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3D printing technologies have distinguished advantages in manufacturing arbitrary shapes and complex structures that have attracted us to use digital light processing (DLP) technology for specialty silica optical fiber preforms. One of the main tasks is to develop an appropriate recipe for DLP resin that is UV sensitive and loaded with silica nanoparticles. In this work, the effects of a UV absorber in highly silica-loaded resin on DLP printing are experimentally investigated. Spot tests and DLP printing are carried out on resins with varying dosages of a typical UV absorber, Sudan Orange G. Based on the experimental results, the UV absorber can significantly improve the resolution of DLP printed green bodies while requiring a larger exposure dose.
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Spatial genetic and phenotypic diversity within solid tumors has been well documented. Nevertheless, how this heterogeneity affects temporal dynamics of tumorigenesis has not been rigorously examined because solid tumors do not evolve as the standard population genetic model due to the spatial constraint. We therefore, propose a neutral spatial (NS) model whereby the mutation accumulation increases toward the periphery; the genealogical relationship is spatially determined and the selection efficacy is blunted (due to kin competition). In this model, neutral mutations are accrued and spatially distributed in manners different from those of advantageous mutations. Importantly, the distinctions could be blurred in the conventional model. To test the NS model, we performed a three-dimensional multiple microsampling of two hepatocellular carcinomas. Whole-genome sequencing (WGS) revealed a 2-fold increase in mutations going from the center to the periphery. The operation of natural selection can then be tested by examining the spatially determined clonal relationships and the clonal sizes. Due to limited migration, only the expansion of highly advantageous clones can sweep through a large part of the tumor to reveal the selective advantages. Hence, even multiregional sampling can only reveal a fraction of fitness differences in solid tumors. Our results suggest that the NS patterns are crucial for testing the influence of natural selection during tumorigenesis, especially for small solid tumors.
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Neoplasias , Carcinogénesis , Humanos , Mutación , Neoplasias/genética , Selección GenéticaRESUMEN
One of the unique features of SARS-CoV-2 is its apparent neutral evolution during the early pandemic (before February 2020). This contrasts with the preceding SARS-CoV epidemics, where viruses evolved adaptively. SARS-CoV-2 may exhibit a unique or adaptive feature which deviates from other coronaviruses. Alternatively, the virus may have been cryptically circulating in humans for a sufficient time to have acquired adaptive changes before the onset of the current pandemic. To test the scenarios above, we analyzed the SARS-CoV-2 sequences from minks (Neovision vision) and parental humans. In the early phase of the mink epidemic (April to May 2020), nonsynonymous to synonymous mutation ratio per site in the spike protein is 2.93, indicating a selection process favoring adaptive amino acid changes. Mutations in the spike protein were concentrated within its receptor-binding domain and receptor-binding motif. An excess of high-frequency derived variants produced by genetic hitchhiking was found during the middle (June to July 2020) and late phase I (August to September 2020) of the mink epidemic. In contrast, the site frequency spectra of early SARS-CoV-2 in humans only show an excess of low-frequency mutations, consistent with the recent outbreak of the virus. Strong positive selection in the mink SARS-CoV-2 implies that the virus may not be preadapted to a wide range of hosts and illustrates how a virus evolves to establish a continuous infection in a new host. Therefore, the lack of positive selection signal during the early pandemic in humans deserves further investigation.
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COVID-19 , Evolución Molecular , SARS-CoV-2 , Animales , COVID-19/virología , Humanos , Visón/virología , Mutación , Pandemias , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
Xanthomonas oryzae pv. oryzae (Xoo) is a causative agent of rice bacterial blight (BB). In 2020-2022, BB re-emerged, and there was a break out in the Yangtze River area, China. The pandemic Xoo strain, LA20, was isolated and identified from cultivar Quanyou1606 and demonstrated to be the Chinese R9 Xoo strain, which is able to override the widely adopted xa5-, Xa7- and xa13-mediated resistance in rice varieties in Yangtze River. Here, we report the complete genome of LA20 by PacBio and Illumina sequencing. The assembled genome consists of one circular chromosome of 4,960,087 bp, sharing 99.65% sequence identity with the traditional representative strain, YC11 (R5), in the Yangtze River. Comparative genome analysis of LA20 and YC11 revealed the obvious variability in Tal genes (the uppermost virulence determinants) in numbers and sequences. Particularly, six Tal genes were only found in LA20, but not in YC11, among which Tal1b (pthXo1)/Tal4 (pthXo6), along with the lost one, pthXo3 (avrXa7), might be the major factors for LA20 to overcome xa5-, Xa7- and xa13-mediated resistance, thus, leading to the resurgence of BB. This complete genome of the new pandemic Xoo strain will provide novel insights into pathogen evolution, the traits of pathogenicity on genomic level and the epidemic disease status in China.
