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This work established a quantitative method to access the shear stability of aerobic granular sludge (AGS) and validated its feasibility by using the mature AGS from a pilot-scale (50 tons/day) membrane bioreactor (MBR) for treating real municipal wastewater. The results showed that the changing rate (ΔS) of the peak area (S) of granule size distribution (GSD) exhibited an exponential relationship (R2≥0.76) with the shear time (y=a-b·cx), which was a suitable indicative index to reflect the shear stability of different AGS samples. The limiting granule size (LGS) was defined and proposed to characterize the equilibrium size for AGS after being sheared for a period of time, whose value in terms of Dv50 showed high correlation (R2=0.92) with the parameter a. The free Ca2+ (28.44-34.21 mg/L) in the influent specifically interacted with polysaccharides (PS) in the granule's extracellular polymeric substance (EPS) as a nucleation site, thereby inducing the formation of Ca precipitation to enhance its Young's modulus, while Ca2+ primarily interacted with PS in soluble metabolic product (SMP) during the initial granulation process. Furthermore, the Young's modulus significantly affected the parameter a related to shear stability (R2=0.99). Since the parameter a was more closely related (R2=1.00) to ΔS than that of the parameter b or c, the excellent correlation (R2=0.99) between the parameter a and the wet density further verified the feasibility of this method.
Subject(s)
Bioreactors , Sewage , Waste Disposal, Fluid , Waste Disposal, Fluid/methods , Pilot Projects , Wastewater/chemistry , Membranes, Artificial , AerobiosisABSTRACT
Background: Depression manifests as a mental disorder characterized by a low mood, suicidal tendencies, disturbances in sleep-wake cycles, psychomotor agitation, and pronounced feelings of hopelessness and anhedonia. Baicalin, a natural flavonoid compound, shows significant promise in alleviating depressive symptoms in animals. This study aims to assess the impact of baicalin on experimental models of depression. Methods: A systematic search of electronic databases was conducted using the search terms "baicalin" AND "depression" OR "depressed" OR "anti-depression". Preclinical animal models representing experimental depression were included in the analysis. The risk of bias in the included studies was evaluated using the CAMARADES tools. Results: Baicalin significantly increased sucrose preference test (SPT) [SMD= 21.31, 95%CI (16.32, 26.31), P < 0.00001]. mThe tail suspension test (TST) duration significantly decreased in the baicalin group compared to the model group [SMD = -39.3, 95%CI (-49.71, -28.89), P < 0.0001]. Furthermore, baicalin reduced immobility time in rats subjected to the forced swim test (FST) [SMD = -39.73, 95%CI (-48.77, -30.69) P < 0.0001]. Compared to the model group, baicalin treatment also significantly increased the frequency of crossings in the open field test (OFT) [SMD = 32.44, 95%CI (17.74, 47.13), P < 0.00001]. Conclusion: Baicalin significantly improves the manifestations of depressive symptoms. The effect of baicalin against depression is exerted through its anti-inflammatory actions, inhibition of oxidative stress, regulation of the HPA axis, and restoration of neuroplasticity. Future studies will be needed to further explore how these promising preclinical findings can be translated into clinical treatment for depression. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472181.
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OBJECTIVE: Posterior condylar offset (PCO) and anterior condylar offset (ACO) exert an influence on the sagittal alignment in total knee arthroplasty (TKA). However, there is no common consensus that the variation range of posterior condylar offset (PCO) is associated with patient-reported outcome measures (PROMs) and the optimum variation range of PCO. This study aims to investigate the correlation between PCO and the PROMs of primary TKA for osteoarthritis (OA) and find out the optimal variation range of the PCO. METHODS: In this study, we performed a radiographic analysis of 106 patients (112 knees) with primary TKA. Patients were divided into two cohorts (A and B) according to the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC). Correlations between the sagittal parameter and WOMAC were investigated using univariate and multivariate analysis. The receiver operating characteristic (ROC) curve was used to establish the cut-off value for the optimal variation range. We then further investigated how different variation range affects the WOMAC subscale score and forgotten-joint-score-12 (FJS-12). RESULTS: Univariate analysis revealed a correlation between the variation range of PCO (p < 0.01), ACO (p < 0.01) and PROMs. Multivariate analysis showed that only PCO was associated with PROMs. In the ROC graph, the cut-off value of the variation range of PCO is 2.85 mm (AUC = 0.66, Youden index = 0.26). The WOMAC functional ability score of the group outside the PCO variation range of 2.85 mm significantly increased compared to the group within the range. CONCLUSION: In this study, PCO variation was significantly associated with clinical outcomes in TKA and the optimal PCO variation range was within 2.85 mm. Maintaining the PCO variation within 2.85 mm could enhance functional recovery and patient satisfaction.
