTT or CT treatment process is often accompanied by exogenous stimuli, tumor cells usually induce pro-survival autophagy to protect the cells from further damage, which will weaken the therapeutic effect. Therefore, an in-depth understanding of PDA NPs modulated PTT, CT, and autophagy is required. However, this association is rarely reviewed. Herein, we briefly described the relationship between PTT/CT, autophagy, and tumor treatment. Then, the outstanding performances of PDA NPs in PTT/CT and their combination with autophagy inhibitors for tumor synergistic therapy have been summarized. This work is expected to shed light on the multi-strategy antitumor therapy applications of PDA NPs.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Indóis/farmacologia , Nanopartículas/química , Neoplasias/tratamento farmacológico , Terapia Fototérmica , Polímeros/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Humanos , Indóis/química , Neoplasias/patologia , Polímeros/química
5.
J Nanobiotechnology ; 19(1): 222, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34320994

RESUMO

BACKGROUND: Rupture of atherosclerotic plaque can cause acute malignant heart and cerebrovascular events, such as acute coronary heart disease, stroke and so on, which seriously threaten the safety of human life and property. Therefore, the early diagnosis and inhibition of atherosclerotic plaque progress still be a vital task. RESULTS: In this study, we presented the development of composite mesoporous silica nanoparticle (Ru(bpy)3@SiO2-mSiO2, CMSN)-based nanomedicines (NMs) (Ru(bpy)3@SiO2-mSiO2@SRT1720@AntiCD36, CMSN@SRT@Anti) for accurate diagnosis and treatment of atherosclerosis (AS). In vitro cell experiments showed that both RAW264.7 and oxidized low density lipoprotein (ox-LDL)-stimulated RAW264.7 cells could significantly uptake CMSN@SRT@Anti. Conversely, little fluorescence signal could be observed in CMSN@SRT group, showing the excellent targeting ability of CMSN@SRT@Anti to Class II scavenger receptor, CD36 on macrophage. Additionally, such fluorescence signal was significantly stronger in ox-LDL-stimulated RAW264.7 cells, which might benefit from the upregulated expression of CD36 on macrophages after ox-LDL treatment. For another, compared with free SRT1720, CMSN@SRT@Anti had a better and more significant effect on the inhibition of macrophage foaming process, which indicated that drug-carrying mesoporous silicon with targeting ability could enhance the efficacy of SRT1720. Animal experimental results showed that after the abdominal injection of CMSN@SRT@Anti, the aortic lesions of ApoE-/-mice could be observed with obvious and persistent fluorescence signals. After 4 weeks post-treatment, the serum total cholesterol, aortic plaque status and area were significantly improved in the mouse, and the effect was better than that in the free SRT1720 group or the CMSN@SRT group. CONCLUSIONS: The designed CMSN@SRT@Anti with excellent biocompatibility, high-performance and superior atherosclerosis-targeting ability has great potential for accurate identification and targeted therapy of atherosclerotic diseases.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Imagem Óptica/métodos , Medicina de Precisão/métodos , Animais , Antígenos CD36 , Liberação Controlada de Fármacos , Fluorescência , Compostos Heterocíclicos de 4 ou mais Anéis , Lipoproteínas LDL , Camundongos , Camundongos Knockout , Células NIH 3T3 , Placa Amiloide , Placa Aterosclerótica , Células RAW 264.7 , Dióxido de Silício , Nanomedicina Teranóstica/métodos
6.
BMC Microbiol ; 20(1): 91, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293266

