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1.
Nat Immunol ; 23(10): 1433-1444, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36138184

RESUMEN

Naive T cells undergo radical changes during the transition from dormant to hyperactive states upon activation, which necessitates de novo protein production via transcription and translation. However, the mechanism whereby T cells globally promote translation remains largely unknown. Here, we show that on exit from quiescence, T cells upregulate transfer RNA (tRNA) m1A58 'writer' proteins TRMT61A and TRMT6, which confer m1A58 RNA modification on a specific subset of early expressed tRNAs. These m1A-modified early tRNAs enhance translation efficiency, enabling rapid and necessary synthesis of MYC and of a specific group of key functional proteins. The MYC protein then guides the exit of naive T cells from a quiescent state into a proliferative state and promotes rapid T cell expansion after activation. Conditional deletion of the Trmt61a gene in mouse CD4+ T cells causes MYC protein deficiency and cell cycle arrest, disrupts T cell expansion upon cognate antigen stimulation and alleviates colitis in a mouse adoptive transfer colitis model. Our study elucidates for the first time, to our knowledge, the in vivo physiological roles of tRNA-m1A58 modification in T cell-mediated pathogenesis and reveals a new mechanism of tRNA-m1A58-controlled T cell homeostasis and signal-dependent translational control of specific key proteins.


Asunto(s)
Colitis , ARN de Transferencia , Traslado Adoptivo , Animales , Proliferación Celular/genética , Colitis/genética , Ratones , Biosíntesis de Proteínas , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Linfocitos T/metabolismo
2.
Nat Methods ; 19(10): 1243-1249, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36109677

RESUMEN

Joint profiling of chromatin accessibility and gene expression from the same single cell provides critical information about cell types in a tissue and cell states during a dynamic process. Here, we develop in situ sequencing hetero RNA-DNA-hybrid after assay for transposase-accessible chromatin-sequencing (ISSAAC-seq), a highly sensitive and flexible single-cell multi-omics method to interrogate chromatin accessibility and gene expression from the same single nucleus. We demonstrated that ISSAAC-seq is sensitive and provides high quality data with orders of magnitude more features than existing methods. Using the joint profiles from over 10,000 nuclei from the mouse cerebral cortex, we uncovered major and rare cell types and cell-type specific regulatory elements and identified heterogeneity at the chromatin level within established cell types defined by gene expression. Finally, we revealed distinct dynamics and relationships of gene expression and chromatin accessibility during an oligodendrocyte maturation trajectory.


Asunto(s)
Cromatina , Secuenciación de Nucleótidos de Alto Rendimiento , Animales , Cromatina/genética , ADN , Expresión Génica , Ratones , ARN , Transposasas/genética , Transposasas/metabolismo
3.
Cancer Sci ; 115(4): 1170-1183, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38287874

RESUMEN

Platinum-based therapies have revolutionized the treatment of high-grade serous ovarian cancer (HGSOC). However, high rates of disease recurrence and progression remain a major clinical concern. Impaired mitochondrial function and dysregulated reactive oxygen species (ROS), hallmarks of cancer, hold potential as therapeutic targets for selectively sensitizing cisplatin treatment. Here, we uncover an oncogenic role of the palmitoyltransferase ZDHHC12 in regulating mitochondrial function and ROS homeostasis in HGSOC cells. Analysis of The Cancer Genome Atlas (TCGA) ovarian cancer data revealed significantly elevated ZDHHC12 expression, demonstrating the strongest positive association with ROS pathways among all ZDHHC enzymes. Transcriptomic analysis of independent ovarian cancer datasets and the SNU119 cell model corroborated this association, highlighting a strong link between ZDHHC12 expression and signature pathways involving mitochondrial oxidative metabolism and ROS regulation. Knockdown of ZDHHC12 disrupted this association, leading to increased cellular complexity, ATP levels, mitochondrial activity, and both mitochondrial and cellular ROS. This dysregulation, achieved by the siRNA knockdown of ZDHHC12 or treatment with the general palmitoylation inhibitor 2BP or the fatty acid synthase inhibitor C75, significantly enhanced cisplatin cytotoxicity in 2D and 3D spheroid models of HGSOC through ROS-mediated mechanisms. Markedly, ZDHHC12 inhibition significantly augmented the anti-tumor activity of cisplatin in an ovarian cancer xenograft tumor model, as well as in an ascites-derived organoid line of platinum-resistant ovarian cancer. Our data suggest the potential of ZDHHC12 as a promising target to improve the outcome of HGSOCs in response to platinum-based chemotherapy.


