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1.
Sensors (Basel) ; 24(18)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39338897

RESUMO

With the development of the Internet of Things (IoT) and edge computing, more and more devices, such as sensor nodes and intelligent automated guided vehicles (AGVs), can serve as edge devices to provide Location-Based Services (LBS) through the IoT. As the number of applications increases, there is an abundance of sensitive information in the communication process, pushing the focus of privacy protection towards the communication process and edge devices. The challenge lies in the fact that most traditional location privacy protection algorithms are not suited for the IoT with edge computing, as they primarily focus on the security of remote servers. To enhance the capability of location privacy protection, this paper proposes a novel K-anonymity algorithm based on clustering. This novel algorithm incorporates a scheme that flexibly combines real and virtual locations based on the requirements of applications. Simulation results demonstrate that the proposed algorithm significantly improves location privacy protection for the IoT with edge computing. When compared to traditional K-anonymity algorithms, the proposed algorithm further enhances the security of location privacy by expanding the potential region in which the real node may be located, thereby limiting the effectiveness of "narrow-region" attacks.

2.
Nat Plants ; 10(8): 1184-1200, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-39103456

RESUMO

Scaffolding is crucial for constructing most chromosome-level genomes. The high-throughput chromatin conformation capture (Hi-C) technology has become the primary scaffolding strategy due to its convenience and cost-effectiveness. As sequencing technologies and assembly algorithms advance, constructing haplotype-resolved genomes is increasingly preferred because haplotypes can provide additional genetic information on allelic and non-allelic variations. ALLHiC is a widely used allele-aware scaffolding tool designed for this purpose. However, its dependence on chromosome-level reference genomes and a higher chromosome misassignment rate still impede the unravelling of haplotype-resolved genomes. Here we present HapHiC, a reference-independent allele-aware scaffolding tool with superior performance on chromosome assignment as well as contig ordering and orientation. In addition, we provide new insights into the challenges in allele-aware scaffolding by conducting comprehensive analyses on various adverse factors. Finally, with the help of HapHiC, we constructed the haplotype-resolved allotriploid genome for Miscanthus × giganteus, an important lignocellulosic bioenergy crop.


Assuntos
Cromossomos de Plantas , Genoma de Planta , Haplótipos , Cromossomos de Plantas/genética , Cromatina/genética , Poaceae/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Alelos
4.
J Dermatol ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923010

RESUMO

Peroxisomal acyl-CoA oxidase 1 (ACOX1), is a peroxisomal enzyme that catalyzes ß-oxidation of very-long-chain fatty acids (VLCFA). The gain-of-function variant p.Asn237Ser in ACOX1 has been shown to cause Mitchell syndrome (MITCH), a neurodegenerative disorder characterized by episodic demyelination, hearing loss, and polyneuropathy, through the overproduction of hydrogen peroxide. Only eight cases of MITCH have been reported. While all these patients experienced cutaneous abnormalities, detailed skin features and potential treatment have not been documented. Herein, we report two MITCH patients who harbored a de novo heterozygous variant p.Asn237Ser in ACOX1 and experienced progressive ichthyosiform erythroderma. Skin histopathology revealed hyperkeratosis and parakeratosis with focal hypogranulosis as well as dyskeratotic keratinocytes. Lipid accumulation in the epidermis was observed using Oil Red O staining. Both patients exhibited a remarkable response to treatment with the topical antioxidant N-acetylcysteine (NAC), with Patient 1 achieving complete recovery after 3 months of consistent treatment. This study provides the first comprehensive description of the clinicopathological characteristics and effective treatment of skin lesions in MITCH patients. The successful treatment with topical NAC suggests excessive reactive oxygen species might play a significant role in the pathogenesis of skin lesions in MITCH.

