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Photothermal therapy (PTT) and photodynamic therapy (PDT) provide targeted approaches to cancer treatment, but each therapy has inherent limitations such as insufficient tissue penetration, uneven heat distribution, extreme hypoxia, and overexpressed HSP90 in tumor cells. To address these issues, herein, by encapsulating the IR780 dye and glucose oxidase (GOx) enzyme within ZIF-8 nanoparticles, we created a versatile system capable of combining photodynamic and enhanced photothermal therapy. The integration of the IR780 dye facilitated the generation of reactive oxygen species and hyperthermia upon light activation, enabling dual-mode cancer cell ablation. Moreover, GOx catalyzes the decomposition of glucose into gluconic acid and hydrogen peroxide, leading to the inhibition of ATP production and downregulation of heat shock protein 90 (HSP90) expression, sensitizing cancer cells to heat-induced cytotoxicity. This synergistic combination resulted in significantly improved therapeutic outcomes. Both in vitro and in vivo results validated that the nanoplatform demonstrated superior specificity and favorable therapeutic responses. Our innovative approach represents a promising strategy for overcoming current limitations in cancer treatments and offers the potential for clinical translation in the future.
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Glucose Oxidase , Estruturas Metalorgânicas , Fotoquimioterapia , Terapia Fototérmica , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Humanos , Animais , Camundongos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/síntese química , Concentração de Íons de Hidrogênio , Indóis/química , Indóis/farmacologia , Linhagem Celular Tumoral , Nanopartículas/química , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Camundongos Nus , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , ImidazóisRESUMO
Hepatitis B virus (HBV) exploits the endosomal sorting complexes required for transport (ESCRT)/multivesicular body (MVB) pathway for virion budding. In addition to enveloped virions, HBV-replicating cells nonlytically release non-enveloped (naked) capsids independent of the integral ESCRT machinery, but the exact secretory mechanism remains elusive. Here, we provide more detailed information about the existence and characteristics of naked capsid, as well as the viral and host regulations of naked capsid egress. HBV capsid/core protein has two highly conserved Lysine residues (K7/K96) that potentially undergo various types of posttranslational modifications for subsequent biological events. Mutagenesis study revealed that the K96 residue is critical for naked capsid egress, and the intracellular egress-competent capsids are associated with ubiquitinated host proteins. Consistent with a previous report, the ESCRT-III-binding protein Alix and its Bro1 domain are required for naked capsid secretion through binding to intracellular capsid, and we further found that the ubiquitinated Alix binds to wild type capsid but not K96R mutant. Moreover, screening of NEDD4 E3 ubiquitin ligase family members revealed that AIP4 stimulates the release of naked capsid, which relies on AIP4 protein integrity and E3 ligase activity. We further demonstrated that AIP4 interacts with Alix and promotes its ubiquitination, and AIP4 is essential for Alix-mediated naked capsid secretion. However, the Bro1 domain of Alix is non-ubiquitinated, indicating that Alix ubiquitination is not absolutely required for AIP4-induced naked capsid secretion. Taken together, our study sheds new light on the mechanism of HBV naked capsid egress in viral life cycle.
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Capsídeo , Vírus da Hepatite B , Ubiquitina-Proteína Ligases Nedd4 , Ubiquitina-Proteína Ligases , Liberação de Vírus , Humanos , Proteínas de Ligação ao Cálcio , Capsídeo/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Hepatite B/metabolismo , Hepatite B/virologia , Vírus da Hepatite B/metabolismo , Vírus da Hepatite B/fisiologia , Vírus da Hepatite B/genética , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Liberação de Vírus/fisiologiaRESUMO
Tumorigenesis and metastasis are highly dependent on the interactions between the tumor and the surrounding microenvironment. In 3D matrix, the fibrous structure of the extracellular matrix (ECM) undergoes dynamic remodeling during tumor progression. In particular, during the late stage of tumor development, the fibers become more aggregated and oriented. However, it remains unclear how cancer cells respond to the organizational change of ECM fibers and exhibit distinct morphology and behavior. Here, we used electrospinning technology to fabricate biomimetic ECM with distinct fiber arrangements, which mimic the structural characteristics of normal or tumor tissues and found that aligned and oriented nanofibers induce cytoskeletal rearrangement to promote directed migration of cancer cells. Mechanistically, caveolin-1(Cav-1)-expressing cancer cells grown on aligned fibers exhibit increased integrin ß1 internalization and actin polymerization, which promoted stress fiber formation, focal adhesion dynamics and YAP activity, thereby accelerating the directional cell migration. In general, the linear fibrous structure of the ECM provides convenient tracks on which tumor cells can invade and migrate. Moreover, histological data from both mice and patients with tumors indicates that tumor tissue exhibits a greater abundance of isotropic ECM fibers compared to normal tissue. And Cav-1 downregulation can suppress cancer cells muscle invasion through the inhibition of YAP-dependent mechanotransduction. Taken together, our findings revealed the Cav-1 is indispensable for the cellular response to topological change of ECM, and that the Cav-1/YAP axis is an attractive target for inhibiting cancer cell directional migration which induced by linearization of ECM fibers.
