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This study aims to invigorate China's Rural Revitalization Strategy by focusing on the training of China's new generation of professional farmers, particularly enhancing the skills of modern agricultural practitioners. Utilizing a mixed-method research approach, which includes the analysis of 343 questionnaire surveys and personal interviews, significant shortcomings in the previous training of farmers were revealed, such as limited reach, high conformity in training content, and outdated methods. These findings highlight the challenges traditional training methods face in the digital technology era. In response to these challenges, this study proposes a novel training model designed for the digital era. This model encompasses seven aspects: training goals, subjects, content, means, management, methods, and effect assessment, with the aspiration to reform traditional farmer training methods. This research expands the existing literature by constructing a comprehensive framework for training the new generation of farmers, bridging the gap between traditional practices and the demands of modern agricultural training influenced by digital advancements. The study's innovation lies in its proposition of a modernized training model for the new generation of farmers, leveraging the advancements of the digital technology era. By modernizing agricultural training and enhancing the capabilities of new professional farmers, it significantly contributes to the progression of China's Rural Revitalization Strategy.
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Antimicrobial resistance has emerged as a significant threat to global public health. To develop novel, high efficiency antibacterial alternatives to combat multidrug-resistant bacteria, A total of thirty-two novel amphiphilic benzopyran derivatives by mimicking the structure and function of antimicrobial peptides were designed and synthesized. Among them, the most promising compounds 4h and 17e displayed excellent antibacterial activity against Gram-positive bacteria (MICs = 1-4 µg/mL) with weak hemolytic activity and good membrane selectivity. Additionally, compounds 4h and 17e had rapid bactericidal properties, low resistance frequency, good plasma stability, and strong capabilities of inhibiting and eliminating bacterial biofilms. Mechanistic studies revealed that compounds 4h and 17e could effectively disrupt the integrity of bacterial cell membranes, and accompanied by an increase in intracellular reactive oxygen species and the leakage of proteins and DNA, ultimately leading to bacterial death. Notably, compound 4h exhibited comparable in vivo antibacterial potency in a mouse septicemia model infected by Staphylococcus aureus ATCC43300, as compared to vancomycin. These findings indicated that 4h might be a promising antibacterial candidate to combat antimicrobial resistance.
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To study the degradation of lncRNAs in EPMI in rat brain tissue, this study provides a new direction for the estimation of EPMI. LncRNA high-throughput sequencing was performed on the brain tissues of hemorrhagic shock model rats at 0 h and 24 h, and the target lncRNAs were screened. Samples at 0, 1, 3, 6, 12, 18 and 24 h after death were collected, and miRNA-9 and miRNA-125b were used as reference genes. The relative expression levels of lncRNAs at each PMI were detected by RT-qPCR, and a functional model involving lncRNAs and EPMI was established. Samples were collected at 6, 9, 15, and 21 h after death for functional model verification. The expression of several lncRNAs decreased with the prolongation of EPMI, and the mathematical model established by several lncRNA indices exhibited good fit. The verification results of the multi-index joint function model are significantly better than those of the single-index function model, and the established model is more practical. There is a linear relationship between lncRNAs and EPMI, and the multi-index function model is significantly better than the single-index function model, which is important for EPMI inference in forensic pathology practice.
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Encéfalo , Cambios Post Mortem , ARN Largo no Codificante , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ratas , Encéfalo/metabolismo , Encéfalo/patología , Masculino , Ratas Sprague-Dawley , Factores de Tiempo , Estabilidad del ARNRESUMEN
CRISPR technologies have revolutionized research areas ranging from fundamental science to translational medicine. CRISPR-based genetic screens offer a powerful platform for unbiased screening in various fields, such as cancer immunology. Immune checkpoint blockade (ICB) therapy has been shown to strongly affect cancer treatment. However, the currently available ICBs are limited and do not work in all cancer patients. Pooled CRISPR screens enable the identification of previously unknown immune regulators that can regulate T-cell activation, cytotoxicity, persistence, infiltration into tumors, cytokine secretion, memory formation, T-cell metabolism, and CD4+ T-cell differentiation. These novel targets can be developed as new immunotherapies or used with the current ICBs as new combination therapies that may yield synergistic efficacy. Here, we review the progress made in the development of CRISPR technologies, particularly technological advances in CRISPR screens and their application in novel target identification for immunotherapy.