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Oryza , Xanthomonas , Oryza/genética , Ríos , Factores de Virulencia/genética , Xanthomonas/genética , Genómica , Enfermedades de las Plantas/microbiologíaRESUMEN
Chilling stress seriously limits grain yield and quality worldwide. However, the genes and the underlying mechanisms that respond to chilling stress remain elusive. This study identified ABF1, a cold-induced transcription factor of the bZIP family. Disruption of ABF1 impaired chilling tolerance with increased ion leakage and reduced proline contents, while ABF1 over-expression lines exhibited the opposite tendency, suggesting that ABF1 positively regulated chilling tolerance in rice. Moreover, SnRK2 protein kinase SAPK10 could phosphorylate ABF1, and strengthen the DNA-binding ability of ABF1 to the G-box cis-element of the promoter of TPS2, a positive regulator of trehalose biosynthesis, consequently elevating the TPS2 transcription and the endogenous trehalose contents. Meanwhile, applying exogenous trehalose enhanced the chilling tolerance of abf1 mutant lines. In summary, this study provides a novel pathway 'SAPK10-ABF1-TPS2' involved in rice chilling tolerance through regulating trehalose homeostasis.
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Oryza , Oryza/metabolismo , Trehalosa/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Quinasas/metabolismo , Regulación de la Expresión Génica de las Plantas , Frío , Proteínas de Plantas/metabolismoRESUMEN
PURPOSE: Nectin-4 is specifically up-regulated in various tumors, exert crucial effects on tumor occurrence and development. Nevertheless, the role and molecular mechanism of Nectin-4 in osteosarcoma (OS) are rarely studied. METHODS: The expression of Nectin-4 and its relationship with clinical characteristics of OS were investigated using OS clinical tissues, tissue microarrays, TCGA, and GEO databases. Moreover, the effect of Nectin-4 on cell growth and mobility was detected by CCK-8, colony formation, transwell, and wound-healing assays. The RT-qPCR, Western blotting, and luciferase reporter assays were performed to explore molecular mechanisms through which Nectin-4 mediates the expression of miR-520c-3p, thus modulating PI3K/AKT/NF-κB signaling. In vivo mice models constructed by subcutaneous transplantation and tail vein injection were used to validate the functional roles of Nectin-4 and miR-520c-3p. RESULTS: Nectin-4 displayed a higher expression in OS tumor tissues compared with normal tissues, and its overexpression was positively associated with tumor stage and metastasis in OS patients. Functionally, Nectin-4 enhanced OS cells growth and mobility in vitro. Mechanistically, Nectin-4 down-regulated the levels of miR-520c-3p that directly targeted AKT-1 and P65, thus leading to the stimulation of PI3K/AKT/NF-κB signaling. In addition, the expression of miR-520c-3p was apparently lower in OS tissues than in normal tissues, and its low expression was significantly related to tumor metastasis. Furthermore, ectopic expression of miR-520c-3p markedly blocked the effect of Nectin-4 on OS cell growth and mobility. Knockdown of Nectin-4 could suppress the tumorigenesis and metastasis in vivo, which could be remarkably reversed by miR-520c-3p silencing. CONCLUSIONS: Nectin-4 as an oncogene can promote OS progression and metastasis by activating PI3K/AKT/NF-κB signaling via down-regulation of miR-520c-3p, which could represent a novel avenue for identifying a potential therapeutic target for improving patient outcomes.
