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Magnesium matrix composites are essential lightweight metal matrix composites, following aluminum matrix composites, with outstanding application prospects in automotive, aerospace lightweight and biomedical materials because of their high specific strength, low density and specific stiffness, good casting performance and rich resources. However, the inherent low plasticity and poor fatigue resistance of magnesium hamper its further application to a certain extent. Many researchers have tried many strengthening methods to improve the properties of magnesium alloys, while the relationship between wear resistance and plasticity still needs to be further improved. The nanoparticles added exhibit a good strengthening effect, especially the ceramic nanoparticles. Nanoparticle-reinforced magnesium matrix composites not only exhibit a high impact toughness, but also maintain the high strength and wear resistance of ceramic materials, effectively balancing the restriction between the strength and toughness. Therefore, this work aims to provide a review of the state of the art of research on the matrix, reinforcement, design, properties and potential applications of nano-reinforced phase-reinforced magnesium matrix composites (especially ceramic nanoparticle-reinforced ones). The conventional and potential matrices for the fabrication of magnesium matrix composites are introduced. The classification and influence of ceramic reinforcements are assessed, and the factors influencing interface bonding strength between reinforcements and matrix, regulation and design, performance and application are analyzed. Finally, the scope of future research in this field is discussed.
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SCOPE: Vitexin, a C-glycosylated flavonoid, is abundant in food sources and has potential health-beneficial properties. However, the targets for its beneficial effects remain largely unknown. This study aims to establish an in vitro cell model of vascular low-grade inflammation and explore the antiinflammatory mechanism of vitexin. METHODS AND RESULTS: Low-dose TNFα and IL-17 are combined to establish a cell model of vascular low-grade inflammation. Cell-based studies show that low-dose TNFα (1 ng mL-1) alone has a slight effect, but its combination with IL-17 can potently induce protein expression of inflammatory cytokines, leading to an inflammatory state. However, the vascular inflammation caused by low-dose TNF plus IL-17 does not lead to oxidative stress, and reactive oxygen species (ROS) does not involved in developing this inflammation. Vitexin can be absorbed by human umbilical vein endothelial (HUVEC) cells to increase the Nrf2 protein level and attenuate inflammation. In addition, the antiinflammatory effect of vitexin is blocked by the knockdown of Nrf2. Further localized surface plasmon resonance, drug affinity responsive target stability, and molecular docking demonstrate that vitexin can directly interact with Keap1 to disrupt Keap1-Nrf2 interaction and thus activate Nrf2. Treatment of mice with a bolus oral gavage of vitexin (100 mg kg-1 body weight) or a high-fat diet supplemented with vitexin (5 mg kg-1 body weight per day) for 12 weeks confirms the rapid increase in blood vitexin levels and subsequent incorporation into blood vessels to activate Nrf2 and ameliorate inflammation in vivo. CONCLUSION: The findings provide a reliable cell model of vascular low-grade inflammation and indicate Nrf2 protein as the potential target of vitexin to inhibit vascular inflammation.