Asunto(s)
Cisplatino , Neoplasias Ováricas , Humanos , Femenino , Cisplatino/farmacología , Cisplatino/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Resistencia a Antineoplásicos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Línea Celular Tumoral
4.
Clin Immunol ; 263: 110231, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692449

RESUMEN

Moderate-to-severe systemic lupus erythematosus (SLE) is characterized by extensive autoantibody deposition and persistent autoinflammation. As the existing animal models are limited in accurately reproducing the pathological characteristics of human SLE, we introduced a novel animal model simulating multi-organ autoinflammation through intra-organ injections. The model closely mimicked key features of SLE, including IgG deposition, inflammation, and tissue damage. The model could be used to assess the roles of IgG, immune cells, cytokines, and Fc gamma receptor (FcγR) in the pathogenesis of autoinflammation. The results obtained from this model could be confirmed by lupus MRL/lpr mice. The review suggested that the diagnostic criteria should be reconsidered to incorporate IgG deposition in tissues and highlighted the limitations of current T-cell and B-cell-focused treatments. To summarize, the IgG deposition model can be used to investigate the pathogenesis and treatment of multi-organ tissue damage associated with SLE.


Asunto(s)
Modelos Animales de Enfermedad , Inmunoglobulina G , Lupus Eritematoso Sistémico , Animales , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Ratones , Inmunoglobulina G/inmunología , Humanos , Ratones Endogámicos MRL lpr , Inflamación/inmunología , Receptores de IgG/inmunología , Receptores de IgG/metabolismo , Linfocitos B/inmunología
5.
Anal Chem ; 96(19): 7787-7796, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38702857

RESUMEN

Microorganism are ubiquitous and intimately connected with human health and disease management. The accurate and fast identification of pathogenic microorganisms is especially important for diagnosing infections. Herein, three tetraphenylethylene derivatives (S-TDs: TBN, TPN, and TPI) featuring different cationic groups, charge numbers, emission wavelengths, and hydrophobicities were successfully synthesized. Benefiting from distinct cell wall binding properties, S-TDs were collectively utilized to create a sensor array capable of imaging various microorganisms through their characteristic fluorescent signatures. Furthermore, the interaction mechanism between S-TDs and different microorganisms was explored by calculating the binding energy between S-TDs and cell membrane/wall constituents, including phospholipid bilayer and peptidoglycan. Using a combination of the fluorescence sensor array and a deep learning model of residual network (ResNet), readily differentiation of Gram-negative bacteria (G-), Gram-positive bacteria (G+), fungi, and their mixtures was achieved. Specifically, by extensive training of two ResNet models with large quantities of images data from 14 kinds of microorganism stained with S-TDs, identification of microorganism was achieved at high-level accuracy: over 92.8% for both Gram species and antibiotic-resistant species, with 90.35% accuracy for the detection of mixed microorganism in infected wound. This novel method provides a rapid and accurate method for microbial classification, potentially aiding in the diagnosis and treatment of infectious diseases.


Asunto(s)
Aprendizaje Profundo , Humanos , Estilbenos/química , Bacterias Grampositivas/aislamiento & purificación , Colorantes Fluorescentes/química , Bacterias Gramnegativas/aislamiento & purificación , Infección de Heridas/microbiología , Infección de Heridas/diagnóstico , Hongos/aislamiento & purificación
6.
J Virol ; 97(8): e0018123, 2023 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-37565750