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BACKGROUND: Chemotherapy is a standard regimen for advanced or relapsed biliary tract cancer (BTC) with a 5-year overall survival (OS) rate of approximately 5% and a median OS of less than a year. Targeted therapies and immunotherapy aimed at providing more personalized treatments for BTCs have been tested. The objective of this study was to evaluate the effects of targeted therapy and immunotherapy on advanced BTC patients. METHODS: Twenty-four advanced/relapsed BTC patients were enrolled and examined with next-generation sequencing (NGS). Eight of them received NGS-guided targeted or immunotherapy, and the other 16 patients underwent routine chemotherapy. Comparison analysis of OS and objective response rate (ORR) was performed. RESULTS: IDH1, BRCA2, MAP2K1, and BRAF (V600E) were the major actionable genes mutated in this cohort. Patients who received NGS-guided therapy exhibited higher OS (not achieved vs. 6.5 months, p < 0.001) and ORR (87.5% vs. 25%, p < 0.001) than those without targetable mutations and who received first-line chemotherapy. BTCs harboring mutations in IDH1, ATM/BRCA2, or MAP2K1/BRAF (V600E) received treatment with dasatinib, olaparib, or trametinib, respectively. Three of the patients had high tumor mutation burden (TMB-H) and were treated with immune-checkpoint inhibitors and chemotherapy. All these patients achieved complete response or partial response. CONCLUSIONS: NGS-guided targeted therapy and immunotherapy are promising personalized therapies for advanced or relapsed BTCs. TMB is a useful biomarker for predicting immunotherapy efficacy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/terapia , Biomarcadores de Tumor/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Inmunoterapia/métodos , Terapia Molecular Dirigida/métodos , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Neoplasias del Sistema Biliar/genética , Neoplasias del Sistema Biliar/inmunología , Neoplasias del Sistema Biliar/patología , Terapia Combinada , Dasatinib/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Ftalazinas/administración & dosificación , Piperazinas/administración & dosificación , Pronóstico , Estudios Prospectivos , Piridonas/administración & dosificación , Pirimidinonas/administración & dosificación , Tasa de SupervivenciaRESUMEN
Avian coccidiosis caused by Eimeria leads to huge economic losses on the global poultry industry. In this study, microneme adhesive repeat regions (MARR) bc1 of E. tenella microneme protein 3 (EtMIC3-bc1) was used as ligand, and peptides binding to EtMIC3 were screened from a phage display peptide library. The positive phage clones were checked by enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was applied to further verify the binding capability between the positive phages and recombinant EtMIC3-bc1 protein or sporozoites protein. The inhibitory effects of target peptides on sporozoites invasion of MDBK cells were measured in vitro. Chickens were orally administrated with target positive phages and the protective effects against homologous challenge were evaluated. The model of three-dimensional (3D) structure for EtMIC3-bc1 was conducted, and molecular docking between target peptides and EtMIC3-bc1 model was analyzed. The results demonstrated that three selected positive phages specifically bind to EtMIC3-bc1 protein. The three peptides A, D and W effectively inhibited invasion of MDBK cells by sporozoites, showing inhibited ratio of 71.8%, 54.6% and 20.8%, respectively. Chickens in the group orally inoculated with phages A displayed more protective efficacies against homologous challenge than other groups. Molecular docking showed that amino acids in three peptides, especially in peptide A, insert into the hydrophobic groove of EtMIC3-bc1 protein, and bind to EtMIC3-bc1 through intermolecular hydrogen bonds. Taken together, the results suggest EtMIC3-binding peptides inhibit sporozoites entry into host cells. This study provides new idea for exploring novel strategies against coccidiosis.