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OBJECTIVE: To evaluate the effectiveness of conventional US (ultrasound), SMI (superb microvascular imaging), and CEUS (contrast-enhanced ultrasound) features for the assessment of the activity of inflammatory bowel disease. METHODS: Conventional US, CEUS and SMI features of 76 patients were retrospectively analyzed. Patients were categorized into two groups: active group (nâ=â57) and inactive group (nâ=â19), with endoscopic results as reference standard. Results in the active group and inactive group were compared using an independent t-test, Mann-Whitney U test, chi-square test, and receiver operating characteristic curve (ROC) analysis. Cut-off values were determined using ROC analysis, and sensitivity and specificity were calculated. US quantitative and TIC-based quantitative parameters were analyzed, and each patient was scored based on the parameters that are statistically significant and immediately available in the clinic to evaluate the diagnostic ability of conventional US, SMI, and CEUS features for active IBD patients. RESULTS: Qualitative parameters such as CEUS enhancement pattern I/II, LimbergIII/IV, and lost bowel stratification were reliable indicators of active patients. Quantitative parameters such as bowel thickness and VI of mSMI were reliable indicators of active patients. Patients scored based on these statistically significant parameters with a score ≥3, were highly suspected to be active patients. For TIC-based quantitative parameters, PE, WiAUC, WoAUC, WiWoAUC, WiR, WiPI, and WoR were statistically significant in the differentiation of active IBD from inactive IBD. CONCLUSIONS: Conventional US, SMI, and CEUS features may help in the differentiation of active IBD from inactive IBD and have potential application value in the choice of treatment options.
Subject(s)
Contrast Media , Inflammatory Bowel Diseases , Ultrasonography , Humans , Female , Male , Inflammatory Bowel Diseases/diagnostic imaging , Adult , Ultrasonography/methods , Middle Aged , Retrospective Studies , Microvessels/diagnostic imaging , Aged , Young Adult , AdolescentABSTRACT
OBJECTIVE: Our objective was to develop a machine learning model capable of predicting irrational medical prescriptions precisely within orthopedic perioperative patients. METHODS: A dataset comprising 3047 instances of suspected irrational medication prescriptions was collected from a sample of 1318 orthopedic perioperative patients from April 2019 to March 2022. Four machine learning models were employed to forecast irrational prescriptions, following which, the performance of each model was meticulously assessed. Subsequently, a thorough variable importance analysis was conducted on the model that performed the best predictive capabilities. Thereafter, the efficacy of integrating this optimal model into the existing audit prescription process was rigorously evaluated. RESULTS: Of the models utilized in this study, the RF model yielded the highest AUC of 92%, whereas the NB model presented the lowest AUC of 68%. Also, the RF model boasted the most robust performance in terms of PPV, reaching 82.4%, and NPV, reaching 86.6%. The ANN and the XGBoost model were neck and neck, with the ANN slightly edging out with a higher PPV of 95.9%, while the XGBoost model boasted an impressive NPV of 98.2%. The RF model singled out the following five factors as the most influential in predicting irrational prescriptions: the type of drug, the type of surgery, the number of comorbidities, the date of surgery after hospitalization, as well as the associated hospital and drug costs. CONCLUSION: The RF model showcased significantly high level of proficiency in predicting irrational prescriptions among orthopedic perioperative patients, outperforming other models by a considerable margin. It effectively enhanced the efficiency of pharmacist interventions, displaying outstanding performance in assisting pharmacists to intervene with irrational prescriptions.