6.
Sci Rep ; 14(1): 9037, 2024 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641617

RESUMO

We aimed to identify different trajectories of remnant cholesterol (RC) and investigate the association of RC trajectories with vascular endothelial function and atherosclerosis progression in a longitudinal cohort of the Chinese population. A total of 521 participants were included in the flow-mediated vasodilation (FMD) subcohort study, and 7775 participants were included in the brachial-ankle pulse wave velocity (baPWV) subcohort study. All participants had ≥ 3 medical examinations during the 10-year follow-up period. In the FMD subcohort study, three distinct RC trajectories were identified according to the RC range and changing pattern over time: "low" (57.58%), "moderate" (30.90%) and "high" (11.52%). The proportion of the three groups with vascular endothelial dysfunction (FMD < 7.0%) was 20.00%, 39.75% and 60.00% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.88 and 2.94 times the odds of vascular endothelial dysfunction (P = 0.048). In the baPWV subcohort study, three distinct RC trajectories were also identified: "low" (54.29%), "moderate" (38.97%) and "high" (6.74%). The proportion of the three groups with atherosclerosis (baPWV > 1400 cm/s) was 38.79%, 51.26% and 59.01% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.46 and 2.16 times the odds of atherosclerosis (P < 0.001). The findings indicated that distinct RC trajectories are significantly associated with vascular endothelial function and atherosclerosis. Regular monitoring to identify persistent increases in RC may be more helpful in identifying individuals with a high risk of cardiovascular disease.


Assuntos
Aterosclerose , Rigidez Vascular , Adulto , Humanos , Estudos Longitudinais , Índice Tornozelo-Braço , Endotélio Vascular , Análise de Onda de Pulso , Aterosclerose/epidemiologia , Colesterol , China/epidemiologia , Fatores de Risco
7.
Ultrason Sonochem ; 105: 106864, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38581796

RESUMO

The effects of ultrasound and different inulin (INU) concentrations (0, 10, 20, 30, and 40 mg/mL) on the structural and functional properties of soybean isolate protein (SPI)-INU complexes were hereby investigated. Fourier transform infrared spectroscopy showed that SPI was bound to INU via hydrogen bonding. All samples showed a decreasing and then increasing trend of α-helix content with increasing INU concentration. SPI-INU complexes by ultrasound with an INU concentration of 20 mg/mL (U-2) had the lowest content of α-helix, the highest content of random coils and the greatest flexibility, indicating the proteins were most tightly bound to INU in U-2. Both UV spectroscopy and intrinsic fluorescence spectroscopy indicated that it was hydrophobic interactions between INU and SPI. The addition of INU prevented the exposure of tryptophan and tyrosine residues to form a more compact tertiary structure compared to SPI alone, and ultrasound caused further unfolding of the structure of SPI. This indicated that the combined effect of ultrasound and INU concentration significantly altered the tertiary structure of SPI. SDS-PAGE and Native-PAGE displayed the formation of complexes through non-covalent interactions between SPI and INU. The ζ-potential and particle size of U-2 were minimized to as low as -34.94 mV and 110 nm, respectively. Additionally, the flexibility, free sulfhydryl groups, solubility, emulsifying and foaming properties of the samples were improved, with the best results for U-2, respectively 0.25, 3.51 µmoL/g, 55.51 %, 269.91 %, 25.90 %, 137.66 % and 136.33 %. Overall, this work provides a theoretical basis for improving the functional properties of plant proteins.


Assuntos
Inulina , Proteínas de Soja , Inulina/química , Proteínas de Soja/química , Ondas Ultrassônicas , Glycine max/química , Sonicação
8.
Front Plant Sci ; 15: 1364826, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38504893

