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The development and progression of diseases in multicellular organisms unfold within the intricate three-dimensional body environment. Thus, to comprehensively understand the molecular mechanisms governing individual development and disease progression, precise acquisition of biological data, including genome, transcriptome, proteome, metabolome, and epigenome, with single-cell resolution and spatial information within the body's three-dimensional context, is essential. This foundational information serves as the basis for deciphering cellular and molecular mechanisms. Although single-cell multi-omics technology can provide biological information such as genome, transcriptome, proteome, metabolome, and epigenome with single-cell resolution, the sample preparation process leads to the loss of spatial information. Spatial multi-omics technology, however, facilitates the characterization of biological data, such as genome, transcriptome, proteome, metabolome, and epigenome in tissue samples, while retaining their spatial context. Consequently, these techniques significantly enhance our understanding of individual development and disease pathology. Currently, spatial multi-omics technology has played a vital role in elucidating various processes in tumor biology, including tumor occurrence, development, and metastasis, particularly in the realms of tumor immunity and the heterogeneity of the tumor microenvironment. Therefore, this article provides a comprehensive overview of spatial transcriptomics, spatial proteomics, and spatial metabolomics-related technologies and their application in research concerning esophageal cancer, gastric cancer, and colorectal cancer. The objective is to foster the research and implementation of spatial multi-omics technology in digestive tumor diseases. This review will provide new technical insights for molecular biology researchers.
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Neoplasias Gastrointestinales , Metabolómica , Proteómica , Humanos , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/metabolismo , Genómica/métodos , Microambiente Tumoral , Transcriptoma , MultiómicaRESUMEN
BACKGROUND: Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. METHODS: The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. RESULTS: In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3ß/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. CONCLUSIONS: Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.
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Trióxido de Arsénico , Proliferación Celular , Sinergismo Farmacológico , Neoplasias Pulmonares , Proteínas Proto-Oncogénicas c-akt , Piridinas , Transducción de Señal , Carcinoma Pulmonar de Células Pequeñas , Serina-Treonina Quinasas TOR , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Trióxido de Arsénico/uso terapéutico , Trióxido de Arsénico/farmacología , Humanos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proliferación Celular/efectos de los fármacos , Animales , Piridinas/farmacología , Piridinas/uso terapéutico , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteína Adaptadora GRB10/genética , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación hacia Abajo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacologíaRESUMEN
Evidence from observational researches have suggested that mental diseases are able to affect thyroid diseases. However, the causal relationship between mental diseases and the risk of thyroid diseases still remains unclear. Herein, we conducted a two-sample Mendelian randomization (MR) statistical analysis method to assess the causality between mental diseases and thyroid diseases. Initially, publicly available genome-wide association studies summary data were leveraged to obtain single-nucleotide polymorphisms based on set parameters. Subsequently, a two-sample MR was utilized to analyze causal relationships between mental diseases (Alzheimer disease, bipolar disorder, major depressive disorder, Parkinson disease, schizophrenia) and thyroid diseases (hyperthyroidism/thyrotoxicosis, hypothyroidism) with removing outliers based on MR-PRESSO method. Finally, 8 regression MR methods (inverse variance weighted [IVW], IVW fixed effects, c, MR Egger, weighted median, penalized weighted median, simple mode, weighted mode) were performed to evaluate bias and effectiveness, of which IVW was considered as the