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Apigenina , Fator 2 Relacionado a NF-E2 , Fator de Necrose Tumoral alfa , Humanos , Animais , Camundongos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-17/metabolismo , Simulação de Acoplamento Molecular , Estresse Oxidativo , Transdução de Sinais , Inflamação/tratamento farmacológico , Peso CorporalRESUMO
Enterotoxigenic Escherichia coli (ETEC) is one of the major bacterial infections, causing substantial economic losses globally in the swine industry. This study aimed to investigate the impact of low Saccharomyces cerevisiae fermentation postbiotics (SCFP), high SCFP, essential oil (EO), or their combination on the growth performance and health of weanling pigs during ETEC infection. Forty-eight male weanling pigs were randomly allocated to five groups: 1) control group (CON-basal diet, nâ =â 16); 2) low SCFP group (LSC-basal dietâ +â 1.25 g/kg SCFP, nâ =â 8); 3) high SCFP group (HSC-basal dietâ +â 2 g/kg SCFP, nâ =â 8); 4) essential oil group (EO-basal dietâ +â 0.4 g/kg EO, nâ =â 8); 5) the SCFP and EO combination group (SE-basal dietâ +â 1.25 g/kg SCFPâ +â 0.4 g/kg EO, nâ =â 8). On day 15 of the trial, pigs in CON were divided into positive control (PC) and negative control (NC), and all pigs, except in NC, were challenged with ETEC. Under the normal condition, dietary LSC, HSC, EO, and EO all increased average daily gain (ADG) (Pâ <â 0.05), and decreased F:G ratio (Pâ <â 0.05) accompanied by decreased malondialdehyde (MDA) and increases in catalase (CAT), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) indicating enhanced anti-oxidative capacity, as well as decreased IL-2, IL-8, INF-γ, indicating mitigated systemic inflammation. During ETEC infection, all treatments alleviated ETEC-induced ADG reduction, diarrhea, damages in intestinal permeability and morphology, and down-regulation of tight junctions (Claudin1, ZO-1, and Occludin), while HSC and EO exhibited additional protections. All treatments increased CAT, T-SOD, and T-AOC, and decreased MDA in serum and jejunal mucosa at similar degrees (Pâ <â 0.05). Moreover, all treatments alleviated ETEC-induced inflammation as shown by decreased IL-6, TNF-α, INF-γ, and increased IL-4 and IL-10 in serum or jejunal mucosa (Pâ <â 0.05), and enhanced the immunity by increased serum IgG and mucosal sIgA (Pâ <â 0.05). HSC and SE further reduced mucosal INF-γ and TNF-α than LSC or EO aligning with their additional protection against diarrhea during ETEC infection. Additionally, the key gut bacteria (e.g., Terrisporobacter) related to the benefits of SCFP and EO were identified. In sum, all treatments enhanced growth performance and protected against ETEC-induced intestinal damage through the regulation of redox and immune homeostasis. HSP and SE offered extra protection during disease for their additional control of inflammation. Our study provided new insight into the use of feed additives in the context of animal health states.
Weanling pigs are vulnerable to a variety of stressors and pathogen infections. Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhea and growth retardation in weanling pigs. The postbiotics, Saccharomyces cerevisiae fermentation postbiotics (SCFP), and essential oil (EO, mainly thymol, and cinnamaldehyde) were reported to exert health benefits in different sites of the intestine. However, whether SCFP and EO have dose and synergistic effects on weanling pigs, especially against ETEC infection, is incompletely understood. Our research has revealed that SCFP, EO, and their combination all enhanced the growth performance and intestinal barrier function, and reduced diarrhea of piglets, albeit to varying degrees, under both health conditions and ETEC infection. We further elucidated the disparity in the regulation of redox and immune homeostasis by SCFP, EO, and their combination contributing to their different action in distinct states. This has led to a reevaluation of the function of additives in the context of gut health and disease susceptibility.
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Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Óleos Voláteis , Doenças dos Suínos , Suínos , Masculino , Animais , Saccharomyces cerevisiae , Fator de Necrose Tumoral alfa , Óleos Voláteis/farmacologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Diarreia/microbiologia , Diarreia/veterinária , Dieta/veterinária , Inflamação/veterinária , Superóxido Dismutase , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/microbiologia , Ração Animal/análise , DesmameRESUMO
