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In this study, rice husk biochar was engineered with abundant iron ion sites to enhance the enrichment of antioxidant peptides from rice protein hydrolysates through metal-chelating interactions. The π-π interactions and metal ion chelation were identified as the primary mechanisms for the enrichment process. Through peptide sequencing, four peptides were identified: LKFL (P1: Leu-Lys-Phe-Leu), QLLF (P2: Gln-Leu-Leu-Phe), WLAYG (P3: Trp-Leu-Ala-Tyr-Gly), and HFCGG (P4: His-Phe-Cys-Gly-Gly). The vitro analysis and molecular docking revealed that peptides P1-P4 possessed remarkable scavenging ability against radicals and Fe2+ chelating ability. Notably, peptide P4 showed radical scavenging activity comparable to glutathione (GSH) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzthiazoline-6-sulphonate (ABTS) radicals. Cellular experiments further confirmed that peptide P4 effectively protected HepG2 cells from oxidative stress-induced damage. The modified rice husk biochar proved to be an effective means for enriching rice antioxidant peptides from protein hydrolysates.
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Antioxidantes , Carvão Vegetal , Oryza , Peptídeos , Hidrolisados de Proteína , Oryza/química , Hidrolisados de Proteína/química , Antioxidantes/química , Antioxidantes/farmacologia , Peptídeos/química , Peptídeos/farmacologia , Humanos , Carvão Vegetal/química , Células Hep G2 , Proteínas de Plantas/química , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacosRESUMO
In recent years, CD9 has been extensively studied as a potential biomarker for cancer. However, the biological role of CD9 in gliomas remains unclear. This study investigates the function of CD9 in gliomas and its molecular mechanisms. Utilizing pan-cancer analysis with TCGA, CGGA, and GEO databases, differential expression of CD9 was observed in 11 tumor types within the TCGA cohort, and it was associated with patient survival rates. Analysis of the CGGA glioma database revealed that patients with high CD9 expression had lower survival rates. The area under the ROC curve (AUC) for GSE16011 was greater than 0.7, indicating a high discriminative ability. Through gene set enrichment analysis (GSEA), immune-related analysis, and CD9 mutation detection, CD9 was found to have the strongest correlation with neutrophil involvement (cor = 0.30, P < 0.05), and the high CD9 expression group exhibited higher rejection responses and TIDE scores, suggesting a lower likelihood of successful immunotherapy. The high CD9 expression group was more sensitive to 81 drugs, indicating potential therapeutic effects for gliomas. Furthermore, overexpression of CD9 in gliomas may be associated with gene mutations. Down-regulation or up-regulation of CD9 expression in the glioblastoma cell line LN229 showed that CD9 could positively regulate the migratory ability of LN229 cells. Further, several marker genes, such as VEGFR-2, TGF-ß1, CASP1 and PI3K, were down regulated in CD9 knockdown cell lines and up regulated in CD9 overexpression cell lines, compared with control cell line. This study preliminarily explores the role of CD9 in gliomas and its prognostic value, providing new insights for personalized treatment strategies in glioma therapy.
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Neoplasias Encefálicas , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Glioma , Tetraspanina 29 , Humanos , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Tetraspanina 29/metabolismo , Tetraspanina 29/genética , Prognóstico , Biologia Computacional/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , MutaçãoRESUMO
Cognitive dysfunction stands as a prevalent and consequential non-motor manifestation in Parkinson's disease (PD). Although dysfunction of the olfactory system has been recognized as an important predictor of cognitive decline, the exact mechanism by which aberrant olfactory circuits contribute to cognitive dysfunction in PD is unclear. Here, we provide the first evidence for abnormal functional connectivity across olfactory bulb (OB) and piriform cortex (PC) or entorhinal cortex (EC) by clinical fMRI, and dysfunction of neural coherence in the olfactory system in PD mice. Moreover, we discovered that 2 subpopulations of mitral/tufted (M/T) cells in OB projecting to anterior PC (aPC) and EC precisely mediated the process of cognitive memory respectively by neural coherence at specific frequencies in mice. In addition, the transcriptomic profiling analysis and functional genetic regulation analysis further revealed that biorientation defective 1 (Bod1) may play a pivotal role in encoding OBM/T-mediated cognitive function. We also verified that a new deep brain stimulation protocol in OB ameliorated the cognitive function of Bod1-deficient mice and PD mice. Together, aberrant coherent activity in the olfactory system can serve as a biomarker for assessing cognitive function and provide a candidate therapeutic target for the treatment of PD.