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Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measures microvascular perfusion by capturing the temporal changes of an MRI contrast agent in a target tissue, and it provides valuable information for the diagnosis and prognosis of a wide range of tumors. Quantitative DCE-MRI analysis commonly relies on the nonlinear least square (NLLS) fitting of a pharmacokinetic (PK) model to concentration curves. However, the voxel-wise application of such nonlinear curve fitting is highly time-consuming. The arterial input function (AIF) needs to be utilized in quantitative DCE-MRI analysis. and in practice, a population-based arterial AIF is often used in PK modeling. The contribution of intravascular dispersion to the measured signal enhancement is assumed to be negligible. The MR dispersion imaging (MRDI) model was recently proposed to account for intravascular dispersion, enabling more accurate PK modeling. However, the complexity of the MRDI hinders its practical usability and makes quantitative PK modeling even more time-consuming. In this paper, we propose fast MR dispersion imaging (fMRDI) to effectively represent the intravascular dispersion and highly accelerated PK parameter estimation. We also propose a deep learning-based, two-stage framework to accelerate PK parameter estimation. We used a deep neural network (NN) to estimate PK parameters directly from enhancement curves. The estimation from NN was further refined using several steps of NLLS, which is significantly faster than performing NLLS from random initializations. A data synthesis module is proposed to generate synthetic training data for the NN. Two data-processing modules were introduced to improve the model's stability against noise and variations. Experiments on our in-house clinical prostate MRI dataset demonstrated that our method significantly reduces the processing time, produces a better distinction between normal and clinically significant prostate cancer (csPCa) lesions, and is more robust against noise than conventional DCE-MRI analysis methods.
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Magnetite nanoparticles (Fe3O4 NPs) have garnered significant attention over the past twenty years, primarily due to their superparamagnetic properties. These properties allow the NPs to respond to external magnetic fields, making them particularly useful in various technological applications. One of the most fascinating aspects of Fe3O4 NPs is their ability to self-assemble into complex structures. Research over this period has focused heavily on how these nanoparticles can be organized into a variety of superstructures, classified by their dimensionality-namely one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) configurations. Despite a wealth of studies, the literature lacks a systematic review that synthesizes these findings. This review aims to fill that gap by providing a thorough overview of the recent progress made in the fabrication and organization of Fe3O4 NP assemblies via a bottom-up self-assembly approach. This methodology enables the controlled construction of assemblies at the nanoscale, which can lead to distinctive functionalities compared to their individual counterparts. Furthermore, the review explores the diverse applications stemming from these nanoparticle assemblies, particularly emphasizing their contributions to important areas such as imaging, drug delivery, and the diagnosis and treatment of cancer.
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Nanopartículas de Magnetita , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Humanos , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , AnimaisRESUMO
A porphyrin-containing nanoscale covalent organic polymer (COP) was fabricated from 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) and cystamine via an acylation reaction. On the one hand, TCPP can induce tumor cell death by laser irradiation. Due to the presence of disulfide bonds of cystamine which can react with glutathione, it exhibits depletion of glutathione and accumulation of peroxides in tumor cells. Ultimately by the hyaluronic acid to encapsulate the COP to get S-COP@HA, the nanoparticle with a size of 168.6 nm also exhibits good tumor accumulation and biosafety. Significant inhibition of tumor cell growth was observed after two consecutive doses of S-COP@HA at relatively low laser densities. This combination therapy was proved to reduce the level of reduced glutathione in tumor cells, where ferroptosis occurs after photodynamic treatment. Overall, this study presents a potent, good therapeutic option for the effective enhancement of photodynamic therapy by glutathione depletion.