RESUMO

Marginal lands, such as those with saline soils, have potential as alternative resources for cultivating dedicated biomass crops used in the production of renewable energy and chemicals. Optimum utilization of marginal lands can not only alleviate the competition for arable land use with primary food crops, but also contribute to bioenergy products and soil improvement. Miscanthus sacchariflorus and M. lutarioriparius are prominent perennial plants suitable for sustainable bioenergy production in saline soils. However, their responses to salt stress remain largely unexplored. In this study, we utilized 318 genotypes of M. sacchariflorus and M. lutarioriparius to assess their salt tolerance levels under 150 mM NaCl using 14 traits, and subsequently established a mini-core elite collection for salt tolerance. Our results revealed substantial variation in salt tolerance among the evaluated genotypes. Salt-tolerant genotypes exhibited significantly lower Na+ content, and K+ content was positively correlated with Na+ content. Interestingly, a few genotypes with higher Na+ levels in shoots showed improved shoot growth characteristics. This observation suggests that M. sacchariflorus and M. lutarioriparius adapt to salt stress by regulating ion homeostasis, primarily through enhanced K+ uptake, shoot Na+ exclusion, and Na+ sequestration in shoot vacuoles. To evaluate salt tolerance comprehensively, we developed an assessment value (D value) based on the membership function values of the 14 traits. We identified three highly salt-tolerant, 50 salt-tolerant, 127 moderately salt-tolerant, 117 salt-sensitive, and 21 highly salt-sensitive genotypes at the seedling stage by employing the D value. A mathematical evaluation model for salt tolerance was established for M. sacchariflorus and M. lutarioriparius at the seedling stage. Notably, the mini-core collection containing 64 genotypes developed using the Core Hunter algorithm effectively represented the overall variability of the entire collection. This mini-core collection serves as a valuable gene pool for future in-depth investigations of salt tolerance mechanisms in Miscanthus.

9.
J Environ Manage ; 355: 120463, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38430882

RESUMO

Biochar could promote humification in composting, nevertheless, its mechanism has not been fully explored from the perspective of the overall bacterial community and its metabolism. This study investigated the effects of bamboo charcoal (BC) and wheat straw biochar (WSB) on the humic acid (HA) and fulvic acid (FA) contents during pig manure composting. The results showed that BC enhanced humification more than WSB, and significantly increased the HA content and HA/FA ratio. The bacterial community structure under BC differed from those under the other treatments, and BC increased the abundance of bacteria associated with the transformation of organic matter compared with the other treatments. Furthermore, biochar enhanced the metabolism of carbohydrates and amino acids in the thermophilic and cooling phases, especially BC. Through Mantel tests and network analysis, we found that HA was mainly related to carbon source metabolism and the bacterial community, and BC might change the interaction patterns among carbohydrates, amino acid metabolism, Bacillales, Clostridiales, and Lactobacillales with HA and FA to improve the humification process during composting. These results are important for understanding the mechanisms associated with the effects of biochar on humification during composting.


Assuntos
Carvão Vegetal , Compostagem , Animais , Suínos , Carvão Vegetal/química , Esterco/microbiologia , Solo/química , Substâncias Húmicas , Carboidratos , Bactérias
11.
J Am Chem Soc ; 146(12): 8716-8726, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38484171

RESUMO

The successful biomimetic or chemoenzymatic synthesis of target natural products (NPs) and their derivatives relies on enzyme discovery. Herein, we discover a fungal P450 BTG5 that can catalyze the formation of a bicyclo[3.2.2]nonane structure through an unusual two-step mechanism of dimerization and cyclization in the biosynthesis of beticolin 1, whose bicyclo[3.2.2]nonane skeleton connects an anthraquinone moiety and a xanthone moiety. Further investigation reveals that BTG5-T318 not only determines the substrate selectivity but also alters the catalytic reactions, which allows the separation of the reaction to two individual steps, thereby understanding its catalytic mechanism. It reveals that the first heterodimerization undergoes the common oxidation process for P450s, while the second uncommon formal redox-neutral cyclization step is proved as a redox-mediated reaction, which has never been reported. Therefore, this work advances our understanding of P450-catalyzed reactions and paves the way for expansion of the diversity of this class of NPs through synthetic biology.


Assuntos
Alcanos , Esqueleto , Oxirredução
12.
Sci Total Environ ; 926: 171796, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513848

RESUMO

Bioaerosol emissions and their associated risks are attracting increasing attention. Bioaerosols are generated during the pretreatment, fermentation, and screening of mature compost when processing various types of solid waste at composting plants (e.g., municipal sludge and animal manure). In this review, we summarize research into bioaerosols at different types of composting plants by focusing on the methods used for sampling bioaerosols, stages when emissions potentially occur, major components of bioaerosols, survival and diffusion factors, and possible control strategies. The six-stage Andersen impactor is the main method used for sampling bioaerosols in composting plants. In addition, different composting management methods mainly affect bioaerosol emissions from composting plants. Studies of the components of bioaerosols produced by composting plants mainly focused on bacteria and fungi, whereas few considered others such as endotoxin. The survival and diffusion of bioaerosols are influenced by seasonal effects due to changes in environmental factors, such as temperature and relative humidity. Finally, three potential strategies have been proposed for controlling bioaerosols in composting plants. Improved policies are required for regulating bioaerosol emissions, as well as bioaerosol concentration diffusion models and measures to protect human health.