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Single-molecule detection with high accuracy and specialty plays an important role in biomedical diagnosis and screening. Zero-mode waveguides (ZMWs) enable the possibility of single biological molecule detection in real time. Nevertheless, the absence of a reliable assessment for single effective complex loading has constrained further applications of ZMWs in complex interaction. Both the quantity and activity of the complex loaded into ZMWs have a critical effect on the efficiency of detection. Herein, a fluorescence evaluation at quenching and accumulation checkpoints was established to assess and optimize single effective complex loading into ZMWs. A primer-template-enzyme ternary complex was designed, and then an evaluation for quantity statistics at the quenching checkpoint and functional activity at the accumulation checkpoint was used to validate the effectiveness of complexes loaded into ZMWs. By optimizing the parameters such as loading time, procedures, and enzyme amount, the single-molecule effective occupancy was increased to 25.48%, achieving 68.86% of the theoretical maximum value (37%) according to Poisson statistics. It is of great significance to provide effective complex-loading validation for improving the sample-loading efficiency of single-molecule assays or sequencing in the future.
Subject(s)
Spectrometry, Fluorescence , FluorescenceABSTRACT
Alzheimer's disease (AD) is the leading cause of dementia worldwide and significantly impacts the essential functions of daily life and social activities. Research on AD has found that its pathogenesis is related to the extracellular accumulation of amyloid-beta (Aß) plaques and intracellular neurofibrillary tangles in the cortical and limbic areas of the human brain, as well as cerebrovascular factors. The detection of Aß or tau can be performed using various probes and methodologies. However, these modalities are expensive to implement and often require invasive procedures, limiting accessibility on a large scale. While magnetic resonance imaging (MRI) and computed tomography (CT) are generally used for morphological and structural brain imaging, they show wide variability in their accuracy for the clinical diagnosis of AD. Several novel imaging modalities have emerged as alternatives that can accurately and vividly display the changes in blood flow and metabolism in each brain area and enable physicians and researchers to gain insights into the generation and progression of the cerebro-microvascular pathologies of AD. In this review, we summarize the current knowledge on microvascular perfusion imaging modalities and their application in AD, including MRI (dynamic susceptibility contrast-MRI, arterial spin labeling-MRI), CT (cerebral CT perfusion imaging), emission computed tomography (positron emission tomography (PET), single-photon emission computed tomography (SPECT)), transcranial doppler ultrasonography (TCD), and retinal microvascular imaging (optical coherence tomography imaging, computer-assisted methods for evaluating retinal vasculature).
Subject(s)
Alzheimer Disease , Perfusion Imaging , Humans , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Perfusion Imaging/methods , Cerebrovascular Circulation/physiology , Microvessels/diagnostic imaging , Brain/diagnostic imagingABSTRACT
Background: Most existing studies have only investigated the direct effects of the built environment on respiratory diseases. However, there is mounting evidence that the built environment of cities has an indirect influence on public health via influencing air pollution. Exploring the "urban built environment-air pollution-respiratory diseases" cascade mechanism is important for creating a healthy respiratory environment, which is the aim of this study. Methods: The study gathered clinical data from 2015 to 2017 on patients with respiratory diseases from Tongji Hospital in Wuhan. Additionally, daily air pollution levels (sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter (PM2.5, PM10), and ozone (O3)), meteorological data (average temperature and relative humidity), and data on urban built environment were gathered. We used Spearman correlation to investigate the connection between air pollution and meteorological variables; distributed lag non-linear model (DLNM) was used to investigate the short-term relationships between respiratory diseases, air pollutants, and meteorological factors; the impacts of spatial heterogeneity in the built environment on air pollution were examined using the multiscale geographically weighted regression model (MGWR). Results: During the study period, the mean level of respiratory diseases (average age 54) was 15.97 persons per day, of which 9.519 for males (average age 57) and 6.451 for females (average age 48); the 24 h mean levels of PM10, PM2.5, NO2, SO2 and O3 were 78.056 µg/m3, 71.962 µg/m3, 54.468 µg/m3, 12.898 µg/m3, and 46.904 µg/m3, respectively; highest association was investigated between PM10 and SO2 (r = 0.762, p < 0.01), followed by NO2 and PM2.5 (r = 0.73, p < 0.01), and PM10 and PM2.5 (r = 0.704, p < 0.01). We observed a significant lag effect of NO2 on respiratory diseases, for lag 0 day and lag 1 day, a 10 µg/m3 increase in NO2 concentration corresponded to 1.009% (95% CI: 1.001, 1.017%) and 1.005% (95% CI: 1.001, 1.011%) increase of respiratory diseases. The spatial distribution of NO2 was significantly influenced by high-density urban development (population density, building density, number of shopping service facilities, and construction land, the bandwidth of these four factors are 43), while green space and parks can effectively reduce air pollution (R2 = 0.649). Conclusion: Previous studies have focused on the effects of air pollution on respiratory diseases and the effects of built environment on air pollution, while this study combines these three aspects and explores the relationship between them. Furthermore, the theory of the "built environment-air pollution-respiratory diseases" cascading mechanism is practically investigated and broken down into specific experimental steps, which has not been found in previous studies. Additionally, we observed a lag effect of NO2 on respiratory diseases and spatial heterogeneity of built environment in the distribution of NO2.
