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A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5. Furthermore, precise control over VC release can be achieved by introducing surface modifications involving SiO2 onto the structure of VC@HSCT-5, while simultaneously adjusting environmental factors such as pH and temperature conditions. Preliminary cell culture experiments and cytotoxicity assays highlight the biocompatibility of HSTC-5, suggesting that it is a promising platform for sustained drug delivery and diverse biomedical applications.
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Ácido Ascórbico , Estruturas Metalorgânicas , Termodinâmica , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Ácido Ascórbico/química , Cinética , Humanos , Teoria da Densidade Funcional , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Estrutura Molecular , Liberação Controlada de FármacosRESUMO
The available evidence on the connection between excessive alcohol consumption and diabetes is controversial. Therefore, the primary objective of this investigation was to examine the connection between excessive alcohol consumption and incident diabetes in a Japanese population through the utilization of propensity score matching (PSM) analysis. Our retrospective cohort study encompassed a sample of 15,464 Japanese individuals who were initially free of diabetes between the years 2004 and 2015. The study utilized comprehensive medical records of individuals who underwent a physical examination. Employing a one:one PSM analysis, the current research included 2298 individuals with and without excessive alcohol consumption. Furthermore, a doubly robust estimation method was employed to ascertain the connection between excessive alcohol consumption and diabetes. The findings revealed that individuals with excessive alcohol consumption exhibited a 73% higher likelihood of developing diabetes (HR = 1.73, 95% CI 1.08-2.77). Furthermore, upon adjusting for variables, the PSM cohort demonstrated that individuals with excessive alcohol consumption had a 78% increased risk of developing diabetes in comparison to those with non-excessive alcohol consumption (HR = 1.78, 95% CI 1.08-2.93). Individuals with excessive alcohol consumption were found to have a 73% higher risk of developing diabetes compared to those with non-excessive alcohol consumption, even after controlling for propensity score (HR = 1.73, 95% CI 1.08-2.78). Participants in the PSM cohort with excessive alcohol consumption had a 73% higher risk of developing diabetes than those with non-excessive alcohol consumption after controlling for confounding factors. These findings underscore the importance of alcohol consumption guidelines aimed at reducing excessive drinking. Clinicians should be vigilant in screening for alcohol use in patients, particularly those at risk for diabetes, and provide appropriate counseling and resources to support alcohol reduction.
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Diabetes Mellitus , Pontuação de Propensão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Japão/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Estudos Retrospectivos , Adulto , Incidência , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Fatores de Risco , Idoso , Alcoolismo/epidemiologia , População do Leste AsiáticoRESUMO
In zebrafish, brain lymphatic endothelial cells (BLECs) are essential for meningeal angiogenesis and cerebrovascular regeneration. Although epidermal growth factor-like domain 7 (Egfl7) has been reported to act as a pro-angiogenic factor, its roles in lymphangiogenesis remain unclear. Here, we show that Egfl7 is expressed in both blood and lymphatic endothelial cells. We generate an egfl7 cq180 mutant with a 13-bp-deletion in exon 3 leading to reduced expression of Egfl7. The egfl7 cq180 mutant zebrafish exhibit defective formation of BLEC bilateral loop-like structures, although trunk and facial lymphatic development remains unaffected. Moreover, while the egfl7 cq180 mutant displays normal BLEC lineage specification, the migration and proliferation of these cells are impaired. Additionally, we identify integrin αvß3 as the receptor for Egfl7. αvß3 is expressed in the CVP and sprouting BLECs, and blocking this integrin inhibits the formation of BLEC bilateral loop-like structures. Thus, this study identifies a role for Egfl7 in BLEC development that is mediated through the integrin αvß3.