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Two-dimensional materials have been extensively studied in field-effect transistors (FETs). However, the performance of p-type FETs has lagged behind that of n-type, which limits the development of complementary logical circuits. Here, we investigate the electronic properties and transport performance of anisotropic monolayer GaSCl for p-type FETs through first-principles calculations. The anisotropic electronic properties of monolayer GaSCl result in excellent device performance. The p-type GaSCl FETs with 10 nm channel length have an on-state current of 2351 µA/µm for high-performance (HP) devices along the y direction and an on-state current of 992 µA/µm with an on/off ratio exceeding 107 for low-power (LP) applications along the x direction. In addition, the delay-time (τ) and power dissipation product of GaSCl FETs can fully meet the International Technology Roadmap for Semiconductors standards for HP and LP applications. Our work illustrates that monolayer GaSCl is a competitive p-type channel for next-generation devices.
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Astragalus membranaceus saponins are the main components of A. membranaceus, a plant widely used in traditional Chinese medicine. Recently, research on the anti-cancer effects of A. membranaceus saponins has received increasing attention. Numerous in vitro and in vivo experimental data indicate that A. membranaceus saponins exhibit significant anti-cancer effects through multiple mechanisms, especially in inhibiting tumor cell proliferation, migration, invasion, and induction of apoptosis, etc. This review compiles relevant studies on the anti-cancer properties of A. membranaceus saponins from various databases over the past two decades. It introduces the mechanism of action of astragalosides, highlighting their therapeutic benefits in the management of cancer. Finally, the urgent problems in the research process are highlighted to promote A. membranaceus saponins as an effective drug against cancer.
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Apoptosis , Astragalus propinquus , Proliferación Celular , Neoplasias , Saponinas , Saponinas/farmacología , Saponinas/química , Astragalus propinquus/química , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Apoptosis/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Movimiento Celular/efectos de los fármacosRESUMEN
OBJECTIVE: We aim to describe the population pharmacokinetics (PPK) of tacrolimus in Chinese pediatric patients under 4 years old after liver transplantation and to develop individualized tacrolimus dosing software. METHODS: A total of 663 blood concentrations from 85 patients aged 4.57 months to 3.97 years were collected in this study. PPK analysis was performed using a nonlinear mixed effects modeling approach with the software, Phoenix. Using C#, an individualized tacrolimus dosing software was created. The software was then used to predict the concentrations of another ten pediatric liver transplantation patients to verify the accuracy of said software. The predictive error (PE) and the absolute predictive error (APE) for each predicted time point were computed. RESULTS: A one-compartment model with first-order elimination best fitted the data. The apparent volume of distribution (V/F) and apparent clearance (CL/F) were 198.65 L and 2.41 L/h. Postoperative days (POD), total bilirubin (TBIL), and the use of voriconazole significantly influenced tacrolimus apparent clearance. The incorporation of an increasing number of actual blood drug concentrations into the prediction resulted in a decrease in both PE (72%, 17%, 7%) and APE (87%, 53%, 26%). CONCLUSIONS: A qualified PPK model of tacrolimus was developed in Chinese pediatric patients. The individualized tacrolimus dosing software could be used as a suitable tool for the personalization of tacrolimus dosing for pediatric patients after liver transplantation.
