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Autophagy and Cell wall integrity (CWI) signaling are critical stress-responsive processes during fungal infection of host plants. In the rice blast fungus Magnaporthe oryzae, autophagy-related (ATG) proteins phosphorylate CWI kinases to regulate virulence; however, how autophagy interplays with CWI signaling to coordinate such regulation remains unknown. Here, we have identified the phosphorylation of ATG protein MoAtg4 as an important process in the coordination between autophagy and CWI in M. oryzae. The ATG kinase MoAtg1 phosphorylates MoAtg4 to inhibit the deconjugation and recycling of the key ATG protein MoAtg8. At the same time, MoMkk1, a core kinase of CWI, also phosphorylates MoAtg4 to attenuate the C-terminal cleavage of MoAtg8. Significantly, these two phosphorylation events maintain proper autophagy levels to coordinate the development and pathogenicity of the rice blast fungus.
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Ascomicetos , Magnaporthe , Oryza , Fosforilación , Virulencia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Magnaporthe/metabolismo , Autofagia , Pared Celular/metabolismo , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Regulación Fúngica de la Expresión GénicaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.
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Anticuerpos Antivirales/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/inmunología , Neumonía Viral/prevención & control , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , COVID-19 , Vacunas contra la COVID-19 , Humanos , Macaca mulatta/inmunología , Macaca mulatta/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Modelos Animales , Modelos Moleculares , Dominios Proteicos , SARS-CoV-2 , Suero/inmunología , Bazo/citología , Bazo/inmunología , Linfocitos T/inmunología , VacunaciónRESUMEN
Chromatin in eukaryotes folds into a complex three-dimensional (3D) structure that is essential for controlling gene expression and cellular function and is dynamically regulated in biological processes. Studies on plant phosphorus signaling have concentrated on single genes and gene interactions. It is critical to expand the existing signaling pathway in terms of its 3D structure. In this study, low-Pi treatment led to greater chromatin volume. Furthermore, low-Pi stress increased the insulation score and the number of TAD-like domains, but the effects on the A/B compartment were not obvious. The methylation levels of target sites (hereafter as RdDM levels) peaked at specific TAD-like boundaries, whereas RdDM peak levels at conserved TAD-like boundaries shifted and decreased sharply. The distribution pattern of RdDM sites originating from the Helitron transposons matched that of genome-wide RdDM sites near TAD-like boundaries. RdDM pathway genes were upregulated in the middle or early stages and downregulated in the later stages under low-Pi conditions. The RdDM pathway mutant ddm1a showed increased tolerance to low-Pi stress, with shortened and thickened roots contributing to higher Pi uptake from the shallow soil layer. ChIP-seq results revealed that ZmDDM1A could bind to Pi- and root development-related genes. Strong associations were found between interacting genes in significantly different chromatin-interaction regions and root traits. These findings not only expand the mechanisms by which plants respond to low-Pi stress through the RdDM pathway but also offer a crucial framework for the analysis of biological issues using 3D genomics.
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Cromatina , Zea mays , Cromatina/genética , Zea mays/genética , Metilación de ADN , Ensamble y Desensamble de Cromatina/genética , Silenciador del Gen , Regulación de la Expresión Génica de las PlantasRESUMEN
AMP-activated protein kinase (AMPK), a crucial regulatory kinase, monitors energy levels, conserving ATP and boosting synthesis in low-nutrition, low-energy states. Its sensitivity links microenvironmental changes to cellular responses. As the primary support structure and endocrine organ, the maintenance, and repair of bones are closely associated with the microenvironment. While a series of studies have explored the effects of specific microenvironments on bone, there is lack of angles to comprehensively evaluate the interactions between microenvironment and bone cells, especially for bone marrow mesenchymal stem cells (BMMSCs) which mediate the differentiation of osteogenic lineage. It is noteworthy that accumulating evidence has indicated that AMPK may serve as a hub between BMMSCs and microenvironment factors, thus providing a new perspective for us to understand the biology and pathophysiology of stem cells and bone. In this review, we emphasize AMPK's pivotal role in bone microenvironment modulation via ATP, inflammation, reactive oxygen species (ROS), calcium, and glucose, particularly in BMMSCs. We further explore the use of AMPK-activating drugs in the context of osteoarthritis and osteoporosis. Moreover, building upon the foundation of AMPK, we elucidate a viewpoint that facilitates a comprehensive understanding of the dynamic relationship between the microenvironment and bone homeostasis, offering valuable insights for prospective investigations into stem cell biology and the treatment of bone diseases.