Subject(s)
Air Pollution , Respiratory Tract Diseases , Male , Female , Humans , Middle Aged , Cities , Nitrogen Dioxide/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Respiratory Tract Diseases/epidemiology , Respiratory Tract Diseases/etiology , Particulate Matter/analysisABSTRACT
Objective: To evaluate the clinical outcomes in the carriers of insertional translocation (IT). Design: Retrospective case series. Setting: University-affiliated reproductive medical center. Patients: Twenty-three couples with ITs. Intervention: No direct interventions were involved; however, this study included patients who underwent preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR). Main Outcome Measure: Outcome of preimplantation genetic testing for structural chromosomal rearrangements and percentage of blastocysts available for transfer. Results: Among 23 IT carriers, 15 were simple interchromosome ITs (type A), 3 were intrachromosome IT carriers (type B), and 5 were interchromosome IT carriers combined with other translocations (type C). A total of 190 blastocysts from 30 cycles were biopsied, 187 embryos were tested successfully, and only 57 blastocysts (30.5%) from 21 patients were available for transfer (normal or balanced). The unbalanced rearrangement rate of type C was 79.2% (42/53), and the proportion of type A was 50.0% (57/114), which was significantly higher than that of type B (5%, 1/20). In type A, the probability of embryos harboring unbalanced rearrangement in female carriers was 56.0% (51/91), which was higher than that in male carriers (26.1%, 6/23). Furthermore, the haploid autosomal length value of the inserted fragment was correlated linearly with the incidence of abnormal embryos. In type A gametes, most gametes produced by 2:2 separation without crossover, and no 3:1 separation gamete was observed. Conclusions: The chance of identifying normal or balanced and mosaic blastocysts per mature oocytes in patients with ITs are 16.6% (67/404). Greater IT complexity results in fewer transferable embryos. For simple interchromosome ITs, female carriers and those with higher haploid autosomal length values have a higher risk of producing embryos with unbalanced rearrangement.
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Autophagy is a process of self-renewal in cells, which not only provides the necessary nutrients for cells, but also clears necrotic organelles. Autophagy disorders are closely related to diseases such as cancer. UNC-51-like kinase 1 (ULK1) is a serine/threonine protein kinase that plays a crucial role in receiving input from energy and nutrient sensors, activating autophagy to maintain cellular homeostasis under stressful conditions. In recent years, targeting ULK1 has become a highly promising strategy for cancer treatment. This review introduces the regulatory mechanism of ULK1 in autophagy through the AMPK/mTOR/ULK1 pathway and reviews the research progress of ULK1 activators and inhibitors and their applications in cancer treatment. In addition, we analyze the binding modes between ULK1 and modulators through virtual molecular docking, which will provide a reliable basis and theoretical guidance for the design and development of new therapeutic drugs targeting ULK1.
Subject(s)
AMP-Activated Protein Kinases , Neoplasms , Autophagy-Related Protein-1 Homolog/metabolism , Molecular Docking Simulation , AMP-Activated Protein Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Autophagy , Neoplasms/drug therapyABSTRACT
Immunotherapy with immune checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.