RESUMO

BACKGROUND: Bacterial blight of cotton (BBC), which is caused by the bacterium Xanthomonas citri pv. malvacearum (Xcm), is a destructive disease in cotton. Transcription activator-like effectors (TALEs), encoded by tal-genes, play critical roles in the pathogenesis of xanthomonads. Characterized strains of cotton pathogenic Xcm harbor 8-12 different tal genes and only one of them is functionally decoded. Further identification of novel tal genes in Xcm strains with virulence contributions are prerequisite to decipher the Xcm-cotton interactions. RESULTS: In this study, we identified six tal genes in Xss-V2-18, a highly-virulent strain of Xcm from China, and assessed their role in BBC. RFLP-based Southern hybridization assays indicated that Xss-V2-18 harbors the six tal genes on a plasmid. The plasmid-encoded tal genes were isolated by cloning BamHI fragments and screening clones by colony hybridization. The tal genes were sequenced by inserting a Tn5 transposon in the DNA encoding the central repeat region (CRR) of each tal gene. Xcm TALome evolutionary relationship based on TALEs CRR revealed relatedness of Xss-V2-18 to MSCT1 and MS14003 from the United States. However, Tal2 of Xss-V2-18 differs at two repeat variable diresidues (RVDs) from Tal6 and Tal26 in MSCT1 and MS14003, respectively, inferred functional dissimilarity. The suicide vector pKMS1 was then used to construct tal deletion mutants in Xcm Xss-V2-18. The mutants were evaluated for pathogenicity in cotton based on symptomology and growth in planta. Four mutants showed attenuated virulence and all contained mutations in tal2. One tal2 mutant designated M2 was further investigated in complementation assays. When tal2 was introduced into Xcm M2 and expressed in trans, the mutant was complemented for both symptoms and growth in planta, thus indicating that tal2 functions as a virulence factor in Xcm Xss-V2-18. CONCLUSIONS: Overall, the results demonstrated that Tal2 is a major pathogenicity factor in Xcm strain Xss-V2-18 that contributes significantly in BBC. This study provides a foundation for future efforts aimed at identifying susceptibility genes in cotton that are targeted by Tal2.


Assuntos
Gossypium/microbiologia , Análise de Sequência de DNA/métodos , Efetores Semelhantes a Ativadores de Transcrição/genética , Xanthomonas/patogenicidade , Proteínas de Bactérias/genética , China , Elementos de DNA Transponíveis , Gossypium/crescimento & desenvolvimento , Mutação INDEL , Filogenia , Doenças das Plantas/microbiologia , Plasmídeos/genética , Polimorfismo de Fragmento de Restrição , Fatores de Virulência/genética , Xanthomonas/genética
7.
Analyst ; 145(3): 836-843, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31830167

RESUMO

Transition-metal dichalcogenides (TMDCs) have attracted a lot of attention due to their electronic, optical, mechanical, and catalytic properties. In addition, TMDCs possess rich redox chemistry that enables the decoration of metal nanoparticles directly on their surfaces. In this paper, MnO2/MoS2 nanocomplexes were obtained by the spontaneous reduction of KMnO4 with MoS2 QDs as the reductive agent. The formed MnO2/MoS2 nanocomplexes exhibited activated fluorescence and MR imaging signal in the presence of glutathione (GSH). After conjugation with an AS1411 aptamer, specific in vivo MR imaging and fluorescence labeling of the 786-O tumor cells were realized, showing their promising potential for biomedical applications.


Assuntos
Dissulfetos/química , Glutationa/química , Molibdênio/química , Permanganato de Potássio/química , Pontos Quânticos/química , Animais , Aptâmeros de Nucleotídeos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Oxirredução , Pontos Quânticos/toxicidade
8.
Biochem Biophys Res Commun ; 516(4): 1090-1096, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31279525

RESUMO

"Bottom-up" method is a popular approach for the preparation of molybdenum disulfide quantum dots (MoS2 QDs) benefitting from less time consumption and no high-powered sonication required. But the relatively low fluorescent quantum yield of the obtained MoS2 QDs and the rare study about their in vivo behavior stimulate us to do more research in this area. In this paper, we proposed a "bottom-up" hydrothermal method to prepare MoS2 QDs with a quantum yield (QY) of 34.55% by optimizing a series of reaction conditions. The successful fluorescence imaging of tumor cells in vitro and in vivo as well as the systematic in vivo behavior study such as biocompatibility, biodistribution and metabolism route provided the good basis for their wider biomedical applications.