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Ferroptose , Glutationa , Fotoquimioterapia , Porfirinas , Glutationa/metabolismo , Fotoquimioterapia/métodos , Porfirinas/química , Porfirinas/farmacologia , Ferroptose/efeitos dos fármacos , Humanos , Animais , Nanopartículas/química , Polímeros/química , Linhagem Celular Tumoral , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Ácido Hialurônico/químicaRESUMO
Spin-crossover (SCO) ferroelectrics with dual-function switches have attracted great attention for significant magnetoelectric application prospects. However, the multiferroic crystals with SCO features have rarely been reported. Herein, a molecular multiferroic Fe(II) crystalline complex [FeII(C8-F-pbh)2] (1-F, C8-F-pbh = (1Z,N'E)-3-F-4-(octyloxy)-N'-(pyridin-2-ylmethylene)-benzo-hydrazonate) showing the coexistence of ferroelectricity, ferroelasticity, and SCO behavior is presented for the first time. By H/F substitution, the low phase transition temperature (270 K) of the non-fluorinated parent compound is significantly increased to 318 K in 1-F, which exhibits a spatial symmetry breaking 222F2 type ferroelectric phase transition with clear room-temperature ferroelectricity. Besides, 1-F also displays a spin transition between high- and low-spin states, accompanied by the d-orbital breaking within the t2g 4eg 2 and t2g 6eg° configuration change of octahedrally coordinated FeII center. Moreover, the 222F2 type ferroelectric phase transition is also a ferroelastic one, verified by the ferroelectric domains reversal and the evolution of ferroelastic domains. To the knowledge, 1-F is the first multiferroic SCO molecular crystal. This unprecedented finding sheds light on the exploration of molecular multistability materials for future smart devices.
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An unprecedented heatwave hit the Yangtze River Basin (YRB) in August 2022. We analyzed changes of anthropogenic CO2 emissions in 8 megacities over lower-middle reaches of the YRB, using a near-real-time gridded daily CO2 emissions dataset. We suggest that the predominant sources of CO2 emissions in these 8 megacities are from the power and industrial sectors. In comparison to the average emissions for August in 2020 and 2021, the heatwave event led to a total increase in power sector emissions of approximately 2.70 Mt CO2, potentially due to the increase in urban cooling demand. Suzhou experienced the largest increase, with a rise of 1.12 Mt CO2 (12.88 %). Importantly, we observed that changes in daily power emissions exhibited strong linear relationships with temperatures during the heatwave, albeit varying sensitivities across different megacities (with an average of 0.0076 ± 0.0075 Mt d-1 °C-1). Conversely, we find that industrial emissions decreased by a total of 8.45 Mt CO2, with Shanghai seeing the largest decrease of 4.71 Mt CO2, while Hangzhou experienced the largest relative decrease (-21.22 %). It is noteworthy that the majority of megacities rebounded in industrial emissions following the conclusion of the heatwave. We convincingly suggest a tight linkage between the reductions in industrial emissions and China's policy to ensure household power supply. Overall, the reduction in industrial emissions offset the increase in power sector emissions, resulting in weaker emissions for majority of megacities during the heatwave. Despite remaining uncertainties in the emissions data, our study may offer valuable insights into the complexities of anthropogenic CO2 emissions in megacities amidst frequent summer heatwaves intensified by greenhouse warming.
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Peroxisome proliferator-activated receptor-γ (PPARγ) plays a protective role against brain injury after stroke in mice. However, the relationship between PPARγ gene polymorphisms and the functional outcome of acute ischemic stroke (AIS) remains unknown. 8822 patients from The Third China National Stroke Registry (CNSR-III) after whole-genome sequencing, two functional single nucleotide polymorphisms(SNPs) in PPARγ, rs1801282 C > G and rs3856806 C > T, were further analysed. The primary outcome was neurological functional disability at three months. Of the 8822 patients, 968 (11.0%) and 3497 (39.6%) were carriers of rs1801282 and rs3856806, respectively. Carriers of rs3856806 showed reduced risks for three-month neurological functional disability (OR, 0.84; 95% CI, 0.73-0.98; p = 0.02) and reduced risks for higher infarct volume (OR 0.90, 95% CI, 0.81-0.99, p = 0.04). They also had a reduced risk of neurological functional disability only in case of lower baseline IL-6 levels (OR 0.64, 95% CI 0.48-0.84, Pinteraction = 0.01). Carriers of rs1801282 had a reduced risk for three-month neurological functional disability (OR 0.77, 95% CI, 0.61-0.99, p = 0.04). Our study suggested that PPARγ polymorphisms are associated with a reduced risk for neurological functional disability and higher infarct volume in AIS. Therefore, PPARγ can be a potential therapeutic target in AIS.