RESUMEN

Vacuolar protein sorting 28 (Vps28), a component of the ESCRT-I (endosomal sorting complex required for transport I), plays an important role in the pathogen life cycle. Here, we investigated the reciprocal regulation between Vps28 and the foot-and-mouth disease virus (FMDV). Overexpression of Vps28 decreased FMDV replication. On the contrary, the knockdown of Vps28 increased viral replication. Subsequently, the mechanistic study showed that Vps28 destabilized the replication complex (RC) by associating with 3A rather than 2C protein. In addition, Vps28 targeted FMDV VP0, VP1, and VP3 for degradation to inhibit viral replication. To counteract this, FMDV utilized tactics to restrict Vps28 to promote viral replication. FMDV degraded Vps28 mainly through the ubiquitin-proteasome pathway. Additional data demonstrated that 2B and 3A proteins recruited E3 ubiquitin ligase tripartite motif-containing protein 21 to degrade Vps28 at Lys58 and Lys25, respectively, and FMDV 3Cpro degraded Vps28 through autophagy and its protease activity. Meantime, the 3Cpro-mediated Vps28 degradation principally alleviated the ability to inhibit viral propagation. Intriguingly, we also demonstrated that the N-terminal and C-terminal domains of Vps28 were responsible for the suppression of FMDV replication, which suggested the elaborated counteraction between FMDV and Vps28. Collectively, our results first investigate the role of ESCRTs in host defense against picornavirus and unveil underlying strategies utilized by FMDV to evade degradation machinery for triumphant propagation. IMPORTANCE ESCRT machinery plays positive roles in virus entry, replication, and budding. However, little has been reported on its negative regulation effects during viral infection. Here, we uncovered the novel roles of ESCRT-I subunit Vps28 on FMDV replication. The data indicated that Vps28 destabilized the RC and impaired viral structural proteins VP0, VP1, and VP3 to inhibit viral replication. To counteract this, FMDV hijacked intracellular protein degradation pathways to downregulate Vps28 expression and thus promoted viral replication. Our findings provide insights into how ESCRT regulates pathogen life cycles and elucidate additional information regarding FMDV counteraction of host antiviral activity.


Asunto(s)
Virus de la Fiebre Aftosa , Fiebre Aftosa , Animales , Virus de la Fiebre Aftosa/metabolismo , Proteínas Virales/metabolismo , Transducción de Señal , Transporte de Proteínas , Replicación Viral/fisiología
7.
J Transl Med ; 22(1): 182, 2024 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-38373959

RESUMEN

BACKGROUND: Digital histopathology provides valuable information for clinical decision-making. We hypothesized that a deep risk network (DeepRisk) based on digital pathology signature (DPS) derived from whole-slide images could improve the prognostic value of the tumor, node, and metastasis (TNM) staging system and offer chemotherapeutic benefits for gastric cancer (GC). METHODS: DeepRisk is a multi-scale, attention-based learning model developed on 1120 GCs in the Zhongshan dataset and validated with two external datasets. Then, we assessed its association with prognosis and treatment response. The multi-omics analysis and multiplex Immunohistochemistry were conducted to evaluate the potential pathogenesis and spatial immune contexture underlying DPS. RESULTS: Multivariate analysis indicated that the DPS was an independent prognosticator with a better C-index (0.84 for overall survival and 0.71 for disease-free survival). Patients with low-DPS after neoadjuvant chemotherapy responded favorably to treatment. Spatial analysis indicated that exhausted immune clusters and increased infiltration of CD11b+CD11c+ immune cells were present at the invasive margin of high-DPS group. Multi-omics data from the Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD) hint at the relevance of DPS to myeloid derived suppressor cells infiltration and immune suppression. CONCLUSION: DeepRisk network is a reliable tool that enhances prognostic value of TNM staging and aid in precise treatment, providing insights into the underlying pathogenic mechanisms.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Terapia Neoadyuvante , Toma de Decisiones Clínicas , Inteligencia Artificial , Pronóstico
8.
J Immunol ; 208(2): 396-406, 2022 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-34911770

RESUMEN

Classic T cell subsets are defined by a small set of cell surface markers, while single-cell RNA sequencing (scRNA-seq) clusters cells using genome-wide gene expression profiles. The relationship between scRNA-seq clustered populations (scCPops) and cell surface marker-defined classic T cell subsets remains unclear. In this article, we integrated six bead-enriched T cell subsets with 62,235 single-cell transcriptomes from human PBMCs and clustered them into nine scCPops. Bead-enriched CD4+/CD45RA+/CD25- naive T and CD8+/CD45RA+ naive T cells were mainly clustered into their scCPop counterparts, while cells from the other T cell subsets were assigned to multiple scCPops, including mucosal-associated invariant T cells and NKT cells. The multiple T cell subsets forming one scCPop exhibit similar expression patterns, but not vice versa, indicating scCPop is a more homogeneous cell population with similar cell states. Interestingly, we discovered and named IFN signaling-associated gene (ISAG) high T (ISAGhi T) cells, a T cell subpopulation that highly expressed ISAGs. We further enriched ISAGhi T cells from human PBMCs by FACS of BST2 for scRNA-seq analyses. The ISAGhi T cell cluster disappeared on t-distributed stochastic neighbor embedding plot after removing ISAGs, whereas the ISAGhi T cell cluster showed up by analysis of ISAGs alone, indicating ISAGs are the major contributor of the ISAGhi T cell cluster. BST2+ and BST2- T cells showing different efficiencies of T cell activation indicate that a high level of ISAGs may contribute to quick immune responses.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Células T Asesinas Naturales/inmunología , RNA-Seq/métodos , Subgrupos de Linfocitos T/inmunología , Antígenos CD/metabolismo , Células Cultivadas , Proteínas Ligadas a GPI/metabolismo , Humanos , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Activación de Linfocitos/inmunología , Análisis de la Célula Individual/métodos , Transcriptoma/genética
9.
Oral Dis ; 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38409677