primary method. Our results demonstrated that most of mental diseases have no causal relationships with thyroid diseases except bipolar disorder and hyperthyroidism/thyrotoxicosis based on IVW method [odds ratio: 0.999, 95% confidence interval: 0.998-1.000, P = .028], and bipolar disorder and hypothyroidism based on IVW method [odds ratio: 0.997, 95% confidence interval: 0.995-0.999, P = .002]. Then we subsequently conducted a consistent robustness analysis to assess heterogeneity and horizontal pleiotropy. Our method reports causal relationships exist mental diseases and the risk of thyroid diseases. Subsequent researches are still warranted to determine how mental diseases influence the development of thyroid diseases.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Mentales , Enfermedades de la Tiroides , Humanos , Enfermedades de la Tiroides/genética , Enfermedades de la Tiroides/epidemiología , Trastornos Mentales/genética , Trastornos Mentales/epidemiología , Polimorfismo de Nucleótido Simple , CausalidadRESUMEN
BACKGROUND: Pediatric asthma poses a significant global health burden, impacting the well-being and daily lives of affected children. Aerobic exercise-based pulmonary rehabilitation emerges as a promising intervention to address the multifaceted challenges faced by pediatric asthma patients. OBJECTIVES: The purpose of this systematic review and meta-analysis was to comprehensively evaluate the effects of aerobic exercise-based pulmonary rehabilitation on pulmonary function and quality of life in pediatric asthma patients. METHODS: Randomized controlled trials (RCTs) involving pediatric participants (5-18 years) were included. Aerobic exercise program-based pulmonary rehabilitation interventions were assessed for their impact on actual and percentage predicted values of lung volumes and flow rates such as forced vital capacity (FVC), maximum mid-expiratory flow (FEF25-75), peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), FEV1/FVC, and on quality of life (QoL) measures. A systematic search of databases, hand-searching, and consultation with experts identified relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines guided study selection, data extraction, and quality assessment. RESULTS: The systematic review included 20 studies with diverse exercise interventions and outcomes. The meta-analysis using fixed-effects model showed that there was a significant improvement in FVC (% predicted) [SMD= 0.30, 95 %CI: 0.13, 0.48] and FEF25-75 (% predicted) [SMD= 0.31, 95 %CI: 0.03, 0.58] in the experimental group compared with the control group. Furthermore, using a random-effects model involving 12 studies, significant increases in the QoL [SMD= 0.70, 95 %CI: 0.14, 1.26] were found in the exercise group. Due to inter-study heterogeneity, additional analyses were conducted. Publication bias analysis indicated robustness, with no significant asymmetry in funnel plots. CONCLUSION: Aerobic exercise-based pulmonary rehabilitation significantly enhances pulmonary function and quality of life in pediatric asthma patients. The findings, supported by improvements in FVC and FEF25-75, demonstrate the efficacy of these interventions. Quality of life measures also showed notable improvements. Despite inter-study heterogeneity, the results are robust, suggesting that aerobic exercise should be considered a valuable non-pharmacological strategy in managing pediatric asthma.
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Winter jasmine (Jasminum nudiflorum Lindl.) is a medium-sized, deciduous shrub native to China that has become a popular choice among gardeners and landscapers. In 2020 to 2021, symptoms of anthracnose including brown necrotic spots, enlarged irregular lesions and leaf blight were observed on leaves of 20 winter jasmine shrubs in a public garden (22°34'58'' N; 113°56'23'' E) in Shenzhen, China, and with an estimated disease incidence of 65%. Tissues samples (6 × 6 mm2) surrounding the necrotic spots were surface sterilized with 75% ethanol for 30 s, followed by 2% NaClO for 1 min, then rinsed with sterile water for three times and dried with sterile filter paper. Tissues were placed on potato dextrose agar (PDA) medium and incubated at 25â. After 3 to 7 d, pure cultures were obtained by transferring hyphal tips to new plates and 32 isolates producing Colletotrichum-like colonies were obtained from 40 tissues (isolation frequency=32/(4×10)=80%). Three representative