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The response of mesophyll conductance (gm) to CO2 plays a key role in photosynthesis and ecosystem carbon cycles under climate change. Despite numerous studies, there is still debate about how gm responds to short-term CO2 variations. Here we used multiple methods and looked at the relationship between stomatal conductance to CO2 (gsc) and gm to address this aspect. We measured chlorophyll fluorescence parameters and online carbon isotope discrimination (Δ) at different CO2 mole fractions in sunflower (Helianthus annuus L.), cowpea (Vigna unguiculata L.), and wheat (Triticum aestivum L.) leaves. The variable J and Δ based methods showed that gm decreased with an increase in CO2 mole fraction, and so did stomatal conductance. There were linear relationships between gm and gsc across CO2 mole fractions. gm obtained from A-Ci curve fitting method was higher than that from the variable J method and was not representative of gm under the growth CO2 concentration. gm could be estimated by empirical models analogous to the Ball-Berry model and the USO model for stomatal conductance. Our results suggest that gm and gsc respond in a coordinated manner to short-term variations in CO2, providing new insight into the role of gm in photosynthesis modelling.
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Dióxido de Carbono , Helianthus , Células do Mesofilo , Estômatos de Plantas , Triticum , Dióxido de Carbono/metabolismo , Estômatos de Plantas/fisiologia , Células do Mesofilo/fisiologia , Células do Mesofilo/metabolismo , Triticum/fisiologia , Triticum/metabolismo , Helianthus/fisiologia , Helianthus/metabolismo , Isótopos de Carbono , Fotossíntese/fisiologia , Fabaceae/fisiologia , Clorofila/metabolismo , Folhas de Planta/fisiologia , Folhas de Planta/metabolismoRESUMO
Learning requires the ability to link actions to outcomes. How motivation facilitates learning is not well understood. We designed a behavioral task in which mice self-initiate trials to learn cue-reward contingencies and found that the anterior cingulate region of the prefrontal cortex (ACC) contains motivation-related signals to maximize rewards. In particular, we found that ACC neural activity was consistently tied to trial initiations where mice seek to leave unrewarded cues to reach reward-associated cues. Notably, this neural signal persisted over consecutive unrewarded cues until reward-associated cues were reached, and was required for learning. To determine how ACC inherits this motivational signal we performed projection-specific photometry recordings from several inputs to ACC during learning. In doing so, we identified a ramp in bulk neural activity in orbitofrontal cortex (OFC)-to-ACC projections as mice received unrewarded cues, which continued ramping across consecutive unrewarded cues, and finally peaked upon reaching a reward-associated cue, thus maintaining an extended motivational state. Cellular resolution imaging of OFC confirmed these neural correlates of motivation, and further delineated separate ensembles of neurons that sequentially tiled the ramp. Together, these results identify a mechanism by which OFC maps out task structure to convey an extended motivational state to ACC to facilitate goal-directed learning.
Achieving goals takes motivation. An individual may have to complete a task many times for a future reward. For example, an animal may have to forage repeatedly to find food, or a person may have to study to get a good grade on a test. How these complex behaviors are encoded in the brain's wiring is not fully understood. Patients with injuries to the frontal cortex of the brain display a lack of motivation to pursue goals. This discovery suggests the frontal cortex plays a vital role in motivation and goal-directed behavior. Animal studies show that part of their brain's frontal cortex, the anterior cingulate cortex (ACC), helps them stay motivated and put extra effort into achieving goals. Yet, scientists wonder how particular actions are associated with specific goals and suspect the orbital frontal cortex (OFC) contains the blueprint to support this association. Regalado et al. show that the OFC and ACC work together during goal-seeking behavior in mice. In the experiments, mice learned to complete a task to achieve a sugar water reward. As the mice were learning, Regalado et al. recorded activity in the ACC and found that the ACC is active during goal-seeking behavior. They also discovered that the activity of neurons in the OFC increased the longer mice went without receiving a reward, up until the reward was achieved, signaling a motivational state. Animals not motivated enough to maximize their rewards did not have an increased OFC activity. The experiments also showed that the motivational signals in the OFC were conveyed to ACC to support goal-directed learning, especially linking actions to positive future outcomes. The experiments help explain how an increase in neuronal activity in the OFC helps to increase motivation and goal-seeking behavior supported by the ACC. More studies will help scientists learn more about these processes and develop drugs or other therapies that can help people who have learning difficulties or struggle with motivation because of an injury or mental illness.