BACKGROUND: The reversible maneuver that mimics the fluid challenge is a widely used test for evaluating volume responsiveness. However, passive leg raising (PLR) does have certain limitations. The aim of the study is to determine whether the supine transfer test could predict fluid responsiveness in adult patients with acute circulatory failure who do not have intra-abdominal hypertension, by measuring changes in cardiac index (CI). METHODS: Single-center, prospective clinical study in a 25-bed surgery intensive care unit at the Fudan University Shanghai Cancer Center. Thirty-four patients who presented with acute circulatory failure and were scheduled for fluid therapy. Every patient underwent supine transfer test and fluid challenge with 500 mL saline for 15-30 min. There were four sequential steps in the protocol: (1) baseline-1: a semi-recumbent position with the head of the bed raised to 45°; (2) supine transfer test: patients were transferred from the 45° semi-recumbent position to the strict supine position; (3) baseline-2: return to baseline-1 position; and (4) fluid challenge: administration of 500 mL saline for 15-30 min. Hemodynamic parameters were recorded at each step with arterial pulse contour analysis (ProAQT/Pulsioflex). A fluid responder was defined as an increase in CI ≥ 15% after fluid challenge. The receiver operating characteristic curve and gray zone were defined for CI. RESULTS: Seventeen patients were fluid challenge. The r value of the linear correlations was 0.73 between the supine transfer test- and fluid challenge-induced relative CI changes. The relative changes in CI induced by supine transfer in predicting fluid responsiveness had an area under the receiver operating characteristic curve of 0.88 (95% confidence interval 0.72-0.97) and predicted a fluid responder with 76.5% (95% confidence interval 50.1-93.2) sensitivity and 88.2% (95% confidence interval 63.6-98.5) specificity, at a best threshold of 5.5%. Nineteen (55%) patients were in the gray zone (CI ranging from -3 and 8 L/min/m2). CONCLUSION: The supine transfer test can potentially assist in detecting fluid responsiveness in patients with acute circulatory failure without intra-abdominal hypertension. Nevertheless, the small threshold and the 55% gray zone were noteworthy limitation. TRIAL REGISTRATION: Predicting fluid responsiveness with supine transition test (ChiCTR2200058264). Registered 2022-04-04 and last refreshed on 2023-03-26, https://www.chictr.org.cn/showproj.html?proj=166175 .
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Hipertensão Intra-Abdominal , Adulto , Humanos , Hipertensão Intra-Abdominal/diagnóstico , Hipertensão Intra-Abdominal/terapia , Estudos Prospectivos , China , Hidratação , Unidades de Terapia Intensiva , Solução SalinaRESUMO
The first total syntheses of polycyclic diterpenes phomopsene (1), methyl phomopsenonate (2), and iso-phomopsene (3) have been accomplished through the unusual cascade reorganization of C-C single bonds. This approach features: (i) a synergistic Nazarov cyclization/double ring expansions in one-step, developed by authors, to rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold bearing contiguous quaternary centers and (ii) a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the requisite 5/5/6/5 tetracyclic skeleton of the target molecules 1-3. This work enables us to determine that the correct structure of iso-phomopsene is, in fact, the C7 epimer of the originally assigned structure. Finally, the absolute configurations of three target molecules were confirmed through enantioselective synthesis.
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To clarify the effect of catheter indwelling depth on the occurrence of thrombophlebitis, a total of 339 hospitalized patients were randomly enrolled and divided by the catheter indwelling depth into 2 groups. Then the effect of indwelling depth on thrombophlebitis was analyzed, and the independent influence factors on the occurrence of thrombophlebitis were clarified. There were 49 cases of thrombophlebitis, including 8 tumor-bearing patients and 41 patients with lung infection. Thirteen of the 135 patients with indwelling depth of 1 cm, and 36 of the 204 patients with indwelling depth of 1.9 cm suffered thrombophlebitis. The relationship between incidence rate of thrombophlebitis and clinicopathological parameters was analyzed. It was found the incidence of thrombophlebitis was significantly correlated with males (X2 = 5.77), lung infection (X2 = 7.79), and indwelling depth of 1.9 cm (X2 = 4.223). Multifactor analysis of variance showed the significant independent risk factors of thrombophlebitis were male [hazard ratio (HR) 3.12 (1.39-6.98)], and lung infection (HR 0.22 [0.06-0.69]), and the indwelling depth of 1.9 cm affected the occurrence of thrombophlebitis (HR 0.79 [0.42 -3.09]) but was not an independent risk factor. In our treatment center, while appropriate fixation was ensured, the catheter indwelling depth shall be as short as possible, so as to reduce the occurrence of thrombophlebitis. For patients with lung infection, nursing at the intubation site shall be strengthened, so as to decrease thrombophlebitis.