isolates YCH09, YCH23 and YCH32 were selected for further study. Three selected isolates were identical in morphological characteristics. Colonies on PDA after 5 d at 25â were white to gray with cottony mycelia and grayish-white on the underside of the culture. Conidia (n = 60) measured 15.4 ± 1.1 µm (13.0 to 17.1 µm) in length and 5.4 ± 0.3 µm (4.9 to 6.0 µm) in width and were hyaline, single-celled, cylindrical with rounded ends. Appressoria (n = 15) measured 7.1 ± 0.1 µm (5.3 to 8.9 µm) in length and 5.2 ± 0.2 µm (4.1 to 6.2 µm) in width and were brown to dark brown, ovoid. These morphological features were aligned with those of Colletotrichum spp. (Weir et al. 2012). Sequences of five genetic markers of representative isolates YCH09, YCH23 and YCH32 including the rDNA internal transcribed spacer region, chitin synthase, partial actin, ß-tubulin 2 and Apn2-Mat1-2 intergenic spacer and partial mating type (Mat1-2) region were 99.3 to 100% identical to the ex-type isolate of C. fructicola strain ICMP 18581 (Zhang et al., 2020). From the maximum likelihood phylogenetic tree which was constructed based on concatenated sequences, three representative isolates (YCH09, YCH23 and YCH32) were clustered with other isolates of C. fructicola. The above morphological and molecular characteristics suggest that causal agent was C. fructicola. Pathogenicity was tested using a whole-plant assay. Five healthy plants were inoculated by spraying a conidial suspension (1.5×104 conidia/ml; 20 ml per plant) of the isolate YCH23 onto the foliage (Marshall et al., 2023). Three noninoculated control plants were sprayed with sterile water. All plants were placed in a greenhouse at 25±2â with approximately 75% relative humidity. Yellow lesions appeared on leaves of inoculated plants as early as 4 days after inoculation (DAI), and irregularly shaped brown spots similar to those observed in the field were formed on 10 DAI. Noninoculated plants remained asymptomatic. Colletotrichum isolates resembling morphological characters of YCH23 were reisolated from all inoculated plants, then identified as C. fructicola by DNA sequence analysis. C. fructicola is a well-known fungus causing anthracnose on more than 63 plant species including agricultural and horticultural plants worldwide (Talhinhas and Baroncelli, 2021). To our knowledge, this is the first report of C. fructicola infecting J. nudiflorum plants in China. Since its potential risk to other horticultural plant species, precautions may be necessary to minimize the spread of this fungi.
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Glutathione (GSH) exhibits considerable potential in the cosmetic industry for reducing intracellular tyrosinase activity and inhibiting melanin synthesis. However, its efficacy is hindered by limited permeability, restricting its ability to reach the basal layer of the skin where melanin production occurs. The transdermal enhancer peptide TD1 has emerged as a promising strategy to facilitate the transdermal transfer of proteins or peptides by creating intercellular gaps in keratinocytes, providing access to the basal layer. The primary objective of this study is to enhance the transdermal absorption capacity of GSH while augmenting its inhibitory effect on melanin. Two coupling structures were designed for investigation: linear (TD1-linker-GSH) and branched (TD1-GSH). The study examined the impact of the peptide skeleton on melanin inhibition ability. Our findings revealed that the linear structure not only inhibited synthetic melanin production in B16F10 cells through a direct pathway but also through a paracrine pathway, demonstrating a significant tyrosinase inhibition of nearly 70 %, attributed to the paracrine effect of human keratinocyte HaCaT. In pigmentation models of guinea pigs and zebrafish, the application of TD1-linker-GSH significantly reduced pigmentation. Notably, electric two-photon microscopy demonstrated that TD1-linker-GSH exhibited significant transdermal ability, penetrating 158.67 ± 9.28 µm into the skin of living guinea pigs. Molecular docking analysis of the binding activity with tyrosinase revealed that both TD1-linker-GSH and TD1-GSH occupy the same active pocket, with TD1-linker-GSH binding more tightly to tyrosinase. These results provide a potential foundation for therapeutic approaches aimed at enriched pigmentation and advance our understanding of the mechanisms underlying melanogenesis inhibition.