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Aldehyde dehydrogenase 1, family member A2, is a retinoic acid-synthesizing enzyme encoded by Aldh1a2 in mice and ALDH1A2 in humans. This enzyme is indispensable for kidney development, but its role in kidney physiology and pathophysiology remains to be fully defined. In this review, we mined single-cell and single-nucleus RNA sequencing databases of mouse and human kidneys and found that glomerular parietal epithelial cells (PECs) express a full set of genes encoding proteins needed for cellular vitamin A uptake, intracellular transport, and metabolism into retinoic acid. In particular, Aldh1a2/ALDH1A2 mRNAs are selectively enriched in mouse and human PECs. Aldh1a2 expression in PECs is greatly increased in a mouse model of anti-glomerular basement membrane glomerulonephritis and moderately induced in a mouse model of ischemia-reperfusion acute kidney injury. Aldh1a2 expression in PECs is substantially repressed in a chronic kidney disease mouse model combining diabetes, hypertension, and partial nephrectomy and is moderately repressed in mouse models of focal segmental glomerulosclerosis and diabetic nephropathy. Single-nucleus RNA sequencing data show that ALDH1A2 mRNA expression in PECs is diminished in patients with chronic kidney disease associated with diabetes, hypertension and polycystic kidney disease. In addition to data mining, we also performed Spearman's rank correlation coefficient analyses and identified gene transcripts correlated with Aldh1a2/ALDH1A2 transcripts in mouse PECs and PEC subtypes, and in human PECs of healthy subjects and patients with AKI or CKD. Furthermore, we conducted Gene Ontology pathway analyses and identified the biological pathways enriched among these Aldh1a2/ALDH1A2-correlated genes. Our data mining and analyses led us to hypothesize that ALDH1A2-mediated retinoic acid synthesis in PECs plays a yet-undefined role in the kidney and that its dysregulation mediates injury. Conditional, PEC-selective Aldh1a2 knockout, RNA silencing and transgenic mouse models will be useful tools to test this hypothesis. Clinical studies on genetics, epigenetics, expression and functions of ALDH1A2 and other genes needed for retinoic acid biosynthesis and signaling are also warranted.
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Família Aldeído Desidrogenase 1 , Células Epiteliais , Retinal Desidrogenase , Análise de Célula Única , Tretinoína , Família Aldeído Desidrogenase 1/metabolismo , Família Aldeído Desidrogenase 1/genética , Animais , Tretinoína/metabolismo , Humanos , Células Epiteliais/metabolismo , Camundongos , Retinal Desidrogenase/metabolismo , Retinal Desidrogenase/genética , Análise de Sequência de RNA , Glomérulos Renais/metabolismo , Glomérulos Renais/patologiaRESUMO
Objective: Diabetes mellitus (DM) is a global epidemic; comorbid depressive symptoms are highly prevalent worldwide and commonly manifests as physical symptoms, including functional dyspepsia (FD), a gastrointestinal psychosomatic disorder. This study aimed to explore the effects of comorbid depressive symptoms and DM on FD in older patients. Methods: In total, 420 older patients with DM completed measures of depression, anxiety, and FD. Relevant demographic characteristics and medical information were self-reported and obtained from the hospital information system. Results: Among older patients with DM, 30.48% had depressive symptoms. Patients with depressive symptoms were more likely to have FD than those without (42.19% vs. 20.21%, P = .000). Dyspepsia symptoms were more frequent in patients with depression (P = .022). The greater the amount of dyspepsia symptoms, the higher the depression symptoms score (P = .000). Furthermore, dyspepsia symptoms were positively correlated with depressive symptoms (r values were 0.292, 0.311, 0.297, 0.369; all had P < .05). Both FD subtypes, postprandial distress, and epigastric pain syndromes affected depressive symptoms (P < .05). Smoking was significantly associated with FD (P < .05). Diabetes mellitus complications, such as diabetic neuropathy, different therapeutic methods, and anxiety symptoms, influenced FD overlap (x 2 values were 6.298, 16.314, and 30.744; P < .05). Anxiety (odds ratio = 1.832, 95% Confidence Intervals (CI) 1.185-2.834) was a risk factor for FD in comorbid depressive symptoms and diabetes (P < .05). Conclusion: Comorbid depressive symptoms and DM overlapped with physical symptoms, such as FD, in older patients with DM. Lifestyle, diabetic factors, and anxiety were the associated risk factors.