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To manufacture flexible batteries, it can be a challenge for silicon base anode materials to maintain structural integrity and electrical connectivity under bending and torsion conditions. In this work, 1D silicon nanowire array structures combined with flexible carbon chains consisting of short carbon nanofibers (CNFs) and long carbon nanotubes (CNTs) are proposed. The CNFs and CNTs serve as chain joints and separate chain units, respectively, weaving the well-ordered Si nanowire array into a robust and integrated configuration. The prepared flexible and stretchable silicon array anode exhibits excellent electrochemical performance during dynamic operation. A high initial specific capacity of 2856 mAh g-1 is achieved. After 1000 cycles, a capacity retention of 60% (1602 mAh g-1) is maintained. Additionally, the capacity attenuation is less than 1% after 100 bending cycles. This excellent cycling stability is obtained with a high Si loading of 6.92 mg cm-2. This novel approach offers great promise for the development of high-loading flexible energy-storage devices.
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Cancer immunotherapy offers significant clinical benefits for patients with advanced or metastatic tumors. However, immunotherapeutic efficacy is often hindered by the tumor microenvironment's high redox levels, leading to variable patient outcomes. Herein, a therapeutic liposomal gold nanocage (MGL) is innovatively developed based on photo-triggered hyperthermia and a releasable strategy by combining a glutathione (GSH) depletion to remodel the tumor immune microenvironment, fostering a more robust anti-tumor immune response. MGL comprises a thermosensitive liposome shell and a gold nanocage core loaded with maleimide. The flexible shell promotes efficient uptake by cancer cells, enabling targeted destruction through photothermal therapy while triggering immunogenic cell death and the maturation of antigen-presenting cells. The photoactivated release of maleimide depletes intracellular GSH, increasing tumor cell sensitivity to oxidative stress and thermal damage. Conversely, GSH reduction also diminishes immunosuppressive cell activity, enhances antigen presentation, and activates T cells. Moreover, photothermal immunotherapy decreases elevated levels of heat shock proteins in tumor cells, further increasing their sensitivity to hyperthermia. In summary, MGL elicited a robust systemic antitumor immune response through GSH depletion, facilitating an effective photothermal immunotherapeutic strategy that reprograms the tumor microenvironment and significantly inhibits primary and metastatic tumors. This approach demonstrates considerable translational potential and clinical applicability.
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Microbe-produced secondary metabolite phenazine-1-carboxylic acid (PCA) facilitates pathogen virulence and defense mechanisms against competitors. Magnaporthe oryzae, a causal agent of the devastating rice blast disease, needs to compete with other phyllosphere microbes and overcome host immunity for successful colonization and infection. However, whether M. oryzae produces PCA or it has any other functions remains unknown. Here, we found that the MoPHZF gene encodes the phenazine biosynthesis protein MoPhzF, synthesizes PCA in M. oryzae, and regulates appressorium formation and host virulence. MoPhzF is likely acquired through an ancient horizontal gene transfer event and has a canonical function in PCA synthesis. In addition, we found that PCA has a role in suppressing the accumulation of host-derived reactive oxygen species (ROS) during infection. Further examination indicated that MoPhzF recruits both the endoplasmic reticulum membrane protein MoEmc2 and the regulator of G-protein signaling MoRgs1 to the plasma membrane (PM) for MoRgs1 phosphorylation, which is a critical regulatory mechanism in appressorium formation and pathogenicity. Collectively, our studies unveiled a canonical function of MoPhzF in PCA synthesis and a noncanonical signaling function in promoting appressorium formation and host infection.