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Encéfalo , Células Endoteliais , Integrina alfaVbeta3 , Linfangiogênese , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Humanos , Animais Geneticamente Modificados , Encéfalo/metabolismo , Movimento Celular/genética , Proliferação de Células , Família de Proteínas EGF/metabolismo , Família de Proteínas EGF/genética , Células Endoteliais/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Integrina alfaVbeta3/metabolismo , Integrina alfaVbeta3/genética , Linfangiogênese/genética , Mutação , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genéticaRESUMO
During vascular development, radial glial cells (RGCs) regulate vascular patterning in the trunk and contribute to the early differentiation of the blood-brain barrier. Ablation of RGCs results in excessive sprouting vessels or the absence of bilateral vertebral arteries. However, interactions of RGCs with later brain vascular networks after pattern formation remain unknown. Here, we generated a her4.3 transgenic line to label RGCs and applied the metronidazole/nitroreductase system to ablate her4.3+ RGCs. The ablation of her4.3+ RGCs led to the collapse of the cerebral vascular network, disruption of the blood-brain barrier, and downregulation of Wnt signaling. The inhibition of Wnt signaling resulted in the collapse of cerebral vasculature, similar to that caused by her4.3+ RGC ablation. The defects in the maintenance of brain vasculature resulting from the absence of her4.3+ RGCs were partially rescued by the activation of Wnt signaling or overexpression of Wnt7aa or Wnt7bb. Together, our study suggests that her4.3+ RGCs maintain the cerebral vascular network through Wnt signaling.
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Trichoderma spp. can enhance plant resistance against a wide range of biotic stressors. However, the fundamental mechanisms by which Trichoderma enhances plant resistance against Meloidogyne incognita, known as root-knot nematodes (RKNs), are still unclear. Here, we identified a strain of Trichoderma asperellum (T141) that could effectively suppress RKN infestation in tomato (Solanum lycopersicum L.). Nematode infestation led to an increase in the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) in roots but pre-inoculation with T141 significantly decreased oxidative stress. The reduction in ROS and MDA was accompanied by an increase in the activity of antioxidant enzymes and the accumulation of flavonoids and phenols. Moreover, split root test-based analysis showed that T141 inoculation in local roots before RKN inoculation increased the concentration of phytohormone jasmonate (JA) and the transcripts of JA synthesis and signaling-related genes in distant roots. UPLC-MS/MS-based metabolomics analysis identified 1051 differentially accumulated metabolites (DAMs) across 4 pairwise comparisons in root division test, including 81 flavonoids. Notably, 180 DAMs were found in comparison between RKN and T141-RKN, whereas KEGG annotation and enrichment analysis showed that the secondary metabolic pathways, especially the flavonoid biosynthesis, played a key role in the T141-induced systemic resistance to RKNs. The role of up-regulated flavonoids in RKN mortality was further verified by in vitro experiments with the exogenous treatment of kaempferol, hesperidin and rutin on J2-stage RKNs. Our results revealed a critical mechanism by which T141 induced resistance of tomato plants against the RKNs by systemically promoting secondary metabolism in distant roots.