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Purpose: To create a diagnostic framework for clinical behavior and pathological tissue prognosis in ovarian cancer by using machine-learning (ML) methods based on multiple biomarkers. Experimental design: Overall, 713 patients with ovarian tumors at Sun Yat Sen Memorial Hospital were randomized into training and test cohorts. Four supervised ML classifiers, namely Support Vector Machine, Random Forest, k-nearest neighbor, and logistic regression were used to derive diagnostic and prognostic information from 10 parameters commonly available from pretreatment peripheral blood tests and age. The best prediction model was selected and validated by comparing the accuracy and the area under the ROC curve of each prediction model and by applying the external data of Guangdong Maternal and Child Health Center. Results: ML techniques were superior to conventional regression-based analyses in predicting multiple clinical parameters pertaining to ovarian tumor. Ensemble methods combining weak decision trees and RF showed the best reference in diagnosis, especially for malignant ovarian cancer. The values for the highest accuracy and area under the ROC curve for malignant ovarian cancer from benign or borderline ovarian tumors with RF were 99.82 % and 0.86 (micro-average ROC curve), respectively. The greatest accuracy and AUC for the diagnosis of pathological tissue with logistic regression curve were 78.0 % and 0.95 (micro-average ROC curve), respectively. In external validation, the random forest prediction model had an accuracy of 0.789 for applying data from external centers to verify tumor benignity and malignancy, and the logistic regression model had an accuracy of 0.719 for predicting the nature of the tumor. Conclusions: An ovarian tumor can be diagnosed and characterized before initial treatment via ML systems to provide critical diagnostic and prognostic information. The use of predictive algorithms can facilitate customized treatment options with patient preprocessing stratification.
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BACKGROUND: Toxocara canis, the most prevalent helminth in dogs and other canines, is one of the socioeconomically important zoonotic parasites, particularly affecting pediatric and adolescent populations in impoverished communities. However, limited information is available regarding the proteomes of female and male adult T. canis. To address this knowledge gap, we performed a comprehensive proteomic analysis to identify the proteins with differential abundance (PDAs) and gender-specifically expressed proteins between the two sexes adult T. canis. METHODS: The comparative proteomic analysis was carried out by the Orbitrap mass spectrometry (MS) with asymmetric track lossless (Astral) analyzer. The difference analysis was conducted using t-test and the proteins verification was achieved through parallel reaction monitoring (PRM). The potential biological functions of identified adult T. canis proteins and PDAs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The domain, transcription factor and subcellular localization of the identified proteins and PDAs were analyzed by InterPro, AnimalTFDB 4.0 and Cell-mPLOC 2.0 databases, respectively. RESULTS: A total of 8565 somatic proteins of adult T. canis were identified. Compared to male adult, 682 up-regulated PDAs and 844 down-regulated PDAs were identified in female adult with P-values < 0.05 and |log2FC| > 1, including 139 proteins exclusively expressed in female and 272 proteins exclusively expressed in male. The GO annotation analysis using all PDAs revealed that the main biological processes, cellular components and molecular functions corresponded to aminoglycan metabolic process, extracellular region and protein tyrosine phosphatase activity, respectively. The KEGG analysis using all PDAs showed that the pathways were mainly associated with adipocytokine signaling pathway, proximal tubule bicarbonate reclamation and PPAR signaling pathway. CONCLUSIONS: This study reveals the differential protein expression between female and male adult T. canis, providing valuable resource for developing the novel intervention strategies against T. canis infection in humans and animals, especially from the perspective of sexual development and reproduction.