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Ascomicetos , Magnaporthe , Oryza , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Oryza/metabolismo , Fenazinas/metabolismo , Enfermedades de las Plantas/genéticaRESUMEN
Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the nonreceptor tyrosine kinase v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) was temporally coordinated with the change of OATP1A2 after irradiation. The overexpression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 because phosphorylation and nuclear accumulation of STAT3 were both enhanced after overexpressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis suggested that these two sites bound to STAT3 specifically and the overexpression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knockdown of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2. SIGNIFICANCE STATEMENT: The present study found that the effect of X-rays on v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) and organic anion transporting polypeptides (OATP)1A2 was temporally coordinated. YES-1 phosphorylates and increases the nuclear accumulation of signal transducer and activator of transcription 3, which in turn binds to the upstream regulatory sequences of SLCO1A2, the coding gene for OATP1A2. Hence, inhibitors of YES-1 may suppress the radiation induction effect on OATP1A2.
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Transportadores de Anión Orgánico , Factor de Transcripción STAT3 , Humanos , Transportadores de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Células MCF-7 , Fosforilación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Femenino , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Observational studies indicate that sleep apnea is associated with non-alcoholic fatty liver disease (NAFLD) and its related metabolic features, independent of confounding factors including obesity. However, the causal relationships remain to be determined. METHODS: Univariable and multivariable Mendelian randomization (MR) analyses were performed to investigate the causal relationship between sleep apnea and NAFLD, along with its typical features including liver function, glycemic traits and lipid profiles. Summary-level data for sleep apnea were obtained from the Finngen consortium (33,423 cases and 307,648 controls). Summary-level data for NAFLD were available from a GWAS meta-analysis (8434 cases and 770,180 controls), and data for 12 NAFLD-related features from corresponding published GWASs. The inverse variance weighted (IVW) analysis was employed as the primary statistical method. Bidirectional MR and CAUSE analysis were conducted to avoid reverse causality and false positive findings. RESULTS: In univariable MR analyses, we found evidence to support a causal effect of genetically predicted sleep apnea on NAFLD (OR = 1.50, 95% CI = 1.18-1.91) and HDL-C (ß = -0.045, 95% CI = -0.090 to -0.001). In reverse MR, genetically predicted serum TG was associated with an increased risk of sleep apnea (OR = 1.07, 95% CI = 1.02-1.12), while genetically predicted HDL-C was associated with a decreased risk of sleep apnea (OR = 0.93, 95% CI = 0.89-0.98). After adjusting body mass index or educational attainment, none of these causal associations were retained. However, CAUSE method and MR analyses focusing on lipoprotein subfractions supported a causal effect of sleep apnea on HDL-C and HDL subfractions. CONCLUSION: This MR study indicated that sleep apnea has no direct causal association with NAFLD, elevated liver enzymes and insulin resistance. Our results showed suggestive inverse associations of genetically predicted sleep apnea on HDL-C and HDL subfractions, indicating that both HDL-C levels and HDL function may be causally implicated in sleep apnea.