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Pollos , Coccidiosis/veterinaria , Eimeria tenella/inmunología , Enfermedades de las Aves de Corral/prevención & control , Proteínas Protozoarias/inmunología , Esporozoítos/inmunología , Animales , Bacteriófagos , Ciego/patología , Coccidiosis/prevención & control , Simulación del Acoplamiento Molecular , Enfermedades de las Aves de Corral/parasitología , Unión Proteica , Conformación ProteicaRESUMEN
Here, we report a case of postoperative recurrence of gallbladder carcinoma (GBC) in a patient who declined systemic chemotherapy. ATM S1905Ifs*25 and STK11 K262Sfs*25 mutations were detected by next-generation sequencing. Oral administration of olaparib was initiated. One month later, the patient experienced relief of clinical symptoms, a decrease in CA19-9 level, and a reduction in abnormal signal in the subcapsular region. The tumor response remained stable for approximately 13 months. This is the first case to demonstrate the clinical benefits of olaparib treatment in a patient with GBC harboring an ATM-inactivating mutation. This observation helps to better inform treatment options to enhance the care of patients with advanced GBC. KEY POINTS: A patient with gallbladder carcinoma harboring an ATM-inactivating mutation responded to olaparib with a progression-free survival of 13 months. This is the first report that demonstrates the clinical benefits of olaparib treatment in a patient with gallbladder carcinoma with an ATM-inactivating mutation. It also highlights the importance of next-generation sequencing, which can provide valuable information for planning effective targeted therapies for gallbladder carcinoma. Evidence-based decisions help determine the best choice of treatment for individualized patient care.
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Neoplasias de la Vesícula Biliar , Proteínas de la Ataxia Telangiectasia Mutada/genética , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/genética , Humanos , Mutación , Recurrencia Local de Neoplasia , Ftalazinas , Piperazinas , Resultado del TratamientoRESUMEN
Understanding the conformation effect on molecular packing, miscibility, and photovoltaic performance is important to open a new avenue for small-molecule acceptor (SMA) design. Herein, two novel acceptor-(donor-acceptor1-donor)-acceptor (A-DA1D-A)-type asymmetric SMAs are developed, namely C-shaped BDTP-4F and S-shaped BTDTP-4F. The BDTP-4F-based polymer solar cells (PSCs) with PM6 as donor, yields a power conversion efficiency (PCE) of 15.24%, significantly higher than that of the BTDTP-4F-based device (13.12%). The better PCE for BDTP-4F-based device is mainly attributed to more balanced charge transport, weaker bimolecular recombination, and more favorable morphology. Additionally, two traditional A-D-A-type SMAs (IDTP-4F and IDTTP-4F) are also synthesized to investigate the conformation effect on morphology and device performance. Different from the device result above, here, IDTP-4F with S-shape conformation outperforms than IDTTP-4F with C-shape conformation. Importantly, it is found that for these two different types of SMA, the better performing binary blend has similar morphological characteristics. Specifically, both PM6:BDTP-4F and PM6:IDTP-4F blend exhibit perfect nanofibril network structure with proper domain size, obvious face-on orientation and enhance donor-acceptor interactions, thereby better device performance. This work indicates tuning molecular conformation plays pivotal role in morphology and device effciciency, shining a light on the molecular design of the SMAs.
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Acting as a brain stimulant, coffee resulted in heightening alertness, keeping arousal, improving executive speed, maintaining vigilance, and promoting memory, which are associated with attention, mood, and cognitive function. Functional near-infrared spectroscopy (fNIRS) is a noninvasive optical method to monitor brain activity by measuring the absorption of the near-infrared light through the intact skull. This study is aimed at acquiring brain activation during executing task performance. The aim is to explore the effect of coffee on cognitive function by the fNIRS neuroimaging method, particularly on the prefrontal cortex regions. The behavioral experimental results on 31 healthy subjects with a Stroop task indicate that coffee can easily and effectively modulate the execute task performance by feedback information of the response time and accuracy rate. The findings of fNIRS showed that apparent hemodynamic changes were detected in the bilateral VLPFC regions and the brain activation regions varied with different coffee conditions.