Subject(s)
Glioblastoma , Mice , Animals , Glioblastoma/pathology , Micelles , Immune Checkpoint Inhibitors/therapeutic use , Polymers/therapeutic use , Cell Line, Tumor , Neoplasm Recurrence, Local/drug therapy , Paclitaxel/therapeutic use , Immunotherapy , Tumor MicroenvironmentABSTRACT
The digital polymerase chain reaction (dPCR) is a new and developing nucleic acid detection technology with high sensitivity that can realize the absolute quantitative analysis of samples. In order to improve the accuracy of quantitative results, real-time digital PCR emphasizes the kinetic information during amplification to identify prominent abnormal data. However, it is challenging to use a unified standard to accurately classify the amplification curve of each well as negative and positive, due to the interference caused by various factors in the experiment. In this work, a normal distribution-based cycle threshold value self-correcting model (NCSM) was established, which focused on the feature of the cycle threshold values in amplification curves and conducted continuous detection and correction on the whole. The cycle threshold value distribution was closer to the ideal normal distribution to avoid the influence of interference. Thus, the model achieves a more accurate classification between positive and negative results. The corrective process was applied to plasmid samples and resulted in an accuracy improvement from 92 to 99%. The coefficient of variation was below 5% when considering the quantitation of a range between 100 and 10,000 copies. At the same time, by utilizing this model, the distribution of cycle threshold values at the endpoint can be predicted with fewer thermal cycles, which can reduce the cycling time by around 25% while maintaining a consistency of more than 98%. Therefore, using the NCSM can effectively enhance the quantitative accuracy and increase the detection efficiency based on the real-time dPCR platform.
Subject(s)
Normal Distribution , Real-Time Polymerase Chain Reaction/methods , PlasmidsABSTRACT
The fruits of Amomum villosum are often considered a medicinal and food homologous material and have been found to have therapeutic effects in chronic enteritis, gastroenteritis, and duodenal ulcer. The aim of this study is to discover the anti-inflammatory active ingredients from dried ripe fruits of A. villosum and to elucidate the molecular mechanisms. We verified that the inhibitory activity of the ethyl acetate extract was superior to Dexamethasone (Dex), so we ultimately chose to study the ethyl acetate extract from the fruits of A. villosum. A total of 33 compounds were isolated from its ethyl acetate extract, including nine known diterpenoids (compounds 1-9), twelve known sesquiterpenoids (compounds 10-21), ten known phenolics (compounds 22, 23, 25-29, 31-33) and two new phenolics (24 and 30). On the basis of chemical evidences and spectral data analysis (UV, ECD, Optical rotation data, 1D and 2D-NMR, HR-ESI-MS, NMR chemical shift calculations), the structures of new compounds were elucidated. Among these compounds, isocoronarin D (5) was found to have good anti-inflammatory activity. Further research has found that isocoronarin D can down-regulate the protein levels of COX2 and NOS2, activate Nrf2/Keap1 and suppress NF-κB signaling pathway in LPS-induced RAW264.7 cells. In addition, isocoronarin D inhibited inflammasome assembly during inflammasome activation by hampering the binding of NLRP3 and ASC. Further evidence revealed that isocoronarin D suppressed the assembly of the NLRP3 inflammasome via blocking the formation of ASC specks. From these results, isocoronarin D may be the important bioactive compound of A. villosum and exhibits anti-inflammatory effects by regulating the NF-κB/Nrf2/NLRP3 axis in macrophages.
Subject(s)
Acetates , Amomum , Diterpenes , Imidazoles , Sulfonamides , Thiophenes , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/metabolism , Amomum/chemistry , Terpenes , NF-kappa B/metabolism , Kelch-Like ECH-Associated Protein 1 , Fruit/chemistry , NF-E2-Related Factor 2/metabolism , Anti-Inflammatory Agents/pharmacology , Lipopolysaccharides/pharmacologyABSTRACT
[This corrects the article DOI: 10.3389/fbioe.2023.1297068.].