Assuntos
Neoplasias do Colo/diagnóstico por imagem , Dissulfetos/análise , Molibdênio/análise , Imagem Óptica/métodos , Pontos Quânticos/análise , Animais , Linhagem Celular Tumoral , Dissulfetos/farmacocinética , Humanos , Camundongos Endogâmicos BALB C , Molibdênio/farmacocinética , Nanotecnologia/métodos , Pontos Quânticos/ultraestrutura , Distribuição Tecidual
9.
J Nanobiotechnology ; 17(1): 44, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30917812

RESUMO

BACKGROUND: The combination of multiple chemotherapeutics has been used in the clinic for enhanced cancer chemotherapy, however, frequent relapse, chemo-resistance and side effects remains therapeutic hurdles. Thus, the development of co-delivery system with enhanced targeting and synergistic different modal treatments has been proposed as promising strategies for intensive improvement of the therapeutic outcomes. RESULTS: We fabricated a nanocarrier based on gold nanorods (Au NRs), cRGD peptide-modified and multi-stimuli-responsive paclitaxel (PTX) and curcumin (CUR) release for synergistic anticancer effect and chemo-photothermal therapy (PTX/CUR/Au NRs@cRGD). The specific banding of cRGD to αvß3 integrin receptor on the tumor cell surfaces facilitated the endocytosis of PTX/CUR/Au NRs@cRGD, and the near-infrared ray (NIR) further enhanced the drug release and chemotherapeutical efficiency. Compared to single drug, single model treatment or undecorated-PTX/CUR/Au NRs, the PTX/CUR/Au NRs@cRGD with a mild NIR showed significantly enhanced apoptosis and S phase arrest in three cancer cell lines in vitro, and improved drug accumulation in tumor sites as well as tumor growth inhibition in vivo. CONCLUSIONS: The tumor targeted chemo-photothermal therapy with the synergistic effect of dual drugs provided a versatile strategy for precise cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ouro/química , Nanotubos/química , Paclitaxel/administração & dosagem , Células A549 , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Células Hep G2 , Humanos , Raios Infravermelhos , Integrina alfaVbeta3/metabolismo , Células KB , Camundongos Endogâmicos BALB C , Paclitaxel/química , Tamanho da Partícula , Peptídeos Cíclicos/metabolismo , Fototerapia/métodos , Propriedades de Superfície
10.
Int J Cancer ; 142(10): 2094-2105, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29277889

RESUMO

Metastasis is the primary cause of death for most cancer patients. Hematogenous arrest of circulating tumor cells (CTCs) is an essential prerequisite for metastases formation. Using transparent transgenic zebrafish (kdrl:eGFP; Casper), together with resonant laser scanning confocal microscopy, we tracked the fate of CTCs in vivo in the blood circulation for days. We found the intra-capillary morphology-switch (ICMS) of individual CTCs from strip to sphere was necessary for their intravascular arrests. Further genetic and pharmacological inhibition experiments indicated that the RhoA signaling was necessary for ICMS and the arrest of CTCs. At last, we demonstrated that early treatment by a clinically approved RhoA/ROCK inhibitor, Fasudil, could efficiently inhibit the initial arrest of individual CTCs and reduce the incidence of tumor metastasis in both zebrafish and mouse models. These results together indicate that RhoA-stimulated ICMS represents a mechanism for the arrest of individual CTCs, providing a potential target for future treatments of hematogenous metastatic disease.