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Resistência à Doença , Flavonoides , Doenças das Plantas , Raízes de Plantas , Solanum lycopersicum , Tylenchoidea , Solanum lycopersicum/parasitologia , Solanum lycopersicum/metabolismo , Solanum lycopersicum/microbiologia , Solanum lycopersicum/genética , Solanum lycopersicum/imunologia , Flavonoides/metabolismo , Animais , Doenças das Plantas/parasitologia , Doenças das Plantas/imunologia , Tylenchoidea/fisiologia , Tylenchoidea/patogenicidade , Raízes de Plantas/parasitologia , Raízes de Plantas/metabolismo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Hypocreales/metabolismo , Resistência Sistêmica Adquirida da PlantaRESUMO
INTRODUCTION: Hemodialysis nurses' cannulation technique, monitoring, and management methods can affect patients' vascular access longevity. An arteriovenous access assessment comprises a medical history and vascular assessment through physical examination and surveillance. However, further exploration is needed to fully understand hemodialysis nurses' knowledge, attitudes, and practices (KAP) in this area. METHODS: Between June and July 2023, we recruited hemodialysis nurses from 21 cities in Guangdong Province using a convenience sampling method. Four questionnaires-the General Data Questionnaire, the KAP Scale of Arteriovenous Access Assessment among Hemodialysis Nurses, the Utrecht Work Engagement Scale, and the NASA Task Load Index-were utilized for data collection through the Questionnaire Star platform. FINDINGS: Of the 530 hemodialysis nurses participating in the study, 458 (86.4%) had a valid response. The participants demonstrated moderate knowledge and practice levels regarding arteriovenous access assessment and exhibited positive attitudes. We identified several factors related to arteriovenous access assessment that predict KAP in hemodialysis nurses. These factors included years of experience as a hemodialysis nurse, whether a nurse's knowledge of physical examination was sufficient to meet clinical needs, whether a nurse had received training in performing physical examination, whether a nurse's department regularly checked the quality of physical examination, and nurses' levels of work engagement and mental workload. All factors explained 32.4% of the variance in participants' KAP regarding arteriovenous access assessment. DISCUSSION: Improving hemodialysis nurses' assessment of arteriovenous access is crucial to ensure optimal patient care. Dialysis center managers and educators should prioritize understanding hemodialysis nurses' KAP of arteriovenous access assessment and any factors influencing these areas.
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Conhecimentos, Atitudes e Prática em Saúde , Diálise Renal , Humanos , Diálise Renal/métodos , Estudos Transversais , Feminino , Masculino , Adulto , Inquéritos e Questionários , Pessoa de Meia-Idade , Enfermeiras e EnfermeirosRESUMO
Background: With the advances in society and in response to changing times, college students have had to face multiple challenges. These challenges frequently affect the mental health of college students, leading to significant consequences for their social lives, personal well-being, and academic achievements, thereby attracting extensive societal attention. Therefore, examining the current status of research topics related to the mental health of college students can assist academia in dissecting the influencing factors and seeking solutions at their source or through early intervention. This can contribute to a better understanding of and effectively address this challenge. Method: CiteSpace and VOSviewer were used to conduct a bibliometric analysis of 1609 journal articles indexed in the Web of Science (WoS) database over the past two decades (2000-2022), which helped identify the current state of research and hot topics in the field based on development trends. Furthermore, this study analyzes and discusses the core authors, high-productivity countries and organizations, key journals, and keyword clustering in this field. This study clarifies the current research landscape, analyzes evolving trends based on developmental trajectories, and identifies forefront research hotspots. This study provides scholars with reference research directions and ideas for conducting subsequent studies. Results: Since the beginning of the 21st century, research on college students' mental health has increased, especially in the past three years, and due to the impact of the COVID-19 pandemic and online distance learning, the number of publications has increased rapidly. With the increase in attention and publication volume, the countries and organizations contributing papers as well as core journals have all started to take shape. Cluster and evolution analyses found that several stable research topics have been formed in this research field, and many new and diverse topics are continuously emerging with time. Conclusion: and prospect: The findings prove that the field of college students' mental health has begun to take shape, gradually shifting from conceptual research to the implementation of specific interventions. However, whether specific interventions are effective and how effective they are require further investigation.
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Metformin (MET) and sitagliptin (STG) are widely used as the first-line and long-term oral hypoglycemic agents for managing type 2 diabetes mellitus (T2DM). However, the current lack of convenient and rapid measurement methods poses a challenge for individualized management. This study developed a point-of-care (POC) assay method utilizing a miniature mass spectrometer, enabling rapid and accurate quantification of MET and STG concentrations in human blood and urine. By combining the miniature mass spectrometer with paper spray ionization, this method simplifies the process into three to four steps, requires minimal amounts of bodily fluids (50 µL of blood and 2 µL of urine), and is able to obtain quantification results within approximately 2 min. Stable isotope-labeled internal standards were employed to enhance the accuracy and stability of measurement. The MS/MS responses exhibited good linear relationship with concentration, with relative standard deviations (RSDs) below 25%. It has the potential to provide immediate treatment feedback and decision support for patients and healthcare professionals in clinical practice.