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Administración Cutánea , Glutatión , Melaninas , Monofenol Monooxigenasa , Pez Cebra , Melaninas/metabolismo , Animales , Humanos , Cobayas , Glutatión/metabolismo , Glutatión/química , Monofenol Monooxigenasa/metabolismo , Monofenol Monooxigenasa/antagonistas & inhibidores , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Péptidos/administración & dosificación , Ratones , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/administración & dosificación , MelanogénesisRESUMEN
Erianin, crepidatin, and chrysotobibenzyl are typical medicinal polymethoxylated bibenzyls (PMBs) that are commercially produced in Dendrobium species. PMBs' chemo-diversity is mediated by the manifold combinations of O-methylation and hydroxylation in a definite order, which remains unsolved. To unequivocally elucidate the methylation mechanism of PMBs, 15 possible intermediates in the biosynthetic pathway of PMBs were chemically synthesized. DcOMT1-5 were highly expressed in tissues where PMBs were biosynthesized, and their expression patterns were well-correlated with the accumulation profiles of PMBs. Moreover, cell-free orthogonal tests based on the synthesized intermediates further confirmed that DcOMT1-5 exhibited distinct substrate preferences and displayed hydroxyl-group regiospecificity during the sequential methylation process. The stepwise methylation of PMBs was discovered from SAM to dihydro-piceatannol (P) in the following order: P â 3-MeP â 4-OH-3-MeP â 4-OH-3,5-diMeP â 3,3'(4'),5-triMeP â 3,4,4',5-tetraMeP (erianin) or 3,3',4,5-tetraMeP (crepidatin) â 3,3',4,4',5-pentaMeP (chrysotobibenzyl). Furthermore, the regioselectivities of DcOMTs were investigated by ligand docking analyses which corresponded precisely with the catalytic activities. In summary, the findings shed light on the sequential catalytic mechanisms of PMB biosynthesis and provide a comprehensive PMB biosynthetic network in D. catenatum. The knowledge gained from this study may also contribute to the development of plant-based medicinal applications and the production of high-value PMBs.
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The authors identity the relationship between the positive and negative aspects of social media and the ideal belief learning and behavior of university students. The cluster sampling method was adopted in the paper, including Guangdong, Shandong, Henan, Sichuan, and Jiangsu provinces. A total of 1014 questionnaires were distributed to a purposive sample of university students between the ages of 16 and 35. The authors applied the uses and gratifications theory to study students' social media behavior. This study identified 18 positive and negative effects of social media. Noteworthy positive outcomes attributed to social media in fostering ideals and beliefs encompass heightened awareness, enhanced communication facilitation, convenient connectivity, reduced expenses on educational materials, improved social and communication proficiencies, as well as diminished stress levels. The negative effects of new media and the Internet include a lack of critical thinking, a waste of time, dysgraphia, disrupted connection to learning, students' laziness, and health risks.
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Pseudomonas aeruginosa (P. aeruginosa) is a major pathogen that causes infectious diseases. It has high tendency to form biofilms, resulting in the failure of traditional antibiotic therapies. Inspired by the phenomenon that co-culture of Escherichia coli (E. coli) and P. aeruginosa leads to a biofilm reduction, we reveal that E. coli exopolysaccharides (EPS) can disrupt P. aeruginosa biofilm and increase its antibiotic susceptibility. The results show that E. coli EPS effectively inhibit biofilm formation and disrupt mature biofilms in P. aeruginosa, Staphylococcus aureus, and E. coli itself. The maximal inhibition and disruption rates against P. aeruginosa biofilm are 40 % and 47 %, respectively. Based on the biofilm-disrupting ability of E. coli EPS, we develop an E. coli EPS/antibiotic combining strategy for the treatment of P. aeruginosa biofilms. The combination with E. coli EPS increases the antibacterial efficiency of tobramycin against P. aeruginosa biofilms in vitro and in vivo. This study provides a promising strategy for treating biofilm infections. STATEMENT OF SIGNIFICANCE: Biofilm formation is a leading cause of chronic infections. It blocks antibiotics, increases antibiotic-tolerance, and aids in immune evasion, thus representing a great challenge in clinic. This study proposes a promising approach to combat pathogenic Pseudomonas aeruginosa (P. aeruginosa) biofilms by combining Escherichia coli exopolysaccharides with antibiotics. This strategy shows high efficiency in different P. aeruginosa stains, including two laboratory strains, PAO1 and ATCC 10145, as well as a clinically acquired carbapenem-resistant strain. In addition, in vivo experiments have shown that this approach is effective against implanted P. aeruginosa biofilms and can prevent systemic inflammation in mice. This strategy offers new possibilities to address the clinical failure of conventional antibiotic therapies for microbial biofilms.