Assuntos
Capilares/patologia , Neoplasias Experimentais/patologia , Células Neoplásicas Circulantes/patologia , Proteína rhoA de Ligação ao GTP/metabolismo , Citoesqueleto de Actina , Animais , Animais Geneticamente Modificados , Capilares/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Neoplasias Experimentais/metabolismo , Células Neoplásicas Circulantes/metabolismo , Peixe-Zebra , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores
11.
J Enzyme Inhib Med Chem ; 31(5): 853-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26207511

RESUMO

A convenient and mild method for the synthesis of substituted furano [3,2-c]tetrahydroquinoline derivatives was developed, using the multi-component Povarov reaction. Of the synthesized tetrahydroquinoline derivatives, compound 10a displayed the greatest cellular proliferation inhibitory activities with IC50 values of 2.5-16.7 µmol/l. In addition, 10a induced murine C6 glioma cell apoptosis in a dose-dependent manner by up-regulating the expression of Bax, caspase-3, and caspase-9, and by down-regulating Bcl-2. Our findings suggest that these novel compounds have potential as therapeutic agents via inducing mitochondrial apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Furanos/síntese química , Furanos/farmacologia , Quinolinas/síntese química , Quinolinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Estrutura Molecular
12.
Microb Pathog ; 78: 87-94, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25450881

RESUMO

Glucose-6-phosphate dehydrogenase (Zwf) catalyzes conversion of glucose 6-phosphate into gluconate 6-phosphate for Entner-Doudoroff (ED) and pentose phosphate pathways in living organisms. However, it is unclear whether the Zwf-coding gene is involved in pathogenesis of phytopathogenic bacterium. In this report, we found that deletion mutation in zwf of Xanthomonas oryzae pv. oryzicola (Xoc), led the pathogen unable to effectively utilize glucose, sucrose, fructose, mannose and galactose for growth. The transcript level of zwf was strongly induced by glucose, sucrose, fructose, mannose and galactose than that by the NY medium (non sugar). The deletion mutagenesis in zwf also altered the transcript level of key genes, such as rpfF, rpfG and clp, in diffusible signal factor (DSF)-signaling network. In addition, the deletion mutation in zwf impaired bacterial virulence and growth capability in rice leaves, reduced bacterial cell motility and extracellular polysaccharide (EPS) production. The lost properties mentioned above in the zwf deletion mutant were completely restored to the wild-type level by the presence of zwf in trans. All these results suggest that zwf is required for the full virulence of Xoc in rice leaves by involving carbohydrate metabolisms that impact bacterial DSF-signaling network.


Assuntos
Proteínas de Bactérias/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Oryza/microbiologia , Doenças das Plantas/microbiologia , Polissacarídeos/biossíntese , Xanthomonas/citologia , Xanthomonas/enzimologia , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Glucosefosfato Desidrogenase/genética , Folhas de Planta/microbiologia , Virulência , Xanthomonas/metabolismo , Xanthomonas/patogenicidade
13.
Appl Environ Microbiol ; 80(13): 3908-19, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24747909

RESUMO

The type III secretion system (T3SS), encoded by hrp (hypersensitive response and pathogenicity) genes in Gram-negative phytopathogenic bacteria, delivers repertoires of T3SS effectors (T3SEs) into plant cells to trigger the hypersensitive response (HR) in nonhost or resistant-host plants and promote pathogenicity in susceptible plants. The expression of hrp genes in Xanthomonas is regulated by two key regulatory proteins, HrpG and HrpX. However, the interactions between hrp gene products in directing T3SE secretion are largely unknown. Here we demonstrated that HrcT of X. oryzae pv. oryzicola functions as a T3SS component and positively regulates the expression of hrpX. Transcription of hrcT occurs via two distinct promoters; one (T1) is with the hrpB operon and the second (T3) within hrpB7 Via either promoter T1 or T3, the defect in Hrp phenotype by hrcT deletion was corrected in the presence of hrcT only from Xanthomonas species but not from other phytopathogenic bacteria. An N-terminally truncated HrcT was able to bind the hrpX promoter and activate the expression of hrpX, supporting that HrcT is a positive regulator of hrpX. A revised model showing the regulatory interactions between HrcT, HrpX, and HrpG is proposed.