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Hipoglicemiantes , Metformina , Sistemas Automatizados de Assistência Junto ao Leito , Fosfato de Sitagliptina , Humanos , Fosfato de Sitagliptina/sangue , Fosfato de Sitagliptina/urina , Metformina/sangue , Metformina/urina , Hipoglicemiantes/urina , Hipoglicemiantes/sangue , Limite de Detecção , Espectrometria de Massas em Tandem/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Espectrometria de Massas/métodos , Reprodutibilidade dos TestesRESUMO
Background: Primary insomnia (PI) refers to syndromes of difficulty falling asleep, poor sleep quality, early awakening, and difficulty falling asleep after waking up. Although there have been numerous studies, the specific etiology and pathogenesis of PI are still misunderstanding. In recent years, the gut microbiota has been proved to be involved in the metabolism of many mental disorders. But the specific mechanisms of its involvement in PI have not been fully elucidated. This study aims to explore the relationship between the gut microbiota and the symptoms, cognitive function changes in PI. Methods: In this study, the gut microbiota of PI patients and healthy controls was profiled by performing stool 16s rRNA gene sequencing. The co-occurrence network was constructed by using Weight Gene Co-expression Network Analysis (WGCNA) algorithm. The correlation between gut microbiota associated pathways and traits in PI were predicted. Results: WGCNA results demonstrated several Operational Taxonomic Units (OTU) modules are correlated to symptoms. By using PICRUSt2 software, we predicted the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of microbiota in modules. For instance, sleep efficiency may be correlated with the presence of Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane and chlorobenzene degradation. Total sleep time may be correlated with the presence of Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation and Biosynthesis of unsaturated fatty acids. The severity of insomnia may be correlated with Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism and RNA polymerase. Change of name score in Montreal Cognitive Assessment (MoCA) may be correlated with Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation in Gut Microbiota (GM). Conclusion: This study revealed the potential relationships between gut microbiota and PI. By using pathway prediction and enrichment analysis, we concluded many metabolic pathways may associated with some important traits of insomnia patients, including sleep efficiency, severe insomnia, total sleep time and change of name score in MoCA. The metabolic pathways include Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane, chlorobenzene degradation, Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation.Our study demonstrated that PI patients demonstrate significant changes in gut microbiota, which will help delineate the relationship between gut microbiota and syndromes of PI.
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In recent years, virtual reality technology, which is able to simulate real-life environments, has been widely used in the field of intervention for individuals with autism and has demonstrated distinct advantages. This review aimed to evaluate the impact of virtual reality technology on safety skills intervention for individuals with autism. After searching and screening three databases, a total of 20 pertinent articles were included. There were six articles dedicated to the VR training of street-crossing skills for individuals with autism, nine articles focusing on the training of driving skills for individuals with ASD, and three studies examining the training of bus riding for individuals with ASD. Furthermore, there were two studies on the training of air travel skills for individuals with ASD. First, we found that training in some complex skills (e.g., driving skills) should be selected for older, high-functioning individuals with ASD, to determine their capacity to participate in the training using scales or questionnaires before the intervention; VR devices with higher levels of immersion are not suitable for younger individuals with ASD. Second, VR is effective in training safety skills for ASD, but there is not enough evidence to determine the relationship between the level of VR immersion and intervention effects. Although the degree of virtual reality involvement has an impact on the ability of ASD to be generalized to the real world, it is important to ensure that future virtual reality settings are realistic and lifelike. Again, adaptive models that provide personalized training to individuals with ASD in VR environments are very promising, and future research should continue in this direction. This paper also discusses the limitations of these studies, as well as potential future research directions.