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Antibacterianos , Biopelículas , Escherichia coli , Polisacáridos Bacterianos , Pseudomonas aeruginosa , Biopelículas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Polisacáridos Bacterianos/farmacología , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Animales , Pruebas de Sensibilidad Microbiana , Ratones , Tobramicina/farmacologíaRESUMEN
BACKGROUND: Norovirus is the predominant pathogen causing foodborne illnesses and acute gastroenteritis (AGE) outbreaks worldwide, imposing a significant disease burden. This study aimed to investigate the epidemiological characteristics and genotypic diversity of norovirus outbreaks in Hongshan District, Wuhan City. METHODS: A total of 463 AGE cases from 39 AGE-related outbreaks in Hongshan District between January 1, 2021, and June 30, 2023, were included in the study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to identify norovirus types GI and GII in anal swab samples from all cases. Norovirus-positive samples were sequenced and analyzed for the open reading frame (ORF) 1/ORF2 hinge region. RESULTS: 26 norovirus infectious outbreaks were reported among 39 acute diarrheal outbreaks, including 14 outbreaks in kindergartens, 8 in elementary schools, and 4 in universities. Based on clinical symptoms and epidemiological investigations, a total of 1295 individuals were identified as having been exposed to norovirus, yielding an attack rate of 35.75 %. A higher proportion of outbreaks was observed during the winter and spring seasons (38.46 %). Additionally, norovirus-positive samples were subjected to sequencing and analysis of the open reading frame (ORF) 1/ORF2 hinge region. Genotypic data for norovirus was successfully obtained from 18 (69.23 %) of the infectious outbreaks, revealing 10 distinct recombinant genotypes. GII.4 Sydney 2012 [P31] and GII.17[P17] were the predominant strains in 2021 and 2022, GII.3 [P12] emerged as the dominant strain in 2023. CONCLUSION: Norovirus outbreaks in Hongshan District predominantly occurred in crowded educational institutions, with peaks in the cold season and a high attack rate in universities. GII.3 [P12] has become the locally predominant strain.
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Infecciones por Caliciviridae , Brotes de Enfermedades , Gastroenteritis , Variación Genética , Genotipo , Norovirus , Humanos , Norovirus/genética , Norovirus/clasificación , Norovirus/aislamiento & purificación , Gastroenteritis/virología , Gastroenteritis/epidemiología , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , China/epidemiología , Niño , Masculino , Femenino , Preescolar , Adolescente , Adulto , Adulto Joven , Filogenia , Lactante , Estaciones del Año , Persona de Mediana Edad , EpidemiasRESUMEN
With the advance of research, non-coding RNA has been found to surpass the traditional definition to directly code functional proteins by coding sequence elements and binding with ribosomes. Among the non-coding RNAs, the function of circRNA encoded proteins has been most extensively studied. This study has used "circRNA", "encoded", and "translation" as the key words to search the PubMed and Web of Science databases. The retrieved literature was screened and traced, with the translation mechanism, related research methods, and correlation with diseases of circRNA reviewed. CircRNA can translate proteins through a non-cap-dependent pathway. Multiple molecular techniques, in particular mass spectrometry analysis, have important value in identifying unique peptide segments of circRNA encoded proteins for confirming their existence. The proteins encoded by the circRNA are involved in the pathogenesis of diseases of the digestive, neurological, urinary systems and the breast, and have the potential to serve as novel targets for disease diagnosis and treatment. This article has provided a comprehensive review for the basic theory, experimental methods, and disease-related research in the field of circRNA translation, which may provide clues for the identification of new diagnostic and therapeutic targets.