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Enfermedad del Hígado Graso no Alcohólico , Síndromes de la Apnea del Sueño , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/genética , Análisis de la Aleatorización Mendeliana , Índice de Masa Corporal , Causalidad , Síndromes de la Apnea del Sueño/epidemiología , Síndromes de la Apnea del Sueño/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Here, we propose a sandwich-like Si-doping scheme (undoped/Si-doped/undoped) in Al0.6Ga0.4N quantum barriers (QBs) to simultaneously promote the optoelectronic performances and reliability of deep ultraviolet light-emitting diodes (DUV-LEDs). Through experimental and numerical analyses, in the case of DUV-LEDs with conventional uniform Si-doping QB structure, severe operation-induced reliability degradation, including the increase of reverse leakage current (IR) and reduction of light output power (LOP), will offset the enhancement of optoelectronic performances as the Si-doping levels increase to an extent, which hinders further development of DUV-LEDs. According to a transmission electron microscope characterization and a numerical simulation, an improved interfacial quality in multiple quantum wells (MQWs) and more uniform carrier distribution within MQWs are demonstrated for our proposed Si-doping structure in comparison to the uniform Si-doping structure. Consequently, the proposed DUV-LED shows superior wall-plug efficiency (4%), IR at -6â V reduced by almost one order of magnitude, and slower LOP degradation after 168-h 100â mA-current-stress operation. This feasible doping scheme provides a promising strategy for the high-efficiency and cost-competitive DUV-LEDs.
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We present an erratum to our Letter [Opt. Lett.49, 2049 (2024)10.1364/OL.522212]. There is a careless omission of some references because our Letter is longer than the maximum allowed four pages. The missing references and their specific quote location are listed in the following. These corrections do not affect the data plotted in figures, discussion, or conclusion of the original Letter.
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BACKGROUND: The aim of the present study was to develop a novel 64Cu-labeled cyclic peptide ([64Cu]Cu-FAP-NOX) that targets fibroblast activation protein (FAP) and may offer advantages in terms of image contrast, imaging time window, and low uptake in normal tissues. METHODS: The novel cyclic peptide featuring with a N-oxalyl modified tail was constructed and conjugated to NOTA for 64Cu labeling. Biochemical and cellular assays were performed with A549.hFAP cells. The performance of [64Cu]Cu-FAP-NOX was compared to that of two established tracers ([64Cu]Cu-FAPI-04 and [68Ga]Ga-FAP-2286) and three different NOTA-conjugates in HEK-293T.hFAP xenograft mice using micro-PET imaging. Ex vivo biodistribution studies were performed to confirm the FAP specificity and to validate the PET data. Furthermore, a first-in-human study of this novel tracer was conducted on one patient with lung cancer. RESULTS: Compared to [64Cu]Cu-FAPI-04, [64Cu]Cu-FAP-NOX demonstrated faster and higher rates of cellular uptake and internalization in A549.hFAP cells, but lower rates of cellular efflux. All six radiotracers were rapidly taken up by the tumor within the first 4 h post-injection. However, [64Cu]Cu-FAP-NOX had more intense tumor accumulation and slower washout from the target. The ratios of the tumor to normal tissue (including kidneys and muscles) increased significantly over time, with [64Cu]Cu-FAP-NOX reaching the highest ratio among all tracers. In the patient, [64Cu]Cu-FAP-NOX PET showed a comparable result to FDG PET in the primary malignant lesion while exhibiting higher uptake in pleural metastases, consistent with elevated FAP expression as confirmed by immunohistochemistry. CONCLUSION: [64Cu]Cu-FAP-NOX is a promising FAP-targeted tracer with a highly flexible imaging time window, as evidenced by preclinical evaluation encompassing biodistribution and micro-PET studies, along with a successful patient application. Furthermore, [64Cu]Cu-FAP-NOX showed enhanced image contrast and favorable pharmacokinetic properties for FAP PET imaging, warranting translation into large cohort studies.
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Radioisótopos de Cobre , Péptidos Cíclicos , Tomografía de Emisión de Positrones , Humanos , Animales , Ratones , Péptidos Cíclicos/farmacocinética , Péptidos Cíclicos/química , Tomografía de Emisión de Positrones/métodos , Distribución Tisular , Células HEK293 , Endopeptidasas , Proteínas de la Membrana/metabolismo , Gelatinasas/metabolismo , Células A549 , Factores de Tiempo , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/metabolismo , Radiofármacos/farmacocinética , Radiofármacos/químicaRESUMEN
PURPOSE: Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [18F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [18F]FAPI-42 and [68Ga]Ga-FAP-2286 in preclinical research, as well as 2-[18F]FDG in pilot clinical study. METHODS: [18F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [18F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[18F]FDG PET. RESULTS: The radiolabeling yield of [18F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [18F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [18F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers. CONCLUSION: [18F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[18F]FDG non-avid cancers PET scan.