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Reactive oxygen species (ROS) are crucial signaling molecules in plants that play multifarious roles in prompt response to environmental stimuli. Despite the classical thoughts that ROS are toxic when accumulate in excess, recent advances in plant ROS signaling biology reveal that ROS participate in biotic and abiotic stress perception, signal integration, and stress-response network activation, hence contributing to plant defense and stress tolerance. ROS production, scavenging and transport are fine-tuned by plant hormones and stress-response signaling pathways. Crucially, the emerging plant hormone melatonin attenuates excessive ROS accumulation under stress, whereas ROS signaling mediates melatonin-induced plant developmental response and stress tolerance. In particular, RESPIRATORY BURST OXIDASE HOMOLOG (RBOH) proteins responsible for apoplastic ROS generation act downstream of melatonin to mediate stress response. In this review, we discuss promising developments in plant ROS signaling and how ROS might mediate melatonin-induced plant resilience to environmental stress.
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Melatonina , Espécies Reativas de Oxigênio/metabolismo , Melatonina/farmacologia , Plantas/metabolismo , Estresse Fisiológico , Desenvolvimento Vegetal , Reguladores de Crescimento de Plantas/metabolismoRESUMO
Interictal epileptiform discharges (IED) as large intermittent electrophysiological events are associated with various severe brain disorders. Automated IED detection has long been a challenging task, and mainstream methods largely focus on singling out IEDs from backgrounds from the perspective of waveform, leaving normal sharp transients/artifacts with similar waveforms almost unattended. An open issue still remains to accurately detect IED events that directly reflect the abnormalities in brain electrophysiological activities, minimizing the interference from irrelevant sharp transients with similar waveforms only. This study then proposes a dual-view learning framework (namely V2IED) to detect IED events from multi-channel EEG via aggregating features from the two phases: (1) Morphological Feature Learning: directly treating the EEG as a sequence with multiple channels, a 1D-CNN (Convolutional Neural Network) is applied to explicitly learning the deep morphological features; and (2) Spatial Feature Learning: viewing the EEG as a 3D tensor embedding channel topology, a CNN captures the spatial features at each sampling point followed by an LSTM (Long Short-Term Memories) to learn the evolution of these features. Experimental results from a public EEG dataset against the state-of-the-art counterparts indicate that: (1) compared with the existing optimal models, V2IED achieves a larger area under the receiver operating characteristic (ROC) curve in detecting IEDs from normal sharp transients with a 5.25% improvement in accuracy; (2) the introduction of spatial features improves performance by 2.4% in accuracy; and (3) V2IED also performs excellently in distinguishing IEDs from background signals especially benign variants.
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Epilepsia , Humanos , Epilepsia/diagnóstico , Eletroencefalografia/métodos , Redes Neurais de Computação , Curva ROCRESUMO
Protein kinase B (AKT) plays a pivotal in regulating cell migration, proliferation, apoptosis, and survival, making it a prominent target for anticancer therapy. While the kinase activity of AKT has been extensively explored, its dephosphorylation have largely remained uncharted. Herein, we aimed to unravel the molecular mechanisms governing AKT dephosphorylation, with a specific emphasis on dual-specificity phosphatases DUSP22. Our investigation sought to shed light on the potential of DUSP22 as a potential therapeutic target for non-small cell lung cancer (NSCLC). To determine the expression level of DUSP22 in NSCLC cell lines, the gene expression profiling interactive analysis (GEPIA) and Oncomine database were searched. Additionally, the effect of DUSP22 on patient survival was analyzed with Kaplan-Meier database. Antitumor effects of DUSP22 were tested in A549 and H1299 cell