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Aprendizagem , Motivação , Córtex Pré-Frontal , Recompensa , Animais , Motivação/fisiologia , Camundongos , Aprendizagem/fisiologia , Córtex Pré-Frontal/fisiologia , Sinais (Psicologia) , Neurônios/fisiologia , Masculino , Giro do Cíngulo/fisiologia , Camundongos Endogâmicos C57BL , Comportamento Animal/fisiologiaRESUMO
We constructed a rapid infection risk assessment model for contacts of COVID-19. The improved Wells-Riley model was used to estimate the probability of infection for contacts of COVID-19 in the same place and evaluate their risk grades. We used COVID-19 outbreaks that were documented to validate the accuracy of the model. We analyzed the relationship between controllable factors and infection probability and constructed common scenarios to analyze the infection risk of contacts in different scenarios. The model showed the robustness of the fitting (mean relative error = 5.89%, mean absolute error = 2.03%, root mean squared error = 2.03%, R2 = 0.991). We found that improving ventilation from poorly ventilated to naturally ventilated and wearing masks can reduce the probability of infection by about two times. Contacts in places of light activity, loud talking or singing, and heavy exercise, oral breathing (e.g., gyms, KTV, choirs) were at higher risk of infection. The model constructed in this study can quickly and accurately assess the infection risk grades of COVID-19 contacts. Simply opening doors and windows for ventilation can significantly reduce the risk of infection in certain places. The places of light activity, loud talking or singing, and heavy exercise, oral breathing, should pay more attention to prevent and control transmission of the epidemic.
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Tripartite motif (TRIM) proteins, comprising a family of over 100 members with conserved motifs, exhibit diverse biological functions. Several TRIM proteins influence viral infections through direct antiviral mechanisms or by regulating host antiviral innate immune responses. To identify TRIM proteins modulating hepatitis B virus (HBV) replication, we assessed 45 human TRIMs in HBV-transfected HepG2 cells. Our study revealed that ectopic expression of 12 TRIM proteins significantly reduced HBV RNA and subsequent capsid-associated DNA levels. Notably, TRIM65 uniquely downregulated viral pregenomic (pg) RNA in an HBV-promoter-specific manner, suggesting a targeted antiviral effect. Mechanistically, TRIM65 inhibited HBV replication primarily at the transcriptional level via its E3 ubiquitin ligase activity and intact B-box domain. Though HNF4α emerged as a potential TRIM65 substrate, disrupting its binding site on the HBV genome did not completely abolish TRIM65's antiviral effect. In addition, neither HBx expression nor cellular MAVS signaling was essential to TRIM65-mediated regulation of HBV transcription. Furthermore, CRISPR-mediated knock-out of TRIM65 in the HepG2-NTCP cells boosted HBV infection, validating its endogenous role. These findings underscore TRIM proteins' capacity to inhibit HBV transcription and highlight TRIM65's pivotal role in this process.
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Vírus da Hepatite B , Transcrição Gênica , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Replicação Viral , Humanos , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Células Hep G2 , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Hepatite B/virologia , Hepatite B/genética , Hepatite B/imunologia , Regiões Promotoras Genéticas , RNA Viral/genética , RNA Viral/metabolismoRESUMO
Global investigation of medulloblastoma has been hindered by the widespread inaccessibility of molecular subgroup testing and paucity of data. To bridge this gap, we established an international molecularly characterized database encompassing 934 medulloblastoma patients from thirteen centers across China and the United States. We demonstrate how image-based machine learning strategies have the potential to create an alternative pathway for non-invasive, presurgical, and low-cost molecular subgroup prediction in the clinical management of medulloblastoma. Our robust validation strategies-including cross-validation, external validation, and consecutive validation-demonstrate the model's efficacy as a generalizable molecular diagnosis classifier. The detailed analysis of MRI characteristics replenishes the understanding of medulloblastoma through a nuanced radiographic lens. Additionally, comparisons between East Asia and North America subsets highlight critical management implications. We made this comprehensive dataset, which includes MRI signatures, clinicopathological features, treatment variables, and survival data, publicly available to advance global medulloblastoma research.