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Cateterismo Periférico , Tromboflebite , Humanos , Masculino , Feminino , Cateterismo Periférico/efeitos adversos , Cateteres de Demora/efeitos adversos , Tromboflebite/epidemiologia , Tromboflebite/etiologia , Fatores de Risco , Bexiga UrináriaRESUMO
The most massive and shortest-lived stars dominate the chemical evolution of the pre-galactic era. On the basis of numerical simulations, it has long been speculated that the mass of such first-generation stars was up to several hundred solar masses1-4. The very massive first-generation stars with a mass range from 140 to 260 solar masses are predicted to enrich the early interstellar medium through pair-instability supernovae (PISNe)5. Decades of observational efforts, however, have not been able to uniquely identify the imprints of such very massive stars on the most metal-poor stars in the Milky Way6,7. Here we report the chemical composition of a very metal-poor (VMP) star with extremely low sodium and cobalt abundances. The sodium with respect to iron in this star is more than two orders of magnitude lower than that of the Sun. This star exhibits very large abundance variance between the odd- and even-charge-number elements, such as sodium/magnesium and cobalt/nickel. Such peculiar odd-even effect, along with deficiencies of sodium and α elements, are consistent with the prediction of primordial pair-instability supernova (PISN) from stars more massive than 140 solar masses. This provides a clear chemical signature indicating the existence of very massive stars in the early universe.
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YIN YANG 1 (YY1) encodes a dual-function transcription factor, evolutionary conserved between the animal and plant kingdom. In Arabidopsis thaliana, AtYY1 is a negative regulator of ABA responses and floral transition. Here, we report the cloning and functional characterization of the two AtYY1 paralogs, YIN and YANG (also named PtYY1a and PtYY1b) from Populus (Populus trichocarpa). Although the duplication of YY1 occurred early during the evolution of the Salicaceae, YIN and YANG are highly conserved in the willow tree family. In the majority of Populus tissues, YIN was more strongly expressed than YANG. Subcellular analysis showed that YIN-GFP and YANG-GFP are mainly localized in the nuclei of Arabidopsis. Stable and constitutive expression of YIN and YANG resulted in curled leaves and accelerated floral transition of Arabidopsis plants, which was accompanied by high expression of the floral identity genes AGAMOUS (AG) and SEPELLATA3 (SEP3) known to promote leaf curling and early flowering. Furthermore, the expression of YIN and YANG had similar effects as AtYY1 overexpression to seed germination and root growth in Arabidopsis. Our results suggest that YIN and YANG are functional orthologues of the dual-function transcription factor AtYY1 with similar roles in plant development conserved between Arabidopsis and Populus.
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Proteínas de Arabidopsis , Arabidopsis , Populus , Arabidopsis/metabolismo , Populus/genética , Populus/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Arabidopsis/genética , Folhas de Planta/metabolismo , Regulação da Expressão Gênica de Plantas , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
As immune checkpoint inhibitors (ICIs) are widely used, a series of immune-related adverse events (irAEs) have been reported, including immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis). The incidence of ICI-pneumonitis is higher in reality than in clinical trials. The diagnosis is challenging, mainly based on clinical and imaging features, and requires the exclusion of other causes. The data on the biological mechanisms of ICI-pneumonitis are scarce, resulting in little knowledge of the best treatment for ICI-pneumonitis. Bronchoalveolar lavage (BAL) may be helpful to identify the biological differences or find predictive biomarkers, and may in turn help to develop phenotype-specific targeted drugs to treat ICI-pneumonitis. Herein, we outline the characterization of immunomodulatory factors and cells in bronchoalveolar lavage fluid for ICI-pneumonitis. Through careful sorting and literature review, we find crosstalk between pathogenic Th17/Th1 cells (i.e., Th17.1) and pro-inflammatory monocytes, and activation of Th17(/Th1)/IL-17A (/IFN-γ) pathways may play a key role in the pathogenesis of ICI-pneumonitis. Disruption of the interaction between pathogenic Th17/Th1 cells and pro-inflammatory monocytes (such as, anti-IL-23) may be a potential treatment for ICI-pneumonitis. We first describe the possible pathophysiological mechanisms of ICI-pneumonitis, hoping to contribute to the optimization of diagnosis and treatment, as well as provide readers with research inspiration.