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Proteínas de Helminto , Proteômica , Toxocara canis , Animais , Feminino , Masculino , Proteômica/métodos , Proteínas de Helminto/metabolismo , Proteínas de Helminto/genética , Proteínas de Helminto/análise , Proteoma , Cães , Toxocaríase/parasitologia , Espectrometria de Massas , Fatores Sexuais , Doenças do Cão/parasitologiaRESUMO
BACKGROUND: Enzymes with critical effects on life systems are regulated by expression and activation to modulate life processes. However, further insights into enzyme functions and mechanisms in various physiological processes are limited to concentration or activation analysis only. Currently, enzyme analysis has received notable attention, particularly simultaneous analysis of their concentration and activation in one system. Herein, N-methyl mesoporphyrin IX (NMM), a specific dye with notable structural selectivity for parallel G-quadruplex nucleic acid enzyme (G4h DNAzyme), is employed for the analysis of its concentration. In addition, the peroxidase activity of G4h DNAzyme is characterized based on G4h DNAzyme-catalyzed decomposition of H2O2 to continuously consume luminol. Accordingly, an increased fluorescence (FL) response of NMM and a decreased FL response of luminol could be simultaneously employed to analyze the concentration and activation of G4h DNAzyme. RESULT: Herein, a novel concentration and activation biresponsive strategy is proposed using a G4h DNAzyme-based model that simultaneously employs a G4h structure-specific signal probe for enzyme concentration analysis and G4h DNAzyme-catalyzed reactions for enzyme activation analysis. Under optimal conditions, the biresponsive strategy can be effectively used for the simultaneous analysis of G4h DNAzyme concentration and activation, with detection limits of 718.7 pM and 233.4 nM respectively, delivering acceptable performances both in cell and in vitro. SIGNIFICANCE: This strategy can not only be applied to concentration and activation analyses of G4h DNAzyme but can also be easily extended to other enzymes by simultaneously combining concentration analysis via target-induced direct reaction and activation analysis via target-induced catalytic reaction, offering deeper insights into various enzymes and enabling their effective implementation in bioanalysis and biochemistry.
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DNA Catalítico , Quadruplex G , Luminol , DNA Catalítico/química , DNA Catalítico/metabolismo , Humanos , Luminol/química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Mesoporfirinas/química , Corantes Fluorescentes/química , Biocatálise , Ativação EnzimáticaRESUMO
Enhancing the electrochemiluminescence (ECL) properties of polycyclic aromatic hydrocarbons (PAHs) is a significant topic in the ECL field. Herein, we elaborately chose PAH derivative luminophore 1,3,6,8-tetrakis(p-benzoic acid)pyrene (H4TBAPy) as the organic ligand to synthesize a new Ru-complex-free ECL-active metal-organic framework Dy-TBAPy. Interestingly, Dy-TBAPy exhibited a more brilliant ECL emission and higher ECL efficiency than H4TBAPy aggregates. On the one hand, TBAPy luminophores were assembled into rigid MOF skeleton via coordination bonds, which not only enlarged the distance between pyrene cores to eliminate the aggregation-caused quenching (ACQ) effect but also obstructed the intramolecular motions of TBAPy to diminish the nonradiative relaxation, thus realizing a remarkable coordination-enhanced ECL. On the other hand, the ultrahigh porosity of Dy-TBAPy was beneficial to the diffusion of electrons, ions, and coreactant (S2O82-) in the skeleton, which efficiently boosted the excitation of interior TBAPy luminophores and led to a high utilization ratio of TBAPy, further improving ECL properties. More intriguingly, the ECL intensity of the Dy-TBAPy/S2O82- system was about 4.1, 87.0-fold higher than those of classic Ru(bpy)32+/TPrA and Ru(bpy)32+/S2O82- systems. Considering the aforementioned fabulous ECL performance, Dy-TBAPy was used as an ECL probe to construct a supersensitive ECL biosensor for microRNA-21 detection, which showed an ultralow detection limit of 7.55 aM. Overall, our study manifests that coordinatively assembling PAHs into MOFs is a simple and practicable way to improve ECL properties, which solves the ACQ issue of PAHs and proposes new ideas for developing highly efficient Ru-complex-free ECL materials, therefore providing promising opportunities to fabricate high-sensitivity ECL biosensors.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Medições Luminescentes , Estruturas Metalorgânicas , Pirenos , Estruturas Metalorgânicas/química , Pirenos/química , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Humanos , Complexos de Coordenação/química , Limite de DetecçãoRESUMO
Previous studies have confirmed that the tire microplastic particles (TMPs) have a variety of toxic biological effects. However, the potential toxic mechanisms of TMPs remain to be elucidated, especially in the interaction between particle behavior and seawater warming. In this study, we investigated the effects of three different concentrations of TMPs suspensions (0 mg/L, 1 mg/L, and 500 mg/L) on Alexandrium pacificum in both the presence and absence of warming. Our results revealed significant differences in toxicity among different concentrations of TMPs towards A. pacificum, i.e., low concentrations promoting but high concentrations inhibiting, furthermore, warming exacerbated these toxicological responses. Specifically, under elevated temperature, high concentrations TMPs could inhibit photosynthetic pigment and chlorophyll fluorescence parameter, as well as the nutrient absorption, and induced oxidative stress. Furthermore, TMPs could adsorb onto microalgae surfaces and thus, forming heterogeneous aggregates through agglomeration with extracellular secretions. This is strongly correlated with biomarker response. Overall, these findings highlight the influence of warming on the toxicity of TMPs and provide valuable data for risk assessment.