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ARN Circular , ARN Circular/genética , Humanos , ARN/genética , Proteínas/genética , Animales , Biosíntesis de Proteínas , Enfermedad/genéticaRESUMEN
Background: The benefits of home enteral nutrition (HEN) are increasingly recognized, with more scholars focusing on this field. This study aimed to comprehensively identify collaborative networks, analyze, and track research trends, focus on current hotspots, and accurately predict the forefront and focus of home enteral nutrition. Methods: A computer search of the Web of Science Core Collection (WoSCC) was conducted for studies related to home enteral nutrition published from January 1, 2004, to December 31, 2023, and select them in compliance with the PRISMA guidelines. The CiteSpace software was used for bibliometric visualization and comparative analysis of countries, institutions, journals, references, and keywords. Results: A total of 1,113 documents were included, showing a steady annual increase in publication volume. The United States and the Mayo Clinic were the top publishing country and institution, with 302 and 41 papers, respectively. "CLIN NUTR" had the highest number of publications, totaling 221, while "ESPEN guideline on home enteral nutrition" was the most cited reference, with 43 citations. The most prolific author was Manpreet S with 29 papers. Conclusion: The management of HEN is a current research hotspot. The safety of HEN and how to improve patient compliance are critical areas for researchers to consider. Future research could focus on these aspects. The blurring of boundaries between hospital and home care and how to utilize telemedicine technologies to serve more patients deserve in-depth exploration. Researchers worldwide should combine their unique characteristics and advantages to strengthen international cooperation.
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Tuberculosis (TB), caused by Mycobacterium tuberculosis ( M. tb), remains one of the leading causes of fatal infectious diseases worldwide. The only licensed vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), has variable efficacy against TB in adults. Insufficiency of immune cell function diminishes the protective effects of the BCG vaccine. It is critical to clarify the mechanism underlying the antimycobacterial immune response during BCG vaccination. Macrophage mannose receptor (MR) is important for enhancing the uptake and processing of glycoconjugated antigens from pathogens for presentation to T cells, but the roles of macrophage MR in the BCG-induced immune response against M. tb are not yet clear. Here, we discover that macrophage MR deficiency impairs the antimycobacterial immune response in BCG-vaccinated mice. Mechanistically, macrophage MR triggers JAK-STAT1 signaling, which promotes antigen presentation via upregulated MHC-II and induces IL-12 production by macrophages, contributing to CD4 + T cell activation and IFN-γ production. MR deficiency in macrophages reduces the vaccine efficacy of BCG and increases susceptibility to M. tb H37Ra challenge in mice. Our results suggest that MR is critical for macrophage antigen presentation and the antimycobacterial immune response to BCG vaccination and offer valuable guidance for the preventive strategy of BCG immunization.