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Inibidores de Checkpoint Imunológico , Pneumonia , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Líquido da Lavagem Broncoalveolar , Pneumonia/induzido quimicamente , Pneumonia/diagnósticoRESUMO
The poor biostability and bioavailability of proanthocyanidins limit their application. In this study, it was hypothesized that encapsulation in lecithin-based nanoliposomes using ultrasonic technology improves the above properties. Based on preliminary experiments, the effects of lecithin mass ratio (1-9%, wt.), pH (3.2-6.8), ultrasonic power (0-540 W), and time (0-10 min) on biostability and bioavailability of purified kiwi leaves proanthocyanidins (PKLPs) were determined. Nanoliposomes prepared optimally with lecithin (5%, wt.), pH = 3.2, ultrasonic power (270 W), and time (5 min) demonstrated a significantly (p < 0.05) improved physicochemical stability, homogeneity, and high encapsulation efficiency (73.84%) relative to control. The PKLPs bioaccessibility during in vitro digestion increased by 2.28-3.07-fold, with a remarkable sustained release and delivery to the small intestine. Similar results were obtained by in vivo analyses, showing over 200% increase in PKLPs bioaccessibility compared to the control. Thus, PKLPs-loaded nanoliposomes are promising candidates for foods and supplements for novel applications.
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Lipossomos , Proantocianidinas , Lipossomos/química , Proantocianidinas/química , Lecitinas , Disponibilidade Biológica , Ultrassom , Folhas de PlantaRESUMO
BACKGROUND: Gorham-Stout disease (GSD) is a very rare disorder characterized by massive osteolysis of poorly understood aetiology. The association between GSD involving the skull base and cerebrospinal fluid (CSF) leakage has been reported in the literature. However, few cases of CSF leakage and Chiari-like tonsillar herniation in GSD involving the spine have been reported. CASE PRESENTATION: We present the case of a 20-year-old man with GSD involving the thoracic and lumbar spine, which caused CSF leakage and Chiari-like tonsillar herniation. The patient underwent four spinal surgeries for osteolytic lesions of the spine over a 10-year period. Here, we discuss the possible aetiology of the development of CSF leakage. Epidural blood patch (EBP) was performed at the T11-T12 level to repair the CSF leakage. After EBP treatment, rebound intracranial hypertension (RIH) developed, and tonsillar herniation disappeared 2 months later. CONCLUSIONS: GSD involving the spine with CSF leakage and Chiari-like tonsillar herniation is relatively rare. For patients who have undergone multiple spinal surgeries, minimally invasive treatment is an alternative treatment for CSF leakage. EBP can repair CSF leakage secondary to GSD and improve chronic brain sagging, with reversibility of Chiari-like malformations.
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Malformação de Arnold-Chiari , Osteólise Essencial , Masculino , Humanos , Adulto Jovem , Adulto , Osteólise Essencial/complicações , Osteólise Essencial/cirurgia , Osteólise Essencial/patologia , Encefalocele/complicações , Encefalocele/cirurgia , Encefalocele/patologia , Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Encéfalo/patologia , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/cirurgiaRESUMO
BACKGROUND: Poor wound healing is a significant complication of diabetes, which is commonly caused by neuropathy, trauma, deformities, plantar hypertension and peripheral arterial disease. Diabetic foot ulcers (DFU) are difficult to heal, which makes patients susceptible to infections and can ultimately conduce to limb amputation or even death in severe cases. An increasing number of studies have found that epigenetic alterations are strongly associated with poor wound healing in diabetes. AIM OF REVIEW: This work provides significant insights into the development of therapeutics for improving chronic diabetic wound healing, particularly by targeting and regulating DNA methylation and demethylation in DFU. Key scientific concepts of review: DNA methylation and demethylation play an important part in diabetic wound healing, via regulating corresponding signaling pathways in different breeds of cells, including macrophages, vascular endothelial cells and keratinocytes. In this review, we describe the four main phases of wound healing and their abnormality in diabetic patients. Furthermore, we provided an in-depth summary and discussion on how DNA methylation and demethylation regulate diabetic wound healing in different types of cells; and gave a brief summary on recent advances in applying cellular reprogramming techniques for improving diabetic wound healing.