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Primula medogensis W.B Ju, B. Xu & X.F. Gao 2023, a new species categorized under P. sect. Cordifoliae, was officially described in 2023. Given its recent classification, the genetic resources for this species are currently very limited. Here, we sequenced and assembled the first complete chloroplast genome of P. medogensis using Illumina sequencing technology. The complete chloroplast genome of P. medogensis is 151,486 bp in length, exhibiting a typical quadripartite structure. It consists of a large single-copy region (LSC; 83,407 bp) and a small single-copy region (SSC;17675 bp), separated by a pair of inverted repeat regions (IRs; 25202 bp). A total of 131 genes were annotated, including 86 protein-coding, 37 tRNA, and eight rRNA genes. The overall GC content was 37.1%. Phylogenetic analysis of 59 Primula species revealed a close relationship between P. medogensis and P. calliantha subsp. bryophila.
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OBJECTIVES: To analyze the risk factors and explore effective treatments for epistaxis in nasopharyngeal carcinoma (NPC) patients. METHODS: From March 2006 to February 2020, 351 epistaxis patients visited our center and 195 patients meeting the inclusion criteria were enrolled in the study. Characteristics and treatments, including step-up hemostatic treatment (including medication, anterior ± posterior nostril packing, or further surgical hemostasis) and the CTPI emergency hemostasis method (including common carotid artery compression, tracheotomy / intubation, packing of nasal and nasopharynx, and interventional treatment), were analyzed. RESULTS: The median total bleeding volume was 100.0 ml (range 20-4430 ml). 126 (64.6 %) and 69 (35.4 %) patients suffered from non-massive epistaxis and massive epistaxis. The 1-year overall survival (OS) rate was 60.1 % for patients with massive epistaxis and 97.3 % for those with non-massive epistaxis treated with step-up hemostatic treatment. Among patients with massive epistaxis, the 1-year OS rate was 80.0 % for those who received CTPI and 13.3 % for those who received step-up hemostatic treatment. CONCLUSION: ICA exposure and hemostasis failure was adverse prognostic factors for OS in NPC patients with epistaxis. The step-up hemostatic treatment is effective for controlling non-massive epistaxis. The CTPI emergency method might be an effective hemostasis treatment for NPC patients with massive epistaxis, especially those with PRNN and ICA exposure.
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The layer-structured oxide cathode for sodium-ion batteries has attracted a widespread attention due to the unique redox properties and the anionic redox activity providing additional capacity. Nevertheless, such excessive oxygen redox reactions will lead to irreversible oxygen release, resulting in a rapid deterioration of the cycling stability. Herein, sulfur ion is successfully introduced to the O3-NaNi0.3Mn0.5Cu0.1Ti0.05W0.05O2 material through high-temperature quenching, thereby developing a novel Na2S-modified O3/P2-NaNi0.3Mn0.5Cu0.1Ti0.05W0.05O2 composite with extended cycling life. The S2- is analyzed for the ability to enhance the reversibility of oxidation-reduction reactions under high voltage and suppress the loss of lattice oxygen during cycling. The stable SâO covalent bonds are found to inhibit the oxygen generation and release within the structure. Benefiting from these improvements, the Na2S-modified O3/P2-NaNi0.3Mn0.5Cu0.1Ti0.05W0.05O2 exhibited a high reversible capacity of 173.1 mA h g-1 over a wide voltage range of 1.5-4.3 V under test conditions at 0.1 C and 81.5% capacity retention after 120 cycles at 1 C. The Na2S-modified O3/P2-NaNi0.3Mn0.5Cu0.1Ti0.05W0.05O2 demonstrates the excellent rate capability with the reversible capacities of 173.1,137.0,114.7,96.7, and 80.1 mA h g-1 at 0.1, 0.2, 0.5, 1, and 2 C.