RESUMEN

OBJECTIVES: A zinc-finger transcription factor family comprising specificity proteins (SPs) and Krüppel-like factor proteins (KLFs) plays an important role in dentin development and regeneration. However, a systematic regulatory network involving SPs/KLFs in odontoblast differentiation has not yet been described. This review examined the expression patterns of SP/KLF gene family members and their current known functions and mechanisms in odontoblast differentiation, and discussed prospective research directions for further exploration of mechanisms involving the SP/KLF gene family in dentin development. MATERIALS AND METHODS: Relevant literature on SP/KLF gene family members and dentin development was acquired from PubMed and Web of Science. RESULTS: We discuss the expression patterns, functions, and related mechanisms of eight members of the SP/KLF gene family in dentin development and genetic disorders with dental problems. We also summarize current knowledge about their complementary or synergistic actions. Finally, we propose future research directions for investigating the mechanisms of dentin development. CONCLUSIONS: The SP/KLF gene family plays a vital role in tooth development. Studying the complex complementary or synergistic interactions between SPs/KLFs is helpful for understanding the process of odontoblast differentiation. Applications of single-cell and spatial multi-omics may provide a more complete investigation of the mechanism involved in dentin development.

10.
Nano Lett ; 23(11): 4699-4707, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-36951377

RESUMEN

Mass transfer is critical in catalytic processes, especially when the reactions are facilitated by nanostructured catalysts. Strong efforts have been devoted to improving the efficacy and quantity of active sites, but often, mass transfer has not been well studied. Herein, we demonstrate the importance of mass transfer in the electrocatalytic oxygen reduction reaction (ORR) by tailoring the pore sizes. Using a confined-etching strategy, we fabricate boron- and nitrogen-doped carbon (B,N@C) electrocatalysts featuring abundant active sites but different porous structures. The ORR performance of these catalysts is found to correlate with diffusion of the reactant. The optimized B,N@C with trimodal-porous structures feature enhanced O2 diffusion and better activity per heteroatomic site toward the ORR process. This work demonstrates the significance of the nanoarchitecture engineering of catalysts and sheds light on how to optimize structures featuring abundant active sites and enhanced mass transfer.

11.
Angew Chem Int Ed Engl ; 63(5): e202315434, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-37973618

RESUMEN

Enhancing anisotropy through the controlled arrangement of anionic groups is essential for improving the nonlinear optical (NLO) performance of non-π-conjugated NLO materials. In this study, we present the successful synthesis of the first examples of mixed alkali metal-alkaline earth metal sulfamate materials, including noncentrosymmetric Cs2 Mg(NH2 SO3 )4 ⋅ 4H2 O (1), as well as centrosymmetric K2 Ca(NH2 SO3 )4 (2) and Rb2 Ca(NH2 SO3 )4 (3). All three compounds feature promising deep ultraviolet cut-off edges, notably 1 with a cut-off edge below 180 nm. The synergy of Cs+ and Mg2+ cations in 1 facilitated the successful alignment of polar [NH2 SO3 ] tetrahedra in a uniform orientation. Remarkably, 1 stands as the sole instance among reported sulfamate compounds with a co-parallel anionic arrangement, yielding a very large dipole moment compared to other non-π-conjugated NLO materials. Moreover, the substantial dipole moment of 1 yields an enhanced second harmonic generation response, approximately 2.3 times that of KH2 PO4 , and a large birefringence of 0.054 at 546.1 nm. The approach of regulating the arrangement of anionic groups using aliovalent cations holds promise for advancing the exploration of non-π-conjugated NLO materials.