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Inmunosupresores , Trasplante de Hígado , Modelos Biológicos , Programas Informáticos , Tacrolimus , Humanos , Tacrolimus/farmacocinética , Tacrolimus/administración & dosificación , Tacrolimus/sangre , Preescolar , Lactante , Masculino , Inmunosupresores/farmacocinética , Inmunosupresores/administración & dosificación , Inmunosupresores/sangre , Femenino , Pueblo Asiatico , China , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: This study aims to analyze the efficacy and safety of different electrical stimulation treatments for post-stroke motor dysfunction, and to quantitatively analyze the advantages between them and their possible benefits for patients. METHODS: We will systematically search seven databases. All of them will be retrieved from inception to 15, April 2024. Two reviewers will evaluation the risk of bias in all included studies with the version 2 of the Cochrane risk-of-bias assessment tool. Data synthesis will be performed using a random-effects model of network meta-analysis to compare the efficacy and safety of different electrical stimulation therapies. The surface under the cumulative ranking curve was used to indicate the possibility of the pros and cons of the intervention. The strength of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation framework. DISCUSSION: This study will provide evidence that electrical stimulation therapy can effectively improve motor function in stroke patients and will also provide some valuable references for clinical decision-making and treatment guidelines. TRIAL REGISTRATION: PROSPERO registration number: CRD42023459102.
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Terapia por Estimulación Eléctrica , Metaanálisis en Red , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Revisiones Sistemáticas como Asunto , Humanos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Terapia por Estimulación Eléctrica/métodos , Rehabilitación de Accidente Cerebrovascular/métodos , Metaanálisis como Asunto , Resultado del TratamientoRESUMEN
Bisphenol analogues (BPs) are a class of typical environmental endocrine-disrupting chemicals (EDCs). This study aimed to establish a highly sensitive and high-throughput method utilizing 96-well solid-phase extraction (96-well SPE) in conjunction with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) employing multiple reaction monitoring (MRM), information-dependent acquisition (IDA), and enhanced product ion (EPI) scan modes for the identification and quantitative analysis of nine BPs in human urine. Urine samples were initially thawed to room temperature, followed by digestion using ß-glucuronidase in an ammonium acetate buffer solution at 37 °C overnight. Subsequently, they were purified using 96-well SPE and finally analyzed by UHPLC-MS/MS. The limits of detection (LOD) for the nine BPs ranged from 0.05 µgâkg-1 to 0.3 µg kg-1. Average recoveries fell within the range of 92.8 % to 111.7 %. Moreover, both the intra-day and inter-day precisions were satisfactory, with relative standard deviations (RSDs) ranging from 2.2 % to 6.7 % and 3.5 % to 6.3 %, respectively. The targets in the samples exhibited a perfect match, with a purity fit value exceeding 70 % from the self-built library. The analytical method developed in this study demonstrates high accuracy and sensitivity. In addition, the MRM-IDA-EPI mode can effectively identifies the target BPs and prevents false positive detection of analytes in the urine.
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Compuestos de Bencidrilo , Límite de Detección , Fenoles , Extracción en Fase Sólida , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Extracción en Fase Sólida/métodos , Fenoles/orina , Compuestos de Bencidrilo/orina , Compuestos de Bencidrilo/química , Disruptores Endocrinos/orina , Reproducibilidad de los Resultados , Femenino , Adulto , MasculinoRESUMEN
Ziprasidone is widely used in the treatment of psychiatric disorders. Despite its prevalence, there is a notable lack of population pharmacokinetics (PPK) studies on ziprasidone in serum, both domestically and internationally. This study aimed to comprehensively investigate the various factors influencing the PPK characteristics of Ziprasidone, thereby providing a scientific basis for personalized treatment strategies in clinical settings. This is a retrospective study. A non-linear mixed-effects modeling method was used for data analysis, with the ziprasidone PPK model established using the Phoenix NLME 8.1 software. Model evaluation employed goodness-of-fit plots, visual predictive checks, and Bootstrap methods to ensure reliability and accuracy. To further validate the model's applicability, data from an additional 30 patients meeting the same inclusion criteria but not included in the final model were collected for external validation. Simulations were performed to explore the personalized dosage regimens. This retrospective analysis collected 547 drug concentration data points from 185 psychiatric disorder patients, along with related medical records. The data included detailed demographic information (such as age, gender, weight), dosing regimens, laboratory test results, and concomitant medication details. In the final model, Ka was fixed at 0.5 h-1 based on literature, and the population typical values for ziprasidone clearance (CL) and volume of distribution (V) were 18.74 L/h and 110.24 L, respectively. Co-administration of lorazepam and valproic acid significantly influenced the clearance of ziprasidone. Moreover, the model evaluation indicated good stability and predictive accuracy. A simple to use dosage regimen table was derived based on the results of simulations. This study successfully established and validated a PPK model for ziprasidone in Chinese patients with psychiatric disorders. The model provides a scientific reference for individualized dosing of ziprasidone and holds the potential to optimize treatment strategies, thereby enhancing therapeutic efficacy and safety.