lines. Experiments are based on: (1) cell viability determined by the cell counting kit-8 assay and colony-formation assay; (2) cell migratory ability assessed through the scratch assay and the transwell migration assay; (3) the mechanism behind the antitumor effects of DUSP22 dissected with co-immunoprecipitation (Co-IP) and in vitro kinase assays. Our study revealed a significant downregulation of DUSP22 in both NSCLC cell lines and tissues. Meanwhile, survival rate analysis results demonstrated that reduced DUSP22 expression was correlated with poorer overall survival in lung cancer patients. Moreover, DUSP22 exhibited an inhibitory effect on the cell viability and migratory capacity of A549 and H1299 cells. This inhibition was accompanied by the decrease in the phosphorylation of AKT and p38. Mechanistically, the phosphatase domain of DUSP22 interacted with AKT, resulting in the inhibition of AKT phosphorylation. This inhibitory effect was contingent upon the phosphatase activity of DUSP22. These findings provide compelling evidence that DUSP22 directly interacted with AKT, leading to the dephosphorylation of AKT at S473 and T308 residues, ultimately curbing the proliferation and migration of lung cancer cells. Additionally, our results also highlight a preclinical rationale for utilizing DUSP22 as a prognostic marker in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Fosfatases de Especificidade Dupla/genética , Fosfatases de Especificidade Dupla/metabolismo , Neoplasias Pulmonares/patologia , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Head-mounted miniaturized fluorescence microscopy (Miniscope) has emerged as a significant tool in neuroscience, particularly for behavioral studies in awake rodents. However, the challenges of image quality control and standardization persist for both Miniscope users and developers. In this study, we propose a cost-effective and comprehensive toolkit named MiniMounter. This toolkit comprises a hardware platform that offers customized grippers and four-degree-of-freedom adjustment for Miniscope, along with software that integrates displacement control, image quality evaluation, and enhancement of 3D visualization. Our toolkit makes it feasible to accurately characterize Miniscope. Furthermore, MiniMounter enables auto-focusing and 3D imaging for Miniscope prototypes that possess solely a 2D imaging function, as demonstrated in phantom and animal experiments. Overall, the implementation of MiniMounter effectively enhances image quality, reduces the time required for experimental operations and image evaluation, and consequently accelerates the development and research cycle for both users and developers within the Miniscope community.
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Neurociências , Software , Animais , Microscopia de Fluorescência , Comportamento Animal , Controle de Qualidade , Aumento da ImagemRESUMO
Immune checkpoint blockade (ICB) therapies display clinical efficacy in microsatellite instable (MSI) endometrial cancer (EC) treatment, the key mechanism of which is reversing T cell exhaustion and restoration of anti-tumor immunity. Here, we demonstrate that transcription factor 19 (TCF19), one of the most significantly differentially expressed genes between MSI and microsatellite stable (MSS) patients in The Cancer Genome Atlas (TCGA)-EC cohort, is associated with poor prognosis and immune exhaustion signature. Specifically, TCF19 is significantly elevated in MSI EC, which in turn promotes tripartite motif-containing 14 (TRIM14) transcription and correlates with hyperactive signaling of the TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 (IRF3)-interferon ß (IFN-ß) pathway. The TCF19-TRIM14 axis promotes tumorigenicity under non-immunological background, and the enhanced downstream secretion of IFN-ß facilitates CD8+ T cell exhaustion through cell differentiation reprogramming. Finally, using humanized models, we show that a combination of TCF19 inhibition and ICB therapy demonstrates more effective anti-tumor responses. Together, our study indicates that targeting TCF19 is a potent strategy for alleviating CD8+ T cell exhaustion and synergizing with ICB in tumor treatment.