Assuntos
Proteínas de Bactérias/biossíntese , Sistemas de Secreção Bacterianos , Regulação Bacteriana da Expressão Gênica , Transativadores/metabolismo , Fatores de Transcrição/biossíntese , Xanthomonas/genética , Xanthomonas/metabolismo , Proteínas de Bactérias/genética , DNA Bacteriano/metabolismo , Deleção de Genes , Perfilação da Expressão Gênica , Teste de Complementação Genética , Regiões Promotoras Genéticas , Ligação Proteica , Transativadores/genética , Fatores de Transcrição/genética , Transcrição Gênica
14.
Ying Yong Sheng Tai Xue Bao ; 35(2): 347-353, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523091

RESUMO

In recent years, PM2.5 pollution has become a most important source of air pollution. Prolonged exposure to high PM2.5 concentrations can give rise to severe health issues. Negative air ion (NAI) is an important indicator for measuring air quality, which is collectively known as the 'air vitamin'. However, the intricate and fluctuating meteorological conditions and vegetation types result in numerous uncertainties in the correlation between PM2.5 and NAI. In this study, we collected data on NAI, PM2.5, and meteorological elements through positioning observation during the period of June to September in 2019 and 2020 under the condition of relatively constant leaf area in Quercus variabilis forest, a typical forest in warm temperate zones. We investigated the spatiotemporal variation of PM2.5 and NAI under consistent meteorological conditions, established the correlation between PM2.5 and NAI, and explicated the impact mechanism of PM2.5 on NAI in natural conditions. The results showed that NAI decreased exponentially with the increases in natural PM2.5, with a significant negative correlation (y=1148.79x-0.123). The decrease rates of NAI in PM2.5 concentrations of 0-20, 20-40, 40-80, 80-100 and 100-120 µg·m-3 were 40.1%, 36.2%, 9.4%, 2.4%, 5.1% and 6.8%, respectively. Results of the sensitivity analysis showed that the PM2.5 concentration range of 0-40 µg·m-3 was the sensitive range that affected NAI. Our findings could provide a scientific basis for better understanding the response mechanisms of NAI to environmental factors.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Quercus , Poluentes Atmosféricos/análise , Material Particulado/análise , Poluição do Ar/análise , Florestas , Monitoramento Ambiental/métodos , China
15.
Acta Pharm Sin B ; 14(3): 1345-1361, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38486995

RESUMO

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy. Here, a new type of spatiotemporal biomimetic "Gemini nanoimmunoregulators" was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death (ICD), tumor-associated macrophages (TAMs) phenotype reprogramming and programmed cell death ligand 1 (PD-L1) degradation. The "Gemini nanoimmunoregulators" PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine (mPDA) as nanovectors to deliver metformin (Met) and toll-like receptor 7/8 agonist resiquimod (R848) to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane (RM) inlaid with T7 or M2 peptides. mPDA/Met@RM-T7 (abbreviated as PM@RM-T7) was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity. Meanwhile, PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion. Subsequently, mPDA/R848@RM-M2 (abbreviated as PR@RM-M2) specifically recognized TAMs and reset the phenotype from M2 to M1 state, thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes. This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity, which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis. This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

16.
J Pharm Anal ; 14(4): 100914, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38694562

RESUMO

Recent trends suggest that Chinese herbal medicine formulas (CHM formulas) are promising treatments for complex diseases. To characterize the precise syndromes, precise diseases and precise targets of the precise targets between complex diseases and CHM formulas, we developed an artificial intelligence-based quantitative predictive algorithm (DeepTCM). DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling, molecular and theoretical levels of traditional Chinese medicine (TCM). As an example, our model simulated the optimal CHM formulas for the treatment of coronary heart disease (CHD) with depression, and through model sensitivity analysis, we calculated the balanced scoring of the formulas. Furthermore, we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions. Finally, we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice. This novel multiscale model opened up a new avenue to combine "disease syndrome" and "macro micro" system modeling to facilitate translational research in CHM formulas.