12.
Int J Cancer ; 153(5): 1096-1107, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37232006

RESUMEN

Non-diagnostic findings are common in transbronchial lung biopsy (TBLB) and endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB). One of the challenges is to improve the detection of lung cancer using these techniques. To address this issue, we utilized an 850 K methylation chip to identify methylation sites that distinguish malignant from benign lung nodules. Our study found that a combination of HOXA7, SHOX2 and SCT methylation analysis has the best diagnostic yield in bronchial washing (sensitivity: 74.1%; AUC: 0.851) and brushing samples (sensitivity: 86.1%; AUC: 0.915). We developed a kit comprising these three genes and validated it in 329 unique bronchial washing samples, 397 unique brushing samples and 179 unique patients with both washing and brushing samples. The panel's accuracy in lung cancer diagnosis was 86.9%, 91.2% and 95% in bronchial washing, brushing and washing + brushing samples, respectively. When combined with cytology, rapid on-site evaluation (ROSE), and histology, the panel's sensitivity in lung cancer diagnosis was 90.8% and 95.8% in bronchial washing and brushing samples, respectively, and 100% in washing + brushing samples. Our findings suggest that quantitative analysis of the three-gene panel can improve the diagnosis of lung cancer using bronchoscopy.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Pulmón/patología , Biopsia/métodos , Broncoscopía , ADN
13.
Anal Chem ; 95(32): 11943-11952, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37526416

RESUMEN

Schizophrenia is a common mental disorder with unclear mechanisms. Oxidative stress and neuroinflammation play important roles in the pathological process of schizophrenia. Superoxide anion (O2•-) is an important oxidative stress biomarker in vivo. However, due to the existence of the blood-brain barrier (BBB), few near-infrared (NIR) fluorescent probes have been used for the sensing and detection of O2•- in the brain. With this research, we developed the first near-infrared fluorescent probe (named CT-CF3) for noninvasive detection of endogenous O2•- in the brain of mice. Enabling fluorescence monitoring of the dynamic changes in O2•- flux due to the prolonged activation of microglia in neuroinflamed and schizophrenic (SZ) mice brains, thereby providing direct evidence for the relationship between oxidative stress, neuroinflammation, and schizophrenia. Furthermore, we confirmed the O2•- burst in the brains of first-episode schizophrenic mice and assessed the effect of two atypical antipsychotic drugs (risperidone and olanzapine) on redox homeostasis.


Asunto(s)
Colorantes Fluorescentes , Enfermedades Neuroinflamatorias , Animales , Ratones , Encéfalo/diagnóstico por imagen , Barrera Hematoencefálica , Estrés Oxidativo
14.
Small ; 19(45): e2303960, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37415532

RESUMEN

Electron density manipulation of active sites in cocatalysts is of great essential to realize the optimal hydrogen adsorption/desorption behavior for constructing high-efficient H2 -evolution photocatalyst. Herein, a strategy about weakening metal-metal bond strength to directionally optimize the electron density of channel-sulfur(S) sites in 1T' Re1- x Mox S2 cocatalyst is clarified to improve their hydrogen adsorption strength (S─H bond) for rapid H2 -production reaction. In this case, the ultrathin Re1- x Mox S2 nanosheet is in situ anchored on the TiO2 surface to form Re1- x Mox S2 /TiO2 photocatalyst by a facial molten salt method. Remarkably, numerous visual H2 bubbles are constantly generated on the optimal Re0.92 Mo0.08 S2 /TiO2 sample with a 10.56 mmol g-1  h-1 rate (apparent quantum efficiency is about 50.6%), which is 2.6 times higher than that of traditional ReS2 /TiO2 sample. Density functional theory and in situ/ex situ X-ray photoelectron spectroscopy results collectively demonstrate that the weakened Re─Re bond strength via Mo introduction can induce the formation of unique electron-deficient channel-S sites with suitable electron density, which yield thermoneutral S─H bonds to realize superior interfacial H2 -generation performance. This work provides fundamental guidance on purposely optimizing the electronic state of active sites by manipulating the intrinsic bonding structure, which opens an avenue for designing efficacious photocatalytic materials.