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Pseudostellaria heterophylla (Miq.) Pax is a well-known medicinal and ecologically important plant. Effectively distinguishing its different genetic resources is essential for its breeding. Plant chloroplast genomes can provide much more information than traditional molecular markers and provide higher-resolution genetic analyses to distinguish closely related planting materials. Here, seventeen P. heterophylla samples from Anhui, Fujian, Guizhou, Hebei, Hunan, Jiangsu, and Shandong provinces were collected, and a genome skimming strategy was employed to obtain their chloroplast genomes. The P. heterophylla chloroplast genomes ranged from 149,356 bp to 149,592 bp in length, and a total of 111 unique genes were annotated, including 77 protein-coding genes, 30 tRNA genes, and four rRNA genes. Codon usage analysis showed that leucine had the highest frequency, while UUU (encoding phenylalanine) and UGC (encoding cysteine) were identified as the most and least frequently used codons, respectively. A total of 75-84 SSRs, 16-21 short tandem repeats, and 27-32 long repeat structures were identified in these chloroplast genomes. Then, four primer pairs were revealed for identifying SSR polymorphisms. Palindromes are the dominant type, accounting for an average of 47.86% of all long repeat sequences. Gene orders were highly collinear, and IR regions were highly conserved. Genome alignment indicated that there were four intergenic regions (psaI-ycf4, ycf3-trnS, ndhC-trnV, and ndhI-ndhG) and three coding genes (ndhJ, ycf1, and rpl20) that were highly variable among different P. heterophylla samples. Moreover, 10 SNP/MNP sites with high polymorphism were selected for further study. Phylogenetic analysis showed that populations of Chinese were clustered into a monophyletic group, in which the non-flowering variety formed a separate subclade with high statistical support. In this study, the comparative analysis of complete chloroplast genomes revealed intraspecific variations in P. heterophylla and further supported the idea that chloroplast genomes could elucidate relatedness among closely related cultivation materials.
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In Zherong county, Fujian province, the black spot of Pseudostellaria heterophylla often breaks out in the rainy season from April to June every year. As one of the main leaf diseases of P. heterophylla, black spot seriously affects the yield and quality of the medicinal material. To identify and characterize the pathogens causing black spot, we isolated the pathogens, identified them as a species of Alternaria according to Koch's postulates, and then tested their pathogenicity and biological characteristics. The results showed that the pathogens causing P. heterophylla black spot were A. gaisen, as evidenced by the similar colony morphology, spore characteristics, sporulation phenotype, and the same clade with A. gaisen on the phylogenetic tree(the maximum likelihood support rate of 100% and the Bayesian posterior probability of 1.00) built based on the tandem sequences of ITS, tef1, gapdh, endoPG, Alta1, OPA10-2, and KOG1077. The optimum conditions for mycelial growth of the pathogen were 25 â, pH 5-8, and 24 h dark culture. The lethal conditions for mycelia and spores were both treatment at 50 â for 10 min. We reported for the first time the A. gaisen-caused black spot of P. heterophylla. The results could provide a theoretical basis for the diagnosis and control of P. heterophylla leaf spot diseases.
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Alternaria , Caryophyllaceae , Doenças das Plantas , Alternaria/classificação , Alternaria/genética , Alternaria/crescimento & desenvolvimento , Alternaria/patogenicidade , Caryophyllaceae/microbiologia , DNA Fúngico/genética , Micélio/crescimento & desenvolvimento , Filogenia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , ChinaRESUMO
OBJECTIVE: To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (PC) chemotherapy regimens on the fertility and prognostic outcomes in malignant ovarian germ cell tumor (MOGCT) patients who underwent fertility-sparing surgery (FSS). METHODS: A propensity score matching algorithm was performed between the BEP and PC groups. The χ² test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS) and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factor of DFS. RESULTS: We included 213 patients, 185 (86.9%) underwent BEP chemotherapy, and 28 (13.1%) underwent PC chemotherapy. The median age was 22 years (range, 8-44 years), and the median follow-up period was 63 months (range, 2-191 months). Fifty-one (29.3%) patients had a pregnancy plan, and 35 (85.4%) delivered successfully. In the before and after propensity score matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during-pregnancy status, and live birth between the BEP and PC groups (p>0.05). Fourteen (6.6%) patients experienced recurrence, including 11 (5.9%) in the BEP group and 3 (10.7%) in the PC group. Four (1.9%) patients in the BEP group died. Kaplan-Meier analysis revealed no significant differences in DFS (p=0.328) and OS (p=0.446) between the BEP and PC groups, and the same survival results were observed in the after matching cohort. CONCLUSION: The PC regimen is as safe as the BEP regimen for MOGCT patients with fertility preservation treatment, and no differences were observed in fertility and clinical prognosis.
Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Feminino , Humanos , Gravidez , Adulto Jovem , Adulto , Cisplatino , Etoposídeo , Carboplatina , Estudos Retrospectivos , Tratamento Conservador , Neoplasias Ovarianas/cirurgia , Bleomicina/efeitos adversos , Prognóstico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica , Paclitaxel/uso terapêuticoRESUMO
In cases of end-stage liver diseases, the proliferation of existing hepatocytes is compromised, a feature of human chronic liver disease, in which most hepatocytes are dysfunctional. So far, liver transplantation represents the only curative therapeutic solution for advanced liver diseases, and the shortage of donor organs leads to high morbidity and mortality worldwide. The promising treatment is to prompt the biliary epithelial cells (BECs) transdifferentiation. However, the critical factors governing the initiation of BEC-derived liver regeneration are largely unknown. The zebrafish has advantages in large-scale genetic screens to identify the critical factors involved in liver regeneration. Here, we combined N-ethyl-N-nitrosourea screen, positional cloning, transgenic lines, antibody staining, and in situ hybridization methods and identified a liver regeneration defect mutant ( lrd ) using the zebrafish extensive liver injury model. Through positional cloning and genomic sequencing, we mapped the mutation site to rngtt . Loss of rngtt leads to the defects of BEC dedifferentiation, bipotential progenitor cell activation, and cell proliferation in the initiation stage of liver regeneration. The transdifferentiation from BECs to hepatocytes did not occur even at the late stage of liver regeneration. Mechanically, Rngtt transcriptionally regulates the attachment of mRNA cap to mTOR complex 1 (mTORC1) components and dnmt1 to maintain the activation of mTORC1 and DNA methylation in BECs after severe liver injury and prompt BEC to hepatocyte conversion. Furthermore, rptor and dnmt1 mutants displayed the same liver regeneration defects as rngtt mutation. In conclusion, our results suggest Rngtt is a new factor that initiates BEC-derived liver regeneration.
Assuntos
Regeneração Hepática , Peixe-Zebra , Animais , Humanos , DNA (Citosina-5-)-Metiltransferase 1 , Células Epiteliais , Hepatócitos/fisiologia , Fígado , Regeneração Hepática/genética , Alvo Mecanístico do Complexo 1 de Rapamicina , Proteínas de Peixe-Zebra/genéticaRESUMO
Violet root rot is one of the main root diseases in the production process of Pseudostellaria heterophylla. To clarify the pathogenic species that cause the violet root rot of P. heterophylla in Fujian province, the roots and the sclerotia with violet root rot symptoms were collected from the main producing areas of P. heterophylla(Fujian province) from 2017 to 2021, and the pathogens were isolated by tissue separation method and identified by morphology and multi-gene phylogenetic analysis. Additionally, the biological characteristics of the pathogens were studied and the fungicides were determined. The results showed that 78 strains of violet root rot were isolated from the collected root samples, which belonged to one type after preliminary morphological identification. Two represen-tative strains were selected from the pathogens for multi-gene phylogenetic analysis, and they were clustered with Helicobasidium mompa together. The suitable culture conditions for the mycelium were OA medium, 25 â, pH 6, and ammonium oxalate as the nitrogen source. The lethal temperature of the mycelium was 50 â for 10 minutes. Moreover, 99.1% propiconazole and 98.7% azoxystrobin had the optimal bacteriostatic effect, and the concentrations with the 50% bacteriostatic rate were 16.85 and 12.24 µg·mL~(-1), respectively. On the basis of the above results, the pathogen causing violet root rot of P. heterophylla in Fujian province was H. mompa. The medium type, growth temperature, pH value, nitrogen source, etc. had significant effect on the growth of mycelium.