17.
J Environ Radioact ; 257: 107087, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36516665

RESUMO

An effective assessment of soil erosion and redistribution is a prerequisite for soil erosion control and is critical to achieving sustainable development goals. The most typical landscape in the karst region of Southwest China is found in the peak-cluster depression area, but little attention has been given to the soil redistribution here. A typical karst peak-cluster depression catchment water area in Southwest China was selected, and 137Cs technology was used to evaluate the soil redistribution rate and soil erosion process along a total transect (hillslope, depression and sinkhole) in the catchment. The results showed that the distribution of 137Cs had a high spatial variability on the total transect of the catchment (CV = 60.04%), the middle slope was the most severely eroded (highest erosion rate of 13.49 t ha-1 yr-1), and the area between the bottom slope and the depression was the primary sedimentary area on the surface in the catchment. The distribution of soil properties on the hillslope was affected by the process of soil redistribution. According to the distribution of the 137Cs soil profile, the soil profile of the hillslope was uniform, and signs of historical tillage activities were evident; the historical tillage activities of depressions were in the range of 0-20 cm depth, while the 137Cs in the sinkhole was mostly distributed in the shallow layers and decreased exponentially with depth, reflecting the depositional characteristics of noncultivated soil. In addition, this study found evidence of underground soil loss in sinkholes since the 1960s; the shallow sediment of these sinkholes mainly came from depressions, with an average deposition rate of 11.77 t ha-1 yr-1. Human disturbance and land-use change controlled recent changes in soil redistribution. The soil erosion rate of the hillslopes in catchments was extremely low (average erosion rate of 1.92 t ha-1 yr-1). The rocky desertification of hillslopes occurred before 1960; it was not a short-term contemporary process that occurred only during recent decades. This study showed that underground soil loss mainly occurred through sinkholes for a short period of time (100 years). These research results are of great significance for understanding the evolution of rocky desertification and the process of soil erosion.


Assuntos
Monitoramento de Radiação , Solo , Humanos , Radioisótopos de Césio/análise , Erosão do Solo , China
18.
Sci Total Environ ; 885: 163778, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37149184

RESUMO

Understanding the water use characteristics of plants is crucial for the sustainability of forest water management and vegetation restoration. The vegetation restoration program in the karst desertification areas of southwest China has been implemented for more than two decades, and remarkable achievements have been made in ecological restoration. However, the water use characteristics of revegetation are still poorly understood. We investigated the water uptake patterns and water use efficiency of four woody plants (Juglans regia, Zanthoxylum bungeanum, Eriobotrya japonica, and Lonicera japonica) using stable isotopes (δ2H, δ18O, and δ13C) in combination with the MixSIAR model. The results showed that plants responded to seasonal changes in soil moisture with flexible water uptake patterns. Differences in water use sources among the four plant species during the growing season indicated the occurrence of hydrological niche separation, which is the key to vegetation symbiosis. Throughout the study period, groundwater made the lowest contribution to plants (9.39 %~16.25 %), and fissure soil water made the highest contribution (39.74 %~64.71 %). Among them, shrubs and vines were more dependent on fissure soil water compared to trees (50.52 %~64.71 %). Furthermore, plant foliar δ13C was higher in the dry season than in the rainy season. Evergreen shrubs (-27.94 ‰) exhibited higher water use efficiency compared to other tree species (-30.48 ‰~-29.04 ‰). The water use efficiency of four plants showed seasonal variation and was influenced by the water availability caused by soil moisture. Our study demonstrates that fissure soil water is an important water source for karst desertification revegetation and that seasonal changes in water use characteristics are influenced by species-level water uptake patterns and water use strategies. This study provides a reference for vegetation restoration and water resource management in karst areas.