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Presentación de Antígeno , Vacuna BCG , Quinasas Janus , Lectinas Tipo C , Macrófagos , Receptor de Manosa , Lectinas de Unión a Manosa , Ratones Endogámicos C57BL , Mycobacterium tuberculosis , Receptores de Superficie Celular , Factor de Transcripción STAT1 , Animales , Vacuna BCG/inmunología , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT1/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Presentación de Antígeno/inmunología , Ratones , Lectinas de Unión a Manosa/inmunología , Lectinas de Unión a Manosa/metabolismo , Lectinas Tipo C/inmunología , Lectinas Tipo C/metabolismo , Mycobacterium tuberculosis/inmunología , Quinasas Janus/metabolismo , Quinasas Janus/inmunología , Receptores de Superficie Celular/inmunología , Receptores de Superficie Celular/metabolismo , Transducción de Señal/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Tuberculosis/inmunología , Tuberculosis/prevención & control , Vacunación , Ratones Noqueados , FemeninoRESUMEN
The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a primary driver of these conditions, commencing silently at an early age and culminating in adverse cardiovascular events that severely impact patients' quality of life or lead to fatality. Dyslipidemia, particularly elevated levels of low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in AS pathogenesis as an independent risk factor. Research indicates that abnormal LDL-C accumulation within arterial walls acts as a crucial trigger for atherosclerotic plaque formation. As the disease progresses, plaque accumulation may rupture or dislodge, resulting in thrombus formation and complete blood supply obstruction, ultimately causing myocardial infarction, cerebral infarction, and other common adverse cardiovascular events. Despite adequate pharmacologic therapy targeting LDL-C reduction, patients with cardiometabolic abnormalities remain at high risk for disease recurrence, highlighting the importance of addressing lipid risk factors beyond LDL-C. Recent attention has focused on the causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), and their remnants in AS risk. Genetic, epidemiologic, and clinical studies suggest a causal relationship between TRLs and their remnants and the increased risk of AS, and this dyslipidemia may be an independent risk factor for adverse cardiovascular events. Particularly in patients with obesity, metabolic syndrome, diabetes, and chronic kidney disease, disordered TRLs and its remnants levels significantly increase the risk of atherosclerosis and cardiovascular disease development. Accumulation of over-synthesized TRLs in plasma, impaired function of enzymes involved in TRLs lipolysis, and impaired hepatic clearance of cholesterol-rich TRLs remnants can lead to arterial deposition of TRLs and its remnants, promoting foam cell formation and arterial wall inflammation. Therefore, understanding the pathogenesis of TRLs-induced AS and targeting it therapeutically could slow or impede AS progression, thereby reducing cardiovascular disease morbidity and mortality, particularly coronary atherosclerotic heart disease.
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Enfermedades Cardiovasculares , Lipoproteínas , Triglicéridos , Humanos , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/etiología , Lipoproteínas/metabolismo , Triglicéridos/metabolismo , Triglicéridos/sangre , Aterosclerosis/metabolismo , Animales , Dislipidemias/metabolismo , Factores de RiesgoRESUMEN
Accurate determination of the number and location of immature small yellow peaches is crucial for bagging, thinning, and estimating yield in modern orchards. However, traditional methods have faced challenges in accurately distinguishing immature yellow peaches due to their resemblance to leaves and susceptibility to variations in shooting angles and distance. To address these issues, we proposed an improved target-detection model (EMA-YOLO) based on YOLOv8. Firstly, the sample space was enhanced algorithmically to improve the diversity of samples. Secondly, an EMA attention-mechanism module was introduced to encode global information; this module could further aggregate pixel-level features through dimensional interaction and strengthen small-target-detection capability by incorporating a 160 × 160 detection head. Finally, EIoU was utilized as a loss function to reduce the incidence of missed detections and false detections of the target small yellow peaches under the condition of high density of yellow peaches. Experimental results show that compared with the original YOLOv8n model, the EMA-YOLO model improves mAP by 4.2%, Furthermore, compared with SDD, Objectbox, YOLOv5n, and YOLOv7n, this model's mAP was improved by 30.1%, 14.2%,15.6%, and 7.2%, respectively. In addition, the EMA-YOLO model achieved good results under different conditions of illumination and shooting distance and significantly reduced the number of missed detections. Therefore, this method can provide technical support for smart management of yellow-peach orchards.