15.
Small ; : e2305117, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37963822

RESUMEN

The icosahedral closo dodecaborate cluster [B12 H12 ]2- is gaining increasing interest due to its unique properties including the ease of functionalization, 3D aromaticity, and formation of metal salts with high ion conductivity. In this work, simple and effective preparation of silver closo dodecaborte (Ag2 B12 H12 ) films is reported by an electrochemical route. The size of the Ag2 B12 H12 particles in the films can be tuned from nanometers to micrometers by varying the electrochemical parameters. Ag nanoclusters with controllable sizes are successfully generated via electrochemical reduction reactions or thermal anneal of the Ag2 B12 H12 films. When tested for hydrogen evolution reaction (HER) in an acidic solution, the as-prepared Ag nanoparticles deliver a current density of 10 mA cm-2 at 376 mV overpotential. This research sheds light on a new synthesis of [B12 H12 ]2- based thin films, the generation of metal nano-powders, and their application in HER or other applications.

16.
BMC Microbiol ; 23(1): 333, 2023 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-37951882

RESUMEN

Human rhinovirus B (HRV-B) is a major human viral pathogen that can be responsible for various kinds of infections. Due to the health risks associated with HRV-B, it is therefore crucial to explore a rapid, specific, and sensitive method for surveillance. Herein, we exploited a novel detection method for HRV-B by combining reverse-transcription recombinase polymerase amplification (RT-RPA) of nucleic acids isothermal amplification and the trans-cleavage activity of Cas12a. Our RT-RPA-Cas12a-based fluorescent assay can be completed within 35-45 min and obtain a lower detection threshold to 0.5 copies/µL of target RNA. Meanwhile, crRNA sequences without a specific protospacer adjacent motif can effectively activate the trans-cleavage activity of Cas12a. Moreover, our RT-RPA-Cas12a-based fluorescent method was examined using 30 clinical samples, and exhibited high accuracy with positive and negative predictive agreement of 90% and 100%, respectively. Taken together, a novel promising, rapid and effective RT-RPA-Cas12a-based detection method was explored and shows promising potential for on-site HRV-B infection in resource-limited settings.


Asunto(s)
Bioensayo , Sistemas CRISPR-Cas , Humanos , Colorantes , Nucleotidiltransferasas , Recombinasas
17.
BMC Cancer ; 23(1): 308, 2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37016303

RESUMEN

BACKGROUND: The Neo-REGATTA study evaluated the effectiveness and safety of Docetaxel, oxaliplatin, and S-1 (DOS regimen) followed by radical resection vs. chemotherapy in advanced gastric adenocarcinoma patients with single non-curable factor. METHODS: This cohort study prospectively enrolled advanced gastric adenocarcinoma patients with single non-curable factor between November 2017 and June 2021. Patients without progression after four cycles of DOS were divided into resection group and chemotherapy group. The outcomes included overall survival (OS), progression-free survival (PFS) and safety. Effectiveness analysis was also performed by propensity score matching (PSM). RESULTS: A total of 73 patients were enrolled and 13 patients were withdrawn due to disease progression after 4 cycles of DOS. Afterwards, 35 and 25 participants were in the resection and chemotherapy groups, respectively. After a median follow-up time of 30.0 months, the median PFS and OS were 9.0 months, and 18.0 months for the chemotherapy group, but not reached in the resection group. After PSM, 19 matched participants were in each group, and the median PFS and OS were longer in resection group than that in chemotherapy group. The most common grade 3 or 4 adverse events both in the resection group and chemotherapy groups were neutropenia (5.7%, 8.0%) and leukopenia (5.7%, 8.0%). CONCLUSIONS: Radical resection might provide survival benefit compared with continuous chemotherapy alone in advanced gastric adenocarcinoma patients who had a disease control after DOS, with a good safety profile. TRIAL REGISTRATION: The study protocol was registered on ClinicalTrial.gov (NCT03001726, 23/12/2016).


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Docetaxel/uso terapéutico , Oxaliplatino/uso terapéutico , Terapia Neoadyuvante , Estudios de Cohortes , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Adenocarcinoma/patología
18.
J Magn Reson Imaging ; 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37855421