Assuntos
Compostagem , Animais , Humanos , Microbiologia do Ar , Bactérias , Endotoxinas , Temperatura , Aerossóis
13.
J Asian Nat Prod Res ; 26(4): 482-488, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37610136

RESUMO

Two new guaiane-type sesquiterpenes, wenyujinolides A (1) and B (2), were isolated from the ethanol extract of Curcuma wenyujin, together with 10 known compounds. Their structures were established by extensive spectroscopic methods (IR, ESIMS, HRESIMS, ECD, 1D and 2D NMR) and comparison of their NMR data with literatures. Compounds 1 and 2 were evaluated for the inhibition of NO production in LPS induced RAW 264.7 macrophages.


Assuntos
Curcuma , Sesquiterpenos , Curcuma/química , Estrutura Molecular , Óxido Nítrico , Lipopolissacarídeos/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos de Guaiano/química
14.
Sci Total Environ ; 912: 168766, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38008310

RESUMO

Coastal wetlands are one of the most important natural sources of nitrous oxide (N2O). Previous studies have shown that copper-containing chemicals are able to reduce N2O emissions from these ecosystems. However, these chemicals may harm organisms present in coastal waters and sediment, and disturb the ecological balance of these areas. Here, we first investigated the physiological characteristics and genetic potential of denitrifying bacteria isolated from coastal wetlands. Based on an isolated denitrifier carrying a complete denitrification pathway, we tested the effect of the natural mineral chalcopyrite on N2O production by the bacteria. The results demonstrated that chalcopyrite addition lowers N2O emissions from the bacteria while increasing its N2 production rate. Among the four denitrification genes of the isolate, only nosZ gene expression was significantly upregulated following the addition of 2 mg L-1 chalcopyrite. Furthermore, chalcopyrite was applied to coastal wetland sediments. The N2O flux was significantly reduced in 50-100 mg L-1 chalcopyrite-amended sets relative to the controls. Notably, the dissolved Cu concentration in chalcopyrite-amended sediment remained within the limit set by the National Sewage Treatment Discharge Standard. qPCR and metagenomic analysis revealed that the abundance of N2O-reducing bacteria with the nosZ or nirK + nosZ genotype increased significantly in the chalcopyrite-amended groups relative to the controls, suggesting their active involvement in the reduction of N2O emissions. Our findings offer valuable insights for the use of natural chalcopyrite in large-scale field applications to reduce N2O emissions.


Assuntos
Cobre , Óxido Nitroso , Óxido Nitroso/análise , Cobre/metabolismo , Áreas Alagadas , Desnitrificação , Ecossistema , Bactérias/metabolismo , Microbiologia do Solo
15.
Front Cardiovasc Med ; 10: 1148353, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37621562

RESUMO

Sedentary behavior is a risk factor for several diseases, and previous studies have mostly reported the effects of acute sedentary behavior on vascular endothelial function. Data on the relationship between sedentary lifestyle habits and vascular function in large sample populations are lacking. Therefore, the aim of this study was to assess the correlation between self-reported sedentary behavior and peripheral vascular function in a check-up population from real-world data. Methods: We recruited 13,220 participants from two health management centers of general tertiary hospitals located in northern and southern China between 2017 and 2021. All participants had undergone both questionnaires and brachial artery flow-mediated dilation (FMD) measurements. Results: In total, 3,205 participants with FMD ≤ 5.0% were identified to have endothelial dysfunction. In a multivariable regression model including lifestyle habits such as sedentary behavior and cardiovascular risk factors, taking leisure sedentary time <2 h/day as a reference, the risk of vascular endothelial dysfunction gradually increased with time: 2-4 h/day (OR = 1.182, 95% CI: 1.058-1.321, P = 0.003), 4-6 h/day (OR = 1.248, 95% CI: 1.100-1.414, P = 0.001) and >6 h/day (OR = 1.618, 95% CI: 1.403-1.866, P < 0.001). Conclusion: Longer leisure sedentary time is associated with a higher prevalence of vascular endothelial dysfunction. These findings suggest that leisure sedentary behavior is a risk factor for the occurrence of vascular endothelial dysfunction in the Chinese check-up population.