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Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/genética , Pé Diabético/terapia , Metilação de DNA , Células Endoteliais/metabolismo , Cicatrização/genética , Desmetilação , Diabetes Mellitus/genéticaRESUMO
Background: Mental health disorders in systemic lupus erythematosus (SLE) are gradually getting recognized; however, less is known regarding the actual structure and compositional alterations in gut microbiome and metabolism and the mechanisms of how they affect depression development in SLE patients. Methods: Twenty-one SLE patients with depression (SLE-d), 17 SLE patients without depression (SLE-nd), and 32 healthy controls (HC) were included in this study. Fecal samples were collected for 16S rRNA gene sequencing and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) based metabolomics. Results: The structure of gut microbiome in the SLE-d group changed compared with that in the other two groups. The microbiome composition of SLE-d group showed decreased species richness indices, characterized by low ACE and Chao1 indices, a decrease in the ratio of phylum Firmicutes to Bacteroidetes, genus Faecalibacterium and Roseburia. A downregulation of the metabolite fexofenadine involved in bile secretion was positively correlated with the genus Faecalibacterium, Subdoligranulum and Agathobacter. Compared with the SLE-nd group, the SLE-d group had elevated serum levels of IL-2 and IL-6 and decreased BDNF. Interestingly, abundance of the genus Faecalibacterium and Roseburia was negatively correlated with IL-6, abundance of the genus Roseburia was negatively correlated with IL-2, and abundance of the genus Bacteroides was positively correlated with IL-2. Conclusion: This study identified specific fecal microbes and their metabolites that may participate in the development of SLE-d. Our findings provide a new perspective for improving depression in SLE patients by regulating the gut-brain axis.
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Interleucina-2 , Lúpus Eritematoso Sistêmico , Humanos , Interleucina-6 , RNA Ribossômico 16S/genética , Fezes , Clostridiales , Lúpus Eritematoso Sistêmico/complicaçõesRESUMO
Pluripotent stem-cells are slowly dividing cells giving rise to daughter cells that can either differentiate to new tissues and organs, or remain stem-cells. In plants, stem-cells are located in specific niches of the shoot and root apical meristems (SAMs and RAMs). After ablation of stem-cell niches, pluripotent meristematic cells can establish new stem-cells, whereas the removal of the whole meristem destructs the regeneration process. In tissue cultures, after detached plant organs are transferred to rooting or callus induction medium (G5 or CIM), vasculature-associated pluripotent cells (VPCs) immediately start proliferation to form adventitious roots or callus, respectively, while other cell types of the organ explants basically play no part in the process. Hence, in contrast to the widely-held assumption that all plant cells have the ability to reproduce a complete organism, only few cell types are pluripotent in practice, raising the question how pluripotent stem-cells differ from differentiated cells. It is now clear that, in addition to gene regulatory networks of pluripotency factors and phytohormone signaling, epigenetics play a crucial role in initiation, maintenance and determination of plant stem-cells. Although, more and more epigenetic regulators have been shown to control plant stem-cell fate, only a few studies demonstrate how they are recruited and how they change the chromatin structure and transcriptional regulation of pluripotency factors. Here, we highlight recent breakthroughs but also revisited classical studies of epigenetic regulation and chromatin dynamics of plant stem-cells and their pluripotent precursor-cells, and point out open questions and future directions.