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Integrating multi-stimuli response properties in one molecule is challenging. This study presents two 2D polymers, [(Bpydp)Ln(H2O)(BDC)]·NO3·2H2O (Ln = Eu(1), Tb(2)), exhibiting rapid photo-responsiveness and the ability to detect specific small-molecule amines. In particular, complex 1 combines the functions of inkless printing, amine detection, anti-counterfeiting, and fluorescence recognition.
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Mevastatin (MVS) is known for its anti-inflammatory effects, potentially achieved by upregulating heme oxygenase-1 (HO-1), an enzyme involved in cytoprotection against oxidative injury. Nonetheless, the specific processes by which MVS stimulates HO-1 expression in human cardiac fibroblasts (HCFs) are not yet fully understood. In this study, we found that MVS treatment increased HO-1 mRNA and protein levels in HCFs. This induction was inhibited by pretreatment with specific inhibitors of p38 MAPK, JNK1/2, and FoxO1, and by siRNAs targeting NOX2, p47phox, p38, JNK1, FoxO1, Keap1, and Nrf2. MVS also triggered ROS generation and activated JNK1/2 and p38 MAPK, both attenuated by NADPH oxidase or ROS inhibitors. Additionally, MVS promoted the phosphorylation of FoxO1 and Nrf2, which was suppressed by p38 MAPK or JNK1/2 inhibitor. Furthermore, MVS inhibited TNF-α-induced NF-κB activation and vascular cell adhesion molecule-1 (VCAM-1) expression via the HO-1/CO pathway in HCFs. In summary, the induction of HO-1 expression in HCFs by MVS is mediated through two primary signaling pathways: NADPH oxidase/ROS/p38 MAPK, and JNK1/2/FoxO1 and Nrf2. This research illuminates the underlying processes through which MVS exerts its anti-inflammatory effects by modulating HO-1 in cardiac fibroblasts.
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Distinguishing stable and fluctuating psychopathological features in young individuals at Ultra High Risk (UHR) for psychosis is challenging, but critical for building robust, accurate, early clinical detection and prevention capabilities. Over a 24-month period, 159 UHR individuals were assessed using the Positive and Negative Symptom Scale (PANSS). Generalisability Theory was used to validate the PANSS with this population and to investigate stable and fluctuating features, by estimating the reliability and generalisability of three factor (Positive, Negative, and General) and five factor (Positive, Negative, Cognitive, Depression, and Hostility) symptom models. Acceptable reliability and generalisability of scores across occasions and sample population were demonstrated by the total PANSS scale (Gr = 0.85). Fluctuating symptoms (delusions, hallucinatory behaviour, lack of spontaneity, flow in conversation, emotional withdrawal, and somatic concern) showed high variability over time, with 50-68% of the variance explained by individual transient states. In contrast, more stable symptoms included excitement, poor rapport, anxiety, guilt feeling, uncooperativeness, and poor impulse control. The 3-factor model of PANSS and its subscales showed robust reliability and generalisability of their assessment scores across the UHR population and evaluation periods (G = 0.77-0.93), offering a suitable means to assess psychosis risk. Certain subscales within the 5-factor PANSS model showed comparatively lower reliability and generalisability (G = 0.33-0.66). The identified and investigated fluctuating symptoms in UHR individuals are more amendable by means of intervention, which could have significant implications for preventing and addressing psychosis. Prioritising the treatment of fluctuating symptoms could enhance intervention efficacy, offering a sharper focus in clinical trials. At the same time, using more reliable total scale and 3 subscales can contribute to more accurate assessment of enduring psychosis patterns in clinical and experimental settings.