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Image moments, as a kind of global feature descriptor of images, have become a valuable tool for pattern recognition and image analysis. However, traditional methods are mainly used to deal with grayscale images. In this paper, we apply quaternions to fast and accurate polar harmonic Fourier moments, proposing a kind of quaternion fast and accurate polar harmonic Fourier moment (QFAPHFM) capable of handling color images. Furthermore, this paper provides a detailed analysis of the invariance of QFAPHFMs under rotation, scaling, and translation transformations. The experimental results show that QFAPHFMs exhibit excellent performance in both image reconstruction and object recognition tasks. QFAPHFMs achieve accurate image reconstruction under noiseless and noisy conditions, and demonstrate excellent recognition performance in the color-based object recognition tasks.
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Exploring two-dimensional (2D) materials with a small carrier effective mass and suitable band gap is crucial for the design of metal oxide semiconductor field effect transistors (MOSFETs). Here, the quantum transport properties of stable 2D SbSeBr are simulated on the basis of first-principles calculations. Monolayer SbSeBr proves to be a competitive channel material, offering a suitable band gap of 1.18 eV and a small electron effective mass (me*) of 0.22m0. The 2D SbSeBr field effect transistor (FET) with 8 nm channel length exhibits a high on-state current of 1869 µA/µm, low power consumption of 0.080 fJ/µm, and small delay time of 0.062 ps, which can satisfy the requirements of the International Technology Roadmap for Semiconductors for high-performance devices. Moreover, despite the monolayer SbSeBr having an isotropic me*, the asymmetrical band trends enable SbSeBr FETs to display transport orientation, which emphasizes the importance of band trends and provides valuable insights for selecting channel materials.
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Agricultural biomass used as solid carbon substrates in ecological floating beds (EFBs) has been proven to be applicable in nitrogen removal for carbon-limited wastewater treatment. However, the subtle interactions among plants, rhizosphere microorganisms, and supplementary carbon sources have not been thoroughly studied. This study combined rice straw mats with different aquatic macrophytes in EFBs to investigate denitrification efficiency in carbon-limited eutrophic waters. Results showed that rice straw significantly enhanced the nitrogen removal efficiency of EFBs, while enriching nitrogen-fixing and denitrifying bacteria (such as Rhizobium, Rubrivivax, and Rhodobacter, etc.). Additionally, during the denitrification process in EFBs, rice straw can release humic acid-like fraction as electron donors to support the metabolic activities of microorganisms, while aquatic macrophytes provide a more diverse range of dissolved organic matters, facilitating a sustainable denitrification process. These findings help to understand the synergistic effect of denitrification processes within wetland ecosystems using agricultural biomass.