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PURPOSE: To explore the value of parameters of the on hepatobiliary phase (HBP) of pre-treatment gadoxetic acid-enhanced magnetic resonance imaging (MRI) for predicting pathological response to systemic therapy in colorectal liver metastases (CRLMs), compared with response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1). METHODS: A total of 96 patients with CRLMs who underwent gadoxetic acid-enhanced MRI prior to treatment and then liver resection from January 2017 to December 2021 were enrolled. The pathological response was assessed by the percentage of residual tumors (RTs), and CRLMs were classified into two groups according to the pathological response grade (PRG): (1) strong response (including PRG2 and PRG3, RTs ≤ 10%), and weak response (PRG1, RTs > 10%). Two radiologists evaluated the enhancement pattern and degree of CRLMs on the HBP. The diameter, mean and standard deviation (SD) value of signal intensity (SI) of CRLMs on pre-contrast and HBP images were recorded. Relative tumor enhancement (RTE) and the SD ratio (SDR) were calculated. These parameters were analyzed in terms of pathological response on a lesion-by-lesion basis. RESULTS: Totally, 263 CRLMs were classified into: the strong response group (PRG2, n = 57; PRG3, n = 7) and the weak response group (PRG1, n = 199). RTE and SDR values were significantly higher in the strong response group than in the weak response group (P < 0.001). RTE values (P < 0.001) and SDR values (P = 0.031) were independent factors for predicting strong response. The area under curve (AUC) of RTE and SDR values were 0.725 and 0.652, respectively. The combination of these parameters was 0.750, which performed better than RECIST 1.1 (0.750 vs 0.531; P < 0.001). CONCLUSIONS: RTE and SDR values on HBP are potential features in predicting pathological response to systemic therapy in CRLMs.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Meios de Contraste , Sensibilidade e Especificidade , Estudos Retrospectivos , Gadolínio DTPA , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fígado/diagnóstico por imagem , Fígado/cirurgia , Fígado/patologiaRESUMO
Background: We evaluated the cost-effectiveness of the screening in mainland China for Alzheimer's disease (AD) patients aged over 60. Methods: Individuals in mainland China, received an initial screening by questionnaire on mental state, and those with scores deemed suspicious for AD were referred to diagnostic tests. A 9-state Markov model was developed to simulate the disease progression of a cohort of 100,000 subjects aging from 60 to 80. In addition, several scenarios were analyzed to assess the robustness under different screening frequency, starting age, the duration of drug effects, and the health status of subjects. Results: The ICER of AD screening was 26413.77 USD per QALY [quality-adjusted life-year (QALY)] compared with no screening. The number of deaths and severe AD cases who did not receive treatment averted by screening accounted for 0.076 and 0.006% of the total population, respectively, and the net monetary benefit was 128.29 USD per capita. Under the thresholds of one and three times the gross domestic product per capita, the probability of screening being cost-effective was approximately 18 and 77%, respectively. The ICER decreased to 18132.96USD per QALY when the drug effect was prolonged, and increased when the frequency of screening was increased, the starting age was postponed, and patients suffering from comorbidities were more. However, the number of severe AD cases and deaths declined when the screening frequency increased. Conclusion: Screening for AD in individuals over 60 can reduce the numbers of severe AD cases and deaths and may be cost-effective, depending on factors such as screening frequency, starting age of screening, and duration of drug effects. Additionally, mild cognitive impairment (MCI) is an important stage at which the burden of progression to AD may be reduced and the cost-effectiveness of screening may be improved.
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Introduction: Immune therapy has ushered in a new era of tumor treatment, at the expense of immune-related adverse events, including rare but fatal adverse cardiovascular events, such as myocarditis. Steroids remain the cornerstone of therapy for immune-related myocarditis, with no clear consensus on additional immunosuppressive treatment for steroid-refractory cases yet. Case report: Here, we report a patient with stage IV nasopharyngeal carcinoma who developed immune-related myocarditis in the fourth course of therapy with immune checkpoint inhibitors. The patient presented with precordial discomfort with elevation of cardiac enzymes and interleukin-6, atypical electrocardiographic abnormalities, and reduced left ventricular ejection fraction. Coronary computed tomography angiography excluded the possibility of acute coronary syndrome. The therapy with tofacitinib targeting the Janus kinase-signal transducer and activator of transcription signal pathway was successfully conducted, since there was no significant improvement in troponin under high-dose steroid and intravenous immunoglobulin treatment. The patient recovered without major adverse cardiac events during hospitalization. Discussion: The safety and efficacy of tofacitinib in a patient with steroid-refractory immune-related myocarditis were investigated, hoping to provide a basis for prospective therapeutic strategies. Tofacitinib led to remarkable remissions in primary autoimmune disease by blocking the inflammatory cascade, indicating its potential therapeutic use in immune-related adverse events.