16.
Sci Total Environ ; 896: 165276, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37406706

RESUMO

Miscanthus lutarioriparius grown in Dongting Lake has an annual biomass yield potential of 1 million tons. However, with the shutdown of its previous utilization for paper-making, abandoning this huge amount of biomass has caused serious economic, ecological, and social problems. Constructing an industrial cluster to continuously convert biomass into various bioproducts is a win-win measure to address this dilemma. With the increasing confirmation of the importance of biomass quality affecting the conservation process, fully understanding the biomass characteristics of Dongting Lake-grown M. lutarioriparius is crucial for building a scientific industrial cluster. The present work is designed to explore the variation in biomass quality across the entire Dongting Lake area. Results show that the biomass contented with Cd, Mn, Zn, and Cr has significant geographical differences, with a general trend of Southern Dongting Lake-grown biomass having a higher concentration than that from Eastern and Western Dongting Lake areas. Moreover, significant differences are found in terms of biomass ash content, lignin content, and the degree of polymerization of cellulose (DP). The biomass with low ash content is generally from the entire Eastern Dongting Lake area and the northern part of the Western Dongting Lake area. Virtually all Western Dongting Lake-grown biomass has a low lignin content (approximately 18 %). Regarding the spatial variation of DP, Eastern Dongting Lake-grown biomass has a higher DP (average at 585.33) than that in Southern (575.15) and then Western Dongting Lake (529.16). Based on these quality indicators, the biomass production potentials for bioethanol, biochar, and xylo-oligosaccharide were calculated and visualized. Results show that biomass from almost the entire Western and Eastern Dongting Lake area is suitable for bioethanol and xylo-oligosaccharide production, while biomass from the Southern Dongting Lake area for biochar production. These results provide scientific guidance for the future utilization of Dongting Lake-grown M. lutarioriparius biomass.


Assuntos
Monitoramento Ambiental , Lignina , Biomassa , Lignina/análise , Lagos/análise , Poaceae , China
17.
Carbohydr Polym ; 317: 121101, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37364963

RESUMO

The effect of the cross-linking mechanism and functional properties of soy glycinin (11S)-potato starch (PS) complexes was investigated in this study. The results showed that the binding effecting and spatial network structure of 11S-PS complexes via heated-induced cross-linking were adjusted by biopolymer ratios. In particular, 11S-PS complexes with the biopolymer ratios of 2:15, had a strongest intermolecular interaction through hydrogen bonds and hydrophobic force. Moreover, 11S-PS complexes at the biopolymer ratios of 2:15 exhibited a finer three-dimensional network structure, which was used as film-forming solution to enhance the barrier performance and mitigate the exposure to the environment. In addition, the 11S-PS complexes coating was effective in moderating the loss of nutrients, thereby extending their storage life in truss tomato preservation experiments. This study provides helpful to insights into the cross-linking mechanism of the 11S-PS complexes and the potential application of food-grade biopolymer composite coatings in food preservation.