RESUMEN

BACKGROUND: Assessment of lymphovascular invasion (LVI) in breast cancer (BC) primarily relies on preoperative needle biopsy. There is an urgent need to develop a non-invasive assessment method. PURPOSE: To develop an effective model to assess the LVI status in patients with BC using magnetic resonance imaging morphological features (MRI-MF), Radiomics, and deep learning (DL) approaches based on dynamic contrast-enhanced MRI (DCE-MRI). STUDY TYPE: Cross-sectional retrospective cohort study. POPULATION: The study included 206 BC patients, with 136 in the training set [97 LVI(-) and 39 LVI(+) cases; median age: 51.5 years] and 70 in the test set [52 LVI(-) and 18 LVI(+) cases; median age: 48 years]. FIELD STRENGTH/SEQUENCE: 1.5 T/T1-weighted images, fat-suppressed T2-weighted images, diffusion-weighted imaging (DWI), and DCE-MRI. ASSESSMENT: The MRI-MF model was developed with conventional MR features using logistic analyses. The Radiomic feature extraction process involved collecting data from categorized DCE-MRI datasets, specifically the first and second post-contrast images (A1 and A2). Next, a DL model was implemented to determine LVI. Finally, we established a joint diagnosis model by combining the MRI-MF, Radiomics, and DL approaches. STATISTICAL TESTS: Diagnostic performance was compared using receiver operating characteristic curve analysis, confusion matrix, and decision curve analysis. RESULTS: Rim sign and peritumoral edema features were used to develop the MRI-MF model, while six Radiomics signature from the A1 and A2 images were used for the Radiomics model. The joint model (MRI-MF + Radiomics + DL models) achieved the highest accuracy (area under the curve [AUC] = 0.857), being significantly superior to the MRI-MF (AUC = 0.724), Radiomics (AUC = 0.736), or DL (AUC = 0.740) model. Furthermore, it also outperformed the pairwise combination models: Radiomics + MRI-MF (AUC = 0.796), DL + MRI-MF (AUC = 0.796), or DL + Radiomics (AUC = 0.826). DATA CONCLUSION: The joint model incorporating MRI-MF, Radiomics, and DL approaches can effectively determine the LVI status in patients with BC before surgery. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

19.
Chemphyschem ; 24(6): e202200716, 2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-36404675

RESUMEN

Room temperature phosphorescence (RTP) materials are characterized with emission after removing the excitation source. Such long-lived emission feature possesses great potential in biological fluorescence imaging because it enables a way regarding temporal dimension for separating the interference of autofluorescence and common noises typically encountered in conventional fluorescence imaging. Herein, we constructed a new type of mesoporous silica nanoparticles (MSNs)-based composite nanoparticles (NPs) with dual-color long-lived emission, namely millisecond-level green phosphorescence and sub-millisecond-level delayed red fluorescence by encapsulating a typical RTP dye and Rhodamine dye in the cavities of the MSNs with the former acting as energy donor (D) while the latter as acceptor (A). Benefiting from the close D-A proximity, energy match between the donor and the acceptor and the optimized D/A ratio in the composite NPs, efficient triplet-to-singlet Förster resonance energy transfer (TS-FRET) in the NPs occurred upon exciting the donor, which enabled dual-color long-lived emission. The preliminary results of dual-color correlation imaging of live cells based on such emission feature unequivocally verified the unique ability of such NPs for distinguishing the false positive generated by common emitters with single-color emission feature.


Asunto(s)
Transferencia Resonante de Energía de Fluorescencia , Nanopartículas , Transferencia Resonante de Energía de Fluorescencia/métodos , Rodaminas , Nanopartículas/química
20.
Crit Rev Food Sci Nutr ; 63(20): 4541-4553, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34793267

RESUMEN

Anthocyanins are important pigments that contribute to fruit quality. The regulation of anthocyanin biosynthesis by several transcription factors via sophisticated regulatory networks has been studied in various plants. Brassinosteroids (BRs), a new class of plant hormone, are involved in regulating anthocyanin biosynthesis in fruits. Furthermore, light directly affects the synthesis and distribution of anthocyanins. Here, we summarize the recent progress toward understanding the impact of BR and light on anthocyanin biosynthesis in climacteric and non-climacteric fruits. We review the BR and light signaling pathways and highlight the important transcription factors that are associated with the synthesis of anthocyanins, such as BZR1 (brassinazole-resistant 1, BR signaling pathway), HY5 (elongated hypocotyl 5) and COP1 (constitutively photomorphogenic 1, light signal transduction pathway), which bind with the target genes involved in anthocyanin synthesis. In addition, we review the mechanism by which light signals interact with hormonal signals to regulate anthocyanin biosynthesis.


Asunto(s)
Antocianinas , Frutas , Antocianinas/metabolismo , Frutas/metabolismo , Brasinoesteroides/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Luz
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