ABSTRACT
Osteoarthritis (OA) is the most prevalent age-related and degenerative joint disease with limited treatment options. Previous studies have identified the therapeutic effects of mesenchymal stem cells (MSCs) therapy. Nevertheless, chronic inflammation impedes MSCs therapeutic effect. There have been reports suggesting that circular RNAs (circRNAs) are involved in OA and chondrogenesis. The combination of MSCs and circRNAs in therapies appears to be a promising option. In this study, we identified circIRAK3 as a significant regulator in cartilage degeneration and chondrogenesis through high-throughput sequencing analyses. We observed increased circIRAK3 in OA cartilage and during MSCs chondrogenesis. Knockdown of circIRAK3 resulted in excessive apoptosis, inhibited proliferation, and degradation of chondrocytes, along with the inhibition of MSCs chondrogenesis. Mechanistically, circIRAK3 bound to HNRNP U and competitively prevented its binding to IL-1ß, TNFα, and IL6 mRNA, thereby promoting mRNA degradation. Notably, circIRAK3 expression in plasma increased with higher OARSI scores. Intra-articular injection of adeno-associated virus-circIRAK3 delayed cartilage degeneration and reduced inflammation in DMM mouse model. Our study highlights a compensatory regulation network of circIRAK3 in chondrocytes in response to inflammation. CircIRAK3 has the potential to serve as a new therapeutic target for OA. Furthermore, therapies targeting circIRAK3 combined with MSCs hold promise.
Subject(s)
Cartilage, Articular , Osteoarthritis , Mice , Animals , Cytokines/genetics , Cytokines/metabolism , Heterogeneous-Nuclear Ribonucleoprotein U/metabolism , Osteoarthritis/genetics , Osteoarthritis/therapy , Osteoarthritis/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Circular/metabolism , Feedback , Chondrogenesis/genetics , Inflammation/genetics , Inflammation/metabolism , ChondrocytesABSTRACT
While surfactants are widely used in phosphogypsum, their interactions with the phosphogypsum-water interface remain unclear. This study investigates the impact of three types of surfactants, namely polycarboxylate-based surfactant (PCE-TPEG), naphthalene-based surfactant (NS), and melamine-based surfactant (MS), on the performance of phosphorus building gypsum (PBG). Additionally, a nanoscale model of the PBG-surfactant-water interface is constructed using molecular dynamics to elucidate the mechanisms underlying the interaction between different surfactants and PBG at multiple scales. The results demonstrate that all surfactants enhance the mechanical properties of PBG. PCE-TPEG exhibits the most pronounced improvement. In the model, PCE-TPEG molecules likely undergo comb-like adsorption, while NS and MS molecules tend to adsorb on both ends of the crystal plane. Changes in the potential difference between CaSO4·2H2O and H2O, as well as between CaSO4·2H2O and the surfactant, play a crucial role in adsorption. PCE-TPEG, NS, and MS molecules tend to spread horizontally in a vacuum state. With the addition of water molecules, they transition to spatial adsorption. Ca2+ easily interacts with -COO- and -SO3- groups, leading to reduced migration and flexibility of the main chain. The adsorption process of surfactants at the gypsum-water interface occurs spontaneously and Electrostatic forces are the main driving factor. This study contributes to a more comprehensive understanding on the behaviour of the phosphorus building gypsum/surfactant composites.