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Fluorodesoxiglucosa F18 , Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Animales , Ratones , Fluorodesoxiglucosa F18/farmacocinética , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Masculino , Femenino , Línea Celular Tumoral , Células HEK293 , Distribución Tisular , Persona de Mediana Edad , Radiofármacos/farmacocinética , Anciano , Proteínas de la Membrana , EndopeptidasasRESUMEN
PURPOSE: To develop and compare 3 different machine learning-based models of clinical information and integrated radiomics features predicting the local recurrence of Stage Ia lung adenocarcinoma after microwave ablation (MWA) for assisting clinical decision making. MATERIALS AND METHODS: The data of 360 patients with Stage Ia lung adenocarcinoma who underwent MWA were included in the training (n = 208), internal test (n = 90), and external test (n = 62) sets based on the inclusion and exclusion criteria. The predictors associated with local recurrence were identified using univariate and multivariate analyses of clinical information. The integrated radiomics features were extracted from pre-MWA and post-MWA (scanned immediately after the ablation) computed tomography (CT) images, and 10 radiomics features were selected by the t-test and least absolute shrinkage and selection operator. The L2-logistic regression of machine learning was applied for the clinical model, CT radiomics model, and combined model including clinical predictors and radiomics features. Model performance was evaluated by the receiver operating characteristic and decision curve analysis. RESULTS: The ablative margin was an independent clinical predictor (P = 0.001; odds ratio [OR], 0.46; 95% CI, 0.29-0.73). The combined model showed the highest area under the curve value among the 3 models (training, 0.86; 95% CI, 0.81-0.91; internal test, 0.93; 95% CI, 0.87-0.98; external test, 0.89; 95% CI, 0.79-0.96). CONCLUSIONS: The combined model could accurately predict the local recurrence of Stage Ia lung adenocarcinoma after MWA to better support a clinical decision.
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Radiology report generation automates diagnostic narrative synthesis from medical imaging data. Current report generation methods primarily employ knowledge graphs for image enhancement, neglecting the interpretability and guiding function of the knowledge graphs themselves. Additionally, few approaches leverage the stable modal alignment information from multimodal pre-trained models to facilitate the generation of radiology reports. We propose the Terms-Guided Radiology Report Generation (TGR), a simple and practical model for generating reports guided primarily by anatomical terms. Specifically, we utilize a dual-stream visual feature extraction module comprised of detail extraction module and a frozen multimodal pre-trained model to separately extract visual detail features and semantic features. Furthermore, a Visual Enhancement Module (VEM) is proposed to further enrich the visual features, thereby facilitating the generation of a list of anatomical terms. We integrate anatomical terms with image features and proceed to engage contrastive learning with frozen text embeddings, utilizing the stable feature space from these embeddings to boost modal alignment capabilities further. Our model incorporates the capability for manual input, enabling it to generate a list of organs for specifically focused abnormal areas or to produce more accurate single-sentence descriptions based on selected anatomical terms. Comprehensive experiments demonstrate the effectiveness of our method in report generation tasks, our TGR-S model reduces training parameters by 38.9% while performing comparably to current state-of-the-art models, and our TGR-B model exceeds the best baseline models across multiple metrics.