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Neoplasias Cerebelares , Imageamento por Ressonância Magnética , Meduloblastoma , Meduloblastoma/genética , Meduloblastoma/diagnóstico por imagem , Meduloblastoma/patologia , Humanos , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/patologia , Imageamento por Ressonância Magnética/métodos , Criança , Feminino , Masculino , Adolescente , Inteligência Artificial , Pré-Escolar , China , Adulto Jovem , Estados Unidos , Adulto , Prognóstico , Lactente , Aprendizado de MáquinaRESUMO
Polygonatum hunanense H.H. Liu & B.Z. Wang (2021) and P. verticillatum (L.) All. (1875) have been widely used as foods and as folk medicines in China and India, and P. caulialatum S. R. Yi (2021) has recently been described as a new medical plant in China. There is at present a lack of genome information regarding the species. Hence, this study reports the complete chloroplast genomes of the three species. The genomes of P. hunanense, P. verticillatum, and P. caulialatum were 155,583 bp, 155,650 bp, and 155,352 bp in length, respectively. They contained large single-copy (LSC) regions of 84,412 bp, 84,404 bp, and 84,285 bp, small single-copy (SSC) regions of 18,427 bp, 18,416 bp, and 18,463 bp, and a pair of inverted repeats of 26,372 bp, 26,415 bp, and 26,302 bp, respectively. The chloroplast genomes of P. hunanense, P. verticillatum, and P. caulialatum had 133 (103 unique) genes, consisting of 87 protein-coding genes, 38 ribosomal ribonucleic acid (RNA) genes, and eight transfer RNA genes, respectively. A maximum-likelihood phylogenetic tree showed that P. kingianum Coll. et Hemsl. var. grandifolium D.M. Liu & W.Z. Zeng (1991) was closer to P. cyrtonema Hua (1892) rather than to P. kingianum Coll. et Hemsl. (1890), further supporting its status as a unique species of the genus. Moreover, P. verticillatum was separated from the easily confused herb P. cirrhifolium (Wall.) Royle (1839), while P. caulialatum was closest to P. humile Fisch. ex Maxim. (1859). This research provides a foundation for further study of these herbs.
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Efferocytosis is defined as the highly effective phagocytic removal of apoptotic cells (ACs) by professional or non-professional phagocytes. Tissue-resident professional phagocytes ("efferocytes"), such as macrophages, have high phagocytic capacity and are crucial to resolve inflammation and aid in homeostasis. Recently, numerous exciting discoveries have revealed divergent (and even diametrically opposite) findings regarding metabolic immune reprogramming associated with efferocytosis by macrophages. In this review, we highlight the key metabolites involved in the three phases of efferocytosis and immune reprogramming of macrophages under physiological and pathological conditions. The next decade is expected to yield further breakthroughs in the regulatory pathways and molecular mechanisms connecting immunological outcomes to metabolic cues as well as avenues for "personalized" therapeutic intervention.
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Macrófagos , Fagocitose , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Apoptose/imunologia , Transdução de Sinais , Inflamação/imunologia , EferocitoseRESUMO
Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.
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Inteligência Artificial , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Programas de Rastreamento/métodos , Idoso , AdultoRESUMO
The efficient, safe and eco-friendly disposal of the chromium-containing sludge (CCS) has attracted an increasing concern. In this study, Co-processing of CCS was developed via employing sintering and ironmaking combined technology for its harmless disposal and resource utilization. Crystalline phase and valence state transformation of chromium (Cr), technical feasibility assessment, leaching risk, characteristics of sintered products, and pollutant release during CCS co-processing were investigated through a series of laboratory-scale sintering pot experiments and large scale industrial trials. The results showed that the content of Cr(VI) in sintered products first increased then decreased with increasing temperature ranges of 300 °C-800 °C, and reached a maximum of 2189.64 mg/kg at 500 °C. 99.99% of Cr(VI) can be reduced to Cr(III) at above 1000 °C, which was attributed to the transformation of the Cr(VI)-containing crystalline phases (such as, MgCrO4 and CaCrO4) to the (Mg, Fe2+)(Cr, Al, Fe3+)2O4. The industrial trial results showed that adding 0.5 wt CCS to sintering feed did not have adverse effects on the properties of the sintered ore and the plant's operating stability. The tumbler index of sinter was above 78% and the leaching concentrations of TCr (0.069 mg/L) was significantly lower than the Chinese National Standard of 1.0 mg/L (GB5085.3-2007). The TCr contents of sintering dust and blast furnace gas (BFG) scrubbing water were less than 0.19 wt and 0.11 mg/L, respectively, which was far below the regulatory limit (1.5 mg/L, GB13456-2012). The mass balance evaluation results indicated that at least 89.9% of the Cr in the CCS migrated into the molten iron in the blast furnace (BF), which became a useful supplement to the molten iron. This study provided a new perspective strategy for the safe disposal and resource utilization of CCS in iron and steel industry.