Subject(s)
Calcium Sulfate , Surface-Active Agents , Surface-Active Agents/chemistry , Molecular Dynamics Simulation , Water/chemistry , PhosphorusABSTRACT
AIMS: To investigate the expression of polo-like kinase 1 protein (PLK1) and its phosphorylation level (p-PLK1) in extranodal NK/T cell lymphoma (NKTCL) and their correlation with clinical characteristics and prognosis. METHODS: We collected 40 cases of NKTCL (referred to as the experimental group), which received diagnoses at the First Affiliated Hospital of Zhengzhou University between January 2018 and October 2022. Concurrently, we assembled a control group, including 20 cases afflicted with nasopharyngeal mucosal lymphoid hyperplasia diseases during the same timeframe. We utilized immunohistochemical techniques to evaluate the levels of PLK1 and p-PLK1 expression in both the experimental and control groups. Subsequently, we conducted an analysis to identify disparities in their expression and explore their relationships with clinical characteristics and patient prognosis. RESULTS: Among the 40 NKTCL patients, there were 27 males and 11 females, with a median age of 51 years (range 12-80 years). Compared to the control group, the tissue samples of NKTCL patients exhibited significantly elevated expression levels and active phosphorylation levels of PLK1 (P < 0.05). Correlation analysis of the immunohistochemical H score and Ki-67 positive rate of PLK1 and p-PLK1, revealed a significant positive correlation for both (P < 0.0001, each). No statistically significant differences were observed in the distribution of PLK1 and p-PLK1 expression in NKTCL patients with respect to gender, age, Ann Arbor stage, PINK-E score, B-symptoms, lactate dehydrogenase, ß2-microglobulin, blood EBV-DNA, bone marrow invasion, and lymph node metastasis (p > 0.05). Grouping based on PLK1 and p-PLK1 immunohistochemical H-scores revealed that the high expression of PLK1 and p-PLK1 was associated with poor prognosis. CONCLUSIONS: The expression levels and active phosphorylation levels of PLK1 were significantly increased in NK/T cell lymphoma, and patients with overexpression of PLK1 and p-PLK1 had a poorer prognosis.
Subject(s)
Lymphoma, Extranodal NK-T-Cell , Lymphoma, T-Cell , Male , Female , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Clinical Relevance , Cell Cycle Proteins , Protein Serine-Threonine Kinases , Prognosis , Lymphoma, T-Cell/diagnosis , Lymphoma, Extranodal NK-T-Cell/pathology , Polo-Like Kinase 1ABSTRACT
Ustilaginoidea virens is a destructive phytopathogenic fungus that causes false smut disease in rice. In this study, the natural product 2,4-di-tert-butylphenol (2,4-DTBP) was found to be an environmentally friendly and effective agent for the first time, which exhibited strong antifungal activity against U. virens, with an EC50 value of 0.087 mmol/L. The scanning electron microscopy, fluorescence staining, and biochemical assays indicated that 2,4-DTBP could destroy the cell wall, cell membrane, and cellular redox homeostasis of U. virens, ultimately resulting in fungal cell death. Through the transcriptomic analysis, a total of 353 genes were significantly upregulated and 367 genes were significantly downregulated, focusing on the spindle microtubule assembly, cell wall and membrane, redox homeostasis, mycotoxin biosynthesis, and intracellular metabolism. These results enhanced the understanding of the antifungal activity and action mechanisms of 2,4-DTBP against U. virens, supporting it to be a potential antifungal agent for the control of false smut disease.
Subject(s)
Hypocreales , Oryza , Antifungal Agents/pharmacology , Hypocreales/genetics , Phenols/pharmacology , Oryza/genetics , Plant Diseases/microbiologyABSTRACT
BACKGROUND: Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury. OBJECTIVE: The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery. METHODS: We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline. RESULTS: Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion. CONCLUSIONS: Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.
ABSTRACT
Functional deficits including cognitive impairment and social dysfunction are the core symptoms of schizophrenia (SCZ), and sensory gating (SG) deficits may be involved in the pathological mechanism of functional deficits in SCZ. This study was to investigate the relationship between defective P50 inhibition and functional deficits in first-episode drug naïve (FEDN) SCZ patients. A total of 95 FEDN SCZ patients and 53 healthy controls (HC) were recruited. The Chinese version of UCSD Performance-Based Skills (UPSA), MATRICS Consensus Cognitive Battery (MCCB), and EEG system were used to assess the social function, cognitive performance, and P50 inhibition, respectively. The MCCB total score and eight domain scores were significantly lower in patients with FEDN SCZ than those in HC (all p < 0.05). The UPSA total score and financial skills scores were also significantly lower in SCZ patients than that in the HC (all p < 0.05). Compared with HC, patients with FEDF SCZ had a higher P50 ratio (all p < 0.05). There was no correlation between P50 components and MCCB scores in patients with FEDF SCZ. However, there was only a correlation between the P50 ratio and UPSA financial skills, communication skills, or total score in patients (all p < 0.05). Defective P50 inhibition in FEDN SCZ patients may be associated with social dysfunction but not cognitive impairment, suggesting that the social dysfunction and cognitive impairment of patients with FEDN SCZ may have different pathogenic mechanisms.