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Carbono , Desnitrificación , Nitrógeno , Oryza , Aguas Residuales , Aguas Residuales/química , Purificación del Agua/métodos , Biomasa , Bacterias/metabolismo , Humedales , Biodegradación AmbientalRESUMEN
A massive mortality event concerning farmed Chinese tongue soles occurred in Tianjin, China, and the causative agent remains unknown. Here, a novel Cynoglossus semilaevis papillomavirus (CsPaV) and parvovirus (CsPV) were simultaneously isolated and identified from diseased fish via electron microscopy, virus isolation, genome sequencing, experimental challenges, and fluorescence in situ hybridization (FISH). Electron microscopy showed large numbers of virus particles present in the tissues of diseased fish. Viruses that were isolated and propagated in flounder gill cells (FG) induced typical cytopathic effects (CPE). The cumulative mortality of fish given intraperitoneal injections reached 100% at 7 dpi. The complete genomes of CsPaV and CsPV comprised 5939 bp and 3663 bp, respectively, and the genomes shared no nucleotide sequence similarities with other viruses. Phylogenetic analysis based on the L1 and NS1 protein sequences revealed that CsPaV and CsPV were novel members of the Papillomaviridae and Parvoviridae families. The FISH results showed positive signals in the spleen tissues of infected fish, and both viruses could co-infect single cells. This study represents the first report where novel papillomavirus and parvovirus are identified in farmed marine cultured fish, and it provides a basis for further studies on the prevention and treatment of emerging viral diseases.
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Enfermedades de los Peces , Peces Planos , Genoma Viral , Papillomaviridae , Infecciones por Parvoviridae , Parvovirus , Filogenia , Animales , Enfermedades de los Peces/virología , Enfermedades de los Peces/mortalidad , China , Peces Planos/virología , Infecciones por Parvoviridae/veterinaria , Infecciones por Parvoviridae/virología , Parvovirus/genética , Parvovirus/aislamiento & purificación , Parvovirus/clasificación , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/veterinaria , Hibridación Fluorescente in SituRESUMEN
CO2 hydrogenation to methanol has emerged as a promising strategy for achieving carbon neutrality and mitigating global warming, in which the supported Pd/In2O3 catalysts are attracting great attention due to their high selectivity. Nonetheless, conventional impregnation methods induce strong metal-support interaction (SMSI) between Pd and In2O3, which leads to the excessive reduction of In2O3 and the formation of undesirable PdIn alloy in hydrogen-rich atmospheres. Herein, we innovatively synthesized Pd/In2O3 nanocatalysts by the electrostatic self-assembly process between surface-modified composite precursors with opposite charges. And the organic ligands concurrently serve as Pd nanoparticle protective agents. The resultant Pd/In2O3 nanocatalyst demonstrates the homogeneous distribution of Pd nanoparticles with controllable sizes on In2O3 supports and the limited formation of PdIn alloy. As a result, it exhibits superior selectivity and stability compared to the counterparts synthesized by the conventional impregnation procedure. Typically, it attains a maximum methanol space-time yield of 0.54â gMeOH h-1gcat -1 (300 °C, 3.5â MPa, 21,000â mL gcat -1 h-1). Notably, the correlation characterization results reveal the significant effect of small-size, highly dispersed Pd nanoparticles in mitigating MSI. These results provide an alternative strategy for synthesizing highly efficient Pd/In2O3 catalysts and offer a new insight into the strong metal-support interaction.
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OBJECTIVE: This study employed Mendelian Randomization (MR) to investigate the causal relationship between genetic susceptibility to vitiligo and the risk of various autoimmune diseases, along with the mediating role of blood metabolites. METHODS: We performed two-sample MR analyses using aggregated genome-wide association studies (GWAS) data on 486 blood metabolites, vitiligo, and nine autoimmune diseases to investigate blood metabolites' causal effects on the susceptibility of vitiligo and the associations of vitiligo with nine autoimmune comorbidities. We also applied multivariable MR to unravel metabolites by which vitiligo influences the pathogenesis of autoimmune diseases. RESULTS: Our findings indicate that vitiligo amplified the risk of several autoimmune diseases, including rheumatoid arthritis (OR 1.17; 95 % CI 1.08-1.27), psoriasis (OR 1.10; 95 % CI 1.04-1.17), type 1 diabetes (OR 1.41; 95 % CI 1.23-1.63), pernicious anemia (OR 1.23; 95 % CI 1.12-1.36), autoimmune hypothyroidism (OR 1.19; 95 % CI 1.11-1.26), alopecia areata (OR 1.22; 95 % CI 1.10-1.35), and autoimmune Addison's disease (OR 1.22; 95 % CI 1.12-1.33). Additionally, our analysis identified correlations with vitiligo for 14 known (nine risk, five protective) and seven uncharacterized serum metabolites. After adjusting for genetically predicted levels of histidine and pyruvate, the associations between vitiligo and these diseases were attenuated. CONCLUSIONS: We substantiated vitiligo's influence on susceptibility to seven autoimmune diseases and conducted a thorough investigation of serum metabolites correlated with vitiligo. Histidine and pyruvate are potential mediators of vitiligo associated with autoimmune diseases.By combining metabolomics with genomics, we provide new perspectives on the etiology of vitiligo and its immune comorbidities.