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Miocardite , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico , Imunoglobulinas Intravenosas , Interleucina-6 , Janus Quinases , Miocardite/diagnóstico , Miocardite/tratamento farmacológico , Miocardite/etiologia , Piperidinas , Pirimidinas , Esteroides , Volume Sistólico , Troponina , Função Ventricular EsquerdaRESUMO
Objective: This study aimed to evaluate the cost-effectiveness of the colorectal cancer screening in China, and that when the screening was implemented in a specific region. Methods: A 13-state Markov model was established to compare four screening protocols, including annual fecal immunochemical testing (FIT1), biennial fecal immunochemical testing (FIT2), electronic colonoscopy every 10 years (e-CSPY10), and electronic colonoscopy every 5 years (e-CSPY5), with no screening from the perspective of Chinese healthcare system. The model simulated the health states of a cohort of 100,000 average-risk individuals aging from 50 to 75. Additionally, scenarios including the implementation in a specific region, starting from 40, and incompletely successful treatment of cancer were also analyzed. Results: Annual and biennial FIT could save 8.13USD (US Dollar) and 44.96USD per person, and increase 0.0705QALYs (Quality-Adjusted Life Years) and 0.2341 QALYs compared with no screening, respectively. Annual FIT could decrease costs by 36.81USD per person and increase 0.1637 QALYs in comparison to biennial FIT. The results showed that both annual and biennial FIT for screening were dominant over no screening, and annual FIT was dominant over biennial FIT. The ICER (Incremental Cost-Effectiveness Ratio) for e-CSPY10 were 1183.51USD/QALY and 536.66USD/QALY compared with FIT1 and FIT2. The ICER for e-CSPY5 were 1158.16USD/QALY and 770.85USD/QALY compared with FIT1 and FIT2. And the ICER for e-CSPY5 relative to e-CSPY10 was 358.71USD/QALY. All the ICER values were lower than the economic threshold of 2021 Chinese GDP (Gross Domestic Product) per capita in 2021(12554.42USD). Conclusions: It is worthwhile to popularize CRC screening in mainland China, as FIT always saving costs and colonoscopy is cost-effective. Regions with high income can take electronic colonoscopy every 10 years, or even every 5 years into consideration when determining the specific strategies.
Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Colonoscopia , Análise Custo-Benefício , Humanos , Sangue OcultoRESUMO
3DOMLaFeO3 was prepared by template method combined with sol-gel method using monodisperse polystyrene (PS) microspheres as template, and Ag/3DOMLaFeO3 perovskite catalyst was prepared by impregnation method combined with sodium borohydride reduction method. The catalysts were characterised by means of TG, XRD, SEM, BET, XPS, UV-vis DRS, etc. The photo-Fenton catalytic performance, stability and catalytic reaction mechanism of Ag/3DOMLaFeO3 were studied with penicillin G potassium (PEN G) as the model pollutant. The results indicated that the as-prepared Ag/3DOMLaFeO3 exhibited a three-dimensional ordered macroporous (3DOM) structure, and the light capture and mass transfer were enhanced through abundant pores and large specific surface area. Based on the surface plasmon resonance effect (SPR), Ag loading enhanced the absorption of the material in the visible light region, and inhibited the recombination of photogenerated carriers, which improved the photocatalytic performance of 3DOMLaFeO3 under visible light. Under the conditions of hydrogen peroxide dosage of 1.5â mL·L-1, initial pH of 5, PEN G initial concentration of 100â mg·L-1, catalyst dosage of 300â mg·L-1, xenon lamp irradiation, the degration ratio of PEN G and the removal rate of TOC reached 99.99% and 85.45% within 120â min, respectively. In addition, it had a wide range of pH application, excellent stability and practical application value. The quenching experiment and ESR test showed that ·OH and ·O2- were the reasons for high catalytic degradation. The least square method was used to fit the experimental data, and the results displayed that the degradation of PEN G was approximately in line with the first-order kinetic reaction.