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Atención/efectos de los fármacos , Cafeína/farmacología , Cognición/efectos de los fármacos , Función Ejecutiva/efectos de los fármacos , Adulto , Atención/fisiología , Mapeo Encefálico/métodos , Función Ejecutiva/fisiología , Femenino , Neuroimagen Funcional/métodos , Humanos , Masculino , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiología , Espectroscopía Infrarroja Corta/métodos , Test de Stroop , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
To investigate the interactive effects of water and N from controlled release urea (CRU) on N metabolism, accumulation, translocation, and yield in Zhengdan958 (a summer maize cultivar planted widely in China), three water levels (adequate water W3, mild water stress W2, severe water stress W1) and four amounts of CRU (N) (N0, N1, N2, and N3 were 0, 105, 210, and 315 kg N ha-1, respectively) were carried out under the waterproof shed and soil column conditions. The results showed that yield, N metabolism, accumulation, and translocation were significantly affected by water, CRU, and their interactions after tasseling. Yields showed an increasing trend in response to N rates from 100.2 to 128.8 g plant-1 under severe water stress (W1), from 124.7 to 174.6 g plant-1 under mild water stress (W2), and from 143.7 to 177.0 g plant-1 under adequate water conditions (W3). There was an associated optimum amount of N for each water level. Under W1 and W2, N3 treatments showed significant advantages in three N metabolism enzymes' activities and the N accumulations, and yield and its components were highest. But the nitrogen harvest index (NHI) of N3 had no significant difference with other nitrogen treatments. Under W3, the N translocation efficiency (NTE) and N translocation conversion rate (NTCR) of N2 in stem and leaf were higher than those of N3, but the N metabolism enzymes' activities and yields of N2 and N3 had no significant difference, which indicated that N2 was superior to N3. The N3 treatment under W2 and N2 under W3 increased the N accumulation capacity in maize grain as well as the N translocation to grain that contributed to the increase of 1000-gain weight and grains per ear after tasseling. Under this experimental condition, a CRU rate of 225 kg ha-1 was the best treatment when the soil moisture content was 75 ± 5% of field capacity, but an N rate of 300 kg ha-1 was superior when soil moisture content was maintained at 55 ± 5% of field capacity during the entire growing season.
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Zea mays , Riego Agrícola , China , Preparaciones de Acción Retardada , Nitrógeno , Suelo , Triticum , Urea , AguaRESUMEN
Dengue virus (DENV) is a mosquito-borne virus that threatens approximately 2.5 billion people worldwide. Vaccines against DENV are currently unavailable. DEAD-box RNA helicases (DDXs) have been reported to participate in viral replication and host innate immune response. In the present study, we analyzed the role of 40 DDX proteins during DENV replication. Among these proteins, DDX3X showed antiviral effect against DENV infection. Viral replication significantly increased in DDX3X-silenced cells compared with the controls. The interferon (IFN)-ß transcription level decreased during the early stage of DENV infection in DDX3X-silenced cells compared with that in the controls. DDX3X could stimulate IFN-ß transcription through the IRF3 and the NFκB branches in DENV-infected cells. Our data imply that DDX3X, a member of DEAD-box RNA helicase, is necessary for IFN production and could inhibit DENV replication.
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ARN Helicasas DEAD-box/metabolismo , Virus del Dengue/fisiología , Regulación Viral de la Expresión Génica , Interferón Tipo I/metabolismo , Replicación Viral , Dengue/virología , Silenciador del Gen , Células HEK293 , Humanos , Inmunidad Innata , Factor 3 Regulador del Interferón/metabolismo , FN-kappa B/metabolismo , Plásmidos/metabolismo , Transcripción GenéticaRESUMEN
This review critically evaluates advancements in multifunctional hydrogels, particularly focusing on their applications in osteoarthritis (OA) therapy. As research evolves from traditional natural materials, there is a significant shift towards synthetic and composite hydrogels, known for their superior mechanical properties and enhanced biodegradability. This review spotlights novel applications such as injectable hydrogels, microneedle technology, and responsive hydrogels, which have revolutionized OA treatment through targeted and efficient therapeutic delivery. Moreover, it discusses innovative hydrogel materials, including protein-based and superlubricating hydrogels, for their potential to reduce joint friction and inflammation. The integration of bioactive compounds within hydrogels to augment therapeutic efficacy is also examined. Furthermore, the review anticipates continued technological advancements and a deeper understanding of hydrogel-based OA therapies. It emphasizes the potential of hydrogels to provide tailored, minimally invasive treatments, thus highlighting their critical role in advancing the dynamic field of biomaterial science for OA management.