Assuntos
Globulinas , Solanum tuberosum , Solanum tuberosum/metabolismo , Proteínas de Soja/química , Globulinas/química , Globulinas/metabolismo , Amido
18.
Plants (Basel) ; 12(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37176816

RESUMO

Cutleaf groundcherry (Physalis angulata L.), an annual plant containing a variety of active ingredients, has great medicinal value. However, studies on the genetic diversity and population structure of P. angulata are limited. In this study, we developed chloroplast microsatellite (cpSSR) markers and applied them to evaluate the genetic diversity and population structure of P. angulata. A total of 57 cpSSRs were identified from the chloroplast genome of P. angulata. Among all cpSSR loci, mononucleotide markers were the most abundant (68.24%), followed by tetranucleotide (12.28%), dinucleotide (10.53%), and trinucleotide (8.77%) markers. In total, 30 newly developed cpSSR markers with rich polymorphism and good stability were selected for further genetic diversity and population structure analyses. These cpSSRs amplified a total of 156 alleles, 132 (84.62%) of which were polymorphic. The percentage of polymorphic alleles and the average polymorphic information content (PIC) value of the cpSSRs were 81.29% and 0.830, respectively. Population genetic diversity analysis indicated that the average observed number of alleles (Na), number of effective alleles (He), Nei's gene diversity (h), and Shannon information indices (I) of 16 P. angulata populations were 1.3161, 1.1754, 0.1023, and 0.1538, respectively. Moreover, unweighted group arithmetic mean, neighbor-joining, principal coordinate, and STRUCTURE analyses indicated that 203 P. angulata individuals from 16 populations were grouped into four clusters. A molecular variance analysis (AMOVA) illustrated the considerable genetic variation among populations, while the gene flow (Nm) value (0.2324) indicated a low level of gene flow among populations. Our study not only provided a batch of efficient genetic markers for research on P. angulata but also laid an important foundation for the protection and genetic breeding of P. angulata resources.

19.
Front Cell Infect Microbiol ; 13: 1149911, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37256114

RESUMO

Viral myocarditis (VMC), characterized by viral infection-induced inflammation, is a life-threatening disease associated with dilated cardiomyopathy or heart failure. Innate immunity plays a crucial role in the progression of inflammation, in which inflammasomes provide a platform for the secretion of cytokines and mediate pyroptosis. Inflammasomes are rising stars gaining increasing attention. The nucleotide oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, the caspase recruitment domain-containing protein 8 (CARD8) inflammasome, and the caspase-11 inflammasome are three inflammasomes that were reported to affect the process and prognosis of VMC. These inflammasomes can be activated by a wide range of cellular events. Accumulating evidence has suggested that inflammasomes are involved in different stages of VMC, including the trigger and progression of myocardial injury and remodeling after infection. In this review, we summarized the pathways involving inflammasomes in VMC and discussed the potential therapies targeting inflammasomes and related pathways.


Assuntos
Miocardite , Viroses , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamação/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo
20.
Adv Healthc Mater ; 12(26): e2300944, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37235739

RESUMO

Brachytherapy, including radioactive seed implantation (RSI) and transarterial radiation therapy embolization (TARE), is an important treatment modality for advanced hepatocellular carcinoma (HCC), but the inability of RSI and TARE to treat tumor metastasis and recurrence limits their benefits for patients in the clinic. Herein, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors-loaded alginate microspheres (IMs) are developed as radionuclide carriers with immunomodulatory functions to achieve effective radio-immunotherapy. The size and swelling properties of IMs can be facilely tailored by adjusting the calcium source during emulsification. Small/large IMs(SIMs/LIMs) are biocompatible and available for RSI and TARE, respectively, after 177 Lu labeling. Among them, 177 Lu-SIMs completely eliminated subcutaneous HCC in mice after intratumoral RSI. Moreover, in combination with anti-PD-L1, 177 Lu-SIMs not only eradicate primary tumors by RSI but also effectively inhibit the growth of distant tumors, wherein the potent abscopal effect can be ascribed to the immune stimulation of RSI and the modulation of the tumor immune microenvironment (TIME) by IDO1 inhibitors. In parallel, LIMs demonstrate excellent embolization efficiency, resulting in visible necrotic lesions in the central auricular artery of rabbits, which are promising for TARE in future studies. Collectively, a versatile therapeutic agent is provided to synchronously modulate the TIME during brachytherapy for efficient radio-immunotherapy of advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Coelhos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Microesferas , Radioisótopos/uso terapêutico , Imunoterapia , Microambiente Tumoral
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