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Cromo , Esgotos , Cromo/química , Esgotos/química , Ferro/químicaRESUMO
Introduction: Rapid identification of infected individuals through viral RNA or antigen detection followed by effective personal isolation is usually the most effective way to prevent the spread of a newly emerging virus. Large-scale detection involves mass specimen collection and transportation. For biosafety reasons, denaturing viral transport medium has been extensively used during the SARS-CoV-2 pandemic. However, the high concentrations of guanidinium isothiocyanate (GITC) in such media have raised issues around sufficient GITC supply and laboratory safety. Moreover, there is a lack of denaturing transport media compatible with SARS-CoV-2 RNA and antigen detection. Methods: Here, we tested whether supplementing media containing low concentrations of GITC with ammonium sulfate (AS) would affect the throat-swab detection of SARS-CoV-2 or a viral inactivation assay targeting coronavirus and other enveloped and non-enveloped viruses. The effect of adding AS to the media on RNA stability and its compatibility with SARS-CoV-2 antigen detection were also tested. Results and discussion: We found that adding AS to the denaturing transport media reduced the need for high levels of GITC, improved SARS-COV-2 RNA detection without compromising virus inactivation, and enabled the denaturing transport media compatible with SARS-CoV-2 antigen detection.
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OBJECTIVES: To compare the quantitative background parenchymal enhancement (BPE) in women with different lifetime risks and BRCA mutation status of breast cancer using screening MRI. MATERIALS AND METHODS: This study included screening MRI of 535 women divided into three groups based on lifetime risk: nonhigh-risk women, high-risk women without BRCA mutation, and BRCA1/2 mutation carriers. Six quantitative BPE measurements, including percent enhancement (PE) and signal enhancement ratio (SER), were calculated on DCE-MRI after segmentation of the whole breast and fibroglandular tissue (FGT). The associations between lifetime risk factors and BPE were analyzed via linear regression analysis. We adjusted for risk factors influencing BPE using propensity score matching (PSM) and compared the BPE between different groups. A two-sided Mann-Whitney U-test was used to compare the BPE with a threshold of 0.1 for multiple testing issue-adjusted p values. RESULTS: Age, BMI, menopausal status, and FGT level were significantly correlated with quantitative BPE based on the univariate and multivariable linear regression analyses. After adjusting for age, BMI, menopausal status, hormonal treatment history, and FGT level using PSM, significant differences were observed between high-risk non-BRCA and BRCA groups in PEFGT (11.5 vs. 8.0%, adjusted p = 0.018) and SERFGT (7.2 vs. 9.3%, adjusted p = 0.066). CONCLUSION: Quantitative BPE varies in women with different lifetime breast cancer risks and BRCA mutation status. These differences may be due to the influence of multiple lifetime risk factors. Quantitative BPE differences remained between groups with and without BRCA mutations after adjusting for known risk factors associated with BPE. CLINICAL RELEVANCE STATEMENT: BRCA germline mutations may be associated with quantitative background parenchymal enhancement, excluding the effects of known confounding factors. This finding can provide potential insights into the cancer pathophysiological mechanisms behind lifetime risk models. KEY POINTS: Expanding understanding of breast cancer pathophysiology allows for improved risk stratification and optimized screening protocols. Quantitative BPE is significantly associated with lifetime risk factors and differs between BRCA mutation carriers and noncarriers. This research offers a possible understanding of the physiological mechanisms underlying quantitative BPE and BRCA germline mutations.