Assuntos
Conservação dos Recursos Naturais , Água , Estações do Ano , Plantas , Árvores , Solo , China , Ecossistema
19.
World Neurosurg ; 176: e297-e305, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37224957

RESUMO

OBJECTIVE: To evaluate the effects of 3 lumbar interbody fusion techniques on the occurrence of complications in an osteoporotic spine under whole-body vibration. METHODS: A previously developed and validated nonlinear finite element model of L1-S1was modified to develop anterior lumbar interbody fusion (ALIF), posterior lumbar interbody fusion (PLIF), and transforaminal lumbar interbody fusion (TLIF) models with osteoporosis. In each model, the lower surface of the sacrum was absolutely fixed, a follower load of 400N was applied through the axis of the lumbar spine, and an axial sinusoidal vertical load of ±40N (5 Hz) was imposed on the superior surface of L1, to perform a transient dynamic analysis. The maximal values of intradiscal pressure, shear stress on annulus substance, disc bulge, facet joint stress, and screw and rod stress, along with their dynamic response curves, were collected. RESULTS: Among these 3 models, the TLIF model generated the greatest screw and rod stress, and the PLIF model generated the greatest cage-bone interface stress. At the L3-L4 level, compared with the other 2 models, the maximal values and dynamic response curves of intradiscal pressure, shear stress of annulus ground substance, and disc bulge were all lower in the ALIF model. However, the facet contact stress at the adjacent segment in the ALIF model was higher than that in the other 2 models. CONCLUSIONS: In an osteoporotic spine under whole-body vibration, TLIF has the highest risk of screw and rod breakage, PLIF has the highest risk of cage subsidence, and ALIF has the lowest risk of upper adjacent disc degeneration, but the highest risk of adjacent facet joint degeneration.


Assuntos
Vértebras Lombares , Fusão Vertebral , Humanos , Vértebras Lombares/cirurgia , Vértebras Lombares/fisiologia , Vibração , Análise de Elementos Finitos , Amplitude de Movimento Articular/fisiologia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Fenômenos Biomecânicos
20.
World Neurosurg ; 171: e432-e439, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36521758

RESUMO

BACKGROUND: Adjacent segmental degeneration (ASD) is one common long-term complication of anterior cervical corpectomy and fusion (ACCF), and osteoporosis is one basic disease in the elderly. After ACCF, patients may experience osteoporosis with age. However, the influence of osteoporosis on ASD remains unclear. The purpose of this study was to determine whether osteoporosis could affect the development of ASD following ACCF. METHODS: Three finite element models of the cervical spine, including 1 normal model, 1 ACCF model, and 1 ACCF with osteoporosis model, were constructed. ACCF was simulated at the C4-C6 level. A 73.6 N follower load and a 1 Nm moment were imposed on the normal model, and the same follower load together with an adjusted moment was applied to the ACCF model and the ACCF with osteoporosis model, to simulate movement in each direction. The range of motion, intradiscal pressure, shear stress on anulus fibrosus, and facet joint stress at C3-C4 and C6-C7 levels of the models were calculated. RESULTS: In this study, the normal model was well validated. In flexion, extension, right lateral bending, and right axial rotation, the overall range of motion was 8.92°, 19.7°, 15.37°, and 45.27° in the normal model, and the adjusted moment was 1.4 Nm, 2.7 Nm, 1.1 Nm, and 2.6 Nm in the ACCF model, and 1.3 Nm, 2.5 Nm, 1.1 Nm, and 2.4 Nm in the ACCF with osteoporosis model. Despite of a few exceptions, the maximum values of the outcome measurements were mostly found in the ACCF model, and the minimum values in the normal model. Compared with the ACCF model, most of the outcome measurements were decreased in the ACCF with osteoporosis model. CONCLUSIONS: Osteoporosis can retard the adverse influence of ACCF on adjacent segments.


Assuntos
Vértebras Cervicais , Fusão Vertebral , Humanos , Idoso , Fenômenos Biomecânicos , Análise de Elementos Finitos , Amplitude de Movimento Articular
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