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AIM: The study was aimed at exploring the current scope of hospital to home transitional care programmes for stroke survivors. BACKGROUND: Stroke survivors face the dilemma of solving many complex problems that leave survivors at high risk for readmission as they discharge from hospital. The transitional care model has proved to be effective in reducing readmissions and mortality, thereby improving health outcomes and enhancing patient satisfaction for survivors with stroke. DESIGN: A scoping review. METHODS: Conducted in accordance with the Joanna Briggs Institute (JBI) Methodology for Scoping Reviews. DATA SOURCES: A comprehensive search was conducted in nine databases, including PubMed, Web of Science, Cochrane Library, EMBASE, CINAHL, Medline, China Knowledge Net-work, Wanfang Database and China Biomedical Literature Database (SinoMed) from January 2014 to June 2023. RESULTS: Title and abstract screening was performed on 10,171 articles resulting in 287 articles for full-text screening. Full-text screening yielded 49 articles that met inclusion criteria. CONCLUSION: This study identified transitional care programmes for stroke survivors, as well as areas for future consideration to be explored in more depth to help improve transitional care for stroke survivors as they transition from hospital to home. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study demonstrates that multidisciplinary collaboration becomes an integral part of the transitional care model for stroke survivors, which provides comprehensive and precise medical care to them. REPORTING METHOD: PRISMA checklist for scoping reviews. PATIENT AND PUBLIC CONTRIBUTION: No patient or public contribution was part of this study.
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Servicios de Atención de Salud a Domicilio , Sobrevivientes , Cuidado de Transición , Humanos , Cuidado de Transición/normas , Sobrevivientes/psicología , Sobrevivientes/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/enfermería , Rehabilitación de Accidente Cerebrovascular/métodos , Femenino , Masculino , Persona de Mediana Edad , AncianoRESUMEN
This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.
Asunto(s)
Linfocitos Infiltrantes de Tumor , Neoplasias de la Próstata , Animales , Humanos , Masculino , Ratones , Línea Celular Tumoral , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Microambiente TumoralRESUMEN
Introduction: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in motor skills, communication, emotional expression, and social interaction. Accurate diagnosis of ASD remains challenging due to the reliance on subjective behavioral observations and assessment scales, lacking objective diagnostic indicators. Methods: In this study, we introduced a novel approach for diagnosing ASD, leveraging T1-based gray matter and ASL-based cerebral blood flow network metrics. Thirty preschool-aged patients with ASD and twenty-two typically developing (TD) individuals were enrolled. Brain network features, including gray matter and cerebral blood flow metrics, were extracted from both T1-weighted magnetic resonance imaging (MRI) and ASL images. Feature selection was performed using statistical t-tests and Minimum Redundancy Maximum Relevance (mRMR). A machine learning model based on random vector functional link network was constructed for diagnosis. Results: The proposed approach demonstrated a classification accuracy of 84.91% in distinguishing ASD from TD. Key discriminating network features were identified in the inferior frontal gyrus and superior occipital gyrus, regions critical for social and executive functions in ASD patients. Discussion: Our study presents an objective and effective approach to the clinical diagnosis of ASD, overcoming the limitations of subjective behavioral observations. The identified brain network features provide insights into the neurobiological mechanisms underlying ASD, potentially leading to more targeted interventions.
RESUMEN
Lung adenocarcinoma (LUAD) is the most common and aggressive subtype of lung cancer, and coronavirus disease 2019 (COVID-19) has become a serious public health threat worldwide. Patients with LUAD and COVID-19 have a poor prognosis. Therefore, finding medications that can be used to treat COVID-19/LUAD patients is essential. Bioinformatics analysis was used to identify 20 possible metformin target genes for the treatment of COVID-19/LUAD. PTEN and mTOR may serve as hub target genes of metformin. Metformin may be able to cure COVID-19/LUAD comorbidity through energy metabolism, oxidoreductase NADH activity, FoxO signalling pathway, AMPK signalling system, and mTOR signalling pathway, among other pathways, according to the results of bioinformatic research. Metformin has ability to inhibit the proliferation of A549 cells, according to the results of colony formation and proliferation assays. In A549 cells, metformin increased glucose uptake and lactate generation, while decreasing ATP synthesis and the NAD+/NADH ratio. In summary, PTEN and mTOR may be potential targets of metformin for the treatment of COVID-19/LUAD. The mechanism by which metformin inhibits lung adenocarcinoma cell proliferation may be related to glucose metabolism regulated by PI3K/AKT signalling and mTOR signalling pathways. Our study provides a new theoretical basis for the treatment of COVID-19/LUAD.