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BACKGROUND: Global and regional cerebral blood flow (CBF) changes in patients with unilateral internal carotid artery occlusion (ICAO) are unclear when the dual post-labeling delays (PLD) arterial spin labeling (ASL) magnetic resonance imaging (MRI) technique is used. Manual delineation of regions of interest for CBF measurement is time-consuming and laborious. AIM: To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique. METHODS: Twenty hospitalized patients with ICAO and sex- and age-matched controls were included in the study. Regional CBF was measured by Dr. Brain's ASL software. The present study evaluated differences in global, middle cerebral artery (MCA) territory, anterior cerebral artery territory, and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) regions (including the caudate nucleus, lentiform nucleus, insula ribbon, internal capsule, and M1-M6) and brain lobes (including frontal, parietal, temporal, and insular lobes) between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s. RESULTS: When comparing CBF between ICAO patients and controls, the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s; the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s, and it was lower in 9 brain regions at PLD 2.5 s; the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s. The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s. The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions, whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions. The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s, and in M6 at PLD 2.5 s. CONCLUSION: Unilateral ICAO results in hypoperfusion in the global and MCA territories, especially in the ASPECTS area. Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.
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The phase with composition Ti4Fe2C0.82O0.18, tetra-titanium diiron carbide oxide, was unexpectedly synthesized by high-pressure sinter-ing (HPS) of a stoichiometric mixture with nominal composition Ti2Fe. The Ti4Fe2C0.82O0.18 phase crystallizes in the Fd m space group and can be considered as the Ti2Fe structure filled with C and O atoms co-occupying the same octa-hedral void [occupancy ratio 0.82â (7):0.18â (7)]. The Ti4Fe2C0.82O0.18 phase is isotypic with Ti4Ni2C and Ti4Fe2O0.407, and is the first example where C and O atoms co-occupy the same site in filled Ti2Fe structures.
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Granzyme A (GzmA) secreted by natural killer (NK) cells has garnered considerable interest as a biomarker to evaluate the efficacy of cancer immunotherapy. However, current methodologies to selectively monitor the spatial distribution of GzmA in cancer cells during NK cell-targeted therapy are extremely challenging, primarily due to the existence of diverse cell populations, the low levels of GzmA expression, and the limited availability of GzmA probes. Herein we develop a multi-modular, structurally-ordered DNA nanodevice for evaluating NK cell-mediated cancer immunotherapy (MODERN), that permits spatioselective imaging of GzmA in cancer cells through GzmA-induced apurinic/apyrimidinic endonuclease 1 (APE1) inactivation. The MODERN incorporates multiple functional modules, including an APE1-gated recognition module, a photo-activated amplification module, an aptamer-mediated tumor-target module, and a polycatenane DNA module, enabling improved sensitivity and specificity towards intracellular GzmA. The MODERN was activated (on) in cancer cells due to the overexpression of APE1, whereas it remained silent (off) in the NK-treated cancer cells owing to the GzmA-induced APE1 inactivation. Furthermore, we demonstrated that GzmA-induced APE1 inactivation blocks the cellular repair of target cells, resulting in efficient cell death. This MODERN that relies on the specific inactivation of APE1 by GzmA should be beneficial for evaluating the efficacy of cancer immunotherapy.
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Green hydrogen production from water splitting is a feasible way for intermittent renewable energy storage and utilization, where the exploration and scale-up preparation of high-performance anodic oxygen evolution electrocatalysts are critical prerequisites for its industrial-level applications. Herein, a chemical bath deposition of FeNi3 intermetallic alloys onto Ni mesh support is performed, which delivers a current density of 0.62 A cm-2 at 1.72 V versus reversible hydrogen electrode for alkaline water oxidation in 1 m KOH and an excellent electrolysis stability at 0.2 A cm-2 for over 300 h. Moreover, via 3D computational fluid dynamics simulation and flow field optimization, a homogeneous deposition of ≈5400 cm2 NiFe anode is demonstrated within 4 min using the developed flow bath reactor. Once integrating the as-prepared NiFe anodes into alkaline electrolyzer stack, the voltage variation between each unit cell is below 40 mV at a total operation current of 71 A, or ca. current density of 0.2 A cm-2, confirming the uniformity of this batch synthesis protocol and its great potential for industrial alkaline water electrolysis.