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The metastasis and recurrence of cancer are related to immunosuppression and hypoxia in the tumor microenvironment. Activating immune activity and improving the hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. The tumor microenvironment changed from the immunosuppressive type to immune type, activated the immune activity of the system, decomposed hydrogen peroxide to generate oxygen based on Fenton-like reaction, and effectively increased the level of intracellular O2 with the assistance of 3-bromopyruvate, a cell respiratory inhibitor. The structure and composition of HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, infrared spectroscopy, etc. Oxygen probe RDPP was used to investigate the oxygen level inside and outside the cell, and hydroxyl radical probe tetramethylbenzidine was used to investigate the Fenton-like reaction ability. The immunofluorescence method investigated the expression of various immune markers and hypoxia-inducing factors in vitro and in vivo after treatment. In vitro and in vivo experiments indicate that HSCCMBC is an excellent antitumor agent and is expected to be a candidate drug for antitumor immunotherapy.
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Nanopartículas , Neoplasias , Humanos , Dióxido de Silicio/farmacología , Cobre/química , Carbono/farmacología , Muerte Celular Inmunogénica , Neoplasias/tratamiento farmacológico , Oxígeno/química , Hipoxia , Línea Celular Tumoral , Peróxido de Hidrógeno/química , Microambiente Tumoral , Nanopartículas/químicaRESUMEN
Cancer metastasis and invasion are closely related to tumor cell immunosuppression and intracellular hypoxia. Activation of immunogenicity and intracellular oxygenation are effective strategies for cancer treatment. In this study, multifunctional nanomicelle hyaluronic acid and cinnamaldehyde is self-assembled into nanomicelles (HPCNPs) were constructed for immunotherapy and tumor cell oxygenation. The Schiff base was constructed of HPCNPs with pyropheophorbide a-Cu (PPa-Cu). HPCNPs are concentrated in tumor sites under the guidance of CD44 proteins, and under the stimulation of tumor environment (weakly acidic), the Schiff base is destroyed to release free PPa. HPCNPs with photodynamic therapeutic functions and chemokinetic therapeutic functions produce a large number of reactive oxygen species (1O2 and â¢OH) under exogenous (laser) and endogenous (H2O2) stimulations, causing cell damage, and then inducing immunogenic cell death (ICD). ICD markers (CRT and ATP) and immunoactivity markers (IL-2 and CD8) were characterized by immunofluorescence. Downregulation of Arg1 protein proved that the tumor microenvironment changed from immunosuppressive type (M2) to antitumor type (M1). The oxidation of glutathione by HPCNP cascades to amplify the concentration of reactive oxygen species. In situ oxygenation by HPCNPs based on a Fenton-like reaction improves the intracellular oxygen level. In vitro and in vivo experiments demonstrated that HPCNPs combined with an immune checkpoint blocker (α-PD-L1) effectively ablated primary tumors, effectively inhibited the growth of distal tumors, and increased the oxygen level in tumor cells.
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Ácido Hialurónico , Peróxido de Hidrógeno , Ácido Hialurónico/farmacología , Especies Reactivas de Oxígeno , Bases de Schiff , Oxígeno , Concentración de Iones de HidrógenoRESUMEN
Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3O4-carbon dots complex (Fe3O4-CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3O4-CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe3O4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe3O4-CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe3O4-CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1α) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe3O4-CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1α was investigated by immunofluorescence method. In vivo, Fe3O4-CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe3O4-CDs@Fc is a promising immune-antitumor drug.
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Carbono , Oxígeno , Puntos Cuánticos , Ratones , Animales , Puntos Cuánticos/química , Carbono/química , Humanos , Catálisis , Oxígeno/química , Inmunoterapia , Tamaño de la Partícula , Antineoplásicos/farmacología , Antineoplásicos/química , Fotoquimioterapia , Ratones Endogámicos BALB C , Línea Celular Tumoral , Hierro/química , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/farmacología , Propiedades de Superficie , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , FemeninoRESUMEN
Global warming poses a significant challenge to global food security, with maize playing a vital role as a staple crop in ensuring food availability worldwide. Therefore, investigating the impact of high temperatures (HT) on maize cultivation is imperative for addressing food security concerns. Despite numerous studies exploring the effects of HT on maize growth and yield, a comprehensive understanding of these effects remains elusive due to variations in experimental environments, varieties, and growth stages. To solve these limitations, a meta-analysis was conducted to assess the effects of HT on maize yield and grain components, synthesizing data from 575 observations across 34 studies. The findings indicate that 1) HT significantly reduced grain yield by 32.7-40.9â¯% and grain starch content by 2.8-10.5â¯%; 2) the vicinity of kernel development stage (include silking, blister, milk) is the period when maize kernels are most sensitive to HT; 3) a significant negative correlation was observed between HT degrees and their impact on grain yield (R2â¯=â¯0.38; Pâ¯=â¯0.043); and 4) the effects of HT days and degree on maize yield were equally important. In conclusion, this meta-analysis establishes a theoretical framework for enhancing the resilience of maize production and cultivation practices by comprehensively evaluating the impact of HT on yield and grain components.