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Procesamiento de Lenguaje Natural , Humanos , Radiología/educación , Radiología/métodos , Algoritmos , Aprendizaje Automático , Semántica , Sistemas de Información Radiológica , Diagnóstico por Imagen/métodosRESUMEN
Bone defects pose significant challenges in healthcare, with over 2 million bone repair surgeries performed globally each year. As a burgeoning force in the field of bone tissue engineering, 3D printing offers novel solutions to traditional bone transplantation procedures. However, current 3D-printed bone scaffolds still face three critical challenges in material selection, printing methods, cellular self-organization and co-culture, significantly impeding their clinical application. In this comprehensive review, we delve into the performance criteria that ideal bone scaffolds should possess, with a particular focus on the three core challenges faced by 3D printing technology during clinical translation. We summarize the latest advancements in non-traditional materials and advanced printing techniques, emphasizing the importance of integrating organ-like technologies with bioprinting. This combined approach enables more precise simulation of natural tissue structure and function. Our aim in writing this review is to propose effective strategies to address these challenges and promote the clinical translation of 3D-printed scaffolds for bone defect treatment.
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Bioimpresión , Huesos , Organoides , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido , Andamios del Tejido/química , Humanos , Ingeniería de Tejidos/métodos , Organoides/citología , Bioimpresión/métodos , Animales , Regeneración Ósea , Trasplante Óseo/métodosRESUMEN
Previous studies have demonstrated the toxic effects of per- and polyfluoroalkyl substances (PFASs) and heavy metals on the reproductive system. However, the interactions and combined effects of these substances remain unexplored. This study utilizes data from the National Health and Nutrition Examination Survey to investigate the associations between coexposure to four types of PFASs, lead (Pb), mercury (Hg) and self-reported pregnancy loss and reproductive lifespan in females. Genes associated with these substances and abortion were identified via the Comparative Toxicogenomics Database. The results revealed that Ln-PFOA (IRR=1.88, 95â¯% CI=1.42-2.50, Ln--: log transformed), Ln-PFOS (IRR=1.58, 95â¯% CI=1.12-2.22), Ln-PFHxS (IRR=1.99, 95â¯% CI=1.57-2.52), and Ln-Hg (IRR=1.92, 95â¯% CI=1.41-2.43) were positively associated with the risk of pregnancy loss. Ln-PFOA (ß=1.27, 95â¯% CI=0.28-2.27), Ln-PFOS (ß=1.01, 95â¯% CI=0.39-1.63), Ln-PFHxS (ß=0.71, 95â¯% CI=0.12-1.63), Ln-PFNA (ß=1.15, 95â¯% CI=0.23-2.08), Ln-Pb (ß=3.87, 95â¯% CI=2.58-5.15), and Ln-Hg (ß=1.01, 95â¯% CI=0.39-1.64) exposures were positively associated with reproductive lifespan. The mixed and overall effects of coexposure to PFASs and heavy metals were positively correlated with the risk of pregnancy loss and reproductive lifespan. Cholesterol partially mediated the association with the risk of pregnancy loss, whereas delay in menopause fully mediated the association with reproductive lifespan. Significant additive interactions were observed between PFOA and Pb and between PFOS, PFHxS, PFNA and Hg at high levels of coexposure. Thirty-nine overlapping genes associated with abortion were identified for these substances, and further analyses revealed that these genes significantly interact and may contribute to abortion through oxidative stress.