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Enfermedades Autoinmunes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Vitíligo , Vitíligo/genética , Vitíligo/sangre , Humanos , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/genética , Polimorfismo de Nucleótido SimpleRESUMEN
With the utilization of advanced microfluidic techniques, the microfluidic particle counter demonstrates significant potential due to its high efficiency, precise manipulation, and portability. This work focuses on a photodetection counter based on optical absorption. To achieve precise particle detection, a Christmas tree-like structure was implemented to separate a single particle from a cluster, which was then detected in independent multiple parallel channels. The system exhibits a high degree of reliability, as evidenced by a linear correlation coefficient over 0.99 obtained during testing with gradient-concentrated beads. Furthermore, when the calculated density of NIH 3T3 cells is compared with that of a traditional flow cytometer, the system achieves a substantial agreement percentage ranging from 87.5 to 99.9%. The system's ability to perform high-throughput analysis with a high acquisition rate positions it as a promising tool for real-time point-of-care testing.
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Técnicas Analíticas Microfluídicas , Ratones , Animales , Células 3T3 NIH , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Ensayos Analíticos de Alto Rendimiento/instrumentación , Citometría de Flujo/métodos , Citometría de Flujo/instrumentación , Microfluídica/métodos , Reproducibilidad de los ResultadosRESUMEN
Dean flow and Dean instability play an important role in inertial microfluidics, with a wide application in mixing and sorting. However, most studies are limited to Dean flow in the microscale. This work first reports the application of Dean instability on organic nanoparticles synthesis at De up to 198. The channel geometry (the tortuous channel) is optimized by simulation, in which the mixing efficiency is considered. With the optimized design, prednisolone nanoparticles are synthesized, and the size of the most abundant prednisolone nanoparticles is down to 100 nm with an increase in the Re and De and smallest size down to 46 nm. This work serves as an ice-breaker to the real application of Dean instability by demonstrating its ability in mixing and nanomaterials like nanoparticle synthesis.
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SUMMARY: Immunocytokines are a promising immunotherapeutic approach in cancer therapy. Anti-VEGFR2-interferon α (IFNα) suppressed colorectal cancer (CRC) growth and enhanced CD8 + T-cell infiltration in the tumor microenvironment, exhibiting great clinical translational potential. However, the mechanism of how the anti-VEGFR2-IFNα recruits T cells has not been elucidated. Here, we demonstrated that anti-VEGFR2-IFNα suppressed CRC metastasis and enhanced CD8 + T-cell infiltration. RNA sequencing revealed a transcriptional activation of CCL5 in metastatic CRC cells, which was correlated with T-cell infiltration. IFNα but not anti-VEGFR2 could further upregulate CCL5 in tumors. In immunocompetent mice, both IFNα and anti-VEGFR2-IFNα increased the subset of tumor-infiltrating CD8 + T cells through upregulation of CCL5. Knocking down CCL5 in tumor cells attenuated the infiltration of CD8 + T cells and dampened the antitumor efficacy of anti-VEGFR2-IFNα treatment. We, therefore, propose upregulation of CCL5 is a key to enhance infiltration of CD8 + T cells in metastatic CRC with IFNα and IFNα-based immunocytokine treatments. These findings may help the development of IFNα related immune cytokines for the treatment of less infiltrated tumors.