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BACKGROUND: Tumor-derived exosomal miRNAs play crucial roles in cancer diagnosis. Current studies aim to identify exosomal miRNAs associated with colorectal cancer (CRC) that are noninvasive, sensitive, and specific. PATIENTS AND METHODS: Exosomes were extracted from CRC patients and healthy donors via ultracentrifugation, followed by verification via transmission electron microscopy (TEM), qNano, and Western blot analysis. The differential expression levels and clinical characteristics of miR-205-5p were analyzed in CRC via data from The Cancer Genome Atlas (TCGA). Real-time quantitative PCR was used to assess the expression levels of exosomal miRNAs in 157 primary CRC patients, 20 patients with benign diseases, and 135 healthy donors. Predictions regarding target genes were made to guide further exploration of the disease's etiopathogenesis through bioinformatics. RESULTS: Compared with that in healthy donors, the expression of miR-205-5p in colorectal cancer (CRC) patients was significantly lower, as determined through analysis of the TCGA database. We conducted a prediction and analysis of the functional enrichment of downstream target genes regulated by miR-205-5p. A lower level of exosomal miR-205-5p in the serum of CRC patients than in that of healthy controls (p < 0.0001) and patients with benign disease (p < 0.0001) was observed. Furthermore, the expression levels of exosomal miR-205-5p were significantly lower in early-stage CRC patients than in the comparison groups (p<0.001 and p < 0.0001). Notably, the expression levels of exosomal miR-205-5p significantly increased postoperatively (p = 0.0053). CONCLUSIONS: The present study demonstrated that serum exosomal miR-205-5p may be a diagnostic biomarker for CRC.
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BACKGROUND: In recent years,the lack of specific markers for the diagnosis of colorectal cancer has led to an upward trend in both morbidity and mortality from this condition. There is an urgent need to identify molecular biomarkers that contribute to early cancer detection. This study aimed to identify specific exosomal microRNAs that hold potential as diagnostic biomarkers for CRC. METHODS: We screened for differentially expressed miRNAs using the CRC exosome dataset GSE39833. To validate the results in the public database, we collected serum from 168 CRC patients and 168 healthy volunteers. The expression levels of exosomal miR-1470 in healthy volunteers and CRC patients were analyzed using qRT-PCR. To evaluate the diagnostic potential of the selected miR-1470 in distinguishing CRC patients from healthy controls, we analyzed its receiver operating characteristic curve. To explore the biological functions of miR-1470 in CRC cell lines, we detected the miR-1470's ability to regulate the growth and metastasis of CRC cells by CCK8, transwell and other assays after transfection of miR-1470 in SW480, HCT-116 cells. RESULTS: Exosomal miR-1470 exhibited significant up-regulation in CRC patients compared to healthy volunteers. The ROC curve analysis revealed an area under the curve (AUC) of 0.74 (95% confidence interval: 0.6876-0.7920) for exosomal miR-1470, indicating its potential as a diagnostic biomarker. Furthermore, the expression level of miR-1470 in CRC patients showed correlations with age, metastasis, and HDL content. We overexpressed miR-1470 in CRC cell lines. CCK8 proliferation assay showed that miR-1470 promoted the proliferation ability of SW480 and HCT-116 cells. Transwell assay showed that miR-1470 promoted the migration and invasion ability of SW480 and HCT-116 cells. CONCLUSION: This suggested that non-invasive diagnosis of CRC is possible by detecting the level of miR-1470 in exosomes, which has important implications for early detection and treatment of this disease.