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Soil loss is an environmental concern of global importance. Accurate simulation of soil loss in small watersheds is crucial for protecting the environment and implementing soil and water conservation measures. However, predicting soil loss while meeting the criteria of high precision, efficiency, and generalizability remains a challenge. Therefore, this study first used three machine learning (ML) algorithms, namely, random forest (RF), support vector machine (SVM), and artificial neural network (ANN) to develop soil loss models and predict soil loss rates (SLRs). These soil loss models were constructed using field observation data with an average SLR of 1756.48 t/km2 from rainfall events and small watersheds in the hilly-gully region of the Loess Plateau, China. During training, testing and generalizability stages, the average coefficients of determination from the RF, SVM, and ANN models were 0.903, 0.860, and 0.836, respectively. Similarly, the average Nash-Sutcliffe coefficients of efficiency from the RF, SVM and ANN models were 0.893, 0.791 and 0.814, respectively. These results indicated that MLs have superior predictive performance and generalizability, and broad prospects for predicting SLRs. This study also demonstrated that the RF model outperformed better than the SVM and ANN models. Therefore, the RF model was used to simulate the SLR of each small watershed in the Chabagou watershed. Our results showed the four-year (2017-2020) average annual SLR of the small watersheds ranged from 0.73 to 1.63 × 104 t/(km2âa) in the Chabagou watershed. Additionally, the results also indicated the SLR of small watersheds under the rainstorm event with a 100-year recurrence interval was 4.4-51.3 times that of other rainfall events.Furthermore, this study confirmed that bare land was the predominant source of soil loss in the Chabagou watershed, followed by cropland land and grassland. This study helps to provide the theoretical basis for deploying soil and water conservation measures to realize the sustainable utilization of soil resources in the future.
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Conservación de los Recursos Hídricos , Suelo , Algoritmos , China , Aprendizaje AutomáticoRESUMEN
AIM: This study aimed to assess inclusive leadership and presenteeism among clinical nurses and to examine the moderating effect of perceived organizational support on presenteeism related to the inclusive leadership among nurses. BACKGROUND: Nurses' presenteeism has become common. In hospitals, inclusive leadership is an acknowledged leadership style that has a positive influence on nurses. However, little emphasis has been paid to research on their relationships and moderating effect. METHODS: A cross-sectional study was undertaken to assess 2222 nurses using a general information questionnaire, Stanford Presenteeism Scale (SPS-6), Perceived Organisational Support Scale, and Inclusive Leadership Scale. Study variables were analyzed using descriptive statistics, correlation, and structural equation modelling (SEM). RESULTS: Presenteeism was relatively severe among clinical nurses. There were correlations between inclusive leadership, perceived organizational support and presenteeism. Perceived organizational support moderated the relationship between inclusive leadership and presenteeism. DISCUSSION AND CONCLUSION: Nursing managers should actively adopt an inclusive leadership style and improve nurses' sense of perceived organizational support to improve clinical nurses' presenteeism behaviors. IMPLICATIONS FOR NURSING POLICY AND PRACTICE: Healthcare organizations and nursing managers should pay attention to the psychological needs of their nurses, provide complete understanding and support, encourage staff to actively participate in their work and contribute new ideas and opinions, reduce the incidence of presenteeism, and improve nurses' sense of well-being at work.
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OBJECTIVES: The accurate localization of the foreign bodies (FBs) is essential. This work presents a new noninvasive technique for subcutaneous metallic FBs under a radiographic grid, a system that simplifies the localization of facial FBs removal using a grid with embedded reference points. METHODS: This work designed a retrospective study to evaluate the effect of a radiographic grid on FBs removal surgery. All patients who met the inclusion criteria and attended the Hospital of Stomatology of China Medical University from January 2022 to June 2023 were enrolled and randomly divided into grid and non-grid groups. The assessment of facial swelling, the primary indicator, was conducted on days 2 and 7 post-surgery. The variables were analyzed using the Student t test and a repeated-measures general linear model. RESULTS: The study sample consisted of 20 patients, with 14 males (70%) and 6 females (30%), who had an average age of 30.30 ± 5.38. The average time of operation was 1.85 ± 0.66 h (range 0.7 to 3.2). In the present cases in this report, of the 20 patients' FBs, 14 were metal, 5 were glass, and 1 was residual root. And the FBs were surgically removed with no postoperative complications. Through comparison, it was found that the degree of swelling on day 2 postoperatively was significantly different between the grid group and the non-grid group (P < 0.05). CONCLUSIONS: This study demonstrates that a radiographic grid with mark points is a more efficient approach compared with traditional methods for FBs removal, and this surgical method is